D

Dabigatran etexilate (Pradaxa)

Abemaciclib [1], dabigatran etexilate ---> SmPC of [1] of EMA

Based on the in vitro inhibition of P-gp and BCRP observed with abemaciclib, in vivo interactions of abemaciclib with narrow therapeutic index substrates of these transporters, such as digoxin or dabigatran etexilate, may occur.

Acetylsalicylic acid, dabigatran etexilate [2] ---> SmPC of [2] of EMA

Concomitant use of antiplatelets, ASA or clopidogrel approximately doubled major bleeding rates with both dabigatran etexilate and warfarin (see section 4.4).

Alectinib [1], dabigatran etexilate ---> SmPC of [1] of EMA

When Alecensa is co-administered with P-gp substrates (e.g., digoxin, dabigatran etexilate, topotecan, sirolimus, everolimus, nilotinib and lapatinib), appropriate monitoring is recommended.

Amiodarone, dabigatran etexilate [2] ---> SmPC of [2] of EMA

Dabigatran etexilate is a substrate for the efflux transporter P-gp. Caution should be exercised with mild to moderate P-gp inhibitors

Anticoagulants, dabigatran etexilate [2] ---> SmPC of [2] of EMA

Concomitant treatment of dabigatran with any other anticoagulants is contraindicated, except under specific circumstances of switching anticoagulant therapy or when UFH is given at doses necessary to maintain an open central venous or arterial catheter

Apixaban, dabigatran etexilate [2] ---> SmPC of [2] of EMA

Breast-feeding, dabigatran etexilate [2] ---> SmPC of [2] of EMA

Lactation should be discontinued during treatment with Pradaxa

Cabozantinib [1], dabigatran etexilate ---> SmPC of [1] of EMA

Cabozantinib may have the potential to increase plasma concentrations of co-administered substrates of P-gp. Subjects should be cautioned regarding taking a P-gp substrate while receiving cabozantinib.

Capmatinib [1], dabigatran etexilate ---> SmPC of [1] of EMA

Caution should be exercised during co-administration of Tabrecta with P-gp (digoxin, dabigatran etexilate, colchicine, sitagliptin, saxagliptin and posaconazole)

Carbamazepine, dabigatran etexilate [2] ---> SmPC of [2] of EMA

Dabigatran etexilate is a substrate for the efflux transporter P-gp. Concomitant administration of a P-gp inducer is expected to result in decreased dabigatran concentrations and should be avoided

Clarithromycin, dabigatran etexilate [2] ---> SmPC of [2] of EMA

Dabigatran etexilate is a substrate for the efflux transporter P-gp. Close clinical surveillance (looking for signs of bleeding or anaemia) is required when dabigatran is co-administered with strong P-gp inhibitors.

Clopidogrel, dabigatran ---> SmPC of [dabigatran etexilate] of EMA

The co-administration may increase the risk of bleeding

Clopidogrel, dabigatran etexilate [2] ---> SmPC of [2] of EMA

Concomitant use of antiplatelets, ASA or clopidogrel approximately doubled major bleeding rates with both dabigatran etexilate and warfarin (see section 4.4).

Cyclosporine, dabigatran etexilate [2] ---> SmPC of [2] of EMA

Dabigatran is a substrate for the efflux transporter P-gp. Concomitant administration of strong P-gp inhibitors is expected to result in increased dabigatran plasma concentrations. The coadministration with cyclosporine is contraindicated

Dabigatran etexilate [1], dalteparin ---> SmPC of [1] of EMA

Dabigatran etexilate [1], desirudin ---> SmPC of [1] of EMA

The co-administration may increase the risk of bleeding

Dabigatran etexilate [1], dextran ---> SmPC of [1] of EMA

The co-administration may increase the risk of bleeding

Dabigatran etexilate [1], digoxin ---> SmPC of [1] of EMA

When dabigatran was co-administered with digoxin, no changes on digoxin and no clinical relevant changes on dabigatran exposure have been observed.

Dabigatran etexilate [1], dronedarone ---> SmPC of [1] of EMA

Dabigatran etexilate [1], enoxaparin ---> SmPC of [1] of EMA

Dabigatran etexilate [1], fertility ---> SmPC of [1] of EMA

In the pre- and post-natal study, an increase in foetal mortality was observed at doses that were toxic to the dams (a dose corresponding to a plasma exposure level 4-fold higher than observed in patients).

Dabigatran etexilate [1], fondaparinux ---> SmPC of [1] of EMA

Dabigatran etexilate [1], glecaprevir/pibrentasvir ---> SmPC of [1] of EMA

The concomitant use of dabigatran etexilate with the fixed-dose combination of the P-gp inhibitors glecaprevir/pibrentasvir has been shown to increase exposure of dabigatran and may increase the risk of bleeding.

Dabigatran etexilate [1], GP IIb/IIIa inhibitors ---> SmPC of [1] of EMA

The co-administration may increase the risk of bleeding

Dabigatran etexilate [1], heparin ---> SmPC of [1] of EMA

The co-administration may increase the risk of bleeding

Dabigatran etexilate [1], inhibitors of intestinal P-gp ---> SmPC of [1] of EMA

Dabigatran etexilate is a substrate for the efflux transporter P-gp. Caution should be exercised with mild to moderate P-gp inhibitors

Dabigatran etexilate [1], itraconazol ---> SmPC of [1] of EMA

Dabigatran etexilate [1], ketoconazole ---> SmPC of [1] of EMA

Dabigatran etexilate [1], low molecular weight heparins ---> SmPC of [1] of EMA

Dabigatran etexilate [1], moderate P-gp inhibitors ---> SmPC of [1] of EMA

Dabigatran etexilate is a substrate for the efflux transporter P-gp. Caution should be exercised with mild to moderate P-gp inhibitors

Dabigatran etexilate [1], NSAID ---> SmPC of [1] of EMA

NSAIDs given for short-term analgesia have been shown not to be associated with increased bleeding risk when given in conjunction with dabigatran etexilate.

Dabigatran etexilate [1], NSAID ---> SmPC of [1] of EMA

With chronic use in the RE-LY study, NSAIDs increased the risk of bleeding by approximately 50% on both dabigatran etexilate and warfarin.

Dabigatran etexilate [1], oral anticoagulants ---> SmPC of [1] of EMA

Dabigatran etexilate [1], P-gp inhibitors ---> SmPC of [1] of EMA

Dabigatran etexilate is a substrate for the efflux transporter P-gp. Caution should be exercised with mild to moderate P-gp inhibitors

Dabigatran etexilate [1], pantoprazole ---> SmPC of [1] of EMA

Pantoprazole and other proton-pump inhibitors (PPI) were co-administered with Pradaxa in clinical trials, and concomitant PPI treatment did not appear to reduce the efficacy of Pradaxa.

Dabigatran etexilate [1], phenytoin ---> SmPC of [1] of EMA

Dabigatran etexilate is a substrate for the efflux transporter P-gp. Concomitant administration of a P-gp inducer is expected to result in decreased dabigatran concentrations and should be avoided

Dabigatran etexilate [1], platelet aggregation inhibitors ---> SmPC of [1] of EMA

The co-administration may increase the risk of bleeding

Dabigatran etexilate [1], posaconazole ---> SmPC of [1] of EMA

Posaconazole also inhibits P-gp to some extent but has not been clinically studied. Caution should be exercised when Pradaxa is co-administered with posaconazole.

Dabigatran etexilate [1], prasugrel ---> SmPC of [1] of EMA

The co-administration may increase the risk of bleeding

Dabigatran etexilate [1], pregnancy ---> SmPC of [1] of EMA

Pradaxa should not be used during pregnancy unless clearly necessary

Dabigatran etexilate [1], protease inhibitors ---> SmPC of [1] of EMA

Protease inhibitors including ritonavir and its combinations with other protease inhibitors affect P-gp (either as inhibitor or as inducer). They have not been studied and are therefore not recommended for concomitant treatment with dabigatran.

Dabigatran etexilate [1], proton pump inhibitors ---> SmPC of [1] of EMA

Pantoprazole and other proton-pump inhibitors (PPI) were co-administered with Pradaxa in clinical trials, and concomitant PPI treatment did not appear to reduce the efficacy of Pradaxa.

Dabigatran etexilate [1], quinidine ---> SmPC of [1] of EMA

Dabigatran etexilate is a substrate for the efflux transporter P-gp. Caution should be exercised with mild to moderate P-gp inhibitors

Dabigatran etexilate [1], ranitidine ---> SmPC of [1] of EMA

Ranitidine administration together with Pradaxa had no clinically relevant effect on the extent of absorption of dabigatran.

Dabigatran etexilate [1], rifampicin ---> SmPC of [1] of EMA

Dabigatran etexilate is a substrate for the efflux transporter P-gp. Concomitant administration of a P-gp inducer is expected to result in decreased dabigatran concentrations and should be avoided

Dabigatran etexilate [1], rivaroxaban ---> SmPC of [1] of EMA

Dabigatran etexilate [1], SNRIs ---> SmPC of [1] of EMA

SSRIs and SNRIs increased the risk of bleeding in RE-LY study in all treatment groups.

Dabigatran etexilate [1], SSNRI ---> SmPC of [1] of EMA

SSRIs and SNRIs increased the risk of bleeding in RE-LY study in all treatment groups.

Dabigatran etexilate [1], St. John's wort ---> SmPC of [1] of EMA

Dabigatran etexilate is a substrate for the efflux transporter P-gp. Concomitant administration of a P-gp inducer is expected to result in decreased dabigatran concentrations and should be avoided

Dabigatran etexilate [1], strong P-gp inductors ---> SmPC of [1] of EMA

Dabigatran etexilate is a substrate for the efflux transporter P-gp. Concomitant administration of a P-gp inducer is expected to result in decreased dabigatran concentrations and should be avoided

Dabigatran etexilate [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

Dabigatran etexilate [1], sulfinpyrazone ---> SmPC of [1] of EMA

The co-administration may increase the risk of bleeding

Dabigatran etexilate [1], tacrolimus ---> SmPC of [1] of EMA

Tacrolimus has been found in vitro to have a similar level of inhibitory effect on Pgp as that seen with itraconazole and cyclosporine.

Dabigatran etexilate [1], thrombolytics ---> SmPC of [1] of EMA

The co-administration may increase the risk of bleeding

Dabigatran etexilate [1], ticagrelor ---> SmPC of [1] of EMA

Dabigatran etexilate is a substrate for the efflux transporter P-gp. Caution should be exercised with mild to moderate P-gp inhibitors

Dabigatran etexilate [1], ticlopidine ---> SmPC of [1] of EMA

The co-administration may increase the risk of bleeding

Dabigatran etexilate [1], unfractionated heparins ---> SmPC of [1] of EMA

Dabigatran etexilate [1], verapamil ---> SmPC of [1] of EMA

Dabigatran etexilate is a substrate for the efflux transporter P-gp. Caution should be exercised with mild to moderate P-gp inhibitors

Dabigatran etexilate [1], vitamin K antagonists ---> SmPC of [1] of EMA

The co-administration may increase the risk of bleeding

Dabigatran etexilate [1], warfarin ---> SmPC of [1] of EMA

Dabigatran etexilate [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should avoid pregnancy during treatment with Pradaxa.

Dabigatran etexilate, daclatasvir [2] ---> SmPC of [2] of EMA

Increased dabigatran level is expected due to P-gp inhibition by daclatasvir. Safety monitoring is advised when initiating therapy with Daklinza in patients receiving dabigatran/other intestinal P-gp substrate that have a narrow therapeutic range.

Dabigatran etexilate, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Co-administration of REZOLSTA with this anticoagulant may increase concentrations of the anticoagulant. (CYP3A and/or P-glycoprotein inhibition). Co-administration of REZOLSTA and this anticoagulant is not recommended.

Dabigatran etexilate, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Based on theoretical considerations co-administration of DRV/COBI with this anticoagulant may increase concentrations of the anticoagulant. (CYP3A and/or P-glycoprotein inhibition). Co-administration of Symtuza and this anticoagulant is not recommended.

Dabigatran etexilate, darunavir/ritonavir ---> SmPC of [darunavir] of EMA

Co-administration of boosted darunavir (CYP3A and/or P-gp inhibition) with this anticoagulant may increase concentrations of the anticoagulant. The use of boosted darunavir and the anticoagulant is not recommended.

Dabigatran etexilate, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [dasabuvir] of EMA

Intestinal Pgp inhibition by paritaprevir and ritonavir may increase the plasma concentrations of dabigatran etexilate. Use with caution.

Dabigatran etexilate, dasabuvir [2] ---> SmPC of [2] of EMA

It may not be excluded that the systemic exposure of dabigatran etexilate is increased by dasabuvir due to inhibition of P-gp in the intestine.

Dabigatran etexilate, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

A risk for increases in dabigatran plasma concentrations cannot be excluded. The combination of Juluca and dabigatran etexilate should be used with caution.

Dabigatran etexilate, elbasvir/grazoprevir [2] ---> SmPC of [2] of EMA

P-gp inhibition. Concentrations of dabigatran may increase when co-administered with elbasvir, with possible increased bleeding risk. Clinical and laboratory monitoring is recommended.

Dabigatran etexilate, emtricitabine/rilpivirine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

A risk for increases in dabigatran plasma concentrations cannot be excluded (inhibition of intestinal P-gp). Co-administration should be used with caution.

Dabigatran etexilate, emtricitabine/rilpivirine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

It may not be completely excluded that rilpivirine can increase the exposure to other medicinal products transported by P-gp that are more sensitive to intestinal P-gp inhibition (e.g. dabigatran etexilate).

Dabigatran etexilate, entrectinib [2] ---> SmPC of [2] of EMA

The effect of entrectinib on digoxin absorption is not considered clinically relevant, but it is unknown whether the effect of entrectinib may be larger on more sensitive oral P-gp substrates such as dabigatran etexilate.

Dabigatran etexilate, enzalutamide [2] ---> SmPC of [2] of EMA

Medicinal products with a narrow therapeutic range that are substrates for P-gp should be used with caution when administered concomitantly with enzalutamide and may require dose adjustment to maintain optimal plasma concentrations.

Dabigatran etexilate, fidaxomicin [2] ---> SmPC of [2] of EMA

A larger effect on P-gp substrates with lower bioavailability more sensitive to intestinal P-gp inhibition such as dabigatran etexilate cannot be excluded.

Dabigatran etexilate, glecaprevir/pibrentasvir [2] ---> SmPC of [2] of EMA

Co-administration with Maviret may increase plasma concentrations of medicinal products that are substrates of P-gp. Co-administration is contraindicated

Dabigatran etexilate, idebenone [2] ---> SmPC of [2] of EMA

Idebenone may inhibit P-glycoprotein (P-gp) with possible exposure increases of, e.g., dabigatran etexilate, digoxin or aliskiren. These medicines should be administered with caution in patients receiving idebenone.

Dabigatran etexilate, idelalisib [2] ---> SmPC of [2] of EMA

A risk for P-gp inhibition in the gastrointestinal tract, that could result in increased exposure of sensitive substrates for intestinal P-gp such as dabigatran etexilate, cannot be excluded.

Dabigatran etexilate, isavuconazole [2] ---> SmPC of [2] of EMA

No CRESEMBA dose adjustment necessary. Dabigatran etexilate has a narrow therapeutic index and should be monitored, and dose reduction if required.

Dabigatran etexilate, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

Clinical monitoring, looking for signs of bleeding and anaemia is recommended when dabigatran etexilate is co-administered with ledipasvir/sofosbuvir (inhibition of P-glycoprotein)

Dabigatran etexilate, lurasidone [2] ---> SmPC of [2] of EMA

Concomitant administration of the P-gp substrate dabigatran etexilate may result in increased dabigatran plasma concentrations.

Dabigatran etexilate, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

Viekirax may increase the plasma exposure to medicinal products that are sensitive for changed intestinal P-gp activity (such as dabigatran etexilate).

Dabigatran etexilate, pirtobrutinib [2] ---> SmPC of [2] of EMA

If co-administration with narrow therapeutic index P-gp substrates (e.g dabigatran etexilate and digoxin) cannot be avoided, close clinical monitoring should be considered.

Dabigatran etexilate, quizartinib [2] ---> SmPC of [2] of EMA

Quizartinib is a weak P-gp inhibitor, and no dose modification is recommended when P-gp substrates are co-administered with VANFLYTA.

Dabigatran etexilate, ritonavir [2] ---> SmPC of [2] of EMA

Clinical monitoring and/or dose reduction of the direct oral anticoagulants (DOAC) should be considered when a DOAC transported by P-gp but not metabolised by CYP3A4, including dabigatran etexilate and edoxaban, is co-administered with ritonavir.

Dabigatran etexilate, rolapitant [2] ---> SmPC of [2] of EMA

Rolapitant is an inhibitor of P-glycoprotein (P-gp). Clinical monitoring of adverse reactions and, if possible, biological monitoring are recommended when rolapitant is combined with digoxin or with other P-gp substrates

Dabigatran etexilate, ruxolitinib [2] ---> SmPC of [2] of EMA

Ruxolitinib may inhibit P-glycoprotein and breast cancer resistance protein (BCRP) in the intestine. This may result in increased systemic exposure of substrates of these transporters

Dabigatran etexilate, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib is an in vitro inhibitor of P-gp and BCRP. Caution should be used when taking a P-gp substrate (e.g., fexofenadine, dabigatran etexilate, digoxin, colchicine, saxagliptin)

Dabigatran etexilate, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Inhibition of P-gp. Clinical monitoring, looking for signs of bleeding and anaemia, is recommended when dabigatran is co-administered with Epclusa. A coagulation test helps to identify patients with an increased bleeding risk

Dabigatran etexilate, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Dabigatran etexilate (P-gp substrate) and rosuvastatin (OATP1B and BCRP substrate) are contraindicate

Dabigatran etexilate, telithromycin [2] ---> SmPC of [2] of EMA

Telithromycin is also a P-glycoprotein inhibitor. Concomitant administration of telithromycin with drugs that are substrates of P-glycoprotein might result in increased exposure to the P-glycoprotein substrates

Dabigatran etexilate, tepotinib [2] ---> SmPC of [2] of EMA

Tepotinib is an inhibitor of P-gp. Dose adjustment of dabigatran etexilate may be needed in case of concomitant use.

Dabigatran etexilate, vemurafenib [2] ---> SmPC of [2] of EMA

Caution should be exercised, dose reduction and/or additional drug level monitoring for P-gp substrate medicinal products with narrow therapeutic index (NTI) may be considered if these medicinal products are used concomitantly with vemurafenib

Dabigatran etexilate, venetoclax [2] ---> SmPC of [2] of EMA

Venetoclax is a P-gp, BCRP and OATP1B1 inhibitor in vitro. Co-administration of narrow therapeutic index P-gp, or BCRP substrates (e.g., digoxin, dabigatran, everolimus, sirolimus) with Venclyxto should be avoided.

Dabigatran etexilate, voclosporine [2] ---> SmPC of [2] of EMA

Caution must be exercised in case of co-administration of voclosporin with sensitive P-gp substrates, especially those with narrow therapeutic index where patients should be appropriately monitored as outlined in respective product labelling.

Dabigatran, desirudin ---> SmPC of [dabigatran etexilate] of EMA

The co-administration may increase the risk of bleeding

CONTRAINDICATIONS of Dabigatran etexilate (Pradaxa)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Severe renal impairment (CrCL <30 mL/min) in adult patients

- eGFR <50 mL/min/1.73m2 in paediatric patients

- Active clinically significant bleeding

- Lesion or condition, if considered a significant risk factor for major bleeding. This may include current or recent gastrointestinal ulceration, presence of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities

- Concomitant treatment with any other anticoagulants e.g. unfractionated heparin (UFH), low molecular weight heparins (enoxaparin, dalteparin etc), heparin derivatives (fondaparinux etc), oral anticoagulants (warfarin, rivaroxaban, apixaban etc) except under specific circumstances. These are switching anticoagulant therapy (see section 4.2), when UFH is given at doses necessary to maintain an open central venous or arterial catheter or when UFH is given during catheter ablation for atrial fibrillation (see section 4.5) ? Hepatic impairment or liver disease expected to have any impact on survival

- Concomitant treatment with the following strong P-gp inhibitors: systemic ketoconazole,

- Prosthetic heart valves requiring anticoagulant treatment (see section 5.1).

https://www.ema.europa.eu/en/documents/product-information/pradaxa-epar-product-information_en.pdf. 24/11/2023

Dabrafenib (Tafinlar)

Ability to drive, dabrafenib [2] ---> SmPC of [2] of EMA

Patients should be made aware of the potential for fatigue and eye problems

Acenocoumarol, dabrafenib [2] ---> SmPC of [2] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Amprenavir, dabrafenib [2] ---> SmPC of [2] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Antacids, dabrafenib [2] ---> SmPC of [2] of EMA

Medicinal products that alter the pH of the upper gastrointestinal (GI) tract (e.g. proton pump inhibitors, H2-receptor antagonists, antacids) are not expected to reduce the bioavailability of dabrafenib.

Atazanavir, dabrafenib [2] ---> SmPC of [2] of EMA

Use caution if strong inhibitors (e.g. ketoconazole, gemfibrozil, nefazodone, clarithromycin, ritonavir, saquinavir, telithromycin, itraconazole, voriconazole, posaconazole, atazanavir) are co-administered with dabrafenib.

Atorvastatin, dabrafenib [2] ---> SmPC of [2] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Avapritinib [1], dabrafenib ---> SmPC of [1] of EMA

Co-administration with strong or moderate CYP3A inducers should be avoided because it may decrease the plasma concentrations of avapritinib

BCRP substrates, dabrafenib [2] ---> SmPC of [2] of EMA

Induction of OATP1B1/1B3 and BCRP is not likely based on the observations from a clinical study with rosuvastatin.

Breast-feeding, dabrafenib [2] ---> SmPC of [2] of EMA

A decision should be made whether to discontinue breast-feeding or discontinue dabrafenib, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Cabazitaxel, dabrafenib [2] ---> SmPC of [2] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Carbamazepine, dabrafenib [2] ---> SmPC of [2] of EMA

Avoid co-administration of dabrafenib with potent inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital, or St John's wort (Hypericum perforatum)) of CYP2C8 or CYP3A4.

Clarithromycin, dabrafenib [2] ---> SmPC of [2] of EMA

Corticosteroids, dabrafenib [2] ---> SmPC of [2] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Cyclosporine, dabrafenib [2] ---> SmPC of [2] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], darunavir ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], delavirdine ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], dexamethasone ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], diazepam ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], digoxin ---> SmPC of [1] of EMA

Concomitant administration of dabrafenib with digoxin may result in decreased digoxin exposure. Caution should be exercised and additional monitoring of digoxin is recommended

Dabrafenib [1], diltiazem ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], doxycycline ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], drugs primarily metabolised by CYP2B6 ---> SmPC of [1] of EMA

Dabrafenib, enzymatic inductor, may increase the metabolism of the medicine product that is metabolised by CYP2B6 and decrease its plasma levels and effect

Dabrafenib [1], drugs primarily metabolised by CYP2C19 ---> SmPC of [1] of EMA

Dabrafenib, enzymatic inductor, may increase the metabolism of the medicine product that is metabolised by CYP2C19 and decrease its plasma levels and effect

Dabrafenib [1], drugs primarily metabolised by CYP2C8 ---> SmPC of [1] of EMA

Dabrafenib, enzymatic inductor, may increase the metabolism of the medicine product that is metabolised by CYP2C8 and decrease its plasma levels and effect

Dabrafenib [1], drugs primarily metabolised by CYP2C9 ---> SmPC of [1] of EMA

Dabrafenib, enzymatic inductor, may increase the metabolism of the medicine product that is metabolised by CYP2C9 and decrease its plasma levels and effect

Dabrafenib [1], drugs primarily metabolised by CYP3A4 ---> SmPC of [1] of EMA

Dabrafenib, enzymatic inductor, may increase the metabolism of the medicine product that is metabolised by CYP3A4 and decrease its plasma levels and effect

Dabrafenib [1], drugs primarily metabolised by glucuronidation ---> SmPC of [1] of EMA

Dabrafenib, enzymatic inductor, may increase the metabolism of the medicine product that is metabolised by glucuronidation and decrease its plasma levels and effect

Dabrafenib [1], efavirenz ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], felodipine ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], fentanyl ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], fertility ---> SmPC of [1] of EMA

Dabrafenib may impair male and female fertility as adverse effects on male and female reproductive organs have been seen in animals (see section 5.3).

Dabrafenib [1], foods ---> SmPC of [1] of EMA

Patients should take dabrafenib as monotherapy or in combination with trametinib at least one hour prior to or two hours after a meal due to the effect of food on dabrafenib absorption (see section 5.2).

Dabrafenib [1], fosamprenavir ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], gastric pH increasing medication ---> SmPC of [1] of EMA

Dabrafenib [1], gemfibrozil ---> SmPC of [1] of EMA

Administration of gemfibrozil (a CYP2C8 inhibitor) 600 mg twice daily, with dabrafenib 75 mg twice daily, resulted in a 47% increase in dabrafenib AUC but did not alter dabrafenib Cmax relative to administration of dabrafenib 75 mg twice daily alone.

Dabrafenib [1], H2 antagonists ---> SmPC of [1] of EMA

Dabrafenib [1], haloperidol ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], hormonal contraceptives ---> SmPC of [1] of EMA

Dabrafenib may decrease the efficacy of oral or any systemic hormonal contraceptives and an effective alternative method of contraception should be used (see section 4.5).

Dabrafenib [1], indinavir ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], itraconazol ---> SmPC of [1] of EMA

Dabrafenib [1], ketoconazole ---> SmPC of [1] of EMA

Administration of ketoconazole (a CYP3A4 inhibitor) 400 mg once daily, with dabrafenib 75 mg twice daily, resulted in a 71% increase in dabrafenib AUC and a 33% increase in dabrafenib Cmax relative to administration of dabrafenib 75 mg twice daily alone.

Dabrafenib [1], lopinavir ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], men ---> SmPC of [1] of EMA

Male patients taking dabrafenib as monotherapy or in combination with trametinib should be informed of the potential risk for impaired spermatogenesis, which may be irreversible.

Dabrafenib [1], metabolism ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. If their therapeutic effect is of large importance to the patient, and dose adjustments are not easily performed

Dabrafenib [1], methadone ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], methylprednisolone ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], midazolam ---> SmPC of [1] of EMA

In a clinical drug interaction study, Cmax and AUC of oral midazolam (a CYP3A4 substrate) decreased by 47% and 65%, respectively with co-administration of repeat-dose dabrafenib.

Dabrafenib [1], nefazodone ---> SmPC of [1] of EMA

Dabrafenib [1], nicardipine ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], nifedipine ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], OATP1B1 substrates ---> SmPC of [1] of EMA

Induction of OATP1B1/1B3 and BCRP is not likely based on the observations from a clinical study with rosuvastatin.

Dabrafenib [1], OATP1B3 substrates ---> SmPC of [1] of EMA

Induction of OATP1B1/1B3 and BCRP is not likely based on the observations from a clinical study with rosuvastatin.

Dabrafenib [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

The transport protein Pgp may also be induced as well as other transporters, e.g. MRP-2.

Dabrafenib [1], pancreatitis ---> SmPC of [1] of EMA

Patients should be closely monitored when re-starting dabrafenib after an episode of pancreatitis

Dabrafenib [1], paracetamol ---> SmPC of [1] of EMA

The risk for liver injury after paracetamol administration is suspected to be higher in patients concomitantly treated with enzyme inducers

Dabrafenib [1], phenobarbital ---> SmPC of [1] of EMA

Avoid co-administration of dabrafenib with potent inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital, or St John's wort (Hypericum perforatum)) of CYP2C8 or CYP3A4.

Dabrafenib [1], phenytoin ---> SmPC of [1] of EMA

Avoid co-administration of dabrafenib with potent inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital, or St John's wort (Hypericum perforatum)) of CYP2C8 or CYP3A4.

Dabrafenib [1], posaconazole ---> SmPC of [1] of EMA

Dabrafenib [1], pregnancy ---> SmPC of [1] of EMA

Dabrafenib should not be administered to pregnant women unless the potential benefit to the mother outweighs the possible risk to the foetus.

Dabrafenib [1], pregnancy ---> SmPC of [1] of EMA

If the patient becomes pregnant while taking dabrafenib, the patient should be informed of the potential hazard to the foetus.

Dabrafenib [1], primidone ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], proton pump inhibitors ---> SmPC of [1] of EMA

Dabrafenib [1], QT interval prolonging drugs ---> SmPC of [1] of EMA

A supratherapeutic dose of 300 mg dabrafenib twice daily was administered in 32 subjects with BRAF V600 mutation-positive tumours. No clinically relevant effect of dabrafenib or its metabolites on the QTc interval was observed.

Dabrafenib [1], rabeprazole ---> SmPC of [1] of EMA

Co-administration of repeat doses of dabrafenib 150 mg twice daily and the pH-elevating agent rabeprazole 40 mg once daily resulted in a 3% increase in AUC and a 12% decrease in dabrafenib Cmax.

Dabrafenib [1], rifampicin ---> SmPC of [1] of EMA

Avoid co-administration of dabrafenib with potent inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital, or St John's wort (Hypericum perforatum)) of CYP2C8 or CYP3A4.

Dabrafenib [1], ritonavir ---> SmPC of [1] of EMA

Dabrafenib [1], rosuvastatin ---> SmPC of [1] of EMA

Cmax of rosuvastatin increased 2.6-fold whereas the AUC was only minimally changed (7% increase). The increased Cmax of rosuvastatin is unlikely to have clinical relevance.

Dabrafenib [1], saquinavir ---> SmPC of [1] of EMA

Dabrafenib [1], simvastatine ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], sirolimus ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], St. John's wort ---> SmPC of [1] of EMA

Avoid co-administration of dabrafenib with potent inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital, or St John's wort (Hypericum perforatum)) of CYP2C8 or CYP3A4.

Dabrafenib [1], statins metabolised by CYP3A4 ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], strong CYP2C8 inductors ---> SmPC of [1] of EMA

Avoid co-administration of dabrafenib with potent inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital, or St John's wort (Hypericum perforatum)) of CYP2C8 or CYP3A4.

Dabrafenib [1], strong CYP2C8 inhibitors ---> SmPC of [1] of EMA

Dabrafenib is a substrate for the metabolising enzymes CYP2C8. Medicines that are strong inhibitors of CYP2C8 are therefore likely to increase dabrafenib concentrations. Use caution if strong inhibitors are coadministered with dabrafenib.

Dabrafenib [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Avoid co-administration of dabrafenib with potent inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital, or St John's wort (Hypericum perforatum)) of CYP2C8 or CYP3A4.

Dabrafenib [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Dabrafenib is a substrate for the metabolising enzymes CYP3A4. Medicines that are strong inhibitors of CYP3A4 are therefore likely to increase dabrafenib concentrations. Use caution if strong inhibitors are coadministered with dabrafenib.

Dabrafenib [1], tacrolimus ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], telithromycin ---> SmPC of [1] of EMA

Dabrafenib [1], tipranavir ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], trametinib ---> SmPC of [1] of EMA

A small decrease in trametinib bioavailability, corresponding to a decrease in AUC of 12%, was estimated when trametinib is administered in combination with dabrafenib, a CYP3A4 inducer, using a population pharmacokinetic analysis.

Dabrafenib [1], valproic acid ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], verapamil ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib [1], voriconazole ---> SmPC of [1] of EMA

Dabrafenib [1], warfarin ---> SmPC of [1] of EMA

Administration of dabrafenib 150 mg twice daily and warfarin resulted in a decrease in AUC of S-and R-warfarin of 37% and 33%, respectively, compared to administration of warfarin alone. Cmax of S-and R-warfarin increased 18% and 19%.

Dabrafenib [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential must use effective methods of contraception during therapy and for 2 weeks following discontinuation of dabrafenib and 16 weeks following the last dose of trametinib when given in combination with dabrafenib.

Dabrafenib [1], zolpidem ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dabrafenib, doravirine [2] ---> SmPC of [2] of EMA

If co-administration with other moderate CYP3A inducers cannot be avoided, the doravirine dose should be increased to 100 mg twice daily (the doses should be taken approximately 12 hours apart)

Dabrafenib, doravirine/lamivudine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

If co-administration with other moderate CYP3A inducers cannot be avoided, a 100 mg dose of doravirine should be administered daily, approximately 12 hours after the administration of doravirine/lamivudine/tenofovir disoproxil dose

Dabrafenib, elacestrant [2] ---> SmPC of [2] of EMA

Concomitant administration of ORSERDU with moderate CYP3A4 inductors should be avoided, which may decrease elacestrant activity

Dabrafenib, macimorelin [2] ---> SmPC of [2] of EMA

Administration of a CYP3A4 inducer may reduce the plasma macimorelin concentrations and may affect the diagnostic performance of the test and therefore should be avoided.

Dabrafenib, trametinib [2] ---> SmPC of [2] of EMA

New malignancies, cutaneous and non-cutaneous, can occur when trametinib is used in combination with dabrafenib.

CONTRAINDICATIONS of Dabrafenib (Tafinlar)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/tafinlar-epar-product-information_en.pdf 07/03/2024

Dacarbazine

Ability to drive, dacarbazine [2] ---> SPC of [2] of eMC

Dacarbazine may influence the ability to drive or operate machines because of its central nervous side effects or because of nausea and vomiting.

Alcohol, dacarbazine [2] ---> SPC of [2] of eMC

Alcohol should be avoided during chemotherapy.

Aldesleukin [1], dacarbazine ---> SPC of [1] of eMC

Fatal tumour lysis syndrome has been reported in combination of aldesleukin with treatment with cis-platinum, vinblastine and dacarbazine. Concomitant use of the mentioned active substances is therefore not recommended.

Breast-feeding, dacarbazine [2] ---> SPC of [2] of eMC

Dacarbazine must not be used during breastfeeding

Cyclosporine, dacarbazine

The co-administration of dacarbazine with cyclosporine (and by extrapolation tacrolimus) is only to be used after carefully weighing because it may result in excessive immunosuppression with risk of lymphoproliferation.

Cytostatics, dacarbazine [2] ---> SPC of [2] of eMC

In case of previous or concomitant treatment having adverse effects on the bone marrow (particularly cytostatic agents, irradiation) myelotoxic interactions are possible.

Dacarbazine [1], drugs primarily metabolised by CYP1A1 ---> SPC of [1] of eMC

Dacarbazine is metabolised by cytochrome P450 (CYP1A1, CYP1A2, and CYP2E1). This has to be taken into account if other drugs are co-administered which are metabolised by the same hepatic enzymes.

Dacarbazine [1], drugs primarily metabolised by CYP1A2 ---> SPC of [1] of eMC

Dacarbazine is metabolised by cytochrome P450 (CYP1A1, CYP1A2, and CYP2E1). This has to be taken into account if other drugs are co-administered which are metabolised by the same hepatic enzymes.

Dacarbazine [1], drugs primarily metabolised by CYP2E1 ---> SPC of [1] of eMC

Dacarbazine is metabolised by cytochrome P450 (CYP1A1, CYP1A2, and CYP2E1). This has to be taken into account if other drugs are co-administered which are metabolised by the same hepatic enzymes.

Dacarbazine [1], hepatotoxic drugs ---> SPC of [1] of eMC

Hepatotoxic drugs should be avoided during chemotherapy.

Dacarbazine [1], medicines with myelotoxic effects ---> SPC of [1] of eMC

In case of previous or concomitant treatment having adverse effects on the bone marrow (particularly cytostatic agents, irradiation) myelotoxic interactions are possible.

Dacarbazine [1], methoxypsoralen ---> SPC of [1] of eMC

Dacarbazine can enhance the effects of methoxypsoralen because of photosensitization.

Dacarbazine [1], pregnancy ---> SPC of [1] of eMC

Dacarbazine must not be used during pregnancy

Dacarbazine [1], radiotherapy ---> SPC of [1] of eMC

In case of previous or concomitant treatment having adverse effects on the bone marrow (particularly cytostatic agents, irradiation) myelotoxic interactions are possible.

Dacarbazine, fotemustine

The co-administration of dacarbazine and fotemustine may cause acute pulmonary toxicity (adult respiratory distress syndrome)

Dacarbazine, ipilimumab [2] ---> SPC of [2] of EMA

No clinically relevant pharmacokinetic drug-drug interaction was observed between ipilimumab and paclitaxel/carboplatin, dacarbazine or its metabolite, 5-aminoimidazole-4-carboxamide (AIC).

Dacarbazine, phenytoin

The co-administration of dacarbazine and phenytoin is to avoid. There is a risk of seizure exacerbation due to decreased gastrointestinal absorption of phenytoin

Dacarbazine, tacrolimus

Dacarbazine, vaccinations with live organism vaccines

The co-administration of dacarbazine with the live vaccine should be avoided due to risk of systemic, possible fatal disease

Dacarbazine, yellow fever vaccine

The co-administration of dacarbazine with the yellow fever vaccine is contraindicated due to risk of fatal systemic disease

CONTRAINDICATIONS of Dacarbazine

Dacarbazine is contraindicated in patients

- who have a history of hypersensitivity reactions to dacarbazine or to any of the excipients,

- in pregnant or breastfeeding women,

- in patients with leucopenia and/or thrombocytopenia,

- in patients with severe liver or kidney diseases.

http://www.medicines.org.uk/emc/

Daclatasvir (Daklinza)

Abacavir, daclatasvir [2] ---> SmPC of [2] of EMA

No dose adjustment of Daklinza or the NRTI is required.

Ability to drive, daclatasvir [2] ---> SmPC of [2] of EMA

Dizziness has been reported during treatment with Daklinza in combination with sofosbuvir, and dizziness, disturbance in attention, blurred vision and reduced visual acuity have been reported during treatment with Daklinza in combination with peginterferon alfa.

ACE inhibitors, daclatasvir [2] ---> SmPC of [2] of EMA

No clinically relevant effects on the pharmacokinetics of either medicinal product are expected when daclatasvir is coadministered with ACE inhibitors

AIIRA, daclatasvir [2] ---> SmPC of [2] of EMA

No clinically relevant effects on the pharmacokinetics of either medicinal product are expected when daclatasvir is coadministered with angiotensin II receptor antagonists

Alprazolam, daclatasvir [2] ---> SmPC of [2] of EMA

No dose adjustment is required

Amiodarone, daclatasvir [2] ---> SmPC of [2] of EMA

Cases of severe bradycardia and heart block have been observed when Daklinza is used in combination with sofosbuvir and concomitant amiodarone with or without other drugs that lower heart rate. The mechanism is not established.

Amlodipine, daclatasvir [2] ---> SmPC of [2] of EMA

Administration of daclatasvir with amlodipine (CYP3A4 inhibitor) may result in increased concentrations of daclatasvir. Caution is advised.

Antacids, daclatasvir [2] ---> SmPC of [2] of EMA

No clinically relevant effects on the pharmacokinetics of either medicinal product are expected when daclatasvir is coadministered with antacids

Atazanavir/cobicistat, daclatasvir [2] ---> SmPC of [2] of EMA

Strong inhibitors of CYP3A4 may increase the plasma levels of daclatasvir. Dose adjustment of daclatasvir is recommended when coadministered with strong inhibitors of CYP3A4

Atazanavir/ritonavir, daclatasvir [2] ---> SmPC of [2] of EMA

Strong inhibitors of CYP3A4 may increase the plasma levels of daclatasvir. Dose adjustment of daclatasvir is recommended when coadministered with strong inhibitors of CYP3A4

Atorvastatin, daclatasvir [2] ---> SmPC of [2] of EMA

Inhibition of OATP 1B1 and/or BCRP by daclatasvir may increase plasma concentration of statin. Caution should be used when daclatasvir is coadministered with rosuvastatin or other substrates of OATP 1B1 or BCRP.

Azithromycin, daclatasvir [2] ---> SmPC of [2] of EMA

No dose adjustment is required

BCRP substrates, daclatasvir [2] ---> SmPC of [2] of EMA

Administration of daclatasvir may increase systemic exposure to medicinal products that are substrates of P-gp, OATP 1B1, OCT1 or BCRP, which could increase or prolong their therapeutic effect and adverse reactions.

Boceprevir, daclatasvir [2] ---> SmPC of [2] of EMA

Strong inhibitors of CYP3A4 may increase the plasma levels of daclatasvir. Dose adjustment of daclatasvir is recommended when coadministered with strong inhibitors of CYP3A4

Breast-feeding, daclatasvir [2] ---> SmPC of [2] of EMA

Available pharmacokinetic and toxicological data in animals have shown excretion of daclatasvir and metabolites in milk. A risk to the newborn/infant cannot be excluded. Mothers should be instructed not to breastfeed if they are taking Daklinza.

Buprenorphine/naloxone, daclatasvir [2] ---> SmPC of [2] of EMA

No dose adjustment is required

Carbamazepine, daclatasvir [2] ---> SmPC of [2] of EMA

Daclatasvir is contraindicated in combination with medicinal products that strongly induce CYP3A4 and P-gp, and thus may lead to lower exposure and loss of efficacy of daclatasvir.

Ciprofloxacin, daclatasvir [2] ---> SmPC of [2] of EMA

No dose adjustment is required

Clarithromycin, daclatasvir [2] ---> SmPC of [2] of EMA

Administration of daclatasvir with the antibacterial (CYP3A4 inhibition) may result in increased concentrations of daclatasvir. Caution is advised.

Cobicistat, daclatasvir [2] ---> SmPC of [2] of EMA

Strong inhibitors of CYP3A4 may increase the plasma levels of daclatasvir. Dose adjustment of daclatasvir is recommended when coadministered with strong inhibitors of CYP3A4

Cyclosporine, daclatasvir [2] ---> SmPC of [2] of EMA

No dose adjustment of either medicinal product is required when daclatasvir is coadministered with cyclosporine

Dabigatran etexilate, daclatasvir [2] ---> SmPC of [2] of EMA

Daclatasvir [1], darunavir/cobicistat ---> SmPC of [1] of EMA

No dose adjustment of Daklinza 60 mg once daily, darunavir/ritonavir (800/100 mg once daily or 600/100 mg twice daily) or darunavir/cobicistat is required.

Daclatasvir [1], darunavir/ritonavir ---> SmPC of [1] of EMA

No dose adjustment of Daklinza 60 mg once daily, darunavir/ritonavir (800/100 mg once daily or 600/100 mg twice daily) or darunavir/cobicistat is required.

Daclatasvir [1], dexamethasone ---> SmPC of [1] of EMA

Daclatasvir is contraindicated in combination with medicinal products that strongly induce CYP3A4 and P-gp, and thus may lead to lower exposure and loss of efficacy of daclatasvir.

Daclatasvir [1], didanosine ---> SmPC of [1] of EMA

No dose adjustment of Daklinza or the NRTI is required.

Daclatasvir [1], digoxin ---> SmPC of [1] of EMA

P-gp inhibition by daclatasvir may increase the serum digoxin concentrations

Daclatasvir [1], diltiazem ---> SmPC of [1] of EMA

Administration of daclatasvir with diltiazem (CYP3A4 inhibitor) may result in increased concentrations of daclatasvir. Caution is advised.

Daclatasvir [1], disopyramide ---> SmPC of [1] of EMA

No clinically relevant effects on the pharmacokinetics of either medicinal product are expected when daclatasvir is coadministered with the other medicinal product

Daclatasvir [1], dolutegravir ---> SmPC of [1] of EMA

No dose adjustments required

Daclatasvir [1], dolutegravir/abacavir/lamivudine ---> SmPC of [1] of EMA

No dose adjustments required

Daclatasvir [1], efavirenz ---> SmPC of [1] of EMA

Induction of CYP3A4 by efavirenz may decrease the daclatasvir concentration

Daclatasvir [1], emtricitabine ---> SmPC of [1] of EMA

No dose adjustment of Daklinza or the NRTI is required.

Daclatasvir [1], enfuvirtide ---> SmPC of [1] of EMA

No dose adjustment is required

Daclatasvir [1], erythromycin ---> SmPC of [1] of EMA

Administration of daclatasvir with erythromycin (CYP3A4 inhibition) may result in increased concentrations of daclatasvir. Caution is advised.

Daclatasvir [1], escitalopram ---> SmPC of [1] of EMA

No dose adjustment is required

Daclatasvir [1], etravirine ---> SmPC of [1] of EMA

Induction of CYP3A4 by etravirine may decrease the daclatasvir concentration. Due to the lack of data, coadministration of daclatasvir and etravirine is not recommended.

Daclatasvir [1], famotidine ---> SmPC of [1] of EMA

No dose adjustment is required

Daclatasvir [1], flecainide ---> SmPC of [1] of EMA

No clinically relevant effects on the pharmacokinetics of either medicinal product are expected when daclatasvir is coadministered with the other medicinal product

Daclatasvir [1], fluconazole ---> SmPC of [1] of EMA

Modest increases in concentrations of daclatasvir are expected, but no dose adjustment of daclatasvir or fluconazole is required.

Daclatasvir [1], fluvastatin ---> SmPC of [1] of EMA

Daclatasvir [1], itraconazol ---> SmPC of [1] of EMA

Strong inhibitors of CYP3A4 may increase the plasma levels of daclatasvir. Dose adjustment of daclatasvir is recommended when coadministered with strong inhibitors of CYP3A4

Daclatasvir [1], ketoconazole ---> SmPC of [1] of EMA

Strong inhibitors of CYP3A4 may increase the plasma levels of daclatasvir. Dose adjustment of daclatasvir is recommended when coadministered with strong inhibitors of CYP3A4

Daclatasvir [1], lamivudine ---> SmPC of [1] of EMA

No dose adjustment of Daklinza or the NRTI is required.

Daclatasvir [1], lopinavir/ritonavir ---> SmPC of [1] of EMA

No dose adjustment of Daklinza 60 mg once daily or lopinavir/ritonavir is required.

Daclatasvir [1], maraviroc ---> SmPC of [1] of EMA

No dose adjustment is required

Daclatasvir [1], methadone ---> SmPC of [1] of EMA

No dose adjustment is required

Daclatasvir [1], mexiletine ---> SmPC of [1] of EMA

No clinically relevant effects on the pharmacokinetics of either medicinal product are expected when daclatasvir is coadministered with the other medicinal product

Daclatasvir [1], midazolam ---> SmPC of [1] of EMA

Daclatasvir is a very weak inducer of CYP3A4 and caused a 13% decrease in midazolam exposure. However, as this is a limited effect, dose adjustment of concomitantly administered CYP3A4 substrates is not necessary.

Daclatasvir [1], moderate CYP3A4 inductors ---> SmPC of [1] of EMA

Daclatasvir is a substrate of CYP3A4. Moderate inducers of CYP3A4 may decrease the plasma levels and therapeutic effect of daclatasvir. Dose adjustment of daclatasvir is recommended when coadministered with moderate inducers of CYP3A4

Daclatasvir [1], moderate inducers of CYP3A4 and P-gp may ---> SmPC of [1] of EMA

Moderate inducers of CYP3A4 and P-gp may decrease the plasma levels and therapeutic effect of daclatasvir. Dose adjustment of daclatasvir is recommended

Daclatasvir [1], moderate P-gp inductors ---> SmPC of [1] of EMA

Daclatasvir is a substrate of P-gp. Moderate inducers of P-gp may decrease the plasma levels and therapeutic effect of daclatasvir. Dose adjustment of daclatasvir is recommended when coadministered with moderate inducers of P-gp

Daclatasvir [1], mycophenolate mofetil ---> SmPC of [1] of EMA

No dose adjustment of either medicinal product is required when daclatasvir is coadministered with mycophenolate mofetil

Daclatasvir [1], nevirapine ---> SmPC of [1] of EMA

Induction of CYP3A4 by etravirine may decrease the daclatasvir concentration. Due to the lack of data, coadministration of daclatasvir and nevirapine is not recommended.

Daclatasvir [1], nifedipine ---> SmPC of [1] of EMA

Administration of daclatasvir with nifedipine (CYP3A4 inhibitor) may result in increased concentrations of daclatasvir. Caution is advised.

Daclatasvir [1], OATP1B1 substrates ---> SmPC of [1] of EMA

Daclatasvir [1], OCT1 inhibitors ---> SmPC of [1] of EMA

Coadministration of medicines that inhibit P-gp or OCT1 activity is likely to have a limited effect on daclatasvir exposure.

Daclatasvir [1], OCT1 substrates ---> SmPC of [1] of EMA

Daclatasvir [1], omeprazole ---> SmPC of [1] of EMA

No dose adjustment is required

Daclatasvir [1], oral contraceptives ---> SmPC of [1] of EMA

An oral contraceptive containing ethinylestradiol 35 痢 and norgestimate 0.180/0.215/0.250 mg is recommended with daclatasvir. Other oral contraceptives have not been studied.

Daclatasvir [1], oxcarbazepine ---> SmPC of [1] of EMA

Daclatasvir is contraindicated in combination with medicinal products that strongly induce CYP3A4 and P-gp, and thus may lead to lower exposure and loss of efficacy of daclatasvir.

Daclatasvir [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

Daclatasvir [1], P-glycoprotein substrates with small therapeutic index ---> SmPC of [1] of EMA

Safety monitoring is advised when initiating treatment with daclatasvir in patients receiving intestinal P-gp substrates that have a narrow therapeutic range.

Daclatasvir [1], P-gp inhibitors ---> SmPC of [1] of EMA

Coadministration of medicines that inhibit P-gp or OCT1 activity is likely to have a limited effect on daclatasvir exposure.

Daclatasvir [1], PDE5 inhibitors ---> SmPC of [1] of EMA

No clinically relevant effects on the pharmacokinetics of either medicinal product are expected when daclatasvir is coadministered with PDE-5 inhibitors

Daclatasvir [1], peginterferon alfa/ribavirin ---> SmPC of [1] of EMA

No dose adjustment is required

Daclatasvir [1], phenobarbital ---> SmPC of [1] of EMA

Daclatasvir is contraindicated in combination with medicinal products that strongly induce CYP3A4 and P-gp, and thus may lead to lower exposure and loss of efficacy of daclatasvir.

Daclatasvir [1], phenytoin ---> SmPC of [1] of EMA

Daclatasvir is contraindicated in combination with medicinal products that strongly induce CYP3A4 and P-gp, and thus may lead to lower exposure and loss of efficacy of daclatasvir.

Daclatasvir [1], pitavastatin ---> SmPC of [1] of EMA

Daclatasvir [1], posaconazole ---> SmPC of [1] of EMA

Strong inhibitors of CYP3A4 may increase the plasma levels of daclatasvir. Dose adjustment of daclatasvir is recommended when coadministered with strong inhibitors of CYP3A4

Daclatasvir [1], pravastatine ---> SmPC of [1] of EMA

Daclatasvir [1], pregnancy ---> SmPC of [1] of EMA

Daklinza should not be used during pregnancy or in women of childbearing potential not using contraception

Daclatasvir [1], propafenone ---> SmPC of [1] of EMA

No clinically relevant effects on the pharmacokinetics of either medicinal product are expected when daclatasvir is coadministered with the other medicinal product

Daclatasvir [1], quinidine ---> SmPC of [1] of EMA

No clinically relevant effects on the pharmacokinetics of either medicinal product are expected when daclatasvir is coadministered with the other medicinal product

Daclatasvir [1], raltegravir ---> SmPC of [1] of EMA

No dose adjustment is required

Daclatasvir [1], rifabutin ---> SmPC of [1] of EMA

Daclatasvir is contraindicated in combination with medicinal products that strongly induce CYP3A4 and P-gp, and thus may lead to lower exposure and loss of efficacy of daclatasvir.

Daclatasvir [1], rifampicin ---> SmPC of [1] of EMA

Daclatasvir is contraindicated in combination with medicinal products that strongly induce CYP3A4 and P-gp, and thus may lead to lower exposure and loss of efficacy of daclatasvir.

Daclatasvir [1], rifapentine ---> SmPC of [1] of EMA

Daclatasvir is contraindicated in combination with medicinal products that strongly induce CYP3A4 and P-gp, and thus may lead to lower exposure and loss of efficacy of daclatasvir.

Daclatasvir [1], rilpivirine ---> SmPC of [1] of EMA

No dose adjustment is required

Daclatasvir [1], rosuvastatin ---> SmPC of [1] of EMA

Inhibition of OATP 1B1 and BCRP by daclatasvir may increase plasma concentration of rosuvastatin. Caution should be used when daclatasvir is coadministered with rosuvastatin or other substrates of OATP 1B1 or BCRP.

Daclatasvir [1], simeprevir ---> SmPC of [1] of EMA

No dose adjustment is required

Daclatasvir [1], simvastatine ---> SmPC of [1] of EMA

Daclatasvir [1], sirolimus ---> SmPC of [1] of EMA

No dose adjustment of either medicinal product is required when daclatasvir is coadministered with sirolimus

Daclatasvir [1], sofosbuvir ---> SmPC of [1] of EMA

No dose adjustment of Daklinza or sofosbuvir is required.

Daclatasvir [1], St. John's wort ---> SmPC of [1] of EMA

Daclatasvir is contraindicated in combination with medicinal products that strongly induce CYP3A4 and P-gp, and thus may lead to lower exposure and loss of efficacy of daclatasvir.

Daclatasvir [1], stavudine ---> SmPC of [1] of EMA

No dose adjustment of Daklinza or the NRTI is required.

Daclatasvir [1], strong CYP3A4 and P-glycoprotein inductors ---> SmPC of [1] of EMA

Daclatasvir is contraindicated in combination with medicinal products that strongly induce CYP3A4 and P-gp, and thus may lead to lower exposure and loss of efficacy of daclatasvir.

Daclatasvir [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Daclatasvir is contraindicated in combination with medicinal products that strongly induce CYP3A4, and thus may lead to lower exposure and loss of efficacy of daclatasvir.

Daclatasvir [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Strong inhibitors of CYP3A4 may increase the plasma levels of daclatasvir. Dose adjustment of daclatasvir is recommended when coadministered with strong inhibitors of CYP3A4

Daclatasvir [1], strong P-gp inductors ---> SmPC of [1] of EMA

Daclatasvir is contraindicated in combination with medicinal products that strongly induce P-gp, and thus may lead to lower exposure and loss of efficacy of daclatasvir.

Daclatasvir [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

Coadministration of medicines that inhibit P-gp activity is likely to a have limited effect on daclatasvir exposure.

Daclatasvir [1], tacrolimus ---> SmPC of [1] of EMA

No dose adjustment of either medicinal product is required when daclatasvir is coadministered with tacrolimus

Daclatasvir [1], telaprevir ---> SmPC of [1] of EMA

Strong inhibitors of CYP3A4 may increase the plasma levels of daclatasvir. Dose adjustment of daclatasvir is recommended when coadministered with strong inhibitors of CYP3A4

Daclatasvir [1], telithromycin ---> SmPC of [1] of EMA

Administration of daclatasvir with the antibacterial (CYP3A4 inhibition) may result in increased concentrations of daclatasvir. Caution is advised.

Daclatasvir [1], tenofovir ---> SmPC of [1] of EMA

No dose adjustment of Daklinza or tenofovir is required.

Daclatasvir [1], triazolam ---> SmPC of [1] of EMA

No dose adjustment is required

Daclatasvir [1], verapamil ---> SmPC of [1] of EMA

Administration of daclatasvir with verapamil (CYP3A4 and P-gp inhibitor) may result in increased concentrations of daclatasvir. Caution is advised.

Daclatasvir [1], vitamin K antagonists ---> SmPC of [1] of EMA

As liver function may change during treatment with Daklinza, a close monitoring of International Normalized Ratio (INR) values is recommended.

Daclatasvir [1], voriconazole ---> SmPC of [1] of EMA

Strong inhibitors of CYP3A4 may increase the plasma levels of daclatasvir. Dose adjustment of daclatasvir is recommended when coadministered with strong inhibitors of CYP3A4

Daclatasvir [1], warfarin ---> SmPC of [1] of EMA

No dose adjustment of daclatasvir or warfarin is required.

Daclatasvir [1], zidovudine ---> SmPC of [1] of EMA

No dose adjustment of Daklinza or the NRTI is required.

Daclatasvir, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Based on theoretical considerations, no clinically relevant interaction is expected.

Daclatasvir, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

Daclatasvir did not change dolutegravir plasma concentration to a clinically relevant extent. Dolutegravir did not change daclatasvir plasma concentration. No dose adjustment is necessary.

Daclatasvir, dolutegravir/lamivudine [2] ---> SmPC of [2] of EMA

No dose adjustment is necessary.

Daclatasvir, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Daclatasvir, doravirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Daclatasvir, doravirine/lamivudine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Daclatasvir, fosamprenavir/ritonavir ---> SmPC of [fosamprenavir] of EMA

Coadministration with fosamprenavir/ritonavir is likely to lead to increased plasma exposures of daclatasvir due to CYP3A4 enzyme inhibition. Not recommended

Daclatasvir, fostemsavir [2] ---> SmPC of [2] of EMA

Although not studied, temsavir may increase plasma concentrations of other HCV DAAs. No dose adjustment is necessary.

Daclatasvir, sofosbuvir [2] ---> SmPC of [2] of EMA

Cases of severe bradycardia and heart block have been observed when sofosbuvir is used in combination with another direct-acting antiviral (DAAs, including daclatasvir, simeprevir and ledipasvir) and concomitant amiodarone

CONTRAINDICATIONS of Daclatasvir (Daklinza)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Coadministration with medicinal products that strongly induce cytochrome P450 3A4 (CYP3A4) and P-glycoprotein transporter (P-gp) and thus may lead to lower exposure and loss of efficacy of Daklinza. These active substances include but are not limited to phenytoin, carbamazepine, oxcarbazepine, phenobarbital, rifampicin, rifabutin, rifapentine, systemic dexamethasone, and the herbal product St John's wort (Hypericum perforatum).

https://www.ema.europa.eu/en/documents/product-information/daklinza-epar-product-information_en.pdf 22/08/2019 (withdrawn)

Daclizumab (Zinbryta)

Breast-feeding, daclizumab [2] ---> SmPC of [2] of EMA

If a woman wishes to breast-feed during treatment with Zinbryta, the benefit of breast-feeding to the child and of therapy to the woman should be considered.

Daclizumab [1], fertility ---> SmPC of [1] of EMA

No impact on male or female fertility as assessed by fertility indices was detected in animal studies (see section 5.3). There are no data on the effects of Zinbryta on human fertility.

Daclizumab [1], hepatotoxic drugs ---> SmPC of [1] of EMA

Cases of hepatic injury have occurred in patients taking Zinbryta with other hepatotoxic drugs, although the role of these medicinal products is uncertain. Caution is recommended

Daclizumab [1], inactivated vaccines ---> SmPC of [1] of EMA

Patients on Zinbryta may receive non-live vaccines.

Daclizumab [1], metabolism ---> SmPC of [1] of EMA

Zinbryta is not expected to undergo metabolism by hepatic enzymes or renal elimination. There is limited data on concomitant use of Zinbryta with MS symptomatic therapies.

Daclizumab [1], pregnancy ---> SmPC of [1] of EMA

Zinbryta should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.

Daclizumab [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

The safety of immunisation with live viral vaccines during treatment with Zinbryta has not been studied. Vaccination with live vaccines is not advised during treatment and up to 4 months after discontinuation.

CONTRAINDICATIONS of Daclizumab (Zinbryta)

- Zinbryta is contraindicated in patients with a history of severe hypersensitivity (e.g. anaphylaxis or anaphylactoid reactions) to daclizumab or to any of the excipients (see section 6.1).

- Pre-existing hepatic disease or hepatic impairment (see section 4.4).

https://www.ema.europa.eu/en/documents/product-information/zinbryta-epar-product-information_en.pdf 28/06/2018 (withdrawn),

Other trade names: Zenapax (withdrawn),

Dacomitinib (Vizimpro)

Ability to drive, dacomitinib [2] ---> SmPC of [2] of EMA

Patients experiencing fatigue or ocular adverse reactions while taking dacomitinib should exercise caution when driving or operating machinery.

Antacids, dacomitinib [2] ---> SmPC of [2] of EMA

Local antacids and H2 receptor antagonists may be used if needed.

Breast-feeding, dacomitinib [2] ---> SmPC of [2] of EMA

Because many medicines are excreted in human milk, and because of the potential for serious adverse reactions in breast-fed infants from exposure to dacomitinib, mothers should be advised against breast-feeding while receiving this medicinal product.

Dacomitinib [1], drugs primarily metabolised by CYP2D6 ---> SmPC of [1] of EMA

Vizimpro may increase exposure (or decrease exposure of active metabolites) of other medicines metabolised by CYP2D6. Concomitant use of medicines predominantly metabolised by CYP2D6 should be avoided unless such products are considered necessary

Dacomitinib [1], drugs primarily metabolised by CYP2D6 ---> SmPC of [1] of EMA

If concomitant use of such medicinal products is considered necessary, they should follow their respective labels for dose recommendation regarding co-administration with strong CYP2D6 inhibitors.

Dacomitinib [1], fertility ---> SmPC of [1] of EMA

Fertility studies have not been performed with dacomitinib. Non-clinical safety studies showed reversible epithelial atrophy in the cervix and vagina of rats (see section 5.3).

Dacomitinib [1], H2 antagonists ---> SmPC of [1] of EMA

H2 receptor antagonists may be used if needed. Dacomitinib should be administered 2 hours before or at least 10 hours after taking H2 receptor antagonists.

Dacomitinib [1], pregnancy ---> SmPC of [1] of EMA

Based on its mechanism of action, dacomitinib may cause foetal harm when administered to a pregnant woman. Dacomitinib should not be used during pregnancy.

Dacomitinib [1], proton pump inhibitors ---> SmPC of [1] of EMA

Concomitant use of proton pump inhibitors (PPIs) with dacomitinib should be avoided

Dacomitinib [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should be advised to avoid becoming pregnant and who are receiving this medicinal product should use adequate contraceptive methods during therapy and for at least 17 days (5 half-lives) after completing therapy.

CONTRAINDICATIONS of Dacomitinib (Vizimpro)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/vizimpro-epar-product-information_en.pdf 21/02/2024

Dalbavancin (Xydalba)

Ability to drive, dalbavancin [2] ---> SmPC of [2] of EMA

Xydalba may have a minor influence on the ability to drive and use machines, as dizziness has been reported in a small number of patients (see section 4.8).

Breast-feeding, dalbavancin [2] ---> SmPC of [2] of EMA

A decision must be made whether to continue/discontinue breast-feeding or to continue/discontinue therapy with Xydalba taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Clarithromycin, dalbavancin [2] ---> SmPC of [2] of EMA

It is not known if dalbavancin is a substrate for hepatic uptake and efflux transporters. Co-administration with inhibitors of these transporters may increase the exposure to dalbavancin.

Cyclosporine, dalbavancin [2] ---> SmPC of [2] of EMA

It is not known if dalbavancin is a substrate for hepatic uptake and efflux transporters. Co-administration with inhibitors of these transporters may increase the exposure to dalbavancin.

CYP enzymes, dalbavancin [2] ---> SmPC of [2] of EMA

The interaction potential of dalbavancin on medicinal products metabolised by CYP enzymes is expected to be low since it is neither an inhibitor nor an inducer of CYP enzymes in vitro.

CYP2C8 inhibitors, dalbavancin [2] ---> SmPC of [2] of EMA

There are no data on dalbavancin as an inhibitor of CYP2C8.

Cytochrome P450, dalbavancin [2] ---> SmPC of [2] of EMA

Dalbavancin is not metabolised by CYP enzymes in vitro, therefore co-administered CYP inducers or inhibitors are unlikely to influence the pharmacokinetics of dalbavancin.

Dalbavancin [1], digoxin ---> SmPC of [1] of EMA

It is not known if dalbavancin is an inhibitor of transporters. Increased exposure to transporter substrates sensitive for inhibited transporter activity, such as statins and digoxin, cannot be excluded if combined with dalbavancin.

Dalbavancin [1], fertility ---> SmPC of [1] of EMA

Studies in animals have shown reduced fertility (see section 5.3). The potential risk for humans is unknown.

Dalbavancin [1], inhibitors of the transporters ---> SmPC of [1] of EMA

It is not known if dalbavancin is a substrate for hepatic uptake and efflux transporters. Co-administration with inhibitors of these transporters may increase the exposure to dalbavancin.

Dalbavancin [1], itraconazol ---> SmPC of [1] of EMA

It is not known if dalbavancin is a substrate for hepatic uptake and efflux transporters. Co-administration with inhibitors of these transporters may increase the exposure to dalbavancin.

Dalbavancin [1], pregnancy ---> SmPC of [1] of EMA

Xydalba is not recommended during pregnancy, unless the potential expected benefit clearly justifies the potential risk to the foetus.

Dalbavancin [1], protease inhibitors ---> SmPC of [1] of EMA

It is not known if dalbavancin is a substrate for hepatic uptake and efflux transporters. Co-administration with inhibitors of these transporters may increase the exposure to dalbavancin.

Dalbavancin [1], quinidine ---> SmPC of [1] of EMA

It is not known if dalbavancin is a substrate for hepatic uptake and efflux transporters. Co-administration with inhibitors of these transporters may increase the exposure to dalbavancin.

Dalbavancin [1], statins ---> SmPC of [1] of EMA

Dalbavancin [1], verapamil ---> SmPC of [1] of EMA

It is not known if dalbavancin is a substrate for hepatic uptake and efflux transporters. Co-administration with inhibitors of these transporters may increase the exposure to dalbavancin.

CONTRAINDICATIONS of Dalbavancin (Xydalba)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/xydalba-epar-product-information_en.pdf 23/09/2024

Dalteparin

Abciximab, dalteparin [2] ---> SmPC of [2] of eMC

Enhancement of the anticoagulant effect of dalteparin by anticoagulant/antiplatelet agents

Acetylsalicylic acid, dalteparin [2] ---> SmPC of [2] of eMC

NSAIDs reduce production of vasodilatatory prostaglandins, and thereby renal blood flow and the renal excretion. Caution is recommended

Anticoagulants, dalteparin [2] ---> SmPC of [2] of eMC

Enhancement of the anticoagulant effect of dalteparin by anticoagulant/antiplatelet agents

Antihistamines, dalteparin [2] ---> SmPC of [2] of eMC

A reduction of the anticoagulant effect may occur with concomitant administration of dalteparin with antihistamines

Apixaban [1], dalteparin ---> SmPC of [1] of EMA

Due to an increased bleeding risk, concomitant treatment of apixaban with any other anticoagulants is contraindicated

Ascorbic acid, dalteparin [2] ---> SmPC of [2] of eMC

A reduction of the anticoagulant effect may occur with concomitant administration of dalteparin with ascorbic acid

Benzodiazepines, dalteparin

Dalteparin may displace the benzodiazepine from its protein binding.

Breast-feeding, dalteparin [2] ---> SmPC of [2] of eMC

A risk to the suckling child cannot be excluded. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with dalteparin should be made taking

Cationic drugs, dalteparin

Dalteparin weakens the effect of basic medicinal products (cationic drugs)

Cytostatics, dalteparin [2] ---> SmPC of [2] of eMC

Enhancement of the anticoagulant effect of dalteparin by anticoagulant/antiplatelet agents

Dabigatran etexilate [1], dalteparin ---> SmPC of [1] of EMA

Dalteparin [1], dextran ---> SmPC of [1] of eMC

Enhancement of the anticoagulant effect of dalteparin by anticoagulant/antiplatelet agents

Dalteparin [1], dicoumarol ---> SmPC of [1] of eMC

Enhancement of the anticoagulant effect of dalteparin by anticoagulant/antiplatelet agents

Dalteparin [1], digital glycosides ---> SmPC of [1] of eMC

A reduction of the anticoagulant effect may occur with concomitant administration of dalteparin with cardiac glycosides

Dalteparin [1], dipyridamole ---> SmPC of [1] of eMC

Enhancement of the anticoagulant effect of dalteparin by anticoagulant/antiplatelet agents

Dalteparin [1], eptifibatide ---> SmPC of [1] of eMC

Enhancement of the anticoagulant effect of dalteparin by anticoagulant/antiplatelet agents

Dalteparin [1], ethacrynic acid ---> SmPC of [1] of eMC

Enhancement of the anticoagulant effect of dalteparin by anticoagulant/antiplatelet agents

Dalteparin [1], GP IIb/IIIa inhibitors ---> SmPC of [1] of eMC

Enhancement of the anticoagulant effect of dalteparin by anticoagulant/antiplatelet agents

Dalteparin [1], nicotine ---> SmPC of [1] of eMC

As heparin has been shown to interact with intravenous nitroglycerine, tobacco smoking interaction cannot be ruled out for dalteparin.

Dalteparin [1], NSAID ---> SmPC of [1] of eMC

NSAIDs reduce production of vasodilatatory prostaglandins, and thereby renal blood flow and the renal excretion. Caution is recommended

Dalteparin [1], penicillins ---> SmPC of [1] of eMC

As heparin has been shown to interact with intravenous nitroglycerine, high dose penicillin interaction cannot be ruled out for dalteparin.

Dalteparin [1], phenylbutazone ---> SmPC of [1] of eMC

Enhancement of the anticoagulant effect of dalteparin by anticoagulant/antiplatelet agents

Dalteparin [1], platelet aggregation inhibitors ---> SmPC of [1] of eMC

Enhancement of the anticoagulant effect of dalteparin by anticoagulant/antiplatelet agents

Dalteparin [1], pregnancy ---> SmPC of [1] of eMC

Dalteparin can be used during pregnancy if clinically needed.

Dalteparin [1], probenecide ---> SmPC of [1] of eMC

Enhancement of the anticoagulant effect of dalteparin by anticoagulant/antiplatelet agents

Dalteparin [1], quinine ---> SmPC of [1] of eMC

As heparin has been shown to interact with intravenous nitroglycerine, quinine interaction cannot be ruled out for dalteparin.

Dalteparin [1], sulfinpyrazone ---> SmPC of [1] of eMC

Enhancement of the anticoagulant effect of dalteparin by anticoagulant/antiplatelet agents

Dalteparin [1], tetracyclines ---> SmPC of [1] of eMC

A reduction of the anticoagulant effect may occur with concomitant administration of dalteparin with tetracycline

Dalteparin [1], thrombolytics ---> SmPC of [1] of eMC

Enhancement of the anticoagulant effect of dalteparin by anticoagulant/antiplatelet agents

Dalteparin [1], ticlopidine ---> SmPC of [1] of eMC

Enhancement of the anticoagulant effect of dalteparin by anticoagulant/antiplatelet agents

Dalteparin [1], vitamin K antagonists ---> SmPC of [1] of eMC

Enhancement of the anticoagulant effect of dalteparin by anticoagulant/antiplatelet agents

Dalteparin, hyperkalemia

The co-administration of dalteparin with medicinal drugs which increase the serum potassium should be done with special care

Dalteparin, nitroglycerine

Nitroglycerin i.v. decreases the anticoagulant effect

Dalteparin, phenytoin

Dalteparin may displace the phenytoin from its protein binding.

Dalteparin, propranolol

Dalteparin may displace propranolol from its protein binding.

Dalteparin, quinidine

Dalteparin may displace the quinidine from its protein binding.

Dalteparin, rivaroxaban [2] ---> SmPC of [2] of EMA

Concomitant treatment with any other anticoagulants is contraindicated, except under specific circumstances of switching anticoagulant therapy or when UFH is given at doses necessary to maintain an open central venous or arterial catheter.

Dalteparin, tricyclic antidepressant

Dalteparin weakens the tricyclic antidepressant effect (basic medicinal product)

CONTRAINDICATIONS of Dalteparin

- Known hypersensitivity to Fragmin or other low molecular weight heparins and/or heparins e.g. history of confirmed or suspected immunologically mediated heparin induced thrombocytopenia (type II); acute gastroduodenal ulcer; cerebral haemorrhage; known haemorrhagic diathesis or other active haemorrhage; serious coagulation disorders; acute or sub-acute septic endocarditis; haemorrhagic pericardial effusion and haemorrhagic pleural effusion; injuries to and operations on the central nervous system, eyes and ears.

- In patients receiving Fragmin for treatment rather than prophylaxis, local and/or regional anaesthesia in elective surgical procedures is contra-indicated with high doses of dalteparin (such as those needed to treat acute deep-vein thrombosis, pulmonary embolism, and unstable coronary artery disease).

- In cancer patients with body weight < 40 kg at time of venous thromboembolic event, Fragmin should not be used for extended treatment of symptomatic VTE and prevention of its recurrences due to lack of data.

- Dalteparin should not be used in patients who have suffered a recent (within 3 months) stroke unless due to systemic emboli.

http://www.medicines.org.uk/emc/

Damoctocog alfa pegol (Jivi)

Breast-feeding, damoctocog alfa pegol [2] ---> SmPC of [2] of EMA

Based on the rare occurrence of haemophilia A in women, experience regarding the use of factor VIII during pregnancy and breast- feeding is not available. Therefore, factor VIII should be used during pregnancy and breast-feeding only if clearly indicated

Damoctocog alfa pegol [1], fertility ---> SmPC of [1] of EMA

In the repeat dose systemic toxicity studies in rats and rabbits with Jivi, treatment related effects on male reproductive organs were not seen (see section 5.3). The effect on fertility in humans is unknown.

Damoctocog alfa pegol [1], medicinal products ---> SmPC of [1] of EMA

Interactions of human coagulation factor VIII (rDNA) products with other medicinal products have not been reported.

Damoctocog alfa pegol [1], pregnancy ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Damoctocog alfa pegol (Jivi)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Known allergic reactions to mouse or hamster proteins.

https://www.ema.europa.eu/en/documents/product-information/jivi-epar-product-information_en.pdf 13/07/2023

Danazol

Alcohol, danazol [2] ---> SmPC of [2] of eMC

Subjective intolerance in the form of nausea and shortness of breath has been reported.

Alfacalcidol, danazol [2] ---> SmPC of [2] of eMC

Danazol may increase the calcaemic response in primary hypoparathyroidism necessitating a reduction in dosage of this agent.

Anisindione, danazol

Danazol may increase the anticoagulant effect of anisindione

Antihypertensives, danazol [2] ---> SmPC of [2] of eMC

Possibly through promotion of fluid retention, danazol can oppose the action of anti-hypertensive agents.

Antimigraine preparations, danazol [2] ---> SmPC of [2] of eMC

Danazol may itself provoke migraine and possibly reduce the effectiveness of medication to prevent that condition.

Atorvastatin, danazol [2] ---> SmPC of [2] of eMC

The risk of myopathy and rhabdomyolysis is increased by concomitant administration of danazol with statins metabolised by CYP3A4

Breast-feeding, danazol [2] ---> SmPC of [2] of eMC

Danazol has the theoretical potential for androgenic effects in breast-fed infants and therefore either danazol therapy or breast-feeding should be discontinued.

Carbamazepine, danazol [2] ---> SmPC of [2] of eMC

The plasma concentrations of carbamazepine may be increased

Coumarin anticoagulants, danazol

Seriously increased bleeding time. The concomitant use should be avoided

Cyclosporine [1], danazol ---> SmPC of [1] of eMC

Danazol can increase the plasma level of ciclosporin, leading to an increase of the renal toxicity

Danazol [1], estrogens ---> SmPC of [1] of eMC

It is likely that interactions will occur between danazol and gonadal steroid therapy.

Danazol [1], insulin ---> SmPC of [1] of eMC

Danazol can cause insulin resistance.

Danazol [1], lovastatine ---> SmPC of [1] of eMC

The risk of myopathy and rhabdomyolysis is increased by concomitant administration of danazol with statins metabolised by CYP3A4

Danazol [1], phenytoin ---> SmPC of [1] of eMC

Danazol may affect possibly the patient's response to phenytoin.

Danazol [1], pregnancy ---> SmPC of [1] of eMC

Danazol is known to be associated with the risk of virilisation to the female foetus if administered during human pregnancy. Danazol should not be used during pregnancy.

Danazol [1], tacrolimus ---> SmPC of [1] of eMC

Danazol can increase the plasma level of tacrolimus, leading to an increase of the renal toxicity

Danazol, dicoumarol

Danazol may increase the anticoagulant effect of dicoumarol

Danazol, digitoxin

The CYP3A4 inhibition may increase the plasma levels of digitoxin

Danazol, ezetimibe/simvastatine ---> SmPC of [simvastatine] of eMC

The risk of myopathy/rhabdomyolysis is increased by concomitant administration of danazol with simvastatin; therefore, use of simvastatin with danazol is contraindicated

Danazol, fenofibrate/simvastatin [2] ---> SmPC of [2] of EMA

The risk of myopathy and rhabdomyolysis is increased by concomitant administration of danazol with simvastatin. The co-administration is contraindicated

Danazol, foods

The bioavailability increases when danazol is taken with a meal with a high fat content

Danazol, gliclazide [2] ---> SmPC of [2] of eMC

Danazol has diabetogenic effect and may cause an increase in blood glucose levels. Combination is not recommended

Danazol, glipizide [2] ---> SmPC of [2] of eMC

Danazol has diabetogenic effect and may cause an increase in blood glucose levels. Combination is not recommended

Danazol, human insulin [2] ---> SmPC of [2] of EMA

Possible increasing in patient's insulin requirement

Danazol, insulin aspart [2] ---> SmPC of [2] of EMA

Possible increase of the insulin requirements

Danazol, insulin degludec [2] ---> SmPC of [2] of EMA

Possible increase of the insulin requirements

Danazol, insulin degludec/insulin aspart [2] ---> SmPC of [2] of EMA

Possible increase of the insulin requirements

Danazol, insulin degludec/liraglutide [2] ---> SmPC of [2] of EMA

Possible increase of the Xultophy requirements

Danazol, insulin detemir [2] ---> SmPC of [2] of EMA

Possible increase of the insulin requirements

Danazol, insulin glargin [2] ---> SmPC of [2] of EMA

Reduced blood-glucose-lowering effect

Danazol, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

This substance may reduce the blood-glucose-lowering effect.

Danazol, insulin glulisin [2] ---> SmPC of [2] of EMA

Possible decrease in blood-glucose-lowering activity

Danazol, insulin lispro [2] ---> SmPC of [2] of EMA

Insulin requirements may be increased by medicinal products with hyperglycaemic activity

Danazol, oral antidiabetics

Danazol has diabetogenic effect and may cause an increase in blood glucose levels.

Danazol, phenobarbital

The co-administration may enhance the effect of phenobarbital

Danazol, repaglinide [2] ---> SmPC of [2] of EMA

Danazol may reduce the hypoglycaemic effect of repaglinide

Danazol, romiplostim [2] ---> SmPC of [2] of EMA

Danazol use may be reduced or discontinued when given in combination with romiplostim

Danazol, simvastatine [2] ---> SmPC of [2] of eMC

The risk of myopathy and rhabdomyolysis is increased by concomitant administration of danazol with simvastatin; therefore, use with danazol is contraindicated

Danazol, sirolimus [2] ---> SmPC of [2] of EMA

Inhibitors of CYP3A4 may decrease the metabolism of sirolimus and increase sirolimus blood levels.

Danazol, statins metabolised by CYP3A4

The risk of myopathy and rhabdomyolysis is increased by concomitant administration of danazol with statins metabolised by CYP3A4

Danazol, warfarin [2] ---> SmPC of [2] of eMC

Danazol can potentiate the action of warfarin.

CONTRAINDICATIONS of Danazol

1. Pregnancy

2. Breast feeding

3. Markedly impaired hepatic, renal or cardiac function

4. Porphyria

5. Active thrombosis or thromboembolic disease and a history of such events

6. Androgen dependent tumour

7. Undiagnosed abnormal genital bleeding

8. Hypersensitivity to danazol or to any of the excipients.

http://www.medicines.org.uk/emc/

Danicopan (Voydeya)

BCRP substrates, danicopan [2] ---> SmPC of [2] of EMA

This result suggests that danicopan is an inhibitor of BCRP. Caution may be needed in co-administering medicinal products that are known to be substrates of BCRP (such as rosuvastatin and sulfasalazine).

Breast-feeding, danicopan [2] ---> SmPC of [2] of EMA

A risk to the newborns/infants cannot be excluded. Voydeya should not be used during breast-feeding and breast-feeding should not be initiated until 3 days after treatment discontinuation.

Dabigatran, danicopan [2] ---> SmPC of [2] of EMA

Caution may be needed in co-administering medicinal products that are known to be substrates of P-gp (such as dabigatran, digoxin, edoxaban, fexofenadine, tacrolimus).

Danicopan [1], digoxin ---> SmPC of [1] of EMA

Caution may be needed in co-administering medicinal products that are known to be substrates of P-gp (such as dabigatran, digoxin, edoxaban, fexofenadine, tacrolimus).

Danicopan [1], edoxaban ---> SmPC of [1] of EMA

Caution may be needed in co-administering medicinal products that are known to be substrates of P-gp (such as dabigatran, digoxin, edoxaban, fexofenadine, tacrolimus).

Danicopan [1], fertility ---> SmPC of [1] of EMA

No human data on the effect of danicopan on fertility are available. Animal studies have shown potential effects on male fertility and reproductive performance (see section 5.3).

Danicopan [1], fexofenadine ---> SmPC of [1] of EMA

Caution may be needed in co-administering medicinal products that are known to be substrates of P-gp (such as dabigatran, digoxin, edoxaban, fexofenadine, tacrolimus).

Danicopan [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

Caution may be needed in co-administering medicinal products that are known to be substrates of P-gp (such as dabigatran, digoxin, edoxaban, fexofenadine, tacrolimus).

Danicopan [1], pregnancy ---> SmPC of [1] of EMA

As a precautionary measure, it is preferable to avoid the use of Voydeya during pregnancy.

Danicopan [1], rosuvastatin ---> SmPC of [1] of EMA

Danicopan [1], sulfasalazine ---> SmPC of [1] of EMA

Danicopan [1], tacrolimus ---> SmPC of [1] of EMA

Caution may be needed in co-administering medicinal products that are known to be substrates of P-gp (such as dabigatran, digoxin, edoxaban, fexofenadine, tacrolimus).

CONTRAINDICATIONS of Danicopan (Voydeya)

-Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

-Patients with unresolved Neisseria meningitidis infection at treatment initiation (see section 4.4).

-Patients who are not currently vaccinated against Neisseria meningitidis unless they receive prophylactic treatment with appropriate antibiotics until 2 weeks after vaccination (see section 4.4).

https://www.ema.europa.eu/en/documents/product-information/voydeya-epar-product-information_en.pdf 17/05/2024

Dantrolene (Agilus)

Ability to drive, dantrolene [2] ---> SmPC of [2] of EMA

Agilus has a major influence on the ability to drive and use machines, as it can lead to skeletal muscle weakness, dizziness and light-headedness. Since some of these symptoms may persist for up to 48 hours, patients must not drive or use machines.

Aliskiren/amlodipine [1], dantrolene ---> SmPC of [1] of EMA

Due to risk of hyperkalaemia, it is recommended that the co-administration of calcium channel blockers be avoided in patients susceptible to malignant hyperthermia and in the management of malignant hyperthermia.

Aliskiren/amlodipine/hydrochlorothiazide [1], dantrolene ---> SmPC of [1] of EMA

Amlodipine, dantrolene ---> SmPC of [aliskiren/amlodipine] of EMA

Amlodipine/valsartan [1], dantrolene ---> SmPC of [1] of EMA

Amlodipine/valsartan/hydrochlorothiazide [1], dantrolene ---> SmPC of [1] of EMA

Atracurium [1], dantrolene ---> SmPC of [1] of eMC

As with all non-depolarising neuromuscular blocking agents the magnitude and/or duration of a non-depolarising neuromuscular block may be increased as a result of interaction with dantrolene

Breast-feeding, dantrolene [2] ---> SmPC of [2] of EMA

Therefore, breastfeeding should be discontinued during administration of Agilus. Based on elimination half-life of dantrolene, breastfeeding can be restarted 60 hours after the last dose.

Calcium antagonists, dantrolene ---> SmPC of [aliskiren/amlodipine] of EMA

Carbamazepine [1], dantrolene ---> SmPC of [1] of eMC

The plasma concentrations of carbamazepine may be increased

CNS depressants, dantrolene

The co-administration of dantrolene and CNS depressants should be avoided due to the adverse reactions of dantrolene may be enhanced (specially the CNS depressant effect and muscle weakness)

Dantrolene [1], diltiazem ---> SmPC of [1] of EMA

Isolated case reports and animal studies indicate an interaction between dantrolene and calcium channel blockers, such as verapamil and diltiazem, in the form of heart failure. Concomitant use of Agilus and calcium channel blockers is not recommended

Dantrolene [1], fertility ---> SmPC of [1] of EMA

Data on the effects of dantrolene on fertility in humans are not available. In animal studies, no adverse effects on fertility were observed (see section 5.3).

Dantrolene [1], hepatotoxic drugs ---> SmPC of [1] of EMA

Liver damage may occur during dantrolene therapy. This has been observed during longer term, oral administration and may run a lethal course.

Dantrolene [1], hydroxypropylbetadex ---> SmPC of [1] of EMA

Hydroxypropylbetadex has been associated with ototoxicity in animal studies (see section 5.3); and cases of hearing impairment have been observed in studies in other clinical settings.

Dantrolene [1], hyperkalemia ---> SmPC of [1] of EMA

As an increase in serum potassium has been demonstrated in animal studies as a result of the co-administration of dantrolene with verapamil. Concomitant use of Agilus and calcium channel blockers is not recommended (see section 4.5).

Dantrolene [1], intravenous line ---> SmPC of [1] of EMA

Agilus is only for intravenous use. Due to the high pH value of the solution (pH 9.5), extravascular injection must be avoided as it can lead to tissue necrosis. Due to the risk of vascular occlusion, intraarterial injections must be avoided.

Dantrolene [1], muscle relaxants (non-depolarizing) ---> SmPC of [1] of EMA

Concomitant administration of Agilus with non-depolarising muscle relaxants, such as vecuronium, can enhance their effect.

Dantrolene [1], pregnancy ---> SmPC of [1] of EMA

Dantrolene crosses the placenta and should only be used during pregnancy when the potential benefit outweighs the possible risk to mother and child.

Dantrolene [1], skin ---> SmPC of [1] of EMA

Spill of solution on skin should be avoided. If solution gets on the skin, it must be removed with sufficient water (see section 6.6).

Dantrolene [1], vecuronium ---> SmPC of [1] of EMA

Concomitant administration of Agilus with non-depolarising muscle relaxants, such as vecuronium, can enhance their effect.

Dantrolene, diltiazem [2] ---> SmPC of [2] of eMC

Lethal ventricular fibrillation is regularly observed in animals when intravenous verapamil and dantrolene are administered concomitantly. The combination of a calcium antagonist and dantrolene is therefore potentially dangerous

Dantrolene, hepatotoxic drugs

The co-administration of dantrolene and other potentially hepatotoxic substances increases the risk of hepatotoxicity

Dantrolene, memantin [2] ---> SmPC of [2] of EMA

Concomitant administration of memantine with the antispasmodic agents, dantrolene or baclofen, can modify their effects and a dose adjustment may be necessary.

Dantrolene, muscle relaxants (non-depolarizing) ---> SmPC of [atracurium] of eMC

As with all non-depolarising neuromuscular blocking agents the magnitude and/or duration of a non-depolarising neuromuscular block may be increased as a result of interaction with dantrolene

Dantrolene, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

Dantrolene, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

In animals, lethal ventricular fibrillation and cardiovascular collapse are observed in association with hyperkalemia after administration of verapamil and intravenous dantrolene.

Dantrolene, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

The simultaneous use of verapamil with dantrolene is not recommended.

Dantrolene, verapamil

Dantrolene, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

The simultaneous use of verapamil with dantrolene is not recommended.

CONTRAINDICATIONS of Dantrolene (Agilus)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/agilus-epar-product-information_en.pdf 01/07/2024

Dapagliflozin (Forxiga)

Ability to drive, dapagliflozin [2] ---> SmPC of [2] of EMA

Forxiga has no or negligible influence on the ability to drive and use machines. Patients should be alerted to the risk of hypoglycaemia when dapagliflozin is used in combination with a sulphonylurea or insulin.

Breast-feeding, dapagliflozin [2] ---> SmPC of [2] of EMA

A risk to the newborns/infants cannot be excluded. Dapagliflozin should not be used while breast-feeding.

Bumetanide, dapagliflozin [2] ---> SmPC of [2] of EMA

Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered

Cytochrome P450, dapagliflozin [2] ---> SmPC of [2] of EMA

In in vitro studies, dapagliflozin neither inhibited cytochrome P450 (CYP) 1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, nor induced CYP1A2, CYP2B6 or CYP3A4.

Dapagliflozin [1], digoxin ---> SmPC of [1] of EMA

In interaction studies conducted in healthy subjects, using mainly a single-dose design, dapagliflozin did not alter the pharmacokinetics

Dapagliflozin [1], enzyme inductors ---> SmPC of [1] of EMA

A clinically relevant effect with other inducers (e.g. carbamazepine, phenytoin, phenobarbital) is not expected.

Dapagliflozin [1], fertility ---> SmPC of [1] of EMA

The effect of dapagliflozin on fertility in humans has not been studied. In male and female rats, dapagliflozin showed no effects on fertility at any dose tested.

Dapagliflozin [1], glimepiride ---> SmPC of [1] of EMA

Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered

Dapagliflozin [1], hydrochlorothiazide ---> SmPC of [1] of EMA

Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered

Dapagliflozin [1], insulin ---> SmPC of [1] of EMA

Insulin and insulin secretagogues, such as sulphonylureas, cause hypoglycaemia. Therefore, a lower dose of insulin or an insulin secretagogue may be required to reduce the risk of hypoglycaemia when used in combination with dapagliflozin

Dapagliflozin [1], insulin secretagogues ---> SmPC of [1] of EMA

Dapagliflozin [1], lithium ---> SmPC of [1] of EMA

Dapagliflozin may increase renal lithium excretion and the blood lithium levels may be decreased. Please refer the patient to the lithium prescribing doctor in order to monitor serum concentration of lithium.

Dapagliflozin [1], loop diuretics ---> SmPC of [1] of EMA

Dapagliflozin may add to the diuretic effect of thiazide and loop diuretics and may increase the risk of dehydration and hypotension (see section 4.4).

Dapagliflozin [1], mefenamic acid ---> SmPC of [1] of EMA

Mefenamic acid, inhibitor of UGT1A9, may increase the dapagliflozin exposition. No dose adjustment is recommended.

Dapagliflozin [1], metformin ---> SmPC of [1] of EMA

Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered

Dapagliflozin [1], pioglitazone ---> SmPC of [1] of EMA

Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered

Dapagliflozin [1], pregnancy ---> SmPC of [1] of EMA

Therefore, the use of dapagliflozin is not recommended during the second and third trimesters of pregnancy. When pregnancy is detected, treatment with dapagliflozin should be discontinued.

Dapagliflozin [1], rifampicin ---> SmPC of [1] of EMA

Following coadministration of dapagliflozin with rifampicin (an inducer) a 22% decrease in dapagliflozin systemic exposure (AUC) was observed, but with no clinically meaningful effect on 24-hour urinary glucose excretion.

Dapagliflozin [1], simvastatine ---> SmPC of [1] of EMA

Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered

Dapagliflozin [1], sitagliptin ---> SmPC of [1] of EMA

Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered

Dapagliflozin [1], sulfonylureas ---> SmPC of [1] of EMA

Dapagliflozin [1], test ---> SmPC of [1] of EMA

Monitoring glycaemic control with 1,5-AG assay is not recommended as measurements of 1,5-AG are unreliable in assessing glycaemic control in patients taking SGLT2 inhibitors. Use of alternative methods to monitor glycaemic control is advised.

Dapagliflozin [1], thiazides ---> SmPC of [1] of EMA

Dapagliflozin may add to the diuretic effect of thiazide and loop diuretics and may increase the risk of dehydration and hypotension (see section 4.4).

Dapagliflozin [1], valsartan ---> SmPC of [1] of EMA

Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered

Dapagliflozin [1], voglibose ---> SmPC of [1] of EMA

Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered

Dapagliflozin [1], warfarin ---> SmPC of [1] of EMA

In interaction studies conducted in healthy subjects, using mainly a single-dose design, dapagliflozin did not alter the pharmacokinetics

Dapagliflozin, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

In studies conducted in healthy subjects, neither the pharmacokinetics of saxagliptin nor its major metabolite were meaningfully altered

Dapagliflozin, patiromer [2] ---> SmPC of [2] of EMA

In vitro studies have shown no potential interaction of patiromer with the other active substances

Dapagliflozin, pioglitazone [2] ---> SmPC of [2] of EMA

While a causal relationship between dapagliflozin and bladder cancer is unlikely, as a precautionary measure, dapagliflozin is not recommended for use in patients concomitantly treated with pioglitazone.

CONTRAINDICATIONS of Dapagliflozin (Forxiga)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/forxiga-epar-product-information_en.pdf 06/02/2024

Other trade names: Edistride, Dapagliflozin Viatris,

Dapagliflozin/metformin (Xigduo)

Ability to drive, dapagliflozin/metformin [2] ---> SmPC of [2] of EMA

Patients should be alerted to the risk of hypoglycaemia when this medicinal product is used in combination with other glucose-lowering medicinal products known to cause hypoglycaemia.

ACE inhibitors, dapagliflozin/metformin [2] ---> SmPC of [2] of EMA

Some medicinal products can adversely affect renal function which may increase the risk of lactic acidosis, e.g. NSAIDs, including COX II inhibitors, ACE inhibitors, ARA II and diuretics, especially loop diuretics.

AIIRA, dapagliflozin/metformin [2] ---> SmPC of [2] of EMA

Alcohol, dapagliflozin/metformin [2] ---> SmPC of [2] of EMA

Alcohol intoxication is associated with an increased risk of lactic acidosis, particularly in the case of fasting, malnutrition or hepatic impairment due to the metformin. Consumption of alcohol and medicinal products containing alcohol should be avoided

Beta2-adrenergic agonists, dapagliflozin/metformin [2] ---> SmPC of [2] of EMA

Intravascular administration of iodinated contrast agents may lead to contrast induced nephropathy, resulting in metformin accumulation and increased risk of lactic acidosis. Xigduo must be discontinued prior to, or at the time of the imaging procedure

Breast-feeding, dapagliflozin/metformin [2] ---> SmPC of [2] of EMA

This medicinal product should not be used while breast-feeding.

Bumetanide, dapagliflozin/metformin [2] ---> SmPC of [2] of EMA

Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered

Carbamazepine, dapagliflozin/metformin [2] ---> SmPC of [2] of EMA

A clinically relevant effect with other inducers (e.g. carbamazepine, phenytoin, phenobarbital) is not expected.

Cationic substances eliminated by renal tubular secretion, dapagliflozin/metformin [2] ---> SmPC of [2] of EMA

Cationic substances that are eliminated by renal tubular secretion (e.g. cimetidine) may interact with metformin by competing for common renal tubular transport systems.

Cimetidine, dapagliflozin/metformin [2] ---> SmPC of [2] of EMA

Cationic substances that are eliminated by renal tubular secretion (e.g. cimetidine) may interact with metformin by competing for common renal tubular transport systems.

Coxibs, dapagliflozin/metformin [2] ---> SmPC of [2] of EMA

Cytochrome P450, dapagliflozin/metformin [2] ---> SmPC of [2] of EMA

In in vitro studies, dapagliflozin neither inhibited cytochrome P450 (CYP) 1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, nor induced CYP1A2, CYP2B6 or CYP3A4.

Dapagliflozin/metformin [1], digoxin ---> SmPC of [1] of EMA

Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered

Dapagliflozin/metformin [1], diuretics ---> SmPC of [1] of EMA

Dapagliflozin/metformin [1], fertility ---> SmPC of [1] of EMA

In male and female rats, dapagliflozin showed no effects on fertility at any dose tested. For metformin, studies in animals have not shown reproductive toxicity (see section 5.3).

Dapagliflozin/metformin [1], glimepiride ---> SmPC of [1] of EMA

Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered

Dapagliflozin/metformin [1], glucocorticoids ---> SmPC of [1] of EMA

Dapagliflozin/metformin [1], hydrochlorothiazide ---> SmPC of [1] of EMA

Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered

Dapagliflozin/metformin [1], insulin ---> SmPC of [1] of EMA

Dapagliflozin/metformin [1], insulin secretagogues ---> SmPC of [1] of EMA

Dapagliflozin/metformin [1], iodinated contrast media ---> SmPC of [1] of EMA

The intravascular administration of iodinated contrast agents may lead to renal failure, resulting in metformin accumulation and a risk of lactic acidosis.

Dapagliflozin/metformin [1], loop diuretics ---> SmPC of [1] of EMA

This medicinal product may add to the diuretic effect of thiazide and loop diuretics and may increase the risk of dehydration and hypotension (see section 4.4).

Dapagliflozin/metformin [1], mefenamic acid ---> SmPC of [1] of EMA

Following coadministration of dapagliflozin with mefenamic acid (an inhibitor of UGT1A9), a 55% increase in dapagliflozin systemic exposure was seen, but with no clinically meaningful effect on 24-hour urinary glucose excretion.

Dapagliflozin/metformin [1], NSAID ---> SmPC of [1] of EMA

Dapagliflozin/metformin [1], phenobarbital ---> SmPC of [1] of EMA

A clinically relevant effect with other inducers (e.g. carbamazepine, phenytoin, phenobarbital) is not expected.

Dapagliflozin/metformin [1], phenytoin ---> SmPC of [1] of EMA

A clinically relevant effect with other inducers (e.g. carbamazepine, phenytoin, phenobarbital) is not expected.

Dapagliflozin/metformin [1], pioglitazone ---> SmPC of [1] of EMA

Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered

Dapagliflozin/metformin [1], pregnancy ---> SmPC of [1] of EMA

The use of this medicinal product is not recommended during the second and third trimesters of pregnancy.

Dapagliflozin/metformin [1], rifampicin ---> SmPC of [1] of EMA

Dapagliflozin/metformin [1], simvastatine ---> SmPC of [1] of EMA

Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered

Dapagliflozin/metformin [1], sitagliptin ---> SmPC of [1] of EMA

Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered

Dapagliflozin/metformin [1], sulfonylureas ---> SmPC of [1] of EMA

Dapagliflozin/metformin [1], test ---> SmPC of [1] of EMA

Dapagliflozin/metformin [1], thiazides ---> SmPC of [1] of EMA

This medicinal product may add to the diuretic effect of thiazide diuretics and may increase the risk of dehydration and hypotension

Dapagliflozin/metformin [1], valsartan ---> SmPC of [1] of EMA

Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered

Dapagliflozin/metformin [1], voglibose ---> SmPC of [1] of EMA

Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered

Dapagliflozin/metformin [1], warfarin ---> SmPC of [1] of EMA

Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered

CONTRAINDICATIONS of Dapagliflozin/metformin (Xigduo)

Xigduo is contraindicated in patients with:

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- diabetic ketoacidosis, diabetic pre-coma;

- moderate and severe renal impairment (creatinine clearance < 60 ml/min; eGFR < 60 ml/min/1.73 m²)

- acute conditions with the potential to alter renal function such as:

- dehydration,

- severe infection,

- shock;

- acute or chronic disease which may cause tissue hypoxia such as:

- cardiac or respiratory failure,

- recent myocardial infarction,

- shock;

- hepatic impairment

- acute alcohol intoxication, alcoholism

https://www.ema.europa.eu/en/documents/product-information/xigduo-epar-product-information_en.pdf 07/02/2024

Other trade names: Ebymect,

Dapoxetine

Ability to drive, dapoxetine [2] ---> SmPC of [2] of eMC

Dizziness, disturbances in attention, syncopes, blurred vision and somnolence have been reported

Acetylsalicylic acid, dapoxetine [2] ---> SmPC of [2] of eMC

There have been reports of bleeding abnormalities with SSRIs. Caution is advised in patients taking dapoxetine, particularly in concomitant use with medicinal products known to affect platelet function

Alcohol, dapoxetine [2] ---> SmPC of [2] of eMC

Patients should be advised to avoid alcohol while taking dapoxetine

Alfa-adrenergic receptor blockers, dapoxetine [2] ---> SmPC of [2] of eMC

Dapoxetine should be prescribed with caution in patients taking medicinal products with vasodilatation properties (such as alpha adrenergic receptor antagonists and nitrates) due to possible reduced orthostatic tolerance

Amprenavir, dapoxetine [2] ---> SmPC of [2] of eMC

Concomitant treatment of dapoxetine with moderate CYP3A4 inhibitors may give rise to significantly increased exposure of dapoxetine and desmethyldapoxetine, especially in CYP2D6 poor metabolizers.

Anticoagulants, dapoxetine [2] ---> SmPC of [2] of eMC

There have been reports of bleeding abnormalities with SSRIs. Caution is advised in patients taking dapoxetine, particularly in concomitant use anticoagulants (e.g., warfarin)

Antidepressants, dapoxetine [2] ---> SmPC of [2] of eMC

Caution is advised if the concomitant administration of dapoxetine and CNS active medicinal products is required

Antiepileptics, dapoxetine [2] ---> SmPC of [2] of eMC

Caution is advised if the concomitant administration of dapoxetine and CNS active medicinal products is required

Anxiolytics, dapoxetine [2] ---> SmPC of [2] of eMC

Caution is advised if the concomitant administration of dapoxetine and CNS active medicinal products is required

Aprepitant, dapoxetine [2] ---> SmPC of [2] of eMC

Concomitant treatment of dapoxetine with moderate CYP3A4 inhibitors may give rise to significantly increased exposure of dapoxetine and desmethyldapoxetine, especially in CYP2D6 poor metabolizers.

Atazanavir, dapoxetine [2] ---> SmPC of [2] of eMC

The strong CYP3A4 inhibition may increase the plasma concentrations of dapoxetine. Concomitant use of dapoxetine and potent CYP3A4 inhibitors is contraindicated

Atypical neuroleptics, dapoxetine [2] ---> SmPC of [2] of eMC

Breast-feeding, dapoxetine [2] ---> SmPC of [2] of eMC

It is not known if either dapoxetine or its metabolites are excreted in human milk

Clarithromycin, dapoxetine [2] ---> SmPC of [2] of eMC

Concomitant treatment of dapoxetine with moderate CYP3A4 inhibitors may give rise to significantly increased exposure of dapoxetine and desmethyldapoxetine, especially in CYP2D6 poor metabolizers.

CNS depressants, dapoxetine [2] ---> SmPC of [2] of eMC

Caution is advised if the concomitant administration of dapoxetine and CNS active medicinal products is required

Dapoxetine [1], diltiazem ---> SmPC of [1] of eMC

Concomitant treatment of dapoxetine with moderate CYP3A4 inhibitors may give rise to significantly increased exposure of dapoxetine and desmethyldapoxetine, especially in CYP2D6 poor metabolizers.

Dapoxetine [1], drugs primarily metabolised by CYP2D6 ---> SmPC of [1] of eMC

Dapoxetine may increase the plasma concentrations of other drugs metabolized by CYP2D6

Dapoxetine [1], drugs primarily metabolised by CYP3A4 with narrow therapeutic index ---> SmPC of [1] of eMC

The increase in CYP3A activity may be of clinical relevance in some individuals concomitantly treated with a medicinal product mainly metabolized by CYP3A and with a narrow therapeutic window.

Dapoxetine [1], erythromycin ---> SmPC of [1] of eMC

Concomitant treatment of dapoxetine with moderate CYP3A4 inhibitors may give rise to significantly increased exposure of dapoxetine and desmethyldapoxetine, especially in CYP2D6 poor metabolizers.

Dapoxetine [1], fluconazole ---> SmPC of [1] of eMC

Concomitant treatment of dapoxetine with moderate CYP3A4 inhibitors may give rise to significantly increased exposure of dapoxetine and desmethyldapoxetine, especially in CYP2D6 poor metabolizers.

Dapoxetine [1], fluoxetine ---> SmPC of [1] of eMC

The Cmax of the active fraction may be increased by approximately 50% and the AUC of the active fraction may be doubled if taken dapoxetine with potent CYP2D6 inhibitors

Dapoxetine [1], fosamprenavir ---> SmPC of [1] of eMC

Concomitant treatment of dapoxetine with moderate CYP3A4 inhibitors may give rise to significantly increased exposure of dapoxetine and desmethyldapoxetine, especially in CYP2D6 poor metabolizers.

Dapoxetine [1], hypnotics ---> SmPC of [1] of eMC

Caution is advised if the concomitant administration of dapoxetine and CNS active medicinal products is required

Dapoxetine [1], IMAOs ---> SmPC of [1] of eMC

Dapoxetine should not be used in combination with an MAOI, or within 14 days of discontinuing treatment with an MAOI. Similarly, an MAOI should not be administered within 7 days after dapoxetine has been discontinued

Dapoxetine [1], itraconazol ---> SmPC of [1] of eMC

The strong CYP3A4 inhibition may increase the plasma concentrations of dapoxetine. Concomitant use of dapoxetine and potent CYP3A4 inhibitors is contraindicated

Dapoxetine [1], ketoconazole ---> SmPC of [1] of eMC

The strong CYP3A4 inhibition may increase the plasma concentrations of dapoxetine. Concomitant use of dapoxetine and potent CYP3A4 inhibitors is contraindicated

Dapoxetine [1], linezolid ---> SmPC of [1] of eMC

Combination dapoxetine and serotonergic drugs (SD) may lead to incidence of serotonin associated effects. Dapoxetine should not be used with SD or in 14 d. of discontinuing SD. SD should not be given in 7 d. after discontinuing dapoxetine

Dapoxetine [1], lithium ---> SmPC of [1] of eMC

Dapoxetine [1], moderate CYP3A4 inhibitors ---> SmPC of [1] of eMC

Concomitant treatment of dapoxetine with moderate CYP3A4 inhibitors may give rise to significantly increased exposure of dapoxetine and desmethyldapoxetine, especially in CYP2D6 poor metabolizers.

Dapoxetine [1], nefazodone ---> SmPC of [1] of eMC

The strong CYP3A4 inhibition may increase the plasma concentrations of dapoxetine. Concomitant use of dapoxetine and potent CYP3A4 inhibitors is contraindicated

Dapoxetine [1], nelfinavir ---> SmPC of [1] of eMC

The strong CYP3A4 inhibition may increase the plasma concentrations of dapoxetine. Concomitant use of dapoxetine and potent CYP3A4 inhibitors is contraindicated

Dapoxetine [1], neuroleptics ---> SmPC of [1] of eMC

Caution is advised if the concomitant administration of dapoxetine and CNS active medicinal products is required

Dapoxetine [1], NSAID ---> SmPC of [1] of eMC

Dapoxetine [1], organic nitrates ---> SmPC of [1] of eMC

Dapoxetine [1], PDE5 inhibitors ---> SmPC of [1] of eMC

Dapoxetine should not be used in patients using PDE5 inhibitors due to possible reduced orthostatic tolerance

Dapoxetine [1], platelet aggregation inhibitors ---> SmPC of [1] of eMC

Dapoxetine [1], pregnancy ---> SmPC of [1] of eMC

Dapoxetine is not indicated for women

Dapoxetine [1], ritonavir ---> SmPC of [1] of eMC

The strong CYP3A4 inhibition may increase the plasma concentrations of dapoxetine. Concomitant use of dapoxetine and potent CYP3A4 inhibitors is contraindicated

Dapoxetine [1], saquinavir ---> SmPC of [1] of eMC

The strong CYP3A4 inhibition may increase the plasma concentrations of dapoxetine. Concomitant use of dapoxetine and potent CYP3A4 inhibitors is contraindicated

Dapoxetine [1], serotonergic medicines ---> SmPC of [1] of eMC

Dapoxetine [1], serotonin agonists ---> SmPC of [1] of eMC

Dapoxetine [1], SSNRI ---> SmPC of [1] of eMC

Dapoxetine [1], SSRI ---> SmPC of [1] of eMC

Dapoxetine [1], St. John's wort ---> SmPC of [1] of eMC

Dapoxetine [1], strong CYP2D6 inhibitors ---> SmPC of [1] of eMC

The Cmax of the active fraction may be increased by approximately 50% and the AUC of the active fraction may be doubled if taken dapoxetine with potent CYP2D6 inhibitors

Dapoxetine [1], strong CYP3A4 inhibitors ---> SmPC of [1] of eMC

The strong CYP3A4 inhibition may increase the plasma concentrations of dapoxetine. Concomitant use of dapoxetine and potent CYP3A4 inhibitors is contraindicated

Dapoxetine [1], telithromycin ---> SmPC of [1] of eMC

The strong CYP3A4 inhibition may increase the plasma concentrations of dapoxetine. Concomitant use of dapoxetine and potent CYP3A4 inhibitors is contraindicated

Dapoxetine [1], thioridazine ---> SmPC of [1] of eMC

Dapoxetine, CYP2D6 inhibitor, may increase thioridazine levels and risk of QTc prolongation. Combination is contraindicated and also within 14 days of discontinuing thioridazine treatment and within 7 days after discontinuing dapoxetine

Dapoxetine [1], tramadol ---> SmPC of [1] of eMC

Dapoxetine [1], triptans ---> SmPC of [1] of eMC

Dapoxetine [1], tryptophan ---> SmPC of [1] of eMC

Dapoxetine [1], vasodilators ---> SmPC of [1] of eMC

Dapoxetine [1], verapamil ---> SmPC of [1] of eMC

Concomitant treatment of dapoxetine with moderate CYP3A4 inhibitors may give rise to significantly increased exposure of dapoxetine and desmethyldapoxetine, especially in CYP2D6 poor metabolizers.

Dapoxetine [1], warfarin ---> SmPC of [1] of eMC

There have been reports of bleeding abnormalities with SSRIs. Caution is advised in patients taking dapoxetine, particularly in concomitant use anticoagulants (e.g., warfarin)

CONTRAINDICATIONS of Dapoxetine

- Hypersensitivity to the active substance or to any of the excipients

- Significant pathological cardiac conditions such as:

- Heart failure (NYHA class II-IV)

- Conduction abnormalities such as AV block or sick sinus syndrome

- Significant ischemic heart disease

- Significant valvular disease

- A history of syncope

- A history of mania or severe depression.

- Concomitant treatment with monoamine oxidase inhibitors (MAOIs), or within 14 days of discontinuing treatment with an MAOI. Similarly, an MAOI should not be administered within 7 days after dapoxetine has been discontinued

- Concomitant treatment with thioridazine, or within 14 days of discontinuing treatment with thioridazine. Similarly, thioridazine should not be administered within 7 days after dapoxetine has been discontinued

- Concomitant treatment with serotonin reuptake inhibitors [selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs)] or other medicinal/herbal products with serotonergic effects [e.g., L-tryptophan, triptans, tramadol, linezolid, lithium, St. John's Wort (Hypericum perforatum)] or within 14 days of discontinuing treatment with these medicinal/herbal products. Similarly, these medicinal/herbal products should not be administered within 7 days after dapoxetine has been discontinued

- Concomitant treatment of potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, saquinavir, telithromycin, nefazadone, nelfinavir, atazanavir, etc.

- Moderate and severe hepatic impairment

http://www.medicines.org.uk/emc/

Daptomycin (Cubicin)

Ability to drive, daptomycin [2] ---> SmPC of [2] of EMA

On the basis of reported adverse drug reactions, Cubicin is presumed to be unlikely to produce an effect on the ability to drive or use machinery.

Anticoagulants, daptomycin [2] ---> SmPC of [2] of EMA

. Studies of Cubicin with anticoagulants other than warfarin have not been conducted. Anticoagulant activity in patients receiving Cubicin and warfarin should be monitored for the first several days after therapy with Cubicin is initiated.

Aztreonam, daptomycin [2] ---> SmPC of [2] of EMA

The pharmacokinetics of daptomycin were not significantly altered by aztreonam.

Breast-feeding, daptomycin [2] ---> SmPC of [2] of EMA

Therefore, until more experience is gained, breast-feeding should be discontinued when Cubicin is administered to nursing women.

Coxibs, daptomycin [2] ---> SmPC of [2] of EMA

Daptomycin wird vorwiegend durch renale Filtration eliminiert. Bei gleichzeitiger Anwendung mit Arzneimitteln, die die renale Filtration vermindern (z. B. NSAIDs und COX-2-Hemmer), können die Plasmaspiegel daher erhöht sein.

CYP450, daptomycin [2] ---> SmPC of [2] of EMA

Daptomycin undergoes little to no Cytochrome P450 (CYP450)-mediated metabolism. It is unlikely that daptomycin will inhibit or induce the metabolism of medicinal products metabolised by the P450 system.

Daptomycin [1], fertility ---> SmPC of [1] of EMA

No clinical data on fertility are available for daptomycin. Animal studies do not indicate direct or indirect harmful effects with respect to fertility (see section 5.3).

Daptomycin [1], myopathy ---> SmPC of [1] of EMA

It is recommended that other medicinal products associated with myopathy should if possible be temporarily discontinued during treatment with daptomycin

Daptomycin [1], myopathy ---> SmPC of [1] of EMA

There is limited experience regarding concomitant administration of daptomycin with other medicinal products that may trigger myopathy (e.g. HMG-CoA reductase inhibitors).

Daptomycin [1], NSAID ---> SmPC of [1] of EMA

Daptomycin [1], pregnancy ---> SmPC of [1] of EMA

Cubicin should not be used during pregnancy unless clearly necessary i.e., only if the expected benefit outweighs the possible risk.

Daptomycin [1], probenecide ---> SmPC of [1] of EMA

Daptomycin had no effect on the pharmacokinetics of warfarin or probenecid, nor did these medicinal products alter the pharmacokinetics of daptomycin.

Daptomycin [1], renal filtration ---> SmPC of [1] of EMA

Therefore, caution is advised when daptomycin is co-administered with any other medicinal product known to reduce renal filtration.

Daptomycin [1], rhabdomyolysis ---> SmPC of [1] of EMA

However, some cases of marked rises in CPK levels and cases of rhabdomyolysis occurred in adult patients taking one of these medicinal products at the same time as Cubicin.

Daptomycin [1], statins ---> SmPC of [1] of EMA

It is recommended that other medicinal products associated with myopathy should if possible be temporarily discontinued during treatment with daptomycin

Daptomycin [1], surveillance ---> SmPC of [1] of EMA

During post-marketing surveillance, cases of interference between daptomycin and particular reagents used in some assays of prothrombin time/international normalised ratio (PT/INR) have been reported.

Daptomycin [1], tobramycin ---> SmPC of [1] of EMA

Although small changes in the pharmacokinetics of daptomycin and tobramycin were observed, the changes were not statistically significant. Caution is warranted when Cubicin is co-administered with tobramycin.

Daptomycin [1], warfarin ---> SmPC of [1] of EMA

Daptomycin had no effect on the pharmacokinetics of warfarin or probenecid, nor did these medicinal products alter the pharmacokinetics of daptomycin. Anticoagulant activity should be monitored for the first several days

CONTRAINDICATIONS of Daptomycin (Cubicin)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/cubicin-epar-product-information_en.pdf 20/06/2024

Other trade names: Daptomycin Hospira,

Daratumumab (Darzalex)

Ability to drive, daratumumab [2] ---> SmPC of [2] of EMA

Fatigue has been reported in patients taking daratumumab and this should be taken into account when driving or using machines.

Bortezomib, daratumumab [2] ---> SmPC of [2] of EMA

Clinical pharmacokinetic assessments of daratumumab in combination with lenalidomide, pomalidomide, thalidomide, bortezomib and dexamethasone indicated no clinically-relevant drug-drug interaction

Breast-feeding, daratumumab [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from DARZALEX therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Daratumumab [1], dexamethasone ---> SmPC of [1] of EMA

Clinical pharmacokinetic assessments of daratumumab in combination with lenalidomide, pomalidomide, thalidomide, bortezomib and dexamethasone indicated no clinically-relevant drug-drug interaction

Daratumumab [1], fertility ---> SmPC of [1] of EMA

No data are available to determine potential effects of daratumumab on fertility in males or females (see section 5.3).

Daratumumab [1], lenalidomide ---> SmPC of [1] of EMA

Clinical pharmacokinetic assessments of daratumumab in combination with lenalidomide, pomalidomide, thalidomide, bortezomib and dexamethasone indicated no clinically-relevant drug-drug interaction

Daratumumab [1], pomalidomide ---> SmPC of [1] of EMA

Clinical pharmacokinetic assessments of daratumumab in combination with lenalidomide, pomalidomide, thalidomide, bortezomib and dexamethasone indicated no clinically-relevant drug-drug interaction

Daratumumab [1], pregnancy ---> SmPC of [1] of EMA

DARZALEX is not recommended during pregnancy and in women of childbearing potential not using contraception.

Daratumumab [1], thalidomide ---> SmPC of [1] of EMA

Clinical pharmacokinetic assessments of daratumumab in combination with lenalidomide, pomalidomide, thalidomide, bortezomib and dexamethasone indicated no clinically-relevant drug-drug interaction

Daratumumab [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of child-bearing potential should use effective contraception during, and for 3 months after cessation of daratumumab treatment.

CONTRAINDICATIONS of Daratumumab (Darzalex)

- Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/darzalex-epar-product-information_en.pdf 19/01/2026

Darbepoetin alfa (Aranesp)

Breast-feeding, darbepoetin alfa [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Aranesp therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Cyclosporine, darbepoetin alfa [2] ---> SmPC of [2] of EMA

There is potential for an interaction with substances that are highly bound to red blood cells e.g. cyclosporin, tacrolimus. Blood levels of these substances should be monitored and the dosage adjusted as the haemoglobin rises.

Darbepoetin alfa [1], fertility ---> SmPC of [1] of EMA

Animal studies do not indicate direct harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. No alteration of fertility was detected.

Darbepoetin alfa [1], pregnancy ---> SmPC of [1] of EMA

Caution should be exercised when prescribing Aranesp to pregnant women.

Darbepoetin alfa [1], tacrolimus ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Darbepoetin alfa (Aranesp)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Poorly controlled hypertension

https://www.ema.europa.eu/en/documents/product-information/aranesp-epar-product-information_en.pdf 28/06/2024

Other trade names: Nespo,

Daridorexant (Quviviq)

Ability to drive, daridorexant [2] ---> SmPC of [2] of EMA

Hypnotics have a major influence on the ability to drive and use machines. In order to minimise this risk, a period of approximately 9 hours is recommended between taking QUVIVIQ and driving or using machines.

Alcohol, daridorexant [2] ---> SmPC of [2] of EMA

Co-administration of 50 mg daridorexant with alcohol led to additive effects on psychomotor performance.

BCRP substrates, daridorexant [2] ---> SmPC of [2] of EMA

Daridorexant did not affect the PK of rosuvastatin, indicating an absence of inhibition of BCRP. BCRP substrates can be administered with QUVIVIQ without dose adjustment.

Breast-feeding, daridorexant [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from QUVIVIQ therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Ciprofloxacin, daridorexant [2] ---> SmPC of [2] of EMA

In patients taking moderate CYP3A4 inhibitors (e.g., erythromycin, ciprofloxacin, cyclosporine), the recommended dose of QUVIVIQ is 25 mg.

Citalopram, daridorexant [2] ---> SmPC of [2] of EMA

No relevant interaction on psychomotor performance was observed when 50 mg daridorexant was co-administered with 20 mg citalopram in healthy subjects at steady state.

Clarithromycin, daridorexant [2] ---> SmPC of [2] of EMA

No clinical study was conducted with a strong CYP3A4 inhibitor. Concomitant use of QUVIVIQ with strong inhibitors of CYP3A4 (e.g., itraconazole, clarithromycin, ritonavir) is contraindicated

CNS depressants [1], daridorexant ---> SmPC of [1] of EMA

In the case of co-administration with CNS-depressant medicinal products, dose adjustments of QUVIVIQ and/or the other medicinal products may be required, based on clinical evaluation, due to potentially additive effects

Contraceptives, daridorexant [2] ---> SmPC of [2] of EMA

In the same study, daridorexant 50 mg administered for 7 days did not induce CYP3A4, therefore contraceptives can be co-administered with QUVIVIQ.

Cyclosporine, daridorexant [2] ---> SmPC of [2] of EMA

In patients taking moderate CYP3A4 inhibitors (e.g., erythromycin, ciprofloxacin, cyclosporine), the recommended dose of QUVIVIQ is 25 mg.

CYP3A4 substrates with a narrow therapeutic index, daridorexant [2] ---> SmPC of [2] of EMA

Simultaneous administration of 50 mg QUVIVIQ with sensitive CYP3A4 substrates with a narrow therapeutic index (e.g., high-dose simvastatin, tacrolimus) should be handled with caution.

Dabigatran, daridorexant [2] ---> SmPC of [2] of EMA

In a clinical study conducted in healthy subjects receiving daridorexant 50 mg and dabigatran etexilate, a sensitive P-gp substrate, dabigatran AUC and Cmax increased by 42% and 29%, respectively, indicating a mild P-gp inhibition.

Daridorexant [1], digoxin ---> SmPC of [1] of EMA

Simultaneous administration of QUVIVIQ with P-gp substrates with a narrow therapeutic index (e.g., digoxin) should be handled with caution.

Daridorexant [1], diltiazem ---> SmPC of [1] of EMA

In healthy subjects, co-administration of daridorexant 25 mg with the moderate CYP3A4 inhibitor diltiazem (240 mg once daily) increased daridorexant exposure parameters AUC and Cmax by 2.4 times and 1.4 times, respectively.

Daridorexant [1], drugs primarily metabolised by CYP2C9 ---> SmPC of [1] of EMA

CYP2C9 substrates can be administered with QUVIVIQ without dose adjustment.

Daridorexant [1], efavirenz ---> SmPC of [1] of EMA

In healthy subjects, co-administration with efavirenz (600 mg once daily), a moderate CYP3A4 inducer, decreased daridorexant exposure parameters AUC and Cmax by 61% and 35%, respectively.

Daridorexant [1], erythromycin ---> SmPC of [1] of EMA

In patients taking moderate CYP3A4 inhibitors (e.g., erythromycin, ciprofloxacin, cyclosporine), the recommended dose of QUVIVIQ is 25 mg.

Daridorexant [1], famotidine ---> SmPC of [1] of EMA

The solubility of daridorexant is pH-dependent. In healthy subjects, co-administration with famotidine (40 mg), an inhibitor of gastric acid secretion, decreased daridorexant Cmax by 39% while AUC remained unchanged.

Daridorexant [1], fertility ---> SmPC of [1] of EMA

There are no data concerning the effect of exposure to daridorexant on human fertility. Animal studies indicate no impact on male or female fertility (see section 5.3).

Daridorexant [1], foods ---> SmPC of [1] of EMA

QUVIVIQ can be taken with or without food. However, taking QUVIVIQ soon after a large meal may reduce the effect on sleep onset

Daridorexant [1], gastric pH increasing medication ---> SmPC of [1] of EMA

No dose adjustment is required when QUVIVIQ is used concomitantly with treatments that reduce gastric acidity.

Daridorexant [1], grapefruit ---> SmPC of [1] of EMA

The consumption of grapefruit or grapefruit juice in the evening should be avoided.

Daridorexant [1], grapefruit juice ---> SmPC of [1] of EMA

The consumption of grapefruit or grapefruit juice in the evening should be avoided.

Daridorexant [1], itraconazol ---> SmPC of [1] of EMA

No clinical study was conducted with a strong CYP3A4 inhibitor. Concomitant use of QUVIVIQ with strong inhibitors of CYP3A4 (e.g., itraconazole, clarithromycin, ritonavir) is contraindicated

Daridorexant [1], midazolam ---> SmPC of [1] of EMA

In a clinical study conducted in healthy subjects receiving daridorexant and midazolam, a sensitive CYP3A4 substrate, daridorexant at a dose of 25 mg did not affect the PK of midazolam, indicating an absence of CYP3A4 induction or inhibition.

Daridorexant [1], moderate CYP3A4 inductors ---> SmPC of [1] of EMA

Based on these results, concomitant use with a moderate or strong CYP3A4 inducer substantially decreases exposure to daridorexant, which may reduce efficacy.

Daridorexant [1], moderate CYP3A4 inhibitors ---> SmPC of [1] of EMA

In patients taking moderate CYP3A4 inhibitors (e.g., erythromycin, ciprofloxacin, cyclosporine), the recommended dose of QUVIVIQ is 25 mg.

Daridorexant [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

Simultaneous administration of QUVIVIQ with P-gp substrates with a narrow therapeutic index (e.g., digoxin) should be handled with caution.

Daridorexant [1], pregnancy ---> SmPC of [1] of EMA

QUVIVIQ should be used during pregnancy only if the clinical condition of the pregnant woman requires treatment with daridorexant.

Daridorexant [1], ritonavir ---> SmPC of [1] of EMA

No clinical study was conducted with a strong CYP3A4 inhibitor. Concomitant use of QUVIVIQ with strong inhibitors of CYP3A4 (e.g., itraconazole, clarithromycin, ritonavir) is contraindicated

Daridorexant [1], rosuvastatin ---> SmPC of [1] of EMA

Daridorexant did not affect the PK of rosuvastatin, indicating an absence of inhibition of BCRP. BCRP substrates can be administered with QUVIVIQ without dose adjustment.

Daridorexant [1], simvastatine ---> SmPC of [1] of EMA

Simultaneous administration of 50 mg QUVIVIQ with sensitive CYP3A4 substrates with a narrow therapeutic index (e.g., high-dose simvastatin, tacrolimus) should be handled with caution.

Daridorexant [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Based on these results, concomitant use with a moderate or strong CYP3A4 inducer substantially decreases exposure to daridorexant, which may reduce efficacy.

Daridorexant [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

No clinical study was conducted with a strong CYP3A4 inhibitor. Concomitant use of QUVIVIQ with strong inhibitors of CYP3A4 (e.g., itraconazole, clarithromycin, ritonavir) is contraindicated

Daridorexant [1], tacrolimus ---> SmPC of [1] of EMA

Simultaneous administration of 50 mg QUVIVIQ with sensitive CYP3A4 substrates with a narrow therapeutic index (e.g., high-dose simvastatin, tacrolimus) should be handled with caution.

Daridorexant [1], warfarin ---> SmPC of [1] of EMA

In a clinical study conducted in healthy subjects receiving daridorexant and warfarin, a sensitive CYP2C9 substrate, daridorexant at a dose of 50 mg did not affect the PK and PD of warfarin, indicating an absence of effect on CYP2C9.

CONTRAINDICATIONS of Daridorexant (Quviviq)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Narcolepsy.

- Concomitant use with strong CYP3A4 inhibitors (see section 4.5).

https://www.ema.europa.eu/en/documents/product-information/quviviq-epar-product-information_en.pdf 07/10/2024

Darifenacin (Emselex)

Ability to drive, darifenacin [2] ---> SmPC of [2] of EMA

As with other antimuscarinic agents, Emselex may produce effects such as dizziness, blurred vision, insomnia and somnolence. Patients experiencing these side effects should not drive or use machines.

Antimuscarinic agents, antiparkinsonian agents ---> SmPC of [darifenacin] of EMA

The potentiation of anticholinergic effects with antiparkinson agents and tricyclic antidepressants may also occur if antimuscarinic agents are used concurrently with such medicinal products.

Antimuscarinic agents, darifenacin [2] ---> SmPC of [2] of EMA

As with any other antimuscarinic agents, concomitant use of medicinal products that possess antimuscarinic properties may result in more pronounced therapeutic and side effects.

Antimuscarinic agents, tricyclic antidepressant ---> SmPC of [darifenacin] of EMA

The potentiation of anticholinergic effects with antiparkinson agents and tricyclic antidepressants may also occur if antimuscarinic agents are used concurrently with such medicinal products.

Barbiturates, darifenacin [2] ---> SmPC of [2] of EMA

Substances that are inducers of CYP3A4, such as rifampicin, carbamazepine, barbiturates and St John's wort (Hypericum perforatum) are likely to decrease the plasma concentrations of darifenacin.

Biphosphonates, darifenacin [2] ---> SmPC of [2] of EMA

Darifenacin should be used with caution in patients who are concurrently taking medicinal products (such as oral bisphosphonates) that can cause or exacerbate oesophagitis.

Breast-feeding, darifenacin [2] ---> SmPC of [2] of EMA

A risk to the nursing child cannot be excluded. A decision whether to avoid breast-feeding or to abstain from Emselex therapy during lactation should be based on a benefit and risk comparison.

Carbamazepine, darifenacin [2] ---> SmPC of [2] of EMA

Substances that are inducers of CYP3A4, such as rifampicin, carbamazepine, barbiturates and St John's wort (Hypericum perforatum) are likely to decrease the plasma concentrations of darifenacin.

Cimetidine, darifenacin [2] ---> SmPC of [2] of EMA

In patients receiving substances that are potent CYP2D6 inhibitors (e.g. paroxetine, terbinafine, cimetidine and quinidine) the recommended starting dose should be 7.5 mg daily.

Clarithromycin, darifenacin [2] ---> SmPC of [2] of EMA

When co-administered with moderate CYP3A4 inhibitors such as erythromycin, clarithromycin, telithromycin, fluconazole and grapefruit juice, the recommended starting dose of darifenacin should be 7.5 mg daily.

Cyclosporine, darifenacin [2] ---> SmPC of [2] of EMA

Concomitant treatment of darifenacin with potent P-glycoprotein inhibitors should be avoided.

CYP3A4 and P-glycoprotein-inhibitors, darifenacin

The strong CYP3A4 and P-glycoprotein inhibition may increase the plasma concentrations of darifenacin. Concomitant use should be avoided

Darifenacin [1], digoxin ---> SmPC of [1] of EMA

Darifenacin co-administered with digoxin at steady state resulted in a small increase in digoxin exposure

Darifenacin [1], drugs primarily metabolised by CYP2D6 ---> SmPC of [1] of EMA

The effects of darifenacin on the metabolism of CYP2D6 substrates are mainly clinically relevant for CYP2D6 substrates which are individually dose titrated.

Darifenacin [1], drugs primarily metabolised by CYP2D6 with narrow therapeutic index ---> SmPC of [1] of EMA

Darifenacin is a moderate inhibitor of the enzyme CYP2D6. Caution should be exercised when darifenacin is used concomitantly with medicinal products that are predominantly metabolised by CYP2D6 and which have a narrow therapeutic window

Darifenacin [1], drugs primarily metabolised by CYP3A4 ---> SmPC of [1] of EMA

Darifenacin administration does not alter the pharmacokinetics of CYP3A4 substrates in vivo. No dose adjustment is needed for CYP3A4 substrates.

Darifenacin [1], erythromycin ---> SmPC of [1] of EMA

Darifenacin [1], fertility ---> SmPC of [1] of EMA

Women of child bearing potential should be made aware of the lack of fertility data, and Emselex should only be given after consideration of individual risks and benefits.

Darifenacin [1], flavoxate ---> SmPC of [1] of EMA

As with any other antimuscarinic agents, concomitant use of medicinal products that possess antimuscarinic properties may result in more pronounced therapeutic and side effects.

Darifenacin [1], flecainide ---> SmPC of [1] of EMA

Darifenacin [1], fluconazole ---> SmPC of [1] of EMA

Darifenacin [1], grapefruit juice ---> SmPC of [1] of EMA

Darifenacin [1], imipramine ---> SmPC of [1] of EMA

Darifenacin [1], itraconazol ---> SmPC of [1] of EMA

Darifenacin should not be used together with potent CYP3A4 inhibitors (see section 4.3) such as protease inhibitors (e.g. ritonavir), ketoconazole and itraconazole.

Darifenacin [1], ketoconazole ---> SmPC of [1] of EMA

Darifenacin should not be used together with potent CYP3A4 inhibitors (see section 4.3) such as protease inhibitors (e.g. ritonavir), ketoconazole and itraconazole.

Darifenacin [1], midazolam ---> SmPC of [1] of EMA

It can be concluded that darifenacin administration does not alter the pharmacokinetics of CYP3A4 substrates in vivo. The interaction with midazolam lacks clinical relevance, and therefore no dose adjustment is needed for CYP3A4 substrates.

Darifenacin [1], moderate CYP3A4 inhibitors ---> SmPC of [1] of EMA

Darifenacin [1], oxybutynine ---> SmPC of [1] of EMA

As with any other antimuscarinic agents, concomitant use of medicinal products that possess antimuscarinic properties may result in more pronounced therapeutic and side effects.

Darifenacin [1], paroxetine ---> SmPC of [1] of EMA

In patients receiving substances that are potent CYP2D6 inhibitors (e.g. paroxetine, terbinafine, cimetidine and quinidine) the recommended starting dose should be 7.5 mg daily.

Darifenacin [1], pregnancy ---> SmPC of [1] of EMA

There are limited amount of data from the use of darifenacin in pregnant women. Studies in animals have shown toxicity to parturition (for details, see section 5.3). Emselex is not recommended during pregnancy.

Darifenacin [1], protease inhibitors ---> SmPC of [1] of EMA

Concomitant treatment of darifenacin with potent CYP3A4 inhibitors is contraindicated

Darifenacin [1], quinidine ---> SmPC of [1] of EMA

In patients receiving substances that are potent CYP2D6 inhibitors (e.g. paroxetine, terbinafine, cimetidine and quinidine) the recommended starting dose should be 7.5 mg daily.

Darifenacin [1], rifampicin ---> SmPC of [1] of EMA

Substances that are inducers of CYP3A4, such as rifampicin, carbamazepine, barbiturates and St John's wort (Hypericum perforatum) are likely to decrease the plasma concentrations of darifenacin.

Darifenacin [1], ritonavir ---> SmPC of [1] of EMA

Darifenacin should not be used together with potent CYP3A4 inhibitors (see section 4.3) such as protease inhibitors (e.g. ritonavir), ketoconazole and itraconazole.

Darifenacin [1], St. John's wort ---> SmPC of [1] of EMA

Substances that are inducers of CYP3A4, such as rifampicin, carbamazepine, barbiturates and St John's wort (Hypericum perforatum) are likely to decrease the plasma concentrations of darifenacin.

Darifenacin [1], strong CYP2D6 inhibitors ---> SmPC of [1] of EMA

Concomitant treatment with potent CYP2D6 inhibitors results in an increase in darifenacin exposure

Darifenacin [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Substances that are inducers of CYP3A4, such as rifampicin, carbamazepine, barbiturates and St John's wort (Hypericum perforatum) are likely to decrease the plasma concentrations of darifenacin.

Darifenacin [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Concomitant treatment of darifenacin with potent CYP3A4 inhibitors is contraindicated

Darifenacin [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

Concomitant treatment of darifenacin with potent P-glycoprotein inhibitors should be avoided.

Darifenacin [1], telithromycin ---> SmPC of [1] of EMA

Darifenacin [1], terbinafine ---> SmPC of [1] of EMA

In patients receiving substances that are potent CYP2D6 inhibitors (e.g. paroxetine, terbinafine, cimetidine and quinidine) the recommended starting dose should be 7.5 mg daily.

Darifenacin [1], thioridazine ---> SmPC of [1] of EMA

Darifenacin [1], tolterodine ---> SmPC of [1] of EMA

As with any other antimuscarinic agents, concomitant use of medicinal products that possess antimuscarinic properties may result in more pronounced therapeutic and side effects.

Darifenacin [1], tricyclic antidepressant ---> SmPC of [1] of EMA

Darifenacin [1], verapamil ---> SmPC of [1] of EMA

Concomitant treatment of darifenacin with potent P-glycoprotein inhibitors should be avoided.

Darifenacin [1], warfarin ---> SmPC of [1] of EMA

Standard therapeutic prothrombin time monitoring for warfarin should be continued. The effect of warfarin on prothrombin time was not altered when co-administered with darifenacin.

Darifenacin, duvelisib [2] ---> SmPC of [2] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Darifenacin, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib increased Cmax and AUC of midazolam (a CYP3A4 substrate) by approximately 39% and 54%, respectively. Therefore, concomitant use with sensitive CYP3A4 substrates should be avoided.

Darifenacin, tucatinib [2] ---> SmPC of [2] of EMA

Co-administration of tucatinib with sensitive CYP3A substrates may increase their systemic exposures which may increase the toxicity associated with a CYP3A substrate.

CONTRAINDICATIONS of Darifenacin (Emselex)

Emselex is contraindicated in patients with:

- Hypersensitivity to the active substance or to any of the excipients.

- Urinary retention.

- Gastric retention.

- Uncontrolled narrow-angle glaucoma.

- Myasthenia gravis.

- Severe hepatic impairment (Child Pugh C).

- Severe ulcerative colitis.

- Toxic megacolon.

- Concomitant treatment with potent CYP3A4 inhibitors

https://www.ema.europa.eu/en/documents/product-information/emselex-epar-product-information_en.pdf 15/09/2025

Darolutamide (Nubeqa)

Amiodarone, darolutamide [2] ---> SmPC of [2] of EMA

Since androgen deprivation treatment may prolong the QT interval, the co-administration with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes should be carefully evaluated.

Atorvastatin, darolutamide [2] ---> SmPC of [2] of EMA

Co-administration of darolutamide may increase the plasma concentrations of other concomitant BCRP, OATP1B1 and OATP1B3 substrates (e.g. methotrexate, sulfasalazine, fluvastatin, atorvastatin, pitavastatin).

BCRP inhibitors, darolutamide [2] ---> SmPC of [2] of EMA

Darolutamide is a substrate of CYP3A4, P-gp and breast cancer resistance protein (BCRP). No clinically relevant drug-drug interaction is expected in case of CYP3A4, P-gp or BCRP inhibitor administration.

BCRP substrates, darolutamide [2] ---> SmPC of [2] of EMA

Co-administration of darolutamide with other BCRP substrates should be avoided where possible.

Breast-feeding, darolutamide [2] ---> SmPC of [2] of EMA

A risk to the breast-fed child cannot be excluded.

Carbamazepine, darolutamide [2] ---> SmPC of [2] of EMA

Use of strong and moderate CYP3A4 inducers and P-gp inducers (e.g. carbamazepine, phenobarbital, St. John's Wort, phenytoin, and rifampicin) during treatment with darolutamide is not recommended, unless there is no therapeutic alternative.

Class IA antiarrhythmic agents, darolutamide [2] ---> SmPC of [2] of EMA

Class III antiarrhythmic agents, darolutamide [2] ---> SmPC of [2] of EMA

CYP3A4 and P-glycoprotein-inhibitors, darolutamide [2] ---> SmPC of [2] of EMA

Concomitant use of darolutamide with a combined P-gp and strong CYP3A4 inhibitor increases darolutamide exposure which may increase the risk of darolutamide adverse reactions.

CYP3A4 inhibitors, darolutamide [2] ---> SmPC of [2] of EMA

Dabigatran, darolutamide [2] ---> SmPC of [2] of EMA

Co-administration of darolutamide together with the sensitive P-gp substrate dabigatran etexilate did not reveal any increase in exposure (AUC and Cmax) of dabigatran.

Darolutamide [1], digoxin ---> SmPC of [1] of EMA

No clinically relevant drug-drug interaction is expected in case of P-gp substrate administration. Darolutamide may be given concomitantly with P-gp substrates (e.g. digoxin, verapamil or nifedipine).

Darolutamide [1], disopyramide ---> SmPC of [1] of EMA

Darolutamide [1], docetaxel ---> SmPC of [1] of EMA

Administration of darolutamide in combination with docetaxel resulted in no clinically relevant changes in the pharmacokinetics of darolutamide in mHSPC patients (see section 5.1).

Darolutamide [1], dofetilide ---> SmPC of [1] of EMA

Darolutamide [1], fertility ---> SmPC of [1] of EMA

Based on animal studies, NUBEQA may impair fertility in males of reproductive potential

Darolutamide [1], fluvastatin ---> SmPC of [1] of EMA

Darolutamide [1], foods ---> SmPC of [1] of EMA

The tablets should be taken whole with food

Darolutamide [1], haloperidol ---> SmPC of [1] of EMA

Darolutamide [1], ibutilide ---> SmPC of [1] of EMA

Darolutamide [1], men ---> SmPC of [1] of EMA

If the patient is engaged in sexual activity with a pregnant woman, a condom should be used during and for 1 week after completion of treatment with NUBEQA.

Darolutamide [1], methadone ---> SmPC of [1] of EMA

Darolutamide [1], methotrexate ---> SmPC of [1] of EMA

Darolutamide [1], midazolam ---> SmPC of [1] of EMA

Administration of darolutamide prior to co-administration of a single dose of the sensitive CYP3A4 substrate midazolam (1 mg) together with food, decreased the mean exposure (AUC) and Cmax of midazolam by 29% and 32%, respectively.

Darolutamide [1], moderate CYP3A4 inductors ---> SmPC of [1] of EMA

Darolutamide [1], moderate CYP3A4 inhibitors ---> SmPC of [1] of EMA

Darolutamide [1], moxifloxacin ---> SmPC of [1] of EMA

Darolutamide [1], neuroleptics ---> SmPC of [1] of EMA

Darolutamide [1], nifedipine ---> SmPC of [1] of EMA

Darolutamide [1], OATP1B1 substrates ---> SmPC of [1] of EMA

Darolutamide [1], OATP1B3 substrates ---> SmPC of [1] of EMA

Darolutamide [1], omeprazole ---> SmPC of [1] of EMA

Darolutamide is a mild inducer of CYP3A4. No clinically relevant drug-drug interaction is expected in case of CYP substrate administration. Darolutamide may be given concomitantly with CYP substrates (e.g. warfarin, L-thyroxine, omeprazole).

Darolutamide [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

Darolutamide [1], P-gp inductors ---> SmPC of [1] of EMA

Darolutamide [1], P-gp inhibitors ---> SmPC of [1] of EMA

Darolutamide [1], phenobarbital ---> SmPC of [1] of EMA

Darolutamide [1], phenytoin ---> SmPC of [1] of EMA

Darolutamide [1], pitavastatin ---> SmPC of [1] of EMA

Darolutamide [1], pregnancy ---> SmPC of [1] of EMA

Exposure of the foetus to an androgen receptor inhibitor through seminal transfer to the pregnant woman has to be avoided, as this could affect development of the foetus.

Darolutamide [1], QT interval prolonging drugs ---> SmPC of [1] of EMA

Darolutamide [1], quinidine ---> SmPC of [1] of EMA

Darolutamide [1], rifampicin ---> SmPC of [1] of EMA

Darolutamide [1], rosuvastatin ---> SmPC of [1] of EMA

Darolutamide is an inhibitor of breast cancer resistance protein (BCRP) and Organic Anion Transporting Polypeptides (OATP) 1B1 and 1B3. Co-administration of rosuvastatin should be avoided unless there is no therapeutic alternative.

Darolutamide [1], sotalol ---> SmPC of [1] of EMA

Darolutamide [1], St. John's wort ---> SmPC of [1] of EMA

Darolutamide [1], strong BCRP inhibitors ---> SmPC of [1] of EMA

Darolutamide [1], strong CYP3A4 and P-glycoprotein-inhibitors ---> SmPC of [1] of EMA

Concomitant use of darolutamide with a combined P-gp and strong CYP3A4 inhibitor increases darolutamide exposure which may increase the risk of darolutamide adverse reactions.

Darolutamide [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Darolutamide [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Darolutamide [1], strong P-gp inductors ---> SmPC of [1] of EMA

Darolutamide [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

Darolutamide [1], strong UGT1A9 inhibitors ---> SmPC of [1] of EMA

No clinically relevant drug-drug interaction is expected in case of UGT1A9 inhibitor administration. Darolutamide may be given concomitantly with UGT1A9 inhibitors.

Darolutamide [1], sulfasalazine ---> SmPC of [1] of EMA

Darolutamide [1], torsades de pointes inducing drugs ---> SmPC of [1] of EMA

Darolutamide [1], UGT1A9 inhibitors ---> SmPC of [1] of EMA

No clinically relevant drug-drug interaction is expected in case of UGT1A9 inhibitor administration. Darolutamide may be given concomitantly with UGT1A9 inhibitors.

Darolutamide [1], verapamil ---> SmPC of [1] of EMA

Darolutamide [1], warfarin ---> SmPC of [1] of EMA

Darolutamide [1], women of childbearing potential ---> SmPC of [1] of EMA

A highly effective contraceptive method (< 1% failure rate per year) should be used during and for 1 week after completion of treatment with NUBEQA to prevent pregnancy.

CONTRAINDICATIONS of Darolutamide (Nubeqa)

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Women who are or may become pregnant (see section 4.6).

https://www.ema.europa.eu/en/documents/product-information/nubeqa-epar-product-information_en.pdf 31/07/2024

Darunavir (Prezista)

Ability to drive, darunavir [2] ---> SmPC of [2] of EMA

Dizziness has been reported in some patients during treatment with regimens containing PREZISTA co-administered with cobicistat or low dose ritonavir and should be borne in mind when considering a patient's ability to drive or operate machinery

Alfentanyl, darunavir [2] ---> SmPC of [2] of EMA

The concomitant use with boosted PREZISTA may require to lower the dose of alfentanil and requires monitoring for risks of prolonged or delayed respiratory depression.

Alfuzosin, darunavir [2] ---> SmPC of [2] of EMA

Co-administration of boosted PREZISTA and alfuzosin is contraindicated (see section 4.3).

Amiodarone, darunavir [2] ---> SmPC of [2] of EMA

Co-administration of boosted PREZISTA and amiodarone, bepridil, dronedarone, ivabradine, quinidine, or ranolazine is contraindicated (see section 4.3).

Amitriptyline, darunavir [2] ---> SmPC of [2] of EMA

Clinical monitoring is recommended when co-administering boosted PREZISTA with these antidepressants and a dose adjustment of the antidepressant may be needed.

Apalutamide [1], darunavir ---> SmPC of [1] of EMA

Concomitant use of Erleada with medicinal products that are primarily metabolised by CYP3A4 (e.g., darunavir, felodipine, midazolam, simvastatin) can result in lower exposure to these medicinal products.

Apixaban, darunavir [2] ---> SmPC of [2] of EMA

The use of boosted PREZISTA with a direct oral anticoagulant (DOAC) that is metabolised by CYP3A4 and transported by P-gp is not recommended as this may lead to an increased bleeding risk.

Atorvastatin [1], darunavir ---> SmPC of [1] of eMC

Potent CYP3A4 inhibitors have been shown to lead to markedly increased concentrations of atorvastatin. Co-administration of potent CYP3A4 inhibitors should be avoided if possible.

Atorvastatin, darunavir [2] ---> SmPC of [2] of EMA

When administration of atorvastatin and boosted PREZISTA is desired, it is recommended to start with an atorvastatin dose of 10 mg once daily. A gradual dose increase of atorvastatin may be tailored to the clinical response.

Bepridil, darunavir [2] ---> SmPC of [2] of EMA

Co-administration of boosted PREZISTA and amiodarone, bepridil, dronedarone, ivabradine, quinidine, or ranolazine is contraindicated (see section 4.3).

Bosutinib [1], darunavir ---> SmPC of [1] of EMA

The concomitant use of bosutinib with moderate CYP3A inhibitors should be avoided, as an increase in bosutinib plasma levels will occur. Selection of an alternate concomitant medicine with no or minimal CYP3A enzyme inhibition potential is recommended.

Breast-feeding, darunavir [2] ---> SmPC of [2] of EMA

Because of the potential for adverse reactions in breast-fed infants, women should be instructed not to breast-feed if they are receiving PREZISTA.

Clarithromycin, darunavir [2] ---> SmPC of [2] of EMA

Caution should be exercised when clarithromycin is combined with boosted PREZISTA. For patients with renal impairment the Summary of Product Characteristics for clarithromycin should be consulted for the recommended dose.

Clopidogrel, darunavir [2] ---> SmPC of [2] of EMA

Co-administration of clopidogrel with boosted PREZISTA is not recommended. Use of other antiplatelets not affected by CYP inhibition or induction (e.g. prasugrel) is recommended.

Cobicistat [1], darunavir ---> SmPC of [1] of EMA

Cobicistat is a strong mechanism-based CYP3A inhibitor. Increased plasma concentrations of medicinal products that are metabolised by CYP3A (including atazanavir and darunavir) are observed on co-administration with cobicistat.

Colchicine, darunavir [2] ---> SmPC of [2] of EMA

Reduction in colchicine dose/interruption of colchicine treatment is recommended in patients with normal renal/hepatic function if treatment with boosted PREZISTA is required. For renal/hepatic impairment colchicine with boosted PREZISTA is contraindicated

Colchicine, strong CYP3A4 and P-glycoprotein-inhibitors ---> SmPC of [darunavir] of EMA

Life-threatening and fatal drug interactions have been reported in patients treated with colchicine and strong inhibitors of CYP3A and P-glycoprotein

Corticosteroids primarily metabolised by CYP3A, darunavir [2] ---> SmPC of [2] of EMA

Concomitant use of boosted PREZISTA and corticosteroids that are metabolised by CYP3A may increase the risk of development of systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression.

CYP3A4 inductors, darunavir

Darunavir and cobicistat are metabolised by CYP3A, and co-administration with CYP3A inducers may therefore result in subtherapeutic plasma exposure to darunavir.

CYP3A4 inductors, darunavir [2] ---> SmPC of [2] of EMA

Darunavir and ritonavir are metabolised by CYP3A. Medicinal products that induce CYP3A activity would be expected to increase the clearance of darunavir and ritonavir, resulting in lowered plasma concentrations of these compounds

CYP3A4 inhibitors, darunavir [2] ---> SmPC of [2] of EMA

Co-administration of darunavir and ritonavir with other medicinal products that inhibit CYP3A may decrease the clearance of darunavir and ritonavir, which may result in increased plasma concentrations of darunavir and ritonavir.

Dabigatran etexilate, darunavir [2] ---> SmPC of [2] of EMA

Darunavir/ritonavir: Clinical monitoring and/or dose reduction of the DOAC should be considered when a DOAC transported by P-gp but not metabolised by CYP3A4, including dabigatran etexilate and edoxaban, is co-administered with PREZISTA/rtv.

Dabrafenib [1], darunavir ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dapoxetine, darunavir [2] ---> SmPC of [2] of EMA

Co-administration of boosted PREZISTA with dapoxetine is contraindicated.

Darunavir [1], desipramine ---> SmPC of [1] of EMA

Clinical monitoring is recommended when co-administering boosted PREZISTA with these antidepressants and a dose adjustment of the antidepressant may be needed.

Darunavir [1], didanosine ---> SmPC of [1] of EMA

Boosted darunavir and didanosine can be used without dose adjustments. Didanosine is to be administered on an empty stomach, thus it should be administered 1 hour before or 2 hours after boosted darunavir given with food.

Darunavir [1], digoxin ---> SmPC of [1] of EMA

Given that digoxin has a narrow therapeutic index, it is recommended that the lowest possible dose of digoxin should initially be prescribed in case digoxin is given to patients on boosted PREZISTA therapy.

Darunavir [1], disopyramide ---> SmPC of [1] of EMA

Caution is warranted and therapeutic concentration monitoring, if available, is recommended for these antiarrhythmics when co-administered with boosted PREZISTA.

Darunavir [1], dolutegravir ---> SmPC of [1] of EMA

Boosted PREZISTA and dolutegravir can be used without dose adjustment.

Darunavir [1], domperidone ---> SmPC of [1] of EMA

Co-administration of domperidone with boosted PREZISTA is contraindicated.

Darunavir [1], dronedarone ---> SmPC of [1] of EMA

Co-administration of boosted PREZISTA and amiodarone, bepridil, dronedarone, ivabradine, quinidine, or ranolazine is contraindicated (see section 4.3).

Darunavir [1], drospirenone ---> SmPC of [1] of EMA

When PREZISTA is co-administered with a drospirenone-containing product, clinical monitoring is recommended due to the potential for hyperkalaemia.

Darunavir [1], edoxaban ---> SmPC of [1] of EMA

Darunavir [1], emtricitabine/tenofovir alafenamide ---> SmPC of [1] of EMA

The recommended dose of emtricitabine/tenofovir alafenamide is 200/10 mg once daily when used with boosted PREZISTA.

Darunavir [1], fentanyl ---> SmPC of [1] of EMA

Based on theoretical considerations boosted PREZISTA may increase plasma concentrations of these analgesics. (CYP2D6 and/or CYP3A inhibition)

Darunavir [1], fertility ---> SmPC of [1] of EMA

No human data on the effect of darunavir on fertility are available. There was no effect on mating or fertility with darunavir treatment in rats (see section 5.3).

Darunavir [1], fesoterodine ---> SmPC of [1] of EMA

Use with caution. Monitor for fesoterodine or solifenacin adverse reactions, dose reduction of fesoterodine or solifenacin may be necessary.

Darunavir [1], flecainide ---> SmPC of [1] of EMA

Caution is warranted and therapeutic concentration monitoring, if available, is recommended for these antiarrhythmics when co-administered with boosted PREZISTA.

Darunavir [1], foods ---> SmPC of [1] of EMA

Patients should be instructed to take PREZISTA with cobicistat or low dose ritonavir within 30 minutes after completion of a meal. The type of food does not affect the exposure to darunavir

Darunavir [1], imipramine ---> SmPC of [1] of EMA

Clinical monitoring is recommended when co-administering boosted PREZISTA with these antidepressants and a dose adjustment of the antidepressant may be needed.

Darunavir [1], indinavir ---> SmPC of [1] of EMA

When used in combination with PREZISTA co-administered with low dose ritonavir, dose adjustment of indinavir from 800 mg twice daily to 600 mg twice daily may be warranted in case of intolerance.

Darunavir [1], indinavir ---> SmPC of [1] of EMA

PREZISTA co-administered with cobicistat should not be used in combination with another antiretroviral agent that requires pharmacoenhancement by means of co-administration with an inhibitor of CYP3A4 (see section 4.5).

Darunavir [1], ivabradine ---> SmPC of [1] of EMA

Co-administration of boosted PREZISTA and amiodarone, bepridil, dronedarone, ivabradine, quinidine, or ranolazine is contraindicated (see section 4.3).

Darunavir [1], lidocaine ---> SmPC of [1] of EMA

Caution is warranted and therapeutic concentration monitoring, if available, is recommended for these antiarrhythmics when co-administered with boosted PREZISTA.

Darunavir [1], lomitapide ---> SmPC of [1] of EMA

Based on theoretical considerations boosted PREZISTA is expected to increase the exposure of lomitapide when co-administered. (CYP3A inhibition) Co-administration is contraindicated (see section 4.3).

Darunavir [1], lurasidone ---> SmPC of [1] of EMA

Concomitant administration of boosted PREZISTA and lurasidone, pimozide or sertindole is contraindicated

Darunavir [1], metformin ---> SmPC of [1] of EMA

Careful patient monitoring and dose adjustment of metformin is recommended in patients who are taking PREZISTA co-administered with cobicistat. (not applicable for PREZISTA co-administered with ritonavir)

Darunavir [1], mexiletine ---> SmPC of [1] of EMA

Caution is warranted and therapeutic concentration monitoring, if available, is recommended for these antiarrhythmics when co-administered with boosted PREZISTA.

Darunavir [1], naloxegol ---> SmPC of [1] of EMA

Co-administration of boosted PREZISTA and naloxegol is contraindicated.

Darunavir [1], nortriptyline ---> SmPC of [1] of EMA

Clinical monitoring is recommended when co-administering boosted PREZISTA with these antidepressants and a dose adjustment of the antidepressant may be needed.

Darunavir [1], oxycodone ---> SmPC of [1] of EMA

Based on theoretical considerations boosted PREZISTA may increase plasma concentrations of these analgesics. (CYP2D6 and/or CYP3A inhibition)

Darunavir [1], pimozide ---> SmPC of [1] of EMA

Concomitant administration of boosted PREZISTA and lurasidone, pimozide or sertindole is contraindicated

Darunavir [1], pregnancy ---> SmPC of [1] of EMA

PREZISTA co-administered with cobicistat or low dose ritonavir should be used during pregnancy only if the potential benefit justifies the potential risk.

Darunavir [1], propafenone ---> SmPC of [1] of EMA

Caution is warranted and therapeutic concentration monitoring, if available, is recommended for these antiarrhythmics when co-administered with boosted PREZISTA.

Darunavir [1], quinidine ---> SmPC of [1] of EMA

Co-administration of boosted PREZISTA and amiodarone, bepridil, dronedarone, ivabradine, quinidine, or ranolazine is contraindicated (see section 4.3).

Darunavir [1], raltegravir ---> SmPC of [1] of EMA

At present the effect of raltegravir on darunavir plasma concentrations does not appear to be clinically relevant. Boosted PREZISTA and raltegravir can be used without dose adjustments.

Darunavir [1], ranolazine ---> SmPC of [1] of EMA

Co-administration of boosted PREZISTA and amiodarone, bepridil, dronedarone, ivabradine, quinidine, or ranolazine is contraindicated (see section 4.3).

Darunavir [1], rilpivirine ---> SmPC of [1] of EMA

Boosted PREZISTA and rilpivirine can be used without dose adjustments.

Darunavir [1], rivaroxaban ---> SmPC of [1] of EMA

The use of boosted PREZISTA with a direct oral anticoagulant (DOAC) that is metabolised by CYP3A4 and transported by P-gp is not recommended as this may lead to an increased bleeding risk.

Darunavir [1], sertindole ---> SmPC of [1] of EMA

Concomitant administration of boosted PREZISTA and lurasidone, pimozide or sertindole is contraindicated

Darunavir [1], solifenacin ---> SmPC of [1] of EMA

Use with caution. Monitor for fesoterodine or solifenacin adverse reactions, dose reduction of fesoterodine or solifenacin may be necessary.

Darunavir [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Co-administration with strong CYP3A4 inhibitors is not recommended and caution is warranted, these interactions are described in the interaction table below (e.g. indinavir, azole antifungals such as clotrimazole).

Darunavir [1], tenofovir disoproxil ---> SmPC of [1] of EMA

Monitoring of renal function may be indicated when boosted PREZISTA is given in combination with tenofovir disoproxil, particularly in patients with underlying systemic or renal disease, or in patients taking nephrotoxic agents.

Darunavir [1], ticagrelor ---> SmPC of [1] of EMA

Concomitant administration of boosted PREZISTA with ticagrelor is contraindicated (see section 4.3).

Darunavir [1], tramadol ---> SmPC of [1] of EMA

Based on theoretical considerations boosted PREZISTA may increase plasma concentrations of these analgesics. (CYP2D6 and/or CYP3A inhibition)

Darunavir [1], trazodone ---> SmPC of [1] of EMA

Clinical monitoring is recommended when co-administering boosted PREZISTA with these antidepressants and a dose adjustment of the antidepressant may be needed.

Darunavir [1], warfarin ---> SmPC of [1] of EMA

Warfarin concentrations may be affected when co-administered with boosted darunavir. It is recommended that the international normalised ratio (INR) be monitored when warfarin is combined with boosted darunavir.

Darunavir, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [dasabuvir] of EMA

The recommended dose of darunavir is 800 mg once daily, without ritonavir, when administered at the same time as ombitasvir/paritaprevir/ritonavir + dasabuvir

Darunavir, duvelisib [2] ---> SmPC of [2] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Darunavir, eliglustat [2] ---> SmPC of [2] of EMA

It is predicted that concomitant use of moderate CYP3A inhibitors would increase eliglustat exposure approximately up to 3-fold. Caution should be used with moderate CYP3A inhibitors in intermediate and extensive metabolisers.

Darunavir, everolimus [2] ---> SmPC of [2] of EMA

Large increase in everolimus concentration is expected. Concomitant treatment of everolimus and potent CYP3A4 inhibitors is not recommended.

Darunavir, ezetimibe/atorvastatin [2] ---> SmPC of [2] of eMC

Potent CYP3A4 inhibitors have been shown to lead to markedly increased concentrations of atorvastatin. Coadministration of potent CYP3A4 inhibitors should be avoided if possible.

Darunavir, flunitrazepam

Substances that inhibit hepatic enzymes may enhance the effect of benzodiazepines. Interactions with strong CYP3A4 inhibitors cannot be excluded

Darunavir, ganciclovir ---> SmPC of [valganciclovir] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Darunavir, glecaprevir/pibrentasvir [2] ---> SmPC of [2] of EMA

Medicinal products that inhibit OATP1B1/3 (e.g. elvitegravir, ciclosporin, darunavir, lopinavir) increase systemic concentrations of glecaprevir. Co-administration with darunavir is not recommended.

Darunavir, lamivudine/raltegravir [2] ---> SmPC of [2] of EMA

In some studies, co-administration of raltegravir with darunavir resulted in a modest decrease in darunavir plasma concentrations

Darunavir, lefamulin [2] ---> SmPC of [2] of EMA

Lefamulin is a moderate CYP3A inhibitor but has no induction potential. Co-administration of oral lefamulin with agents metabolised by CYP3A may result in increased plasma concentrations of these medicinal products.

Darunavir, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

No dose adjustment is required

Darunavir, protease inhibitors

Generally, dual therapy with protease inhibitors is not recommended

Darunavir, raltegravir [2] ---> SmPC of [2] of EMA

The co-administration of raltegravir with darunavir resulted in a modest decrease in darunavir plasma concentrations. However, the effect of raltegravir on darunavir plasma concentrations does not appear to be clinically meaningful.

Darunavir, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir increases the serum levels of darunavir as a result of CYP3A4 inhibition. Darunavir must be given with ritonavir to ensure its therapeutic effect.

Darunavir, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib increased Cmax and AUC of midazolam (a CYP3A4 substrate) by approximately 39% and 54%, respectively. Therefore, concomitant use with sensitive CYP3A4 substrates should be avoided.

Darunavir, tadalafil

Possible decreased tadalafil metabolism

Darunavir, talazoparib [2] ---> SmPC of [2] of EMA

Concomitant use of strong P-gp inhibitors should be avoided. If co-administration with a strong P-gp inhibitor is unavoidable, the Talzenna dose should be reduced (see section 4.2).

Darunavir, tecovirimat [2] ---> SmPC of [2] of EMA

A risk for decreases in darunavir plasma concentrations cannot be excluded (CYP3A4 substrate). The combination of tecovirimat and darunavir should be used with caution.

Darunavir, tucatinib [2] ---> SmPC of [2] of EMA

Co-administration of tucatinib with sensitive CYP3A substrates may increase their systemic exposures which may increase the toxicity associated with a CYP3A substrate.

Darunavir, valganciclovir [2] ---> SmPC of [2] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

CONTRAINDICATIONS of Darunavir (Prezista)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Use in patients with severe (Child-Pugh Class C) hepatic impairment.

- Concomitant treatment with any of the following medicinal products given the expected decrease in plasma concentrations of darunavir, ritonavir and cobicistat and the potential for loss of therapeutic effect (see sections 4.4 and 4.5).

Applicable to darunavir boosted with either ritonavir or cobicistat:

- The combination product lopinavir/ritonavir (see section 4.5).

- Strong CYP3A inducers such as rifampicin and herbal preparations containing St John's Wort (Hypericum perforatum). Co-administration is expected to reduce plasma concentrations of darunavir, ritonavir and cobicistat, which could lead to loss of therapeutic effect and possible development of resistance (see sections 4.4 and 4.5).

Applicable to darunavir boosted with cobicistat, not when boosted with ritonavir:

- Darunavir boosted with cobicistat is more sensitive for CYP3A induction than darunavir boosted with ritonavir. Concomitant use with strong CYP3A inducers is contraindicated, since these may reduce the exposure to cobicistat and darunavir leading to loss of therapeutic effect. Strong CYP3A inducers include e.g. carbamazepine, phenobarbital and phenytoin (see sections 4.4 and 4.5).

- Darunavir boosted with either ritonavir or cobicistat inhibits the elimination of active substances that are highly dependent on CYP3A for clearance, which results in increased exposure to the co-administered medicinal product. Therefore, concomitant for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated (applies to darunavir boosted with either ritonavir or cobicistat). These active substances include e.g.:

- alfuzosin

- amiodarone, bepridil, dronedarone, ivabradine, quinidine, ranolazine

- astemizole, terfenadine

- colchicine when used in patients with renal and/or hepatic impairment (see section 4.5)

- ergot derivatives (e.g. dihydroergotamine, ergometrine, ergotamine, methylergonovine)

- elbasvir/grazoprevir

- cisapride

- dapoxetine

- domperidone

- naloxegol

- lurasidone, pimozide, quetiapine, sertindole (see section 4.5)

- triazolam, midazolam administered orally (for caution on parenterally administered midazolam, see section 4.5)

- sildenafil -when used for the treatment of pulmonary arterial hypertension, avanafil

- simvastatin, lovastatin, lomitapide (see section 4.5)

- ticagrelor (see section 4.5).

https://www.ema.europa.eu/en/documents/product-information/prezista-epar-product-information_en.pdf 26/07/2024

Other trade names: Darunavir Krka d.d., Darunavir Mylan,

Darunavir/cobicistat (Rezolsta)

Abacavir, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Based on the different elimination pathways, no interactions are expected with darunavir/cobicistat. The can be used without dose adjustment.

Ability to drive, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Dizziness has been reported in some patients during treatment with regimens containing darunavir administered with cobicistat and should be borne in mind when considering a patient's ability to drive or operate machinery.

Alfentanyl, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

REZOLSTA is expected to increase alfentanil plasma concentrations. The concomitant use with REZOLSTA may require to lower the dose of alfentanil and requires monitoring for risks of prolonged or delayed respiratory depression.

Alfuzosin, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Co-administration of darunavir/cobicistat with active substances that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated

Aluminium hydroxide, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

No mechanistic interaction expected based on theoretical consideration. Darunavir/cobicistat and antacids can be used concomitantly without dose adjustment.

Amiodarone, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Amitriptyline, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Concomitant use of boosted darunavir/cobicistat (CYP2D6 and/or CYP3A inhibition) and this antidepressant may increase concentrations of the antidepressant.

Amlodipine, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Darunavir/cobicistat is expected to increase the calcium channel blocker plasma concentrations. (CYP3A and/or CYP2D6 inhibition)

Antacids, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

No mechanistic interaction expected based on theoretical consideration. Darunavir/cobicistat and antacids can be used concomitantly without dose adjustment.

Apixaban, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Artemether/lumefantrine, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

REZOLSTA and artemether/lumefantrine can be used without dose adjustments; however, due to the increase in lumefantrine exposure, the combination should be used with caution.

Astemizole, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Atorvastatin, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Concomitant use of a HMG CoA reductase inhibitor and darunavir/cobicistat may increase plasma concentrations of the lipid lowering agent, which may lead to adverse events such as myopathy.

Avanafil, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Azole antifungals, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Co-administration of REZOLSTA and other medicinal products that inhibit CYP3A may decrease the clearance of darunavir and cobicistat and may result in increased plasma concentrations of darunavir and cobicistat

BCRP substrates, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Cobicistat inhibits the transporters BCRP. Co-administration of cobicistat with medicinal products that are substrates of these transporters can result in increased plasma concentrations of the co-administered medicinal products.

Bepridil, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Betamethasone, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Concomitant use of REZOLSTA and corticosteroids that are metabolised by CYP3A may increase the risk of development of systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression.

Boceprevir, darunavir/cobicistat ---> SmPC of [darunavir] of EMA

Concomitant use of darunavir/cobicistat with weak to moderate CYP3A4 inductors may result in subtherapeutic plasma exposure to darunavir. Co-administration of darunavir/cobicistat with weak to moderate CYP3A inducers is not recommended

Boosted protease-inhibitors, darunavir/cobicistat ---> SmPC of [cobicistat] of EMA

The combination may result in decreased plasma concentrations of darunavir and/or the other antiretroviral agent that require pharmacoenhancement leading to loss of antiviral activity and development of resistance.

Bosentan, darunavir/cobicistat ---> SmPC of [darunavir] of EMA

Breast-feeding, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Because of the potential for adverse reactions in breast-fed infants, women should be instructed not to breast-feed if they are receiving REZOLSTA.

Budesonide, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Buprenorphine/naloxone, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

REZOLSTA may increase buprenorphine and/or norbuprenorphine plasma concentrations. Dose adjustment for buprenorphine may not be necessary when co-administered with REZOLSTA but a careful clinical monitoring for signs of opiate toxicity is recommended.

Buspirone, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

REZOLSTA is expected to increase the sedative/hypnotic plasma concentrations. (CYP3A inhibition). Clinical monitoring is recommended when co-administering REZOLSTA with this sedative/hypnotic and a lower dose of the sedative/hypnotic should be considered

Calcium carbonate, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

No mechanistic interaction expected based on theoretical consideration. Darunavir/cobicistat and antacids can be used concomitantly without dose adjustment.

Carbamazepine, darunavir/cobicistat

Co-administration of REZOLSTA and these anticonvulsants is contraindicated (see section 4.3).

Carbamazepine, darunavir/cobicistat ---> SmPC of [darunavir] of EMA

Darunavir and cobicistat are metabolised by CYP3A, and co-administration with CYP3A inducers may result in subtherapeutic plasma exposure to darunavir. Co-administration of darunavir/cobicistat with strong inducers of CYP3A is contraindicated

Carvedilol, darunavir/cobicistat ---> SmPC of [darunavir] of EMA

Boosted darunavir is expected to increase betablocker plasma concentrations. (CYP2D6 inhibition)

Cimetidine, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. Darunavir/cobicistat can be co-administered with H2-receptor antagonists without dose adjustments.

Cisapride, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Clarithromycin, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Clarithromycin (CYP3A inhibition) is expected to increase darunavir and/or cobicistat plasma concentrations. Concentrations of clarithromycin may be increased upon co-administration with darunavir/cobicistat (CYP3A inhibition)

Clonazepam, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Based on theoretical considerations REZOLSTA is expected to increase concentrations of clonazepam (inhibition of CYP3A). Clinical monitoring is recommended when co-administering REZOLSTA with clonazepam.

Clopidogrel, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Co-administration of REZOLSTA with clopidogrel is not recommended. Use of other antiplatelets not affected by CYP inhibition or induction (e.g. prasugrel) is recommended (see section 4.3).

Clotrimazole, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase the antifungal plasma concentrations, and darunavir and/or cobicistat plasma concentrations may be increased by the antifungal (CYP3A inhibition)

Cobicistat, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Darunavir/cobicistat should not be used in combination with the individual components (darunavir or cobicistat)

Colchicine, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A and/or P-glycoprotein inhibition) is expected to increase colchicine plasma concentrations. The combination is contraindicated in patients with renal or hepatic impairment

Corticosteroids primarily metabolised by CYP3A, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Cyclosporine, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase the immunosuppressant plasma concentrations.

CYP3A4 inductors, darunavir/cobicistat ---> SmPC of [darunavir] of EMA

Dabigatran etexilate, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Clinical monitoring and dose reduction is required when a DOAC transported by P-gp but not metabolised by CYP3A4, including dabigatran etexilate and edoxaban, is co-administered with REZOLSTA.

Daclatasvir [1], darunavir/cobicistat ---> SmPC of [1] of EMA

No dose adjustment of Daklinza 60 mg once daily, darunavir/ritonavir (800/100 mg once daily or 600/100 mg twice daily) or darunavir/cobicistat is required.

Dapoxetine, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Co-administration of REZOLSTA with dapoxetine is contraindicated.

Darunavir, darunavir/cobicistat [2] ---> SmPC of [2] of EMA

Darunavir/cobicistat should not be used in combination with the individual components (darunavir or cobicistat)

Darunavir/cobicistat [1], dasatinib ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase the anti-neoplastic plasma concentrations.

Darunavir/cobicistat [1], desipramine ---> SmPC of [1] of EMA

Concomitant use of boosted darunavir/cobicistat (CYP2D6 and/or CYP3A inhibition) and this antidepressant may increase concentrations of the antidepressant.

Darunavir/cobicistat [1], dexamethasone ---> SmPC of [1] of EMA

Based on theoretical considerations (systemic) dexamethasone is expected to decrease darunavir and/or cobicistat plasma concentrations. (CYP3A induction) Systemic dexamethasone should be used with caution when combined with REZOLSTA

Darunavir/cobicistat [1], dexlansoprazole ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. REZOLSTA can be co-administered with proton pump inhibitors without dose adjustments.

Darunavir/cobicistat [1], diazepam ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], didanosine ---> SmPC of [1] of EMA

REZOLSTA and didanosine can be used without dose adjustments. When didanosine is co-administered with REZOLSTA, didanosine should be administered on an empty stomach 1 hour before or 2 hours after REZOLSTA (which is administered with food).

Darunavir/cobicistat [1], digoxin ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (P-glycoprotein inhibition) is expected to increase digoxin plasma concentrations.

Darunavir/cobicistat [1], dihydroergotamine ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], diltiazem ---> SmPC of [1] of EMA

Darunavir/cobicistat is expected to increase the calcium channel blocker plasma concentrations. (CYP3A and/or CYP2D6 inhibition)

Darunavir/cobicistat [1], dipotassium clorazepate ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], disopyramide ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase the antiarrhythmic plasma concentrations. Caution is warranted

Darunavir/cobicistat [1], dolutegravir ---> SmPC of [1] of EMA

Based on theoretical considerations dolutegravir is not expected to affect the pharmacokinetics of REZOLSTA. REZOLSTA and dolutegravir can be used without dose adjustments.

Darunavir/cobicistat [1], domperidone ---> SmPC of [1] of EMA

Co-administration of domperidone with REZOLSTA is contraindicated.

Darunavir/cobicistat [1], dronedarone ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], drospirenone ---> SmPC of [1] of EMA

When REZOLSTA is co-administered with a drospirenone-containing product, clinical monitoring is recommended due to the potential for hyperkalaemia.

Darunavir/cobicistat [1], drugs primarily metabolised by CYP3A4 ---> SmPC of [1] of EMA

Co-administration of darunavir/cobicistat and medicinal products primarily metabolised by CYP3A may result in increased systemic exposure to such medicinal products, which could increase or prolong their therapeutic effect and adverse reactions.

Darunavir/cobicistat [1], drugs primarily metabolised by CYP3A4 with narrow therapeutic index ---> SmPC of [1] of

REZOLSTA must not be combined with medicinal products that are highly dependent on CYP3A for clearance and for which increased systemic exposure is associated with serious and/or life-threatening events (narrow therapeutic index).

Darunavir/cobicistat [1], edoxaban ---> SmPC of [1] of EMA

Clinical monitoring and dose reduction is required when a DOAC transported by P-gp but not metabolised by CYP3A4, including dabigatran etexilate and edoxaban, is co-administered with REZOLSTA.

Darunavir/cobicistat [1], efavirenz ---> SmPC of [1] of EMA

Co-administration of REZOLSTA and efavirenz is not recommended. This recommendation is different from ritonavir-boosted darunavir. Consult the Summary of Product Characteristics for darunavir for further details.

Darunavir/cobicistat [1], emtricitabine ---> SmPC of [1] of EMA

Based on the different elimination pathways, no interactions are expected with darunavir/cobicistat. The can be used without dose adjustment.

Darunavir/cobicistat [1], emtricitabine/tenofovir alafenamide ---> SmPC of [1] of EMA

The recommended dose of emtricitabine/tenofovir alafenamide is 200/10 mg once daily when used with REZOLSTA.

Darunavir/cobicistat [1], ergometrine ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], ergot derivatives ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], ergotamine ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], esomeprazole ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. REZOLSTA can be co-administered with proton pump inhibitors without dose adjustments.

Darunavir/cobicistat [1], estazolam ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], ethinyl estradiol ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition, UGT/SULT induction) may alter ethinyl estradiol and/or norethindrone plasma concentrations. Alternative forms of contraception should be considered.

Darunavir/cobicistat [1], etravirine ---> SmPC of [1] of EMA

Co-administration of REZOLSTA and etravirine is not recommended. This recommendation is different from ritonavir-boosted darunavir. Consult the Summary of Product Characteristics for darunavir for further details.

Darunavir/cobicistat [1], everolimus ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase everolimus plasma concentrations. Concomitant use is not recommended.

Darunavir/cobicistat [1], famotidine ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. Darunavir/cobicistat can be co-administered with H2-receptor antagonists without dose adjustments.

Darunavir/cobicistat [1], felodipine ---> SmPC of [1] of EMA

Darunavir/cobicistat is expected to increase the calcium channel blocker plasma concentrations. (CYP3A and/or CYP2D6 inhibition)

Darunavir/cobicistat [1], fentanyl ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP2D6 and/or CYP3A inhibition) may increase analgesic plasma concentrations. Clinical monitoring is recommended

Darunavir/cobicistat [1], fertility ---> SmPC of [1] of EMA

No human data on the effect of darunavir or cobicistat on fertility are available. There was no effect on mating or fertility in animals (see section 5.3). Based on animal studies, no effect on mating or fertility is expected with REZOLSTA.

Darunavir/cobicistat [1], fesoterodine ---> SmPC of [1] of EMA

Use with caution. Monitor for fesoterodine or solifenacin adverse reactions, dose reduction of fesoterodine or solifenacin may be necessary.

Darunavir/cobicistat [1], flecainide ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase the antiarrhythmic plasma concentrations. Caution is warranted

Darunavir/cobicistat [1], fluconazole ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], flurazepam ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], fluvastatin ---> SmPC of [1] of EMA

Concomitant use of a HMG CoA reductase inhibitor and darunavir/cobicistat may increase plasma concentrations of the lipid lowering agent, which may lead to adverse events such as myopathy.

Darunavir/cobicistat [1], foods ---> SmPC of [1] of EMA

When administered with food, the relative exposure of darunavir is 1.7-fold higher as compared to intake without food. Patients should be instructed to take REZOLSTA within 30 minutes after completion of a meal

Darunavir/cobicistat [1], glecaprevir/pibrentasvir ---> SmPC of [1] of EMA

It is not recommended to co-administer REZOLSTA with glecaprevir/pibrentasvir.

Darunavir/cobicistat [1], H2 antagonists ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. Darunavir/cobicistat can be co-administered with H2-receptor antagonists without dose adjustments.

Darunavir/cobicistat [1], HMG-CoA reductase inhibitors ---> SmPC of [1] of EMA

When administration of HMG CoA reductase inhibitors and REZOLSTA is desired, it is recommended to start with the lowest dose and titrate up to the desired clinical effect while monitoring for safety.

Darunavir/cobicistat [1], imipramine ---> SmPC of [1] of EMA

Concomitant use of boosted darunavir/cobicistat (CYP2D6 and/or CYP3A inhibition) and this antidepressant may increase concentrations of the antidepressant.

Darunavir/cobicistat [1], irinotecan ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase everolimus plasma concentrations. Concomitant use is not recommended.

Darunavir/cobicistat [1], isavuconazole ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], itraconazol ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], ivabradine ---> SmPC of [1] of EMA

Co-administration of amiodarone, bepridil, dronedarone, ivabradine, quinidine, or ranolazine and REZOLSTA is contraindicated (see section 4.3).

Darunavir/cobicistat [1], ketoconazole ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], lamivudine ---> SmPC of [1] of EMA

Based on the different elimination pathways, no interactions are expected with darunavir/cobicistat. The can be used without dose adjustment.

Darunavir/cobicistat [1], lansoprazole ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. REZOLSTA can be co-administered with proton pump inhibitors without dose adjustments.

Darunavir/cobicistat [1], lidocaine ---> SmPC of [1] of EMA

Co-administration of darunavir/cobicistat with systemic lidocaine that is highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated

Darunavir/cobicistat [1], lomitapide ---> SmPC of [1] of EMA

Based on theoretical considerations, REZOLSTA is expected to increase the exposure of lomitapide when coadministered. CYP3A inhibition. Co-administration is contraindicated

Darunavir/cobicistat [1], lovastatine ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], lurasidone ---> SmPC of [1] of EMA

Based on theoretical considerations REZOLSTA is expected to increase this neuroleptic plasma concentration. CYP3A, CYP2D6 and/or P-gp inhibition. The combination is contraindicated.

Darunavir/cobicistat [1], magnesium hydroxide ---> SmPC of [1] of EMA

No mechanistic interaction expected based on theoretical consideration. Darunavir/cobicistat and antacids can be used concomitantly without dose adjustment.

Darunavir/cobicistat [1], maraviroc ---> SmPC of [1] of EMA

Darunavir/cobicistat (CYP3A inhibition) is expected to increase maraviroc plasma concentrations.

Darunavir/cobicistat [1], MATE1 substrates ---> SmPC of [1] of EMA

Cobicistat inhibits the transporters MATE1. Co-administration of cobicistat with medicinal products that are substrates of these transporters can result in increased plasma concentrations of the co-administered medicinal products.

Darunavir/cobicistat [1], metformin ---> SmPC of [1] of EMA

Based on theoretical considerations REZOLSTA is expected to increase metformin plasma concentrations. (MATE1 inhibition). Careful patient monitoring and dose adjustment of metformin is recommended in patients who are taking REZOLSTA.

Darunavir/cobicistat [1], methadone ---> SmPC of [1] of EMA

Darunavir/cobicistat may increase methadone plasma concentrations. No adjustment of methadone dosage is expected

Darunavir/cobicistat [1], methylergonovine ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], mexiletine ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase the antiarrhythmic plasma concentrations. Caution is warranted

Darunavir/cobicistat [1], midazolam ---> SmPC of [1] of EMA

Darunavir, CYP3A4 inhibitor, may increase the plasma concentrations of midazolam. Midazolam oral: contraindicated, intravenous: close clinical monitoring

Darunavir/cobicistat [1], mometasone ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], naloxegol ---> SmPC of [1] of EMA

Co-administration of REZOLSTA and naloxegol is contraindicated.

Darunavir/cobicistat [1], nevirapine ---> SmPC of [1] of EMA

Co-administration of REZOLSTA and nevirapine is not recommended. This recommendation is different from ritonavir-boosted darunavir. Consult the Summary of Product Characteristics for darunavir for further details.

Darunavir/cobicistat [1], nicardipine ---> SmPC of [1] of EMA

Darunavir/cobicistat is expected to increase the calcium channel blocker plasma concentrations. (CYP3A and/or CYP2D6 inhibition)

Darunavir/cobicistat [1], nifedipine ---> SmPC of [1] of EMA

Darunavir/cobicistat is expected to increase the calcium channel blocker plasma concentrations. (CYP3A and/or CYP2D6 inhibition)

Darunavir/cobicistat [1], nilotinib ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase the anti-neoplastic plasma concentrations.

Darunavir/cobicistat [1], nizatidine ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. Darunavir/cobicistat can be co-administered with H2-receptor antagonists without dose adjustments.

Darunavir/cobicistat [1], norethindrone ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], nortriptyline ---> SmPC of [1] of EMA

Concomitant use of boosted darunavir/cobicistat (CYP2D6 and/or CYP3A inhibition) and this antidepressant may increase concentrations of the antidepressant.

Darunavir/cobicistat [1], OATP1B1 substrates ---> SmPC of [1] of EMA

Cobicistat inhibits the transporters OATP1B1. Co-administration of cobicistat with medicinal products that are substrates of these transporters can result in increased plasma concentrations of the co-administered medicinal products.

Darunavir/cobicistat [1], OATP1B3 substrates ---> SmPC of [1] of EMA

Cobicistat inhibits the transporters OATP1B3. Co-administration of cobicistat with medicinal products that are substrates of these transporters can result in increased plasma concentrations of the co-administered medicinal products.

Darunavir/cobicistat [1], oestrogen-based contraceptives ---> SmPC of [1] of EMA

Alternative or additional contraceptive measures are recommended when oestrogen based contraceptives are co-administered with REZOLSTA.

Darunavir/cobicistat [1], omeprazole ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. REZOLSTA can be co-administered with proton pump inhibitors without dose adjustments.

Darunavir/cobicistat [1], oxycodone ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP2D6 and/or CYP3A inhibition) may increase analgesic plasma concentrations. Clinical monitoring is recommended

Darunavir/cobicistat [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

Cobicistat inhibits the transporters p-glycoprotein (P-gp). Co-administration of cobicistat with medicinal products that are substrates of these transporters can result in increased plasma concentrations of the co-administered medicinal products.

Darunavir/cobicistat [1], pantoprazole ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. REZOLSTA can be co-administered with proton pump inhibitors without dose adjustments.

Darunavir/cobicistat [1], paroxetine ---> SmPC of [1] of EMA

Concomitant use of boosted darunavir/cobicistat (CYP2D6 and/or CYP3A inhibition) and this antidepressant may increase concentrations of the antidepressant.

Darunavir/cobicistat [1], perphenazine ---> SmPC of [1] of EMA

REZOLSTA is expected to increase the neuroleptic plasma concentrations. (CYP2D6 inhibition). For this neuroleptics, consider reducing the dose of the neuroleptic upon co-administration with REZOLSTA.

Darunavir/cobicistat [1], phenobarbital ---> SmPC of [1] of EMA

Co-administration of REZOLSTA and these anticonvulsants is contraindicated (see section 4.3).

Darunavir/cobicistat [1], phenytoin ---> SmPC of [1] of EMA

Co-administration of REZOLSTA and these anticonvulsants is contraindicated (see section 4.3).

Darunavir/cobicistat [1], pimozide ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], pitavastatin ---> SmPC of [1] of EMA

Concomitant use of a HMG CoA reductase inhibitor and darunavir/cobicistat may increase plasma concentrations of the lipid lowering agent, which may lead to adverse events such as myopathy.

Darunavir/cobicistat [1], posaconazole ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], pravastatine ---> SmPC of [1] of EMA

Concomitant use of a HMG CoA reductase inhibitor and darunavir/cobicistat may increase plasma concentrations of the lipid lowering agent, which may lead to adverse events such as myopathy.

Darunavir/cobicistat [1], prednisone ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], pregnancy ---> SmPC of [1] of EMA

Therapy with REZOLSTA should not be initiated during pregnancy, and women who become pregnant during therapy with REZOLSTA should be switched to an alternative regimen (see sections 4.2 and 4.4).

Darunavir/cobicistat [1], propafenone ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase the antiarrhythmic plasma concentrations. Caution is warranted

Darunavir/cobicistat [1], quetiapine ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], quinidine ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], rabeprazole ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. REZOLSTA can be co-administered with proton pump inhibitors without dose adjustments.

Darunavir/cobicistat [1], raltegravir ---> SmPC of [1] of EMA

At present the effect of raltegravir on darunavir plasma concentrations does not appear to be clinically relevant; REZOLSTA and raltegravir can be used without dose adjustments.

Darunavir/cobicistat [1], ranitidine ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. Darunavir/cobicistat can be co-administered with H2-receptor antagonists without dose adjustments.

Darunavir/cobicistat [1], ranolazine ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], rifabutin ---> SmPC of [1] of EMA

Based on theoretical considerations rifabutin (CYP3A induction) is expected to decrease darunavir and/or cobicistat plasma concentrations. Co-administration of darunavir/cobicistat with rifabutin is not recommended.

Darunavir/cobicistat [1], rifampicin ---> SmPC of [1] of EMA

The combination of rifampicin and REZOLSTA is contraindicated (see section 4.3).

Darunavir/cobicistat [1], rifapentine ---> SmPC of [1] of EMA

Based on theoretical considerations rifapentine (CYP3A induction) is expected to decrease darunavir and/or cobicistat plasma concentrations. Co-administration of darunavir/cobicistat with rifapentine is not recommended.

Darunavir/cobicistat [1], rilpivirine ---> SmPC of [1] of EMA

Based on theoretical considerations REZOLSTA is expected to increase rilpivirine plasma concentrations. (CYP3A inhibition). Co-administration of REZOLSTA and rilpivirine can be used without dose adjustments

Darunavir/cobicistat [1], risperidone ---> SmPC of [1] of EMA

REZOLSTA is expected to increase the neuroleptic plasma concentrations. (CYP2D6 inhibition). For this neuroleptics, consider reducing the dose of the neuroleptic upon co-administration with REZOLSTA.

Darunavir/cobicistat [1], ritonavir ---> SmPC of [1] of EMA

REZOLSTA should not be used concurrently with products containing ritonavir or regimens containing ritonavir or cobicistat.

Darunavir/cobicistat [1], rivaroxaban ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], rosuvastatin ---> SmPC of [1] of EMA

Concomitant use of a HMG CoA reductase inhibitor and darunavir/cobicistat may increase plasma concentrations of the lipid lowering agent, which may lead to adverse events such as myopathy.

Darunavir/cobicistat [1], salmeterol ---> SmPC of [1] of EMA

Concomitant use of salmeterol and darunavir/cobicistat is not recommended. The combination may result in increased risk of cardiovascular adverse event with salmeterol, including QT prolongation, palpitations and sinus tachycardia.

Darunavir/cobicistat [1], sertindole ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], sertraline ---> SmPC of [1] of EMA

Concomitant use of boosted darunavir/cobicistat (CYP2D6 and/or CYP3A inhibition) and this antidepressant may increase concentrations of the antidepressant.

Darunavir/cobicistat [1], sildenafil ---> SmPC of [1] of EMA

Darunavir/cobicistat (CYP3A inhibition) is expected to increase sildenafil plasma concentrations. Co-administration of darunavir/cobicistat and sildenafil when used for the treatment of pulmonary arterial hypertension is contraindicated

Darunavir/cobicistat [1], simeprevir ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat is expected to increase simeprevir plasma concentrations. Simeprevir may increase darunavir and/or cobicistat plasma concentrations. Co-administration is not recommended

Darunavir/cobicistat [1], simvastatine ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], sirolimus ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase the immunosuppressant plasma concentrations.

Darunavir/cobicistat [1], solifenacin ---> SmPC of [1] of EMA

Use with caution. Monitor for fesoterodine or solifenacin adverse reactions, dose reduction of fesoterodine or solifenacin may be necessary.

Darunavir/cobicistat [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of St John's Wort and REZOLSTA is contraindicated (see section 4.3).

Darunavir/cobicistat [1], stavudine ---> SmPC of [1] of EMA

Based on the different elimination pathways, no interactions are expected with darunavir/cobicistat. The can be used without dose adjustment.

Darunavir/cobicistat [1], tacrolimus ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase the immunosuppressant plasma concentrations.

Darunavir/cobicistat [1], tadalafil ---> SmPC of [1] of EMA

Darunavir/cobicistat (CYP3A inhibition) is expected to increase tadalafil plasma concentrations. Co-administration of tadalafil for the treatment of pulmonary arterial hypertension is not recommended.

Darunavir/cobicistat [1], tenofovir ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (P-glycoprotein inhibition) is expected to increase tenofovir plasma concentrations. The can be used without dose adjustments. Renal function should be closely monitored

Darunavir/cobicistat [1], terfenadine ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], thioridazine ---> SmPC of [1] of EMA

REZOLSTA is expected to increase the neuroleptic plasma concentrations. (CYP2D6 inhibition). For this neuroleptics, consider reducing the dose of the neuroleptic upon co-administration with REZOLSTA.

Darunavir/cobicistat [1], ticagrelor ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], tramadol ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP2D6 and/or CYP3A inhibition) may increase analgesic plasma concentrations. Clinical monitoring is recommended

Darunavir/cobicistat [1], trazodone ---> SmPC of [1] of EMA

Concomitant use of boosted darunavir/cobicistat (CYP2D6 and/or CYP3A inhibition) and this antidepressant may increase concentrations of the antidepressant.

Darunavir/cobicistat [1], triamcinolone ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], triazolam ---> SmPC of [1] of EMA

Darunavir/cobicistat [1], vardenafil ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase the PDE-5 inhibitor plasma concentrations.

Darunavir/cobicistat [1], verapamil ---> SmPC of [1] of EMA

Darunavir/cobicistat is expected to increase the calcium channel blocker plasma concentrations. (CYP3A and/or CYP2D6 inhibition)

Darunavir/cobicistat [1], vinblastine ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase the anti-neoplastic plasma concentrations.

Darunavir/cobicistat [1], vincristine ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase the anti-neoplastic plasma concentrations.

Darunavir/cobicistat [1], voriconazole ---> SmPC of [1] of EMA

Concentrations of voriconazole may increase or decrease when co-administered with REZOLSTA. Voriconazole should not be combined with REZOLSTA unless an assessment of the benefit/risk ratio justifies the use of voriconazole.

Darunavir/cobicistat [1], warfarin ---> SmPC of [1] of EMA

Based on theoretical considerations REZOLSTA may alter warfarin plasma concentrations. It is recommended that the international normalised ratio (INR) be monitored when warfarin is co-administered with REZOLSTA.

Darunavir/cobicistat [1], zidovudine ---> SmPC of [1] of EMA

Based on the different elimination pathways, no interactions are expected with darunavir/cobicistat. The can be used without dose adjustment.

Darunavir/cobicistat [1], zolpidem ---> SmPC of [1] of EMA

Darunavir/cobicistat, efavirenz ---> SmPC of [darunavir] of EMA

Darunavir/cobicistat, elbasvir/grazoprevir ---> SmPC of [darunavir] of EMA

Concomitant use of boosted PREZISTA and elbasvir/grazoprevir is contraindicated

Darunavir/cobicistat, emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

The recommended dose of Descovy is 200/10 mg once daily.

Darunavir/cobicistat, estrogens ---> SmPC of [darunavir] of EMA

Alternative or additional contraceptive measures are recommended when oestrogen-based contraceptives are co-administered with darunavir/cobicistat

Darunavir/cobicistat, etravirine ---> SmPC of [darunavir] of EMA

Darunavir/cobicistat, fluticasone ---> SmPC of [darunavir] of EMA

Darunavir/cobicistat, fostemsavir [2] ---> SmPC of [2] of EMA

Temsavir (inhibition of CYP3A enzymes, P-gp and/or BCRP). Darunavir/cobicistat increased temsavir plasma concentrations. No dose adjustment is necessary.

Darunavir/cobicistat, indinavir ---> SmPC of [darunavir] of EMA

Co-administration of darunavir and cobicistat with other medicinal products that inhibit CYP3A may result in increased plasma concentrations of darunavir and cobicistat. Co-administration with strong CYP3A4 inhibitors is not recommended

Darunavir/cobicistat, lenacapavir [2] ---> SmPC of [2] of EMA

No dose adjustment of lenacapavir is required.

Darunavir/cobicistat, lopinavir/ritonavir ---> SmPC of [darunavir] of EMA

Concomitant treatment of darunavir/cobicistat with lopinavir/ritonavir is contraindicated given the expected decrease in plasma concentrations of darunavir and cobicistat and the potential for loss of therapeutic effect

Darunavir/cobicistat, metoprolol ---> SmPC of [darunavir] of EMA

Boosted darunavir is expected to increase betablocker plasma concentrations. (CYP2D6 inhibition)

Darunavir/cobicistat, moderate CYP3A4 inductors ---> SmPC of [darunavir] of EMA

Darunavir/cobicistat, nevirapine ---> SmPC of [darunavir] of EMA

Darunavir/cobicistat, phenobarbital ---> SmPC of [darunavir] of EMA

Darunavir/cobicistat, phenytoin ---> SmPC of [darunavir] of EMA

Darunavir/cobicistat, proton pump inhibitors ---> SmPC of [darunavir] of EMA

Darunavir/cobicistat can be co-administered with proton pump inhibitors without dose adjustments.

Darunavir/cobicistat, rifampicin ---> SmPC of [darunavir] of EMA

Darunavir/cobicistat, St. John's wort ---> SmPC of [darunavir] of EMA

Darunavir/cobicistat, statins ---> SmPC of [darunavir] of EMA

Ritonavir inhibits the transporters P-glycoprotein, OATP1B1 and OATP1B3, and co-administration with substrates of these transporters can result in increased plasma levels of these compounds (e.g. dabigatran etexilate, digoxin, statins and bosentan)

Darunavir/cobicistat, strong CYP3A4 inductors ---> SmPC of [darunavir] of EMA

Darunavir/cobicistat, strong CYP3A4 inhibitors ---> SmPC of [darunavir] of EMA

Darunavir/cobicistat, telaprevir ---> SmPC of [darunavir] of EMA

Darunavir/cobicistat, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Co-administration is not recommended.

Darunavir/cobicistat, timolol ---> SmPC of [darunavir] of EMA

Boosted darunavir is expected to increase betablocker plasma concentrations. (CYP2D6 inhibition)

CONTRAINDICATIONS of Darunavir/cobicistat (Rezolsta)

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

Patients with severe (Child-Pugh Class C) hepatic impairment.

Co-administration with strong CYP3A inducers such as the medicinal products listed below due to the potential for loss of therapeutic effect (see section 4.5):

- carbamazepine, phenobarbital, phenytoin

- rifampicin

- lopinavir/ritonavir

- St John's wort, (Hypericum perforatum).

Co-administration with medicinal products such as those products listed below due to the potential for serious and/or life-threatening adverse reactions (see section 4.5):

- alfuzosin

- amiodarone, bepridil, dronedarone, ivabradine, quinidine, ranolazine

- astemizole, terfenadine

- colchicine, when used in patients with renal and/or hepatic impairment (see section 4.5)

- rifampicin

- ergot derivatives (e.g. dihydroergotamine, ergometrine, ergotamine, methylergonovine)

- cisapride

- dapoxetine

- domperidone

- naloxegol

- lurasidone, pimozide, quetiapine, sertindole (see section 4.5)

- elbasvir/grazoprevir

- triazolam, midazolam administered orally (for caution on parenterally administered midazolam, see section 4.5)

- sildenafil

- when used for the treatment of pulmonary arterial hypertension, avanafil

- simvastatin, lovastatin and lomitapide (see section 4.5)

- ticagrelor.

https://www.ema.europa.eu/en/documents/product-information/rezolsta-epar-product-information_en.pdf 25/07/2024

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (Symtuza)

Ability to drive, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Symtuza has minor influence on the ability to drive and use machines. Patients should be informed that dizziness may occur when treated with Symtuza (see section 4.8).

Adefovir dipivoxil, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Symtuza should not be administered concomitantly with medicinal products containing tenofovir disoproxil (as fumarate, phosphate or succinate), lamivudine, or adefovir dipivoxil used for the treatment of HBV infection.

Alfentanyl, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

It is expected to increase alfentanil plasma concentrations. The concomitant use with Symtuza may require to lower the dose of alfentanil and requires monitoring for risks of prolonged or delayed respiratory depression.

Alfuzosin, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Based on theoretical consideration DRV/COBI is expected to increase alfuzosin concentrations (CYP3A4 inhibition). The concomitant use of Symtuza with alfuzosin is contra-indicated

Aluminium hydroxide, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No mechanistic interaction expected based on theoretical consideration. Symtuza and antacids can be used concomitantly without dose adjustment.

Amiodarone, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Co-administration is contraindicated due to the potential for serious and/or life-threatening adverse reactions

Amitriptyline, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

It is expected to increase these anti-depressant plasma concentrations. CYP2D6 and/or CYP3A inhibition. If this anti-depressant is to be used with Symtuza clinical monitoring is recommended and a dose adjustment of the anti-depressant may be needed.

Amlodipine, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Based on theoretical considerations DRV/COBI is expected to increase this calcium channel blocker plasma concentrations. CYP3A inhibition

Antacids, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No mechanistic interaction expected based on theoretical consideration. Symtuza and antacids can be used concomitantly without dose adjustment.

Antiretrovirals, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Symtuza is indicated for use as a complete regimen for the treatment of HIV-1 infection and should not be administered with other antiretroviral products

Apixaban, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Co-administration of Symtuza with a direct oral anticoagulant (DOAC) that is metabolised by CYP3A4 and transported by P-gp is not recommended as this may lead to an increased bleeding risk.

Artemether/lumefantrine, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Symtuza and artemether/lumefantrine can be used without dose adjustments; however, due to the increase in lumefantrine exposure, the combination should be used with caution.

Atorvastatin, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Concomitant use may increase plasma concentrations of the lipid lowering agent, which may lead to adverse reactions such as myopathy. When administration is desired, it is recommended to start with the lowest dose

Avanafil, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Co-administration is contraindicated due to the potential for serious and/or life-threatening adverse reactions

Azole antifungals, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Co-administration of Symtuza and other medicinal products that inhibit CYP3A may decrease the clearance of darunavir and cobicistat and may result in increased plasma concentrations of darunavir and cobicistat

BCRP substrates, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Co-administration of cobicistat with medicinal products that are substrates of this transporter can result in increased plasma concentrations of the co-administered medicinal products.

Boceprevir, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

This antiviral may decrease darunavir and/or cobicistat plasma levels and adversely affect the intracellular activation and clinical antiviral efficacy of tenofovir alafenamide. Symtuza may decrease this antiviral plasma concentration.

Bosentan, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Based on theoretical considerations bosentan is expected to decrease darunavir and/or cobicistat plasma concentrations. CYP3A induction. Symtuza is expected to increase bosentan plasma concentrations. CYP3A inhibition

Breast-feeding, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Because of the potential for adverse reactions in breast-fed infants, women should be instructed not to breast-feed if they are receiving Symtuza.

Budesonide, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Based on theoretical considerations DRV/COBI is expected to increase this corticosteroid plasma concentrations. CYP3A inhibition

Buprenorphine/naloxone, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Based on theoretical considerations DRV/COBI may increase buprenorphine and/or norbuprenorphine plasma concentrations. Dose adjustment for buprenorphine may not be necessary when co-administered with Symtuza

Buspirone, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Based on theoretical considerations DRV/COBI is expected to increase this sedative/hypnotic plasma concentrations. CYP3A inhibition

Carbamazepine, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Based on theoretical considerations these anticonvulsants are expected to decrease darunavir and/or cobicistat and/or tenofovir alafenamide plasma concentrations. (CYP3A and/or P-gp induction). Co-administration is contraindicated (see section 4.3).

Carvedilol, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Based on theoretical considerations DRV/COBI is expected to increase this beta-blocker plasma concentrations. CYP2D6 inhibition

Cimetidine, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. Symtuza can be co-administered with H2-receptor antagonists without dose adjustments.

Clarithromycin, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Concentrations of clarithromycin may be increased upon co-administration with DRV/COBI. CYP3A inhibition. Caution should be exercised when clarithromycin is combined with Symtuza.

Clonazepam, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Based on theoretical considerations Symtuza is expected to increase concentrations of clonazepam (inhibition of CYP3A) Clinical monitoring is recommended when co-administering Symtuza with clonazepam.

Clopidogrel, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Co-administration of Symtuza with clopidogrel is not recommended. Use of other antiplatelets not affected by CYP inhibition or induction (e.g. prasugrel) is recommended (see section 4.3).

Clorazepate, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Based on theoretical considerations DRV/COBI is expected to increase this sedative/hypnotic plasma concentrations. CYP3A inhibition

Clotrimazole, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Colchicine, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

A reduction in colchicine dose/an interruption of colchicine treatment is recommended with normal renal/hepatic function if treatment with Symtuza is required. The combination is contraindicated in patients with renal or hepatic impairment

Cyclosporine, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Based on theoretical considerations DRV/COBI is expected to increase these immunosuppressant plasma concentrations. CYP3A inhibition. Co-administration of ciclosporin is expected to increase plasma concentrations of tenofovir alafenamide. P-gp inhibition

Dabigatran etexilate, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Clinical monitoring and dose reduction is required when a DOAC transported by P-gp but not metabolised by CYP3A4, including dabigatran etexilate and edoxaban, is co-administered with Symtuza.

Daclatasvir, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Based on theoretical considerations, no clinically relevant interaction is expected. Symtuza and sofosbuvir, sofosbuvir/ledipasvir, or daclatasvir can be used concomitantly without dose adjustment

Dapoxetine, darunavir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Co-administration of Symtuza with dapoxetine is contraindicated.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], dasatinib ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase these anti-neoplastic plasma concentrations. CYP3A inhibition. Caution should be exercised when combining

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], desipramine ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], dexamethasone ---> SmPC of [1] of EMA

Based on theoretical considerations (systemic) dexamethasone is expected to decrease darunavir and/or cobicistat plasma concentrations. CYP3A induction

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], dexlansoprazole ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. Symtuza can be co-administered with proton pump inhibitors without dose adjustments.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], digoxin ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase digoxin plasma concentrations. P-glycoprotein inhibition. It is recommended that the lowest possible dose of digoxin should initially be given to patients on Symtuza

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], dihydroergotamine ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI may increase ergot derivative exposure. Co-administration of Symtuza and ergot derivatives is contraindicated (see section 4.3).

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], diltiazem ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase this calcium channel blocker plasma concentrations. CYP3A inhibition

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], disopyramide ---> SmPC of [1] of EMA

It is expected to increase these antiarrhythmic plasma concentrations. CYP3A inhibition. Caution is warranted and therapeutic concentration monitoring, if available, is recommended for these antiarrhythmics when co-administered with Symtuza.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], domperidone ---> SmPC of [1] of EMA

Co-administration of domperidone with Symtuza is contraindicated.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], dronedarone ---> SmPC of [1] of EMA

Co-administration is contraindicated due to the potential for serious and/or life-threatening adverse reactions

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], drospirenone/ethinylestradiol ---> SmPC of [1] of EM

When Symtuza is co-administered with a drospirenone-containing product, clinical monitoring is recommended due to the potential for hyperkalaemia.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], drugs primarily metabolised by CYP3A4 ---> SmPC of [

Symtuza, therefore, must not be combined with medicinal products that are highly dependent on CYP3A for clearance and for which increased systemic exposure is associated with serious and/or life-threatening events (narrow therapeutic index)

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], drugs primarily metabolised by CYP3A4 with narrow th

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], edoxaban ---> SmPC of [1] of EMA

Clinical monitoring and dose reduction is required when a DOAC transported by P-gp but not metabolised by CYP3A4, including dabigatran etexilate and edoxaban, is co-administered with Symtuza.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], efavirenz ---> SmPC of [1] of EMA

Medicinal products that induce CYP3A activity would be expected to increase the clearance of darunavir and cobicistat, resulting in lowered plasma concentrations of darunavir and cobicistat

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], elbasvir/grazoprevir ---> SmPC of [1] of EMA

Based on theoretical considerations Symtuza may increase the exposure to grazoprevir. (OATP1B and CYP3A inhibition) Concomitant use of Symtuza with elbasvir/grazoprevir is contraindicated (see section 4.3).

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], ergometrine ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI may increase ergot derivative exposure. Co-administration of Symtuza and ergot derivatives is contraindicated (see section 4.3).

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], ergot derivatives ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI may increase ergot derivative exposure. Co-administration of Symtuza and ergot derivatives is contraindicated (see section 4.3).

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], ergotamine ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI may increase ergot derivative exposure. Co-administration of Symtuza and ergot derivatives is contraindicated (see section 4.3).

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], esomeprazole ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. Symtuza can be co-administered with proton pump inhibitors without dose adjustments.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], estazolam ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase this sedative/hypnotic plasma concentrations. CYP3A inhibition

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], ethinyl estradiol ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI may alter ethinyl estradiol and/or norethindrone plasma concentrations.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], everolimus ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase these anti-neoplastic plasma concentrations. CYP3A inhibition. Concomitant use is not recommended.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], famotidine ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. Symtuza can be co-administered with H2-receptor antagonists without dose adjustments.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], felodipine ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase this calcium channel blocker plasma concentrations. CYP3A inhibition

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], fentanyl ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI may increase analgesic plasma concentrations. CYP2D6 and/or CYP3A inhibition

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], fertility ---> SmPC of [1] of EMA

There was no effect on mating or fertility in animals (see section 5.3). Based on animal studies, no effect on reproduction or fertility is expected with Symtuza.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], fesoterodine ---> SmPC of [1] of EMA

Use with caution. Monitor for fesoterodine or solifenacin adverse reactions, dose reduction of fesoterodine or solifenacin may be necessary.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], flecainide ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], fluconazole ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase this antifungal plasma concentration, and darunavir, cobicistat and/or tenofovir alafenamide plasma concentrations may be increased by the antifungals. CYP3A and/or P-gp inhibition

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], flurazepam ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase this sedative/hypnotic plasma concentrations. CYP3A inhibition

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], fluticasone ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase this corticosteroid plasma concentrations. CYP3A inhibition

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], fluvastatin ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], foods ---> SmPC of [1] of EMA

Symtuza tablets should be taken with food. The type of food does not affect exposure to Symtuza.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], glecaprevir/pibrentasvir ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI may increase the exposure to glecaprevir and pibrentasvir. (P-gp, BCRP and/or OATP1B1/3 inhibition) It is not recommended to co-administer Symtuza with glecaprevir/pibrentasvir.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], imipramine ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], irinotecan ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase these anti-neoplastic plasma concentrations. CYP3A inhibition. Concomitant use is not recommended.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], isavuconazole ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], itraconazol ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], ivabradine ---> SmPC of [1] of EMA

Co-administration is contraindicated due to the potential for serious and/or life-threatening adverse reactions

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], ketoconazole ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], lamivudine ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], lansoprazole ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. Symtuza can be co-administered with proton pump inhibitors without dose adjustments.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], ledipasvir ---> SmPC of [1] of EMA

Based on theoretical considerations, no clinically relevant interaction is expected. Symtuza and sofosbuvir, sofosbuvir/ledipasvir, or daclatasvir can be used concomitantly without dose adjustment

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], lomitapide ---> SmPC of [1] of EMA

Based on theoretical considerations, Symtuza is expected to increase the exposure of lomitapide when coadministered. (CYP3A inhibition). Co-administration is contraindicated (see section 4.3).

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], lopinavir/ritonavir ---> SmPC of [1] of EMA

Co-administration is contraindicated due to the potential for loss of therapeutic effect

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], lovastatine ---> SmPC of [1] of EMA

Co-administration is contraindicated due to the potential for serious and/or life-threatening adverse reactions

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], lurasidone ---> SmPC of [1] of EMA

The combination of lurasidone, pimozide, quetiapine or sertindole and Symtuza is contraindicated (see section 4.3).

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], magnesium hydroxide ---> SmPC of [1] of EMA

No mechanistic interaction expected based on theoretical consideration. Symtuza and antacids can be used concomitantly without dose adjustment.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], MATE1 substrates ---> SmPC of [1] of EMA

Co-administration of cobicistat with medicinal products that are substrates of this transporter can result in increased plasma concentrations of the co-administered medicinal products.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], metformin ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase metformin plasma concentrations. MATE1 inhibition. Careful patient monitoring and dose adjustment of metformin is recommended in patients who are taking Symtuza.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], methadone ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI may increase methadone plasma concentrations.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], methylergonovine ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI may increase ergot derivative exposure. Co-administration of Symtuza and ergot derivatives is contraindicated (see section 4.3).

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], metoprolol ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase this beta-blocker plasma concentrations. CYP2D6 inhibition

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], mexiletine ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], midazolam ---> SmPC of [1] of EMA

Co-administration is contraindicated with midazolam administered orally due to the potential for serious and/or life-threatening adverse reactions

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], naloxegol ---> SmPC of [1] of EMA

Co-administration of Symtuza and naloxegol is contraindicated.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], nicardipine ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase this calcium channel blocker plasma concentrations. CYP3A inhibition

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], nifedipine ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase this calcium channel blocker plasma concentrations. CYP3A inhibition

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], nilotinib ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase these anti-neoplastic plasma concentrations. CYP3A inhibition. Caution should be exercised when combining

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], nizatidine ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. Symtuza can be co-administered with H2-receptor antagonists without dose adjustments.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], norethindrone ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI may alter ethinyl estradiol and/or norethindrone plasma concentrations.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], nortriptyline ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], OATP1B1 substrates ---> SmPC of [1] of EMA

Co-administration of cobicistat with medicinal products that are substrates of this transporter can result in increased plasma concentrations of the co-administered medicinal products.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], OATP1B3 substrates ---> SmPC of [1] of EMA

Co-administration of cobicistat with medicinal products that are substrates of this transporter can result in increased plasma concentrations of the co-administered medicinal products.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], omeprazole ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. Symtuza can be co-administered with proton pump inhibitors without dose adjustments.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], oxcarbazepine ---> SmPC of [1] of EMA

Co-administration of Symtuza with oxcarbazepine is not recommended. Alternative anticonvulsants should be considered.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], oxycodone ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI may increase analgesic plasma concentrations. CYP2D6 and/or CYP3A inhibition

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

Co-administration of cobicistat with medicinal products that are substrates of this transporter can result in increased plasma concentrations of the co-administered medicinal products.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], pantoprazole ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. Symtuza can be co-administered with proton pump inhibitors without dose adjustments.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], paroxetine ---> SmPC of [1] of EMA

If this anti-depressant is to be used with Symtuza clinical monitoring is recommended and a dose adjustment of the anti-depressant may be needed.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], perphenazine ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase these neuroleptic plasma concentrations. CYP2D6 inhibition

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], pharmacokinetic enhancer ---> SmPC of [1] of EMA

Symtuza should not be administered concomitantly with medicinal products requiring pharmacokinetic enhancement with ritonavir or cobicistat.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], phenobarbital ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], phenytoin ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], pimozide ---> SmPC of [1] of EMA

The combination of lurasidone, pimozide, quetiapine or sertindole and Symtuza is contraindicated (see section 4.3).

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], pitavastatin ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], posaconazole ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], pravastatine ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], pregnancy ---> SmPC of [1] of EMA

Therefore, therapy with Symtuza should not be initiated during pregnancy, and women who become pregnant during therapy with Symtuza should be switched to an alternative regimen (see sections 4.2 and 4.4).

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], propafenone ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], proton pump inhibitors ---> SmPC of [1] of EMA

Symtuza can be co-administered with proton pump inhibitors without dose adjustments.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], quetiapine ---> SmPC of [1] of EMA

The combination of lurasidone, pimozide, quetiapine or sertindole and Symtuza is contraindicated (see section 4.3).

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], quinidine ---> SmPC of [1] of EMA

Co-administration is contraindicated due to the potential for serious and/or life-threatening adverse reactions

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], rabeprazole ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. Symtuza can be co-administered with proton pump inhibitors without dose adjustments.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], ranitidine ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. Symtuza can be co-administered with H2-receptor antagonists without dose adjustments.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], ranolazine ---> SmPC of [1] of EMA

Co-administration is contraindicated due to the potential for serious and/or life-threatening adverse reactions

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], rifabutin ---> SmPC of [1] of EMA

Based on theoretical considerations these antimycobacterials are expected to decrease darunavir and/or cobicistat and/or tenofovir alafenamide plasma concentrations. CYP3A and/or P-gp induction. Co-administration is not recommended.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], rifampicin ---> SmPC of [1] of EMA

Based on theoretical considerations rifampicin is expected to decrease darunavir and/or cobicistat and/or tenofovir alafenamide plasma concentrations. (CYP3A and/or P-gp induction) The combination of rifampicin and Symtuza is contraindicated

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], rifapentine ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], risperidone ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase these neuroleptic plasma concentrations. CYP2D6 inhibition

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], rivaroxaban ---> SmPC of [1] of EMA

Co-administration of Symtuza with a direct oral anticoagulant (DOAC) that is metabolised by CYP3A4 and transported by P-gp is not recommended as this may lead to an increased bleeding risk.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], rosuvastatin ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], salmeterol ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase salmeterol plasma concentrations. CYP3A inhibition. Concomitant use of salmeterol and Symtuza is not recommended.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], sertindole ---> SmPC of [1] of EMA

The combination of lurasidone, pimozide, quetiapine or sertindole and Symtuza is contraindicated (see section 4.3).

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], sertraline ---> SmPC of [1] of EMA

If this anti-depressant is to be used with Symtuza clinical monitoring is recommended and a dose adjustment of the anti-depressant may be needed.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], sildenafil ---> SmPC of [1] of EMA

Co-administration is contraindicated (sildenafil - when used for the treatment of pulmonary arterial hypertension) due to the potential for serious and/or life-threatening adverse reactions

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], simeprevir ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase simeprevir plasma concentrations. Simeprevir may increase darunavir and/or cobicistat plasma concentrations.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], simvastatine ---> SmPC of [1] of EMA

Co-administration is contraindicated due to the potential for serious and/or life-threatening adverse reactions

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], sirolimus ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase these immunosuppressant plasma concentrations. CYP3A inhibition.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], sofosbuvir ---> SmPC of [1] of EMA

Based on theoretical considerations, no clinically relevant interaction is expected. Symtuza and sofosbuvir, sofosbuvir/ledipasvir, or daclatasvir can be used concomitantly without dose adjustment

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], solifenacin ---> SmPC of [1] of EMA

Use with caution. Monitor for fesoterodine or solifenacin adverse reactions, dose reduction of fesoterodine or solifenacin may be necessary.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], St. John's wort ---> SmPC of [1] of EMA

Based on theoretical considerations St. John's Wort is expected to decrease darunavir and/or cobicistat and/or tenofovir alafenamide plasma concentrations. (CYP3A and/or P-gp induction) Co-administration is contraindicated (see section 4.3).

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Medicinal products that induce CYP3A activity would be expected to increase the clearance of darunavir and cobicistat, resulting in lowered plasma concentrations of darunavir and cobicistat

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

o-administration of Symtuza and other medicinal products that inhibit CYP3A may decrease the clearance of darunavir and cobicistat and may result in increased plasma concentrations of darunavir and cobicistat

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], strong P-gp inductors ---> SmPC of [1] of EMA

Medicines that induce P-gp activity are expected to decrease tenofovir alafenamide absorption, resulting in decreased plasma level of tenofovir alafenamide, which may lead to loss of therapeutic effect and development of resistance.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

Co-administration of tenofovir alafenamide with other medicinal products that inhibit P-gp (e.g., cobicistat, ritonavir, ciclosporin) are expected to increase the absorption and plasma concentration of tenofovir alafenamide.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], systemic lidocaine ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], tacrolimus ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase these immunosuppressant plasma concentrations. CYP3A inhibition.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], tadalafil ---> SmPC of [1] of EMA

Concomitant use of PDE-5 inhibitors for the treatment of erectile dysfunction with Symtuza should be done with caution.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], telaprevir ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], tenofovir disoproxil ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], thioridazine ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase these neuroleptic plasma concentrations. CYP2D6 inhibition

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], ticagrelor ---> SmPC of [1] of EMA

Based on theoretical considerations co-administration of DRV/COBI with ticagrelor may increase concentrations of ticagrelor. (CYP3A and/or P-glycoprotein inhibition). Concomitant administration of Symtuza with ticagrelor is contraindicated (see section 4

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], timolol ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase this beta-blocker plasma concentrations. CYP2D6 inhibition

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], tramadol ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI may increase analgesic plasma concentrations. CYP2D6 and/or CYP3A inhibition

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], trazodone ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], triazolam ---> SmPC of [1] of EMA

Co-administration is contraindicated due to the potential for serious and/or life-threatening adverse reactions

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], tubular secretion ---> SmPC of [1] of EMA

Co-administration of emtricitabine with medicinal products that are eliminated by active tubular secretion may increase concentrations of emtricitabine, and/or the co-administered medicinal product.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], vardenafil ---> SmPC of [1] of EMA

Concomitant use of PDE-5 inhibitors for the treatment of erectile dysfunction with Symtuza should be done with caution.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], verapamil ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase this calcium channel blocker plasma concentrations. CYP3A inhibition

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], vinblastine ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase these anti-neoplastic plasma concentrations. CYP3A inhibition. Caution should be exercised when combining

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], vincristine ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase these anti-neoplastic plasma concentrations. CYP3A inhibition. Caution should be exercised when combining

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], voriconazole ---> SmPC of [1] of EMA

Concentrations of voriconazole may increase or decrease when co-administered with DRV/COBI.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], warfarin ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI may alter warfarin plasma concentrations. It is recommended that the international normalised ratio (INR) be monitored when warfarin is co-administered with Symtuza.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], xanthine oxidase inhibitors ---> SmPC of [1] of EMA

It is not known whether the co-administration of tenofovir alafenamide and xanthine oxidase inhibitors (e.g. febuxostat) would increase systemic exposure to tenofovir.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], zolpidem ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase this sedative/hypnotic plasma concentrations. CYP3A inhibition

CONTRAINDICATIONS of Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (Symtuza)

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

Patients with severe (Child-Pugh Class C) hepatic impairment.

Co-administration with strong CYP3A inducers such as the medicinal products listed below due to the potential for loss of therapeutic effect (see section 4.5):

- carbamazepine, phenobarbital, phenytoin

- rifampicin

- lopinavir/ritonavir

- St. John’s wort (Hypericum perforatum)

Co-administration with medicinal products such as those products listed below due to the potential for serious and/or life-threatening adverse reactions (see section 4.5):

- alfuzosin

- amiodarone, dronedarone, quinidine, ranolazine

- colchicine when used in patients with renal and/or hepatic impairment (see section 4.5)

- rifampicin

- ergot derivatives (e.g. dihydroergotamine, ergometrine, ergotamine, methylergonovine)

- dapoxetine

- domperidone

- naloxegol

- pimozide, quetiapine, sertindole, lurasidone (see section 4.5)

- elbasvir/grazoprevir

- triazolam, midazolam administered orally (for caution on parenterally administered midazolam, see section 4.5)

- sildenafil -when used for the treatment of pulmonary arterial hypertension, avanafil

- simvastatin, lovastatin and lomitapide (see section 4.5)

- ticagrelor

https://www.ema.europa.eu/en/documents/product-information/symtuza-epar-product-information_en.pdf 25/07/2024

Darvadstrocel (Alofisel)

Azathioprine, darvadstrocel [2] ---> SmPC of [2] of EMA

In vitro interaction studies have shown that the cell viability and immunomodulatory function of Alofisel is not affected by the presence of clinically-relevant concentrations of conventional therapies for Crohn's disease.

Breast-feeding, darvadstrocel [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Alofisel therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Darvadstrocel [1], fertility ---> SmPC of [1] of EMA

No data are available.

Darvadstrocel [1], infliximab ---> SmPC of [1] of EMA

Darvadstrocel [1], methotrexate ---> SmPC of [1] of EMA

Darvadstrocel [1], pregnancy ---> SmPC of [1] of EMA

Darvadstrocel is not recommended during pregnancy and in women of childbearing potential not using contraception.

Darvadstrocel [1], sodium chloride solution ---> SmPC of [1] of EMA

The injection of any substance other than sodium chloride 9 mg/mL (0.9%) solution through the fistula tracts and use of local anaesthesia is not recommended due to the unknown effect on the injected cells.

CONTRAINDICATIONS of Darvadstrocel (Alofisel)

- Hypersensitivity to the active substance, bovine serum or any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/alofisel-epar-product-information_en.pdf 21/01/2025 (withdrawn)

Dasabuvir (Exviera)

Abacavir/lamivudine, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [dasabuvir] of EMA

No dose adjustment needed for abacavir or lamivudine when administered with Exviera + ombitasvir/paritaprevir/ritonavir.

Ability to drive, dasabuvir [2] ---> SmPC of [2] of EMA

Patients should be informed that fatigue has been reported during treatment with dasabuvir in combination with ombitasvir/paritaprevir/ritonavir and ribavirin

AIIRA, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EMA

CYP3A4 and/or OATP1B inhibition by paritaprevir. Clinical monitoring and dose reduction is recommended for angiotensin receptor blockers when co-administered with Viekirax with or without dasabuvir.

Alfuzosin, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EM

Ritonavir is a strong inhibitor of CYP3A. Medicinal products that are highly dependent on CYP3A for clearance and for which elevated plasma levels are associated with serious events are contraindicated

Alprazolam, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [dasabuvir] of EMA

CYP3A4 inhibition by ritonavir. Clinical monitoring of patients is recommended. A decrease in alprazolam dose can be considered based on clinical response.

Amiodarone, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of E

Amlodipine, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [dasabuvir] of EMA

CYP3A4 inhibition by ritonavir may increase amlodipine and decrease paritaprevir plasma concentrations. Decrease in amlodipine dose by 50% and monitor patients for clinical effects.

Antivirals, dasabuvir [2] ---> SmPC of [2] of EMA

Co-administration of dasabuvir with other antivirals has not been studied and, therefore, cannot be recommended.

Apalutamide, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [dasabuvir] of EMA

CYP3A4 induction by apalutamide may decrease the plasma concentrations of dasabuvir, ombitasvir and paritaprevir. Concomitant use is contraindicated

Astemizole, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of E

Atazanavir, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [dasabuvir] of EMA

Atazanavir can be used in combination with dasabuvir with ombitasvir/paritaprevir/ritonavir if administered at the same time. To be noted, atazanavir should be taken without ritonavir

Atazanavir/ritonavir, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [ombitasvir/paritaprevir/riton

The combination carries an increased risk for hyperbilirubinemia (including ocular icterus), in particular when ribavirin is part of the hepatitis C regimen.

Atorvastatin, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of

BCRP inhibitors, dasabuvir [2] ---> SmPC of [2] of EMA

Dasabuvir is a substrate of P-gp and BCRP and its major metabolite M1 is a substrate of OCT1 in vitro. Inhibition of P-gp and BCRP is not expected to show clinically relevant increases in exposures of dasabuvir

BCRP substrates, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [dasabuvir] of EMA

Dasabuvir is an inhibitor of BCRP in vivo. Co-administration of dasabuvir with ombitasvir/paritaprevir/ritonavir together with medicinal products that are substrates of BCRP may increase plasma concentrations of these transporter substrates

Breast-feeding, dasabuvir [2] ---> SmPC of [2] of EMA

Because of the potential for adverse reactions from the medicinal product in breastfed infants, a decision must be made whether to discontinue breastfeeding or discontinue treatment, taking into account the importance of the therapy to the mother.

Buprenorphine/naloxone, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [dasabuvir] of EMA

CYP3A4 inhibition by ritonavir and UGT inhibition by paritaprevir, ombitasvir and dasabuvir. No dose adjustment is necessary

Caffeine, dasabuvir with ombitasvir/paritaprevir/ritonavir

Clinical monitoring and dose adjustment may be needed for other CYP1A2 substrates (e.g. ciprofloxacin, cyclobenzaprine, theophylline and caffeine).

Caffeine, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EMA

Viekirax administered with or without dasabuvir. Exposures of cyclobenzaprine, a CYP1A2 substrate, were decreased. Clinical monitoring and dose adjustment may be needed for other CYP1A2 substrates (e.g. ciprofloxacin, theophylline and caffeine).

Calcium antagonists, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [ombitasvir/paritaprevir/ritona

Dose decrease and clinical monitoring of calcium channel blockers is recommended when coadministered with Viekirax with and without dasabuvir.

Candesartan, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of

CYP3A4 and/or OATP1B inhibition by paritaprevir. Clinical monitoring and dose reduction is recommended for angiotensin receptor blockers when co-administered with Viekirax with or without dasabuvir.

Carbamazepine, dasabuvir with ombitasvir/paritaprevir/ritonavir

CYP3A4 induction by carbamazepine may decrease the plasma concentrations of carbamazepine 10, 11-epoxide, dasabuvir, ombitasvir and paritaprevir. Concomitant use is contraindicated

Carbamazepine, dasabuvir [2] ---> SmPC of [2] of EMA

Co-administration (contraindicated) of dasabuvir with medicinal products that are strong or moderate enzyme inducers is expected to decrease dasabuvir plasma concentrations and reduce its therapeutic effect

Carisoprodol, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [dasabuvir] of EMA

CYP2C19 induction by ritonavir. No dose adjustment required for carisoprodol; increase dose if clinically indicated.

Ciprofloxacin, dasabuvir with ombitasvir/paritaprevir/ritonavir

Clinical monitoring and dose adjustment may be needed for other CYP1A2 substrates (e.g. ciprofloxacin, cyclobenzaprine, theophylline and caffeine).

Ciprofloxacin, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [ombitasvir/paritaprevir/ritonavir] o

Cisapride, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EM

Clarithromycin, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [ombitasvir/paritaprevir/ritonavir]

Co-administration of ombitasvir/paritaprevir/ritonavir with or without dasabuvir with medicinal products that are strong inhibitors of CYP3A4 is expected to increase paritaprevir plasma concentrations. The coadministration is contraindicated

Cobicistat, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of E

Colchicine, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of E

The strong CYP3A inhibition by ritonavir may increase the plasma levels of colchicine. Concomitant use is contraindicated in patients with renal or hepatic impairment

Conivaptan, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of E

Cyclobenzaprine, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [dasabuvir] of EMA

No dose adjustment for cyclobenzaprine required; increase dose if clinically indicated.

Cyclosporine, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [dasabuvir] of EMA

Effect on ciclosporin is due to CYP3A4 inhibition by ritonavir and increase in paritaprevir exposures may be due to OATP/BCRP/P-gp inhibition by ciclosporin.

CYP1A2 substrates, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [dasabuvir] of EMA

Exposures of cyclobenzaprine, a CYP1A2 substrate, were decreased. Clinical monitoring and dose adjustment may be needed for other CYP1A2 substrates.

CYP2C8 inhibitors, dasabuvir [2] ---> SmPC of [2] of EMA

Co-administration of dasabuvir with medicinal products that inhibit CYP2C8 (e.g. teriflunomide, deferasirox) may increase dasabuvir plasma concentrations. Strong CYP2C8 inhibitors are contraindicated with dasabuvir

CYP2D6 substrates, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [dasabuvir] of EMA

CYP2D6 substrates (e.g. desipramine, metoprolol and dextromethorphan) are not expected to require dose adjustments.

Dabigatran etexilate, dasabuvir with ombitasvir/paritaprevir/ritonavir

Intestinal Pgp inhibition by paritaprevir and ritonavir may increase the plasma concentrations of dabigatran etexilate. Use with caution.

Dabigatran etexilate, dasabuvir [2] ---> SmPC of [2] of EMA

It may not be excluded that the systemic exposure of dabigatran etexilate is increased by dasabuvir due to inhibition of P-gp in the intestine.

Darunavir, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [dasabuvir] of EMA

The recommended dose of darunavir is 800 mg once daily, without ritonavir, when administered at the same time as ombitasvir/paritaprevir/ritonavir + dasabuvir

Dasabuvir with ombitasvir/paritaprevir/ritonavir, deferasirox ---> SmPC of [dasabuvir] of EMA

Deferasirox may increase dasabuvir exposures and should be used with caution.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, desipramine ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of

Viekirax administered with or without dasabuvir. CYP2D6 substrates (e.g. desipramine, metoprolol and dextromethorphan) are not expected to require dose adjustments.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, dextromethorphan ---> SmPC of [dasabuvir] of EMA

CYP2D6 substrates (e.g. desipramine, metoprolol and dextromethorphan) are not expected to require dose adjustments.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, diazepam ---> SmPC of [dasabuvir] of EMA

CYP2C19 induction by ritonavir. No dose adjustment required for diazepam; increase dose if clinically indicated.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, digoxin ---> SmPC of [dasabuvir] of EMA

While no dose adjustment is necessary for digoxin, appropriate monitoring of serum digoxin levels is recommended.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, dihydroergotamine ---> SmPC of [ombitasvir/paritaprevir/ritonavi

Dasabuvir with ombitasvir/paritaprevir/ritonavir, diltiazem ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EM

CYP3A4/P-gp inhibition. Caution is advised due to the expected increase in paritaprevir exposures. Dose decrease and clinical monitoring of calcium channel blockers is recommended when coadministered with Viekirax with and without dasabuvir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, dolutegravir ---> SmPC of [dasabuvir] of EMA

No dose adjustment needed for dolutegravir when administered with Exviera + ombitasvir/paritaprevir/ritonavir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, doravirine/lamivudine/tenofovir disoproxil ---> SmPC of [ombitas

No dose adjustment is required.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, drospirenone/estetrol [2] ---> SmPC of [2] of EMA

Concomitant use with the HCV medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin, may increase the risk of ALT elevations in women using ethinylestradiol containing medicinal products such as CHCs

Dasabuvir with ombitasvir/paritaprevir/ritonavir, drugs metabolised by CYP2C19 ---> SmPC of [dasabuvir] of EMA

Co-administration of dasabuvir with ombitasvir/paritaprevir/ritonavir can decrease exposures of medicinal products that are metabolized by CYP2C19, which may require dose adjustment/clinical monitoring.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, drugs primarily metabolised by CYP1A2 ---> SmPC of [ombitasvir/p

Dasabuvir with ombitasvir/paritaprevir/ritonavir, drugs primarily metabolised by CYP2C19 ---> SmPC of [dasabuvir]

Dasabuvir with ombitasvir/paritaprevir/ritonavir, drugs primarily metabolised by CYP2D6 ---> SmPC of [ombitasvir/p

Viekirax administered with or without dasabuvir. CYP2D6 substrates (e.g. desipramine, metoprolol and dextromethorphan) are not expected to require dose adjustments.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, drugs primarily metabolised by UGT1A1 ---> SmPC of [ombitasvir/p

Paritaprevir, ombitasvir and dasabuvir are inhibitors of UGT1A1. Co-administration of Viekirax with or without dasabuvir with medicinal products that are primarily metabolized by UGT1A1 result in increased plasma concentrations of such medicinal products

Dasabuvir with ombitasvir/paritaprevir/ritonavir, duloxetine

Viekirax administered with or without dasabuvir did not affect the exposures of the CYP2D6/CYP1A2 substrate, duloxetine.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, duloxetine ---> SmPC of [dasabuvir] of EMA

No dose adjustment is necessary for duloxetine. No dose adjustment needed for dasabuvir + ombitasvir/paritaprevir /ritonavir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, efavirenz ---> SmPC of [dasabuvir] of EMA

Dasabuvir with ombitasvir/paritaprevir/ritonavir, efavirenz/emtricitabine/tenofovir disoproxil ---> SmPC of [dasab

Concomitant use with efavirenz containing regimens is contraindicated (see section 4.3).

Dasabuvir with ombitasvir/paritaprevir/ritonavir, emtricitabine ---> SmPC of [dasabuvir] of EMA

No dose adjustment is necessary for emtricitabine/tenofovir and dasabuvir + ombitasvir/paritaprevir/ ritonavir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, emtricitabine/tenofovir ---> SmPC of [ombitasvir/paritaprevir/ri

No dose adjustment is necessary for emtricitabine/tenofovir and Viekirax with or without dasabuvir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, enzalutamide ---> SmPC of [dasabuvir] of EMA

CYP3A4 induction by enzalutamide decreases plasma concentrations of dasabuvir, ombitasvir and paritaprevir. Concomitant use is contraindicated

Dasabuvir with ombitasvir/paritaprevir/ritonavir, enzyme inductors ---> SmPC of [ombitasvir/paritaprevir/ritonavir

Coadministration of Viekirax with/without dasabuvir with drugs that are strong or moderate enzyme inducers is expected to decrease ombitasvir, paritaprevir, and ritonavir plasma levels and reduce their therapeutic effect. Concomitant use contraindicated

Dasabuvir with ombitasvir/paritaprevir/ritonavir, ergonovine ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of E

Dasabuvir with ombitasvir/paritaprevir/ritonavir, ergotamine ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of E

Dasabuvir with ombitasvir/paritaprevir/ritonavir, erythromycin ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of

Caution is advised if co-administering Viekirax with medicinal products that are both moderate inhibitors of CYP3A4 and inhibitors of multiple transporters. These medicinal products may show clinically relevant increases in exposures of paritaprevir

Dasabuvir with ombitasvir/paritaprevir/ritonavir, escitalopram ---> SmPC of [dasabuvir] of EMA

Co-administration of dasabuvir with ombitasvir/paritaprevir/ritonavir can decrease exposures of medicinal products that are metabolized by CYP2C19. No dose adjustment is necessary

Dasabuvir with ombitasvir/paritaprevir/ritonavir, esomeprazole ---> SmPC of [dasabuvir] of EMA

Dasabuvir with ombitasvir/paritaprevir/ritonavir, ethinyl estradiol ---> SmPC of [dasabuvir] of EMA

It is contraindicated the use of dasabuvir with ethinylestradiol-containing medicinal products such as those contained in most combined oral contraceptives or contraceptive vaginal rings

Dasabuvir with ombitasvir/paritaprevir/ritonavir, ethinylestradiol/norgestimate ---> SmPC of [ombitasvir/paritapre

Mechanism: possibly due to UGT inhibition by paritaprevir, ombitasvir and dasabuvir Ethinylestradiol-containing oral contraceptives are contraindicated

Dasabuvir with ombitasvir/paritaprevir/ritonavir, etravirine ---> SmPC of [dasabuvir] of EMA

Possibly decreases plasma concentrations of dasabuvir, ombitasvir and paritaprevir. Concomitant use is contraindicated

Dasabuvir with ombitasvir/paritaprevir/ritonavir, everolimus ---> SmPC of [dasabuvir] of EMA

Co-administration of dasabuvir + ombitasvir/paritaprevir/ ritonavir with everolimus is not recommended because of a significant increase in everolimus exposures which cannot be properly dose adjusted with available dose strengths.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, fertility ---> SmPC of [dasabuvir] of EMA

No human data on the effect of dasabuvir on fertility are available. Animal studies do not indicate harmful effects on fertility (see section 5.3).

Dasabuvir with ombitasvir/paritaprevir/ritonavir, fexofenadine ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of

Co-administration of ombitasvir/paritaprevir/ritonavir with or without dasabuvir with medicinal products that are substrates of OATP1B1, OATP1B3, OATP2B1 or OCT1 may increase plasma concentrations of these transporter substrates

Dasabuvir with ombitasvir/paritaprevir/ritonavir, fluticasone ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of

Concomitant use of fluticasone can increase systemic exposures of fluticasone. CYP3A4 inhibition by ritonavir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, fluvastatin ---> SmPC of [dasabuvir] of EMA

OATP1B/BCRP inhibition by paritaprevir. A temporary suspension of fluvastatin is recommended for the duration of treatment.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, fosamprenavir/ritonavir ---> SmPC of [fosamprenavir] of EMA

Co-administration of paritaprevir and fosamprenavir/ritonavir is contraindicated due to the expected increase of paritaprevir exposure and the lack of clinical data assessing the magnitude of this increase

Dasabuvir with ombitasvir/paritaprevir/ritonavir, furosemide ---> SmPC of [dasabuvir] of EMA

Possibly increased furosemide plasma concentrations due to UGT1A1 inhibition by paritaprevir, ombitasvir and dasabuvir. Monitor patients for clinical effects; a decrease in furosemide dose of up to 50% may be required.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, fusidic acid ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of

Dasabuvir with ombitasvir/paritaprevir/ritonavir, gemfibrozil ---> SmPC of [dasabuvir] of EMA

Increase in dasabuvir exposure is due to CYP2C8 inhibition and increase in paritaprevir is possibly due to OATP1B1 inhibition by gemfibrozil. Concomitant use is contraindicated

Dasabuvir with ombitasvir/paritaprevir/ritonavir, glimepiride ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of

Ombitasvir/paritaprevir/ritonavir administered with or without dasabuvir did not affect the exposures of the CYP2C9 substrate, warfarin. Other CYP2C9 substrates are not expected to require dose adjustments.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, glipizide ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EM

Dasabuvir with ombitasvir/paritaprevir/ritonavir, hydrocodone ---> SmPC of [dasabuvir] of EMA

CYP3A4 inhibition by ritonavir. A reduction of hydrocodone dose by 50% and/or clinical monitoring should be considered when administered with Exviera + ombitasvir/paritaprevir/ritonavir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, ibuprofen ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EM

Dasabuvir with ombitasvir/paritaprevir/ritonavir, imatinib ---> SmPC of [dasabuvir] of EMA

Dasabuvir with ombitasvir/paritaprevir/ritonavir, indinavir ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EM

Dasabuvir with ombitasvir/paritaprevir/ritonavir, itraconazol ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of

Dasabuvir with ombitasvir/paritaprevir/ritonavir, ketoconazole ---> SmPC of [dasabuvir] of EMA

CYP3A4/Pgp inhibition by ketoconazole and ombitasvir/paritaprevir/ritonavir may increase the plasma concentrations of ketoconazole and dasabuvir. Concomitant use is contraindicated

Dasabuvir with ombitasvir/paritaprevir/ritonavir, lansoprazole ---> SmPC of [dasabuvir] of EMA

Dasabuvir with ombitasvir/paritaprevir/ritonavir, levothyroxine

Clinical monitoring and dose adjustment may be required for levothyroxine.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, levothyroxine ---> SmPC of [ombitasvir/paritaprevir/ritonavir] o

Co-administration of Viekirax with medicinal products that are primarily metabolized by UGT1A1 increased plasma concentrations of such medicinal products, routine clinical monitoring is recommended for narrow therapeutic index medicinal products

Dasabuvir with ombitasvir/paritaprevir/ritonavir, lopinavir/ritonavir ---> SmPC of [dasabuvir] of EMA

Increase in paritaprevir exposures that may be due to inhibition of CYP3A/efflux transporters by lopinavir and higher dose of ritonavir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, losartan ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EMA

CYP3A4 and/or OATP1B inhibition by paritaprevir. Clinical monitoring and dose reduction is recommended for angiotensin receptor blockers when co-administered with Viekirax with or without dasabuvir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, lovastatine ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of

Dasabuvir with ombitasvir/paritaprevir/ritonavir, men ---> SmPC of [dasabuvir] of EMA

Either male patients or their female partners of childbearing potential must use a form of effective contraception during treatment with ribavirin and for 7 months after treatment.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, mephenytoin ---> SmPC of [dasabuvir] of EMA

CYP2C19 induction by ritonavir may decrease the plasma concentrations of S-mephenytoin. Clinical monitoring and dose adjustment may be needed for S-mephenytoin.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, metformin ---> SmPC of [dasabuvir] of EMA

No dose adjustment needed for metformin when co-administered with Exviera + ombitasvir/paritaprevir/ritonavir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, methadone ---> SmPC of [dasabuvir] of EM

No dose adjustment is necessary for methadone and dasabuvir + ombitasvir/paritaprevir/ ritonavir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, methadone ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EM

No dose adjustment needed for methadone when administered with Viekirax with or without dasabuvir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, methylergometrine ---> SmPC of [ombitasvir/paritaprevir/ritonavi

Dasabuvir with ombitasvir/paritaprevir/ritonavir, metoprolol ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of E

Viekirax administered with or without dasabuvir. CYP2D6 substrates (e.g. desipramine, metoprolol and dextromethorphan) are not expected to require dose adjustments.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, midazolam ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EM

The strong CYP3A inhibition by ritonavir may increase the plasma levels of midazolam. Concomitant use with oral midazolam is contraindicated

Dasabuvir with ombitasvir/paritaprevir/ritonavir, mitotane ---> SmPC of [dasabuvir] of EMA

CYP3A4 induction by mitotane may decrease the plasma concentrations of dasabuvir, ombitasvir and paritaprevir. Concomitant use is contraindicated

Dasabuvir with ombitasvir/paritaprevir/ritonavir, moderate CYP3A4 inductors ---> SmPC of [ombitasvir/paritaprevir/

Co-administration of Viekirax and dasabuvir with medicinal products that are moderate or strong enzyme inducers is expected to decrease ombitasvir, paritaprevir, ritonavir and dasabuvir plasma concentrations and reduce their therapeutic effect.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, nevirapine ---> SmPC of [dasabuvir] of EMA

Possibly decreases plasma concentrations of dasabuvir, ombitasvir and paritaprevir. Concomitant use is contraindicated

Dasabuvir with ombitasvir/paritaprevir/ritonavir, nifedipine ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of E

CYP3A4 inhibition. Dose decrease and clinical monitoring of calcium channel blockers is recommended when coadministered with Viekirax with and without dasabuvir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, norethindrone ---> SmPC of [dasabuvir] of EMA

No dose adjustment is necessary

Dasabuvir with ombitasvir/paritaprevir/ritonavir, norethisterone ---> SmPC of [dasabuvir] of EMA

No dose adjustment is necessary

Dasabuvir with ombitasvir/paritaprevir/ritonavir, OATP1B1 substrates ---> SmPC of [ombitasvir/paritaprevir/ritonav

Dasabuvir with ombitasvir/paritaprevir/ritonavir, OATP1B3 substrates ---> SmPC of [ombitasvir/paritaprevir/ritonav

Dasabuvir with ombitasvir/paritaprevir/ritonavir, OATP2B1 substrates ---> SmPC of [ombitasvir/paritaprevir/ritonav

Dasabuvir with ombitasvir/paritaprevir/ritonavir, OCT1 substrates ---> SmPC of [ombitasvir/paritaprevir/ritonavir]

Dasabuvir with ombitasvir/paritaprevir/ritonavir, omeprazole ---> SmPC of [dasabuvir] of EMA

Dasabuvir with ombitasvir/paritaprevir/ritonavir, paracetamol ---> SmPC of [dasabuvir] of EMA

No dose adjustment needed for paracetamol when administered with Exviera + ombitasvir/paritaprevir/ritonavir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, phenobarbital ---> SmPC of [dasabuvir] of EMA

CYP3A4 induction by phenobarbital may decrease the plasma concentrations of dasabuvir, ombitasvir and paritaprevir. Concomitant use is contraindicated

Dasabuvir with ombitasvir/paritaprevir/ritonavir, phenytoin ---> SmPC of [dasabuvir] of EMA

CYP3A4 induction by phenytoin may decrease the plasma concentrations of dasabuvir, ombitasvir and paritaprevir. Concomitant use is contraindicated

Dasabuvir with ombitasvir/paritaprevir/ritonavir, pimozide ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EMA

Dasabuvir with ombitasvir/paritaprevir/ritonavir, pitavastatin ---> SmPC of [dasabuvir] of EMA

OATP1B/BCRP inhibition by paritaprevir. A temporary suspension of pitavastatin is recommended for the duration of treatment.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, posaconazole ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of

Dasabuvir with ombitasvir/paritaprevir/ritonavir, pravastatine ---> SmPC of [dasabuvir] of EMA

OATP1B1 inhibition by paritaprevir may increase the plasma concentrations of pravastatin. Reduce pravastatin dose by 50%.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, pregnancy ---> SmPC of [dasabuvir] of EMA

If ribavirin is co-administered with dasabuvir and ombitasvir/paritaprevir/ritonavir, the contraindications regarding use of ribavirin during pregnancy apply (see also the Summary of Product Characteristics of ribavirin).

Dasabuvir with ombitasvir/paritaprevir/ritonavir, quetiapine ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of E

Dasabuvir with ombitasvir/paritaprevir/ritonavir, quinidine ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EM

Dasabuvir with ombitasvir/paritaprevir/ritonavir, raltegravir ---> SmPC of [dasabuvir] of EMA

UGT1A1 inhibition by paritaprevir, ombitasvir and dasabuvir. No dose adjustment is necessary

Dasabuvir with ombitasvir/paritaprevir/ritonavir, repaglinide ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of

OATP1B1 inhibition by paritaprevir. Caution should be used and dose decrease maybe needed for repaglinide when administered with Viekirax with or without dasabuvir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, rifampicin ---> SmPC of [dasabuvir] of EMA

CYP3A4/CYP2C8 induction by rifampicin may decrease the plasma concentrations of dasabuvir, ombitasvir and paritaprevir. Concomitant use is contraindicated

Dasabuvir with ombitasvir/paritaprevir/ritonavir, rilpivirine ---> SmPC of [dasabuvir] of EMA

Co-administration of Exviera and ombitasvir/paritaprevir/ritonavir with rilpivirine once daily should only be considered in patients without known QT-prolongation, and without other QT-prolongation coadministered medicinal products.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, rosuvastatin ---> SmPC of [dasabuvir] of EMA

OATP1B inhibition by paritaprevir and BCRP inhibition by dasabuvir, paritaprevir, and ritonavir. The maximum daily dose of rosuvastatin should be 5 mg

Dasabuvir with ombitasvir/paritaprevir/ritonavir, salmeterol ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of E

Dasabuvir with ombitasvir/paritaprevir/ritonavir, saquinavir ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of E

Dasabuvir with ombitasvir/paritaprevir/ritonavir, sildenafil ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of E

The strong CYP3A inhibition by ritonavir may increase the plasma levels of sildenafil. Concomitant use is contraindicated when sildenafil used for the treatment of pulmonary arterial hypertension

Dasabuvir with ombitasvir/paritaprevir/ritonavir, simvastatine ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of

Dasabuvir with ombitasvir/paritaprevir/ritonavir, sirolimus ---> SmPC of [dasabuvir] of EMA

Concomitant use of sirolimus with dasabuvir + ombitasvir/paritaprevir/ ritonavir is not recommended unless the benefits outweigh the risks (see section 4.4).

Dasabuvir with ombitasvir/paritaprevir/ritonavir, sofosbuvir ---> SmPC of [dasabuvir] of EMA

No dose adjustment needed for sofosbuvir when co-administered with Exviera + ombitasvir/paritaprevir/ritonavir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, St. John's wort ---> SmPC of [dasabuvir] of EMA

CYP3A4 induction by St. John's Wort may decrease the plasma concentrations of dasabuvir, ombitasvir and paritaprevir. Concomitant use is contraindicated

Dasabuvir with ombitasvir/paritaprevir/ritonavir, strong CYP3A4 inductors ---> SmPC of [ombitasvir/paritaprevir/ri

Dasabuvir with ombitasvir/paritaprevir/ritonavir, strong CYP3A4 inhibitors ---> SmPC of [ombitasvir/paritaprevir/r

Dasabuvir with ombitasvir/paritaprevir/ritonavir, sulfamethoxazol/trimethoprim ---> SmPC of [dasabuvir] of EMA

Increase in dasabuvir possibly due to CYP2C8 inhibition by trimethoprim. No dose adjustment needed for Exviera + ombitasvir/paritaprevir/ritonavir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, sulfasalazine

Caution should be used

Dasabuvir with ombitasvir/paritaprevir/ritonavir, sulfasalazine ---> SmPC of [ombitasvir/paritaprevir/ritonavir] o

BCRP inhibition by paritaprevir, ritonavir and dasabuvir. Caution should be used when sulfasalazine is coadministered with Viekirax with or without dasabuvir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, tacrolimus ---> SmPC of [dasabuvir] of EMA

Concomitant use of tacrolimus with dasabuvir and ombitasvir/paritaprevir/ ritonavir is not recommended unless the benefits outweigh the risks (see section 4.4).

Dasabuvir with ombitasvir/paritaprevir/ritonavir, telithromycin ---> SmPC of [ombitasvir/paritaprevir/ritonavir] o

Dasabuvir with ombitasvir/paritaprevir/ritonavir, tenofovir ---> SmPC of [dasabuvir] of EMA

No dose adjustment is necessary for emtricitabine/tenofovir and dasabuvir + ombitasvir/paritaprevir/ ritonavir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, terfenadine ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of

Dasabuvir with ombitasvir/paritaprevir/ritonavir, teriflunomide ---> SmPC of [dasabuvir] of EMA

Teriflunomide may increase dasabuvir exposures and should be used with caution.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, theophylline

Clinical monitoring and dose adjustment may be needed for other CYP1A2 substrates (e.g. ciprofloxacin, cyclobenzaprine, theophylline and caffeine).

Dasabuvir with ombitasvir/paritaprevir/ritonavir, theophylline ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of

Dasabuvir with ombitasvir/paritaprevir/ritonavir, ticagrelor ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of E

Dasabuvir with ombitasvir/paritaprevir/ritonavir, tipranavir ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of E

Dasabuvir with ombitasvir/paritaprevir/ritonavir, triazolam ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EM

Dasabuvir with ombitasvir/paritaprevir/ritonavir, UGT1A1 substrates with narrow therapeutic index ---> SmPC of [om

Dasabuvir with ombitasvir/paritaprevir/ritonavir, valsartan ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EM

CYP3A4 and/or OATP1B inhibition by paritaprevir. Clinical monitoring and dose reduction is recommended for angiotensin receptor blockers when co-administered with Viekirax with or without dasabuvir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, verapamil ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EM

Dasabuvir with ombitasvir/paritaprevir/ritonavir, vitamin K antagonists ---> SmPC of [dasabubir] of EMA

While no change in the pharmacokinetics of warfarin is expected, close monitoring of INR is recommended with all vitamin K antagonists.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, voriconazole ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of

Dasabuvir with ombitasvir/paritaprevir/ritonavir, warfarin

While no change in the pharmacokinetics of warfarin is expected, close monitoring of INR is recommended with all vitamin K antagonists.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, warfarin ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EMA

Dasabuvir with ombitasvir/paritaprevir/ritonavir, women of childbearing potential ---> SmPC of [dasabuvir] of EMA

Women of childbearing potential should not receive ribavirin unless they are using an effective form of contraception during treatment with ribavirin and for 4 months after treatment.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, zolpidem

No dose adjustment is necessary for zolpidem. No dose adjustment needed for dasabuvir + ombitasvir/paritaprevir/ ritonavir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, zolpidem ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EMA

Zolpidem is metabolized by CYP3A, drug interaction studies indicate that no dose adjustment is needed when co-administering zolpidem with ombitasvir/paritaprevir/ritonavir with or without dasabuvir

Dasabuvir [1], drugs primarily metabolised by UGT1A1 ---> SmPC of [1] of EMA

Dasabuvir is an inhibitor of UGT1A1 in vivo. Co-administration of dasabuvir with medicinal products that are primarily metabolized by UGT1A1 result in increased plasma concentrations of such medicinal products

Dasabuvir [1], efavirenz ---> SmPC of [1] of EMA

Dasabuvir [1], enzalutamide ---> SmPC of [1] of EMA

Dasabuvir [1], enzyme inductors ---> SmPC of [1] of EMA

Dasabuvir [1], ethinyl estradiol ---> SmPC of [1] of EMA

It is contraindicated the use of dasabuvir with ethinylestradiol-containing medicinal products such as those contained in most combined oral contraceptives or contraceptive vaginal rings

Dasabuvir [1], etravirine ---> SmPC of [1] of EMA

Dasabuvir [1], foods ---> SmPC of [1] of EMA

To maximise absorption, Exviera tablets should be taken with food, without regard to fat and calorie content

Dasabuvir [1], gemfibrozil ---> SmPC of [1] of EMA

Medicinal products that are strong CYP2C8 inhibitors may increase dasabuvir plasma concentrations and must not be co-administered with dasabuvir

Dasabuvir [1], mitotane ---> SmPC of [1] of EMA

Dasabuvir [1], nevirapine ---> SmPC of [1] of EMA

Dasabuvir [1], non-nucleoside reverse transcriptase inhibitors ---> SmPC of [1] of EMA

NNRTIs other than rilpivirine (efavirenz, etravirine, and nevirapine) are contraindicated

Dasabuvir [1], ombitasvir/paritaprevir/ritonavir ---> SmPC of [1] of EMA

As liver function may change during treatment with dasabuvir administered with ombitasvir/paritaprevir/ritonavir, a close monitoring of International Normalised Ratio (INR) values is recommended.

Dasabuvir [1], P-gp inhibitors ---> SmPC of [1] of EMA

Dasabuvir [1], phenobarbital ---> SmPC of [1] of EMA

Dasabuvir [1], phenytoin ---> SmPC of [1] of EMA

Dasabuvir [1], pregnancy ---> SmPC of [1] of EMA

As a precautionary measure, it is preferable to avoid the use of dasabuvir during pregnancy.

Dasabuvir [1], renal excretion ---> SmPC of [1] of EMA

Dasabuvir is not expected to affect medicinal products which are primarily excreted by the renal route via the transporters OAT1, OAT3, OCT2, MATE1 and MATE2K

Dasabuvir [1], rifampicin ---> SmPC of [1] of EMA

Dasabuvir [1], St. John's wort ---> SmPC of [1] of EMA

Dasabuvir [1], strong CYP2C8 inhibitors ---> SmPC of [1] of EMA

Strong CYP2C8 inhibitors are contraindicated with dasabuvir (see section 4.3 and Table 2).

Dasabuvir [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

Dasabuvir [1], teriflunomide ---> SmPC of [1] of EMA

Dasabuvir [1], UGT1A1 substrates with narrow therapeutic index ---> SmPC of [1] of EMA

Dasabuvir is an inhibitor of UGT1A1 in vivo. Routine clinical monitoring is recommended for medicinal products metabolized by UGT1A1 with narrow therapeutic index (i.e. levothyroxine).

Dasabuvir, doravirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Dasabuvir, doravirine/lamivudine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Dasabuvir, iptacopan [2] ---> SmPC of [2] of EMA

In vitro data showed iptacopan has potential for time-dependent inhibition of CYP2C8 and may increase the exposure of sensitive CYP2C8 substrates, such as repaglinide, dasabuvir or paclitaxel. Caution should be exercised

Dasabuvir, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

Viekirax may be administered with or without dasabuvir. When co-administered, they exert mutual effects on each other (see section 5.2). Therefore, the interaction profile of the compounds must be considered as a combination.

Dasabuvir, pirtobrutinib [2] ---> SmPC of [2] of EMA

Since pirtobrutinib can increase the plasma concentrations of CYP2C8 substrates, caution is advised when co-administering with CYP2C8 substrates (e.g. repaglinide, dasabuvir, selexipag, rosiglitazone, pioglitazone, and montelukast).

Dasabuvir, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib increased the Cmax and AUC of repaglinide (a substrate of CYP2C8) by approximately 91% and 188% respectively. Therefore, coadministration with sensitive CYP2C8 substrates should be avoided.

CONTRAINDICATIONS of Dasabuvir (Exviera)

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

- Patients with moderate to severe hepatic impairment (Child-Pugh B or C) (see section 5.2).

- Use of ethinylestradiol-containing medicinal products such as those contained in most combined oral contraceptives or contraceptive vaginal rings

- Co-administration of Exviera with medicinal products that are strong or moderate enzyme inducers is expected to decrease dasabuvir plasma concentrations and

reduce its therapeutic effect. Examples of contraindicated inducers are provided below.

Enzyme inducers:

- carbamazepine, phenytoin, phenobarbital

- efavirenz, nevirapine, etravirine

- apalutamide, enzalutamide

- mitotane

- rifampicin

- St. John's Wort (Hypericum perforatum)

- Medicinal products that are strong CYP2C8 inhibitors may increase dasabuvir plasma concentrations and must not be co-administered with Exviera (see section 4.5).

Examples of contraindicated CYP2C8 inhibitors are provided below.

CYP2C8 inhibitor:

- gemfibrozil

- Dasabuvir is administered with ombitasvir/paritaprevir /ritonavir. For contra-indications with ombitasvir/paritaprevir/ritonavir refer to the Summary of Product Characteristics.

https://www.ema.europa.eu/en/documents/product-information/exviera-epar-product-information_en.pdf 01/10/2024 (withdrawn)

Dasatinib (Sprycel)

Ability to drive, dasatinib [2] ---> SmPC of [2] of EMA

Patients should be advised that they may experience adverse reactions such as dizziness or blurred vision during treatment with dasatinib.

Aluminium hydroxide, dasatinib [2] ---> SmPC of [2] of EMA

Non-clinical data demonstrate that the solubility of dasatinib is pH-dependent. Antacids may be administered up to 2 hours prior to or 2 hours following dasatinib

Aluminium, dasatinib [2] ---> SmPC of [2] of EMA

Non-clinical data demonstrate that the solubility of dasatinib is pH-dependent. Antacids may be administered up to 2 hours prior to or 2 hours following dasatinib

Antacids, dasatinib [2] ---> SmPC of [2] of EMA

Non-clinical data demonstrate that the solubility of dasatinib is pH-dependent. Antacids may be administered up to 2 hours prior to or 2 hours following dasatinib

Astemizole, dasatinib [2] ---> SmPC of [2] of EMA

Concomitant use of dasatinib and a CYP3A4 substrate may increase exposure to the CYP3A4 substrate. CYP3A4 substrates known to have a narrow therapeutic index should be administered with caution in patients receiving dasatinib

Atazanavir/cobicistat [1], dasatinib ---> SmPC of [1] of EMA

Concentrations of the antineoplastic may be increased when coadministered with EVOTAZ resulting in the potential for increased adverse events. The mechanism of interaction is CYP3A4 inhibition by cobicistat.

Azithromycin, dasatinib

The concomitant use with azithromycin may increase the risk of cardiac arrhythmia.

Bepridil, dasatinib [2] ---> SmPC of [2] of EMA

Breast-feeding, dasatinib [2] ---> SmPC of [2] of EMA

Breast-feeding should be stopped during treatment with SPRYCEL.

Carbamazepine, dasatinib [2] ---> SmPC of [2] of EMA

The administration of dasatinib with a strong CYP3A4 inductor may increase metabolism and decrease dasatinib plasma concentrations. Therefore, concomitant use of potent CYP3A4 inducers with dasatinib is not recommended.

Cisapride, dasatinib [2] ---> SmPC of [2] of EMA

Clarithromycin, dasatinib [2] ---> SmPC of [2] of EMA

Concomitant use of dasatinib and medicinal products or substances which potently inhibit CYP3A4 may increase exposure to dasatinib. Therefore, in patients receiving dasatinib, systemic administration of a potent CYP3A4 inhibitor is not recommended

Cobicistat [1], dasatinib ---> SmPC of [1] of EMA

Concentrations of dasatinib may be increased when co-administered with cobicistat resulting in the potential for increased adverse events usually associated with this anticancer medicinal product.

CYP3A4 inductors, dasatinib [2] ---> SmPC of [2] of EMA

The CYP3A4 induction may decrease the plasma concentrations of dasatinib.

Darunavir/cobicistat [1], dasatinib ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase the anti-neoplastic plasma concentrations.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], dasatinib ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase these anti-neoplastic plasma concentrations. CYP3A inhibition

Darunavir/ritonavir, dasatinib ---> SmPC of [darunavir] of EMA

Boosted darunavir is expected to increase the antineoplastic plasma concentrations. (CYP3A inhibition)

Dasatinib [1], dexamethasone ---> SmPC of [1] of EMA

Concomitant use of dexamethasone, a weak CYP3A4 inducer, with dasatinib is allowed; dasatinib AUC is predicted to decrease approximately 25% with concomitant use of dexamethasone, which is not likely to be clinically meaningful.

Dasatinib [1], dihydroergotamine ---> SmPC of [1] of EMA

Dasatinib [1], drugs primarily metabolised by CYP2C8 ---> SmPC of [1] of EMA

In vitro data indicate a potential risk for interaction with CYP2C8 substrates, such as glitazones.

Dasatinib [1], drugs primarily metabolised by CYP3A4 ---> SmPC of [1] of EMA

Concomitant use of dasatinib and a CYP3A4 substrate may increase exposure to the CYP3A4 substrate.

Dasatinib [1], drugs primarily metabolised by CYP3A4 with narrow therapeutic index ---> SmPC of [1] of EMA

Dasatinib [1], drugs with high protein binding ---> SmPC of [1] of EMA

At clinically relevant concentrations, binding of dasatinib to plasma proteins is approximately 96% on the basis of in vitro experiments. No studies have been performed to evaluate dasatinib interaction with other protein-bound medicinal products.

Dasatinib [1], ergot derivatives ---> SmPC of [1] of EMA

Dasatinib [1], ergotamine ---> SmPC of [1] of EMA

Dasatinib [1], erythromycin ---> SmPC of [1] of EMA

Dasatinib [1], esomeprazole ---> SmPC of [1] of EMA

Long-term suppression of gastric acid secretion by H2 antagonists or proton pump inhibitors (e.g. famotidine and omeprazole) is likely to reduce dasatinib exposure.

Dasatinib [1], famotidine ---> SmPC of [1] of EMA

Long-term suppression of gastric acid secretion by H2 antagonists or proton pump inhibitors (e.g. famotidine and omeprazole) is likely to reduce dasatinib exposure.

Dasatinib [1], fertility ---> SmPC of [1] of EMA

Physicians and other healthcare providers should counsel male patients of appropriate age about possible effects of SPRYCEL on fertility, and this counseling may include consideration of semen deposition

Dasatinib [1], glitazones ---> SmPC of [1] of EMA

In vitro data indicate a potential risk for interaction with CYP2C8 substrates, such as glitazones.

Dasatinib [1], grapefruit juice ---> SmPC of [1] of EMA

Dasatinib [1], H2 antagonists ---> SmPC of [1] of EMA

Long-term suppression of gastric acid secretion by H2 antagonists or proton pump inhibitors (e.g. famotidine and omeprazole) is likely to reduce dasatinib exposure.

Dasatinib [1], hypokalemia ---> SmPC of [1] of EMA

In vitro data suggest that dasatinib has the potential to prolong cardiac ventricular repolarisation (QT Interval). Dasatinib should be administered with caution to patients who have or may develop prolongation of QTc.

Dasatinib [1], hypomagnesemia ---> SmPC of [1] of EMA

Dasatinib [1], itraconazol ---> SmPC of [1] of EMA

Dasatinib [1], ketoconazole ---> SmPC of [1] of EMA

Dasatinib [1], magnesium ---> SmPC of [1] of EMA

Non-clinical data demonstrate that the solubility of dasatinib is pH-dependent. Antacids may be administered up to 2 hours prior to or 2 hours following dasatinib

Dasatinib [1], magnesium hydroxide ---> SmPC of [1] of EMA

Non-clinical data demonstrate that the solubility of dasatinib is pH-dependent. Antacids may be administered up to 2 hours prior to or 2 hours following dasatinib

Dasatinib [1], men ---> SmPC of [1] of EMA

Both sexually active men and women of childbearing potential should use effective methods of contraception during treatment.

Dasatinib [1], omeprazole ---> SmPC of [1] of EMA

Long-term suppression of gastric acid secretion by H2 antagonists or proton pump inhibitors (e.g. famotidine and omeprazole) is likely to reduce dasatinib exposure.

Dasatinib [1], phenobarbital ---> SmPC of [1] of EMA

Dasatinib [1], phenytoin ---> SmPC of [1] of EMA

Dasatinib [1], pimozide ---> SmPC of [1] of EMA

Dasatinib [1], pregnancy ---> SmPC of [1] of EMA

SPRYCEL should not be used during pregnancy unless the clinical condition of the woman requires treatment with dasatinib. If SPRYCEL is used during pregnancy, the patient must be informed of the potential risk to the foetus.

Dasatinib [1], proton pump inhibitors ---> SmPC of [1] of EMA

Long-term suppression of gastric acid secretion by H2 antagonists or proton pump inhibitors (e.g. famotidine and omeprazole) is likely to reduce dasatinib exposure.

Dasatinib [1], QT interval prolonging drugs ---> SmPC of [1] of EMA

Dasatinib [1], quinidine ---> SmPC of [1] of EMA

Dasatinib [1], rifampicin ---> SmPC of [1] of EMA

Dasatinib [1], ritonavir ---> SmPC of [1] of EMA

Dasatinib [1], simvastatine ---> SmPC of [1] of EMA

In a study in healthy subjects, a dose of dasatinib increased AUC and Cmax exposure to simvastatin, a known CYP3A4 substrate, by 20 and 37% respectively

Dasatinib [1], St. John's wort ---> SmPC of [1] of EMA

Dasatinib [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Dasatinib [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Dasatinib [1], telithromycin ---> SmPC of [1] of EMA

Dasatinib [1], terfenadine ---> SmPC of [1] of EMA

Dasatinib [1], women of childbearing potential ---> SmPC of [1] of EMA

Both sexually active men and women of childbearing potential should use effective methods of contraception during treatment.

Dasatinib, duvelisib [2] ---> SmPC of [2] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Dasatinib, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with dasatinib may increase the serum concentrations of dasatinib. Careful monitoring of the tolerance to these anti-cancer agents is recommended.

Dasatinib, lopinavir/ritonavir [2] ---> SmPC of [2] of EMA

Most tyrosine kinase inhibitors such as dasatinib and nilotinib, also vincristine and vinblastine: Risk of increased adverse events due to higher serum concentrations because of CYP3A4 inhibition by Kaletra.

Dasatinib, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Serum concentrations may be increased when coadministered with ritonavir resulting in the potential for increased incidence of adverse events.

Dasatinib, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole may increase plasma concentrations of tyrosine kinase inhibitors metabolised by CYP3A4. If concomitant use cannot be avoided, dose reduction of the tyrosine kinase inhibitor is recommended (see section 4.4).

CONTRAINDICATIONS of Dasatinib (Sprycel)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/sprycel-epar-product-information_en.pdf 15/05/2025

Other trade names: Dasatinib Accord Healthcare,

Dasiglucagon (Zegalogue)

Ability to drive, dasiglucagon [2] ---> SmPC of [2] of EMA

The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia which may persist for a brief period after receiving treatment.

Betablockers, dasiglucagon [2] ---> SmPC of [2] of EMA

Patients taking beta-blockers might be expected to have a greater increase in both pulse and blood pressure when taking dasiglucagon, an increase of which will be transient because of the short half-life of dasiglucagon.

Breast-feeding, dasiglucagon [2] ---> SmPC of [2] of EMA

As dasiglucagon is degraded in the digestive tract and cannot be absorbed in its intact form, it will not exert any metabolic effect in the child. Zegalogue can be used during breast-feeding.

Coronary artery disease, dasiglucagon [2] ---> SmPC of [2] of EMA

The increase in blood pressure and pulse rate may require therapy in patients with coronary artery disease.

Cytochrome P450, dasiglucagon [2] ---> SmPC of [2] of EMA

Dasiglucagon does not inhibit CYP enzymes and drug transporters in vitro at clinically relevant concentrations.

Dasiglucagon [1], fertility ---> SmPC of [1] of EMA

Based on animal data, dasiglucagon had no effect on male or female fertility (see section 5.3).

Dasiglucagon [1], indometacin ---> SmPC of [1] of EMA

When used with indometacin, dasiglucagon may lose its ability to raise blood glucose or may even produce hypoglycaemia.

Dasiglucagon [1], insulin ---> SmPC of [1] of EMA

Reacts antagonistically towards dasiglucagon.

Dasiglucagon [1], pregnancy ---> SmPC of [1] of EMA

Studies in animals with dasiglucagon have shown reproductive toxicity (see section 5.3). Untreated hypoglycaemia in pregnancy can cause complications and may be fatal.

Dasiglucagon [1], pregnancy ---> SmPC of [1] of EMA

The use of Zegalogue during pregnancy should be considered only if the expected benefit justifies the potential risk to the foetus.

Dasiglucagon [1], warfarin ---> SmPC of [1] of EMA

Dasiglucagon may increase the anticoagulant effect of warfarin.

CONTRAINDICATIONS of Dasiglucagon (Zegalogue)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Phaeocromocytoma (see section 4.4).

https://www.ema.europa.eu/en/documents/product-information/zegalogue-epar-product-information_en.pdf 23/08/2024

Datopotamab (Datroway)

Ability to drive, datopotamab [2] ---> SmPC of [2] of EMA

Datroway may influence the ability to drive and use machines. Patients should be advised to use caution when driving or operating machines in case they experience fatigue or vision changes during treatment with Datroway (see section 4.8).

Breast-feeding, datopotamab [2] ---> SmPC of [2] of EMA

Because of the potential for serious adverse reactions in breast-fed children, women should discontinue breast-feeding prior to initiating treatment with Datroway. Women may begin breast-feeding 1 month after concluding treatment.

CYP3A4 inhibitors, datopotamab [2] ---> SmPC of [2] of EMA

Therefore, inhibitors of CYP3A4, OATP1B1 and OATP1B3 will most likely not have a clinically relevant effect on the PK of deruxtecan released from datopotamab deruxtecan.

Datopotamab [1], fertility ---> SmPC of [1] of EMA

Based on results from animal toxicity studies, Datroway may impair male and female reproductive function and fertility (see section 5.3). Both men and women should seek advice on fertility preservation before treatment.

Datopotamab [1], men ---> SmPC of [1] of EMA

Men with female partners of childbearing potential should use effective contraception during treatment with Datroway and for at least 4 months following the last dose.

Datopotamab [1], pregnancy ---> SmPC of [1] of EMA

Patients should be informed of the potential risks to the foetus before they become pregnant and to contact their doctor immediately if they become pregnant.

Datopotamab [1], women of childbearing potential ---> SmPC of [1] of EMA

The pregnancy status of women of childbearing potential should be verified prior to initiation of Datroway.

Datopotamab [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should use effective contraception during treatment with Datroway and for at least 7 months following the last dose.

CONTRAINDICATIONS of Datopotamab (Datroway)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/datroway-epar-product-information_en.pdf 13/05/2025

Daunorubicin/cytarabine (Vyxeos liposomal)

Ability to drive, daunorubicin/cytarabine [2] ---> SmPC of [2] of EMA

Vyxeos liposomal has minor influence on the ability to drive and use machines. Fatigue and dizziness have been reported with the use of Vyxeos liposomal. Therefore, caution is recommended when driving or operating machines.

Breast-feeding, daunorubicin/cytarabine [2] ---> SmPC of [2] of EMA

It is not known whether Vyxeos liposomal is excreted in human milk. Because of the potential for serious adverse reactions in breast-feeding children from Vyxeos liposomal, women should be advised not to breast-feed during Vyxeos liposomal therapy.

Daunorubicin/cytarabine [1], fertility ---> SmPC of [1] of EMA

Based on findings in animals, male fertility may be compromised by treatment with Vyxeos liposomal (see section 5.3).

Daunorubicin/cytarabine [1], hepatotoxic drugs ---> SmPC of [1] of EMA

Hepatic function should be monitored more frequently when Vyxeos is coadministered with hepatoxic agents.

Daunorubicin/cytarabine [1], medicines with cardiotoxic effects ---> SmPC of [1] of EMA

Do not administer Vyxeos in combination with other cardiotoxic agents unless the patient's cardiac function is closely monitored.

Daunorubicin/cytarabine [1], men ---> SmPC of [1] of EMA

Both male patients with partners of childbearing potential and female patients should use effective contraception during treatment with Vyxeos liposomal and for 6 months following the last dose.

Daunorubicin/cytarabine [1], pregnancy ---> SmPC of [1] of EMA

Based on results from animal studies and its mechanism of action, Vyxeos liposomal should not be used during pregnancy, unless the clinical condition of the woman requires treatment and justifies the potential risk to the foetus (see section 5.3).

Daunorubicin/cytarabine [1], women of childbearing potential ---> SmPC of [1] of EMA

To exclude pregnancy, women of childbearing potential should undergo pregnancy testing before initiation of Vyxeos liposomal.

CONTRAINDICATIONS of Daunorubicin/cytarabine (Vyxeos liposomal)

- History of serious hypersensitivity to the active substances or to any of the excipients listed in section 6.1

https://www.ema.europa.eu/en/documents/product-information/vyxeos-liposomal-epar-product-information_en.pdf 24/05/2024

Decitabine (Dacogen)

Ability to drive, decitabine [2] ---> SmPC of [2] of EMA

Dacogen has moderate influence on the ability to drive and use machines. Patients should be advised that they may experience undesirable effects such as anaemia during treatment.

Breast-feeding, decitabine [2] ---> SmPC of [2] of EMA

It is not known whether decitabine or its metabolites are excreted in breast milk. Dacogen is contraindicated during breast-feeding; therefore, if treatment with this medicine is required, breast-feeding must be discontinued (see section 4.3).

Contraceptives, decitabine [2] ---> SmPC of [2] of EMA

The use of decitabine with hormonal contraceptives has not been studied.

Cytochrome P450, decitabine [2] ---> SmPC of [2] of EMA

Cytochrome (CYP) 450-mediated metabolic interactions are not anticipated as decitabine metabolism is not mediated by this system but by oxidative deamination.

Decitabine [1], fertility ---> SmPC of [1] of EMA

No human data on the effect of decitabine on fertility are available. In non-clinical animal studies, decitabine alters male fertility and is mutagenic.

Decitabine [1], interactions ---> SmPC of [1] of EMA

There is the potential for a drug-drug interaction with other agents which are also activated by sequential phosphorylation and/or metabolised by enzymes implicated in the inactivation of decitabine (e.g., cytidine deaminase).

Decitabine [1], men ---> SmPC of [1] of EMA

Men should use effective contraceptive measures and be advised to not father a child while receiving Dacogen, and for 3 months following completion of treatment (see section 5.3).

Decitabine [1], men ---> SmPC of [1] of EMA

Men should seek advice on conservation of sperm and female patients of childbearing potential should seek consultation regarding oocyte cryopreservation prior to initiation of treatment.

Decitabine [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

Decitabine has been shown to be a weak inhibitor of P-gp mediated transport in vitro and is therefore also not expected to affect P-gp mediated transport of co-administered medicinal products

Decitabine [1], pregnancy ---> SmPC of [1] of EMA

Dacogen should not be used during pregnancy and in women of childbearing potential not using effective contraception. A pregnancy test should be performed on all women of childbearing potential before treatment is started.

Decitabine [1], pregnancy ---> SmPC of [1] of EMA

If Dacogen is used during pregnancy, or if a patient becomes pregnant while receiving this medicinal product, the patient should be apprised of the potential hazard to the foetus.

Decitabine [1], protein binding ---> SmPC of [1] of EMA

Impact of decitabine on co-administered medicinal products Given its low in vitro plasma protein binding (< 1%), decitabine is unlikely to displace co-administered medicinal products from their plasma protein binding.

Decitabine [1], women of childbearing potential ---> SmPC of [1] of EMA

Due to the genotoxic potential of decitabine (see section 5.3), women of childbearing potential must use effective contraceptive measures and avoid becoming pregnant while being treated with Dacogen and for 6 months following completion of treatment.

CONTRAINDICATIONS of Decitabine (Dacogen)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Breast-feeding

https://www.ema.europa.eu/en/documents/product-information/dacogen-epar-product-information_en.pdf 02/10/2024

Decitabine/cedazuridine (Inaqovi

Ability to drive, decitabine/cedazuridine [2] ---> SmPC of [2] of EMA

Inaqovi has moderate influence on the ability to drive and use machines. Patients should be advised that they may experience undesirable effects, such as anaemia during treatment.

Azacitidine, decitabine/cedazuridine [2] ---> SmPC of [2] of EMA

Concomitant administration of Inaqovi with medicinal products metabolised by CDA (i.e., cytarabine, gemcitabine, azacitidine) may result in increased systemic exposure with a potential for increased toxicity of these medicinal products.

Breast-feeding, decitabine/cedazuridine [2] ---> SmPC of [2] of EMA

It is unknown whether decitabine, cedazuridine, or their metabolites are excreted in breast milk. A risk to the newborns/infants cannot be excluded. Inaqovi is contraindicated during breast-feeding (see section 4.3).

Contraceptives, decitabine/cedazuridine [2] ---> SmPC of [2] of EMA

The use of decitabine and cedazuridine with hormonal contraceptives has not been studied.

CYP450, decitabine/cedazuridine [2] ---> SmPC of [2] of EMA

Decitabine and cedazuridine are not substrates or inhibitors for cytochrome P450 (CYP450); thus interactions with CYP inhibitors or inducers are not expected.

Cytarabine, decitabine/cedazuridine [2] ---> SmPC of [2] of EMA

Decitabine/cedazuridine [1], fertility ---> SmPC of [1] of EMA

No human data on the effect of decitabine and cedazuridine on fertility are available. Ovarian and testicular toxicity, including mutagenicity, has been observed in repeat-dose toxicity studies in mice.

Decitabine/cedazuridine [1], foods ---> SmPC of [1] of EMA

Overall decitabine exposure has been shown to be reduced when decitabine is administered with a high fat, high-calorie meal (see section 4.2).

Decitabine/cedazuridine [1], gemcitabine ---> SmPC of [1] of EMA

Decitabine/cedazuridine [1], men ---> SmPC of [1] of EMA

Men should use effective contraceptive measures and be advised to not father a child while receiving Inaqovi, and for 3 months following completion of treatment (see section 5.3).

Decitabine/cedazuridine [1], men ---> SmPC of [1] of EMA

Because of the possibility of infertility as a consequence of therapy, men should seek advice on conservation of sperm

Decitabine/cedazuridine [1], substrate for the cytidine deaminase enzyme ---> SmPC of [1] of EMA

Because decitabine is a substrate for the cytidine deaminase (CDA) enzyme, other medicinal products inhibiting CDA should be avoided, as co-administration may result in increased decitabine exposure.

Decitabine/cedazuridine [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential must use effective contraceptive measures and avoid becoming pregnant while being treated with Inaqovi and for 6 months following completion of treatment.

Decitabine/cedazuridine [1], women of childbearing potential ---> SmPC of [1] of EMA

Because of the possibility of infertility as a consequence of therapy, female patients of childbearing potential should seek consultation regarding oocyte cryopreservation prior to initiating treatment.

Decitabine/cedazuridine, pregnancy [2] ---> SmPC of [2] of EMA

Inaqovi may harm the foetus when administered to pregnant women. Inaqovi is not recommended during pregnancy and in women of childbearing potential not using effective contraception.

CONTRAINDICATIONS of Decitabine/cedazuridine (Inaqovi

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

- Breast-feeding (see section 4.6).

https://www.ema.europa.eu/en/documents/product-information/inaqovi-epar-product-information_en.pdf 10/03/2025

Deferasirox (Exjade)

Ability to drive, deferasirox [2] ---> SmPC of [2] of EMA

Patients experiencing the uncommon adverse reaction of dizziness should exercise caution when driving or operating machinery

Acetylsalicylic acid, deferasirox [2] ---> SmPC of [2] of EMA

The concomitant administration of deferasirox with substances that have known ulcerogenic potential, such as NSAIDs (including acetylsalicylic acid at high dosage), may increase the risk of gastrointestinal toxicity

Aluminium, deferasirox [2] ---> SmPC of [2] of EMA

It is not recommended to take deferasirox tablets with aluminium-containing antacid preparations.

Anticoagulants, deferasirox [2] ---> SmPC of [2] of EMA

The concomitant administration of deferasirox with anticoagulants may increase the risk of gastrointestinal haemorrhage. Close clinical monitoring is required when deferasirox is combined with these substances.

Bepridil, deferasirox [2] ---> SmPC of [2] of EMA

Due to a possible decrease in efficacy, caution should be exercised when deferasirox is combined with substances metabolised through CYP3A4

Biphosphonates, deferasirox [2] ---> SmPC of [2] of EMA

The concomitant administration of deferasirox with substances that have known ulcerogenic potential, such as oral bisphosphonates, may increase the risk of gastrointestinal toxicity

Breast-feeding, deferasirox [2] ---> SmPC of [2] of EMA

Breast-feeding is not recommended during treatment with EXJADE

Busulfan, deferasirox [2] ---> SmPC of [2] of EMA

Concomitant administration of deferasirox and busulfan resulted in an increase of busulfan exposure (AUC), but the mechanism of the interaction remains unclear.

Carbamazepine, deferasirox [2] ---> SmPC of [2] of EMA

The concomitant use of EXJADE with potent UGT inducers may result in a decrease in EXJADE efficacy.

Cholestyramine, deferasirox [2] ---> SmPC of [2] of EMA

Cholestyramine significantly reduced the deferasirox exposure in a mechanistic study to determine the degree of enterohepatic recycling

Clozapine, deferasirox [2] ---> SmPC of [2] of EMA

For substances that are predominantly metabolised by CYP1A2 and that have a narrow therapeutic index (e.g. clozapine, tizanidine), the same recommendations apply as for theophylline.

Contraceptives, deferasirox [2] ---> SmPC of [2] of EMA

EXJADE may decrease the efficacy of hormonal contraceptives (see section 4.5).

Corticosteroids, deferasirox [2] ---> SmPC of [2] of EMA

The concomitant administration of deferasirox with substances that have known ulcerogenic potential, such as corticosteroids, may increase the risk of gastrointestinal toxicity

Cyclosporine, deferasirox [2] ---> SmPC of [2] of EMA

Due to a possible decrease in efficacy, caution should be exercised when deferasirox is combined with substances metabolised through CYP3A4

CYP1A2 substrates with narrow therapeutic index, deferasirox [2] ---> SmPC of [2] of EMA

For substances that are predominantly metabolised by CYP1A2 and that have a narrow therapeutic index (e.g. clozapine, tizanidine), the same recommendations apply as for theophylline.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, deferasirox ---> SmPC of [dasabuvir] of EMA

Deferasirox may increase dasabuvir exposures and should be used with caution.

Dasabuvir [1], deferasirox ---> SmPC of [1] of EMA

Deferasirox [1], digoxin ---> SmPC of [1] of EMA

No interaction was observed between deferasirox and digoxin in healthy adult volunteers.

Deferasirox [1], drugs primarily metabolised by CYP1A2 ---> SmPC of [1] of EMA

Concomitant administration of deferasirox as a CYP1A2 inhibitor and the CYP1A2 substrate theophylline resulted in an increase of theophylline AUC. An interaction between deferasirox and other CYP1A2 substrates cannot be excluded.

Deferasirox [1], drugs primarily metabolised by CYP2C8 ---> SmPC of [1] of EMA

Concomitant administration of deferasirox as a moderate CYP2C8 inhibitor, with repaglinide, a CYP2C8 substrate, increased repaglinide AUC and Cmax. An interaction between deferasirox and other CYP2C8 substrates like cannot be excluded.

Deferasirox [1], drugs primarily metabolised by CYP3A4 ---> SmPC of [1] of EMA

Due to a possible decrease in efficacy, caution should be exercised when deferasirox is combined with substances metabolised through CYP3A4

Deferasirox [1], ergotamine ---> SmPC of [1] of EMA

Due to a possible decrease in efficacy, caution should be exercised when deferasirox is combined with substances metabolised through CYP3A4

Deferasirox [1], fertility ---> SmPC of [1] of EMA

No fertility data is available for humans. In animals, no adverse effects on male or female fertility were found (see section 5.3).

Deferasirox [1], foods ---> SmPC of [1] of EMA

EXJADE film-coated tablets may be taken either on an empty stomach or with a light meal, preferably at the same time each day (see sections 4.2 and 5.2).

Deferasirox [1], iron chelators ---> SmPC of [1] of EMA

The safety of deferasirox in combination with other iron chelators has not been established. Therefore, it must not be combined with other iron chelator therapies (see section 4.3).

Deferasirox [1], midazolam ---> SmPC of [1] of EMA

In a healthy volunteer study, the coadministration of EXJADE and midazolam decreased midazolam exposure. Due to a possible decrease in efficacy, caution should be exercised when deferasirox is combined with substances metabolised through CYP3A4

Deferasirox [1], NSAID ---> SmPC of [1] of EMA

Deferasirox [1], oral contraceptives ---> SmPC of [1] of EMA

Due to a possible decrease in efficacy, caution should be exercised when deferasirox is combined with substances metabolised through CYP3A4

Deferasirox [1], paclitaxel ---> SmPC of [1] of EMA

An interaction between deferasirox and other CYP2C8 substrates like paclitaxel cannot be excluded.

Deferasirox [1], phenobarbital ---> SmPC of [1] of EMA

The concomitant use of EXJADE with potent UGT inducers may result in a decrease in EXJADE efficacy.

Deferasirox [1], phenytoin ---> SmPC of [1] of EMA

The concomitant use of EXJADE with potent UGT inducers may result in a decrease in EXJADE efficacy.

Deferasirox [1], pregnancy ---> SmPC of [1] of EMA

As a precaution, it is recommended that EXJADE is not used during pregnancy unless clearly necessary.

Deferasirox [1], rifampicin ---> SmPC of [1] of EMA

The concomitant use of EXJADE with potent UGT inducers may result in a decrease in EXJADE efficacy.

Deferasirox [1], ritonavir ---> SmPC of [1] of EMA

The concomitant use of EXJADE with potent UGT inducers may result in a decrease in EXJADE efficacy.

Deferasirox [1], simvastatine ---> SmPC of [1] of EMA

Due to a possible decrease in efficacy, caution should be exercised when deferasirox is combined with substances metabolised through CYP3A4

Deferasirox [1], strong glucuronidation inductors ---> SmPC of [1] of EMA

The concomitant use of EXJADE with potent UGT inducers may result in a decrease in EXJADE efficacy.

Deferasirox [1], theophylline ---> SmPC of [1] of EMA

Concomitant administration of deferasirox as a CYP1A2 inhibitor and the CYP1A2 substrate theophylline resulted in an increase of theophylline AUC. Therefore, the concomitant use of deferasirox with theophylline is not recommended.

Deferasirox [1], tizanidine ---> SmPC of [1] of EMA

For substances that are predominantly metabolised by CYP1A2 and that have a narrow therapeutic index (e.g. clozapine, tizanidine), the same recommendations apply as for theophylline.

Deferasirox [1], ulcerogenic drugs ---> SmPC of [1] of EMA

The concomitant administration of deferasirox with substances that have known ulcerogenic potential may increase the risk of gastrointestinal toxicity

Deferasirox [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential are recommended to use additional or alternative non-hormonal methods of contraception when using EXJADE.

Deferasirox, repaglinide [2] ---> SmPC of [2] of EMA

Concomitant administration of deferasirox, a moderate inhibitor of CYP2C8 and CYP3A4, with repaglinide, a CYP2C8 substrate, increased repaglinide AUC and Cmax. The concomitant use of deferasirox with repaglinide should be avoided.

Deferasirox, selexipag [2] ---> SmPC of [2] of EMA

Coadministration of selexipag with moderate CYP2C8 inhibitors may increase the exposure to selexipag and its main metabolite. An adjustment of the selexipag dose should be considered in case a moderate CYP2C8 inhibitor is coadministered or discontinued.

Deferasirox, treprostinil [2] ---> SmPC of [2] of EMA

In case a CYP2C8 inhibitor (e.g. gemfibrozil, trimethoprim and deferasirox) is added to or omitted from the patient's treatment after the titration phase, a dose adjustment of treprostinil has to be considered.

CONTRAINDICATIONS of Deferasirox (Exjade)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Combination with other iron chelator therapies as the safety of such combinations has not been established

- Patients with estimated creatinine clearance <60 ml/min.

https://www.ema.europa.eu/en/documents/product-information/exjade-epar-product-information_en.pdf 05/02/2026

Other trade names: Deferasirox Accord, Deferasirox Mylan,

Deferiprone (Ferriprox)

Agranulocytosis, deferiprone [2] ---> SmPC of [2] of EMA

Due to the unknown mechanism of deferiprone-induced neutropenia, patients must not take medicinal products known to be associated with neutropenia or those that can cause agranulocytosis (see section 4.3).

Antacids, deferiprone [2] ---> SmPC of [2] of EMA

The potential exists for interactions between deferiprone and trivalent cation-dependent medicinal products such as aluminium-based antacids. Therefore, it is not recommended to concomitantly ingest aluminium-based antacids and deferiprone.

Breast-feeding, deferiprone [2] ---> SmPC of [2] of EMA

Deferiprone must not be used by breast-feeding mothers. If treatment is unavoidable, breast-feeding must be stopped

Deferiprone [1], fertility ---> SmPC of [1] of EMA

No effects on fertility or early embryonic development were noted in animals (see section 5.3).

Deferiprone [1], men ---> SmPC of [1] of EMA

Men are recommended to use effective contraceptive measures and to not father a child while receiving Ferriprox and for 3 months following completion of treatment.

Deferiprone [1], neutropenia ---> SmPC of [1] of EMA

Deferiprone [1], pregnancy ---> SmPC of [1] of EMA

Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Pregnant women must be advised to immediately stop taking deferiprone (see section 4.3).

Deferiprone [1], trivalent cations ---> SmPC of [1] of EMA

Deferiprone [1], vitamin C ---> SmPC of [1] of EMA

Based on the reported adverse interaction that can occur between deferoxamine and vitamin C, caution should be used when administering deferiprone and vitamin C concurrently.

Deferiprone, women of childbearing potential [2] ---> SmPC of [2] of EMA

Women of childbearing potential are recommended to use effective contraceptive measures and avoid becoming pregnant while being treated with Ferriprox and for 6 months following the completion of treatment.

CONTRAINDICATIONS of Deferiprone (Ferriprox)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- History of recurrent episodes of neutropenia.

- History of agranulocytosis.

- Pregnancy

- Breast-feeding

- Due to the unknown mechanism of deferiprone-induced neutropenia, patients must not take medicinal products known to be associated with neutropenia or those that can cause agranulocytosis

https://www.ema.europa.eu/en/documents/product-information/ferriprox-epar-product-information_en.pdf 13/08/2025

Other trade names: Deferiprone Lipomed,

Deferoxamine

Ability to drive, deferoxamine

Dizziness and other central nervous system disorders or vision and hearing disorders may occur

Ascorbic acid, deferoxamine [2] ---> SmPC of [2] of eMC

Concurrent administration of ascorbic acid with desferrioxamine enhances urinary iron excretion.

Breast-feeding, deferoxamine

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Deferoxamine [1], gallium ---> SmPC of [1] of eMC

Gallium 67 imaging results may be distorted because of the rapid urinary excretion of deferoxamine-bound radiolabel. Discontinuation of deferoxamine 48 hours prior to scintigraphy is advised.

Deferoxamine [1], vitamin C ---> SmPC of [1] of eMC

Concurrent administration of ascorbic acid with desferrioxamine enhances urinary iron excretion.

Deferoxamine, pregnancy

Deferoxamine may only be used during pregnancy after a careful benefit/risk assessment

Deferoxamine, prochlorperazine

Co-administration induces a transient metabolic encephalopathy, characterized by loss of consciousness for 48 to 72 hours.

Deferoxamine, trifluoperazine [2] ---> SmPC of [2] of eMC

Desferrioxamine should not be used in combination with trifluoperazine, since prolonged unconsciousness has occurred after combination with the related prochlorperazine.

Defibrotide (Defitelio)

Ability to drive, defibrotide [2] ---> SmPC of [2] of EMA

Defitelio has no or negligible influence on the ability to drive and use machines. However, patients would not be expected to drive or operate machinery due to the nature of the underlying disease.

Antithrombotics, defibrotide [2] ---> SmPC of [2] of EMA

Defibrotide has a profibrinolytic effect and this may potentially enhance the activity of antithrombotic/fibrinolytic medicinal products. The use of defibrotide with antithrombotic/fibrinolytic medicinal products is not recommended.

Apixaban, defibrotide [2] ---> SmPC of [2] of EMA

The use of defibrotide with antithrombotic/fibrinolytic medicinal products is not recommended. However, if used, in exceptional cases, caution should be exercised by closely monitoring the coagulation parameters (see section 4.4).

Breast-feeding, defibrotide [2] ---> SmPC of [2] of EMA

Considering the nature of the product, a risk to the newborns/infants is not expected. Defitelio may be used during breastfeeding.

Contraceptives, defibrotide [2] ---> SmPC of [2] of EMA

Effective contraception is required for patients and partners of patients during exposure to Defitelio and for one week subsequent to discontinuation.

CYP450, defibrotide [2] ---> SmPC of [2] of EMA

Defibrotide does not inhibit or induce CYP450s (see section 5.2).

Dabigatran, defibrotide [2] ---> SmPC of [2] of EMA

Defibrotide [1], direct Factor Xa inhibitors ---> SmPC of [1] of EMA

Defibrotide [1], direct thrombin inhibitors ---> SmPC of [1] of EMA

Defibrotide [1], fertility ---> SmPC of [1] of EMA

There are no studies investigating the effects of defibrotide on human fertility.

Defibrotide [1], heparin ---> SmPC of [1] of EMA

Defibrotide [1], NSAID ---> SmPC of [1] of EMA

Medicinal products that affect platelet aggregation should be administered with care, under close medical supervision

Defibrotide [1], platelet aggregation inhibitors ---> SmPC of [1] of EMA

Medicinal products that affect platelet aggregation should be administered with care, under close medical supervision

Defibrotide [1], pregnancy ---> SmPC of [1] of EMA

Defitelio should not be used during pregnancy unless the clinical condition of the woman requires treatment with Defitelio.

Defibrotide [1], recombinant t-PA ---> SmPC of [1] of EMA

In a mouse model of thromboembolism, recombinant t-PA potentiated the antithrombotic effect of defibrotide when given intravenously and thus co-administration may present an increased risk of haemorrhage and is contraindicated (see section 4.3).

Defibrotide [1], rivaroxaban ---> SmPC of [1] of EMA

Defibrotide [1], thrombolytics ---> SmPC of [1] of EMA

Defibrotide [1], tissue-type plasminogen activator ---> SmPC of [1] of EMA

Defibrotide [1], warfarin ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Defibrotide (Defitelio)

- Hypersensitivity to defibrotide or to any of the excipients listed in section 6.1

- Concomitant use of thrombolytic therapy (e.g. t-PA)

https://www.ema.europa.eu/en/documents/product-information/defitelio-epar-product-information_en.pdf. 25/10/2023

Deflazacort

ACE inhibitors, deflazacort

Increased risk of changes in blood counts

Acetazolamide, deflazacort

Hypokalaemic effects of acetazolamide are enhanced by corticosteroids.

Aluminium hydroxide, deflazacort

Decreased bioavailability of glucocorticoid in chronic liver desease

Antacids, deflazacort

Antacids may reduce bioavailability of glucocorticoid; leave at least 2 hours between administrations

Antibiotics, deflazacort

It is important to ensure that any anti-infective therapy is effective and it is recommended to monitor patients closely.

Anticholinergics, deflazacort

Additional increase in the intraocular pressure

Anticholinesterase, deflazacort

Anticholinesterase drugs may interact with glucocorticoids and cause severe muscle weakness in patients with myasthenia gravis

Anticholinesterase, glucocorticoids

Anticholinesterase drugs may interact with glucocorticoids and cause severe muscle weakness in patients with myasthenia gravis

Anticoagulants, corticosteroids

Corticosteroids may increase or decrease the effects of anticoagulant drugs

Anticoagulants, deflazacort

Corticosteroids may increase or decrease the effects of anticoagulant drugs

Antidiabetics, deflazacort

The desired effects of hypoglycaemic agents (including insulin) are antagonized by corticosteroids

Antihypertensives, deflazacort

The desired effects of antihypertensives are antagonized by corticosteroids

Aprepitant, deflazacort

A transient moderate increase followed by a mild decrease in exposure of immunosuppressants metabolised by CYP3A4 is expected

Ataluren [1], deflazacort ---> SmPC of [1] of EMA

Coadministration of corticosteroids (deflazacort, prednisone, or prednisolone) with ataluren did not affect the plasma concentrations of ataluren.

Atropine, deflazacort

Additional increase in the intraocular pressure

Barbiturates, deflazacort

The strong CYP3A4 induction may decrease the plasma concentrations of glucocorticoid

Breast-feeding, deflazacort [2] ---> SmPC of [2] of eMC

Corticosteroids are excreted in breast milk. Infants of mothers taking higher doses than 50 mg daily of deflazacort may have a degree of adrenal suppression but the benefits of breast feeding are likely to outweigh any theoretical risk.

Calcitriol, deflazacort

Functional antagonism. The D vitamin analog promotes the calcium absorption and the glucocorticoid inhibits it.

Calcium, deflazacort

Glucocorticoid inhibits the calcium absorption

Carbamazepine, deflazacort

Deflazacort is metabolised in the liver. It is recommended to increase the maintenance dose of deflazacort if drugs which are liver enzyme inducers are co-administered

Carbenoxolone, deflazacort

Hypokalaemic effects of carbenoxolone are enhanced by corticosteroids.

Chloroquine, deflazacort

The co-administration of chloroquine and corticoids may increase the risk of myopathies and cardiomyopathies

Corticosteroids, estrogens ---> SmPC of [deflazacort] of eMC

In patients taking estrogens, corticosteroid requirements may be reduced.

Corticosteroids, muscle relaxants (non-depolarizing) ---> SmPC of [deflazacort] of eMC

In patients treated with systemic corticosteroids, use of non-depolarising muscle relaxants can result in prolonged relaxation and acute myopathy.

Corticosteroids, non-potassium-sparing diuretics ---> SmPC of [deflazacort] of eMC

The hypokalaemic effect of diuretics may be potentiated by corticosteroids

Corticosteroids, thiazides ---> SmPC of [deflazacort] of eMC

Corticosteroids may exacerbate the hypokalaemia associated with thiazide use.

Coumarin anticoagulants, deflazacort

Decreased anticoagulant effect

Cyclosporine, deflazacort

Increased plasma concentration of cyclosporine and the risk of cerebral seizures

CYP3A4 inductors, deflazacort

The CYP3A4 induction may decrease the plasma concentrations of glucocorticoid

CYP3A4 inhibitors, deflazacort

The CYP3A4 inhibition may increase the plasma concentrations of glucocorticoid

Deflazacort [1], estrogens ---> SmPC of [1] of eMC

In patients taking estrogens, corticosteroid requirements may be reduced.

Deflazacort [1], insulin ---> SmPC of [1] of eMC

The desired effects of hypoglycaemic agents (including insulin) are antagonized by corticosteroids

Deflazacort [1], muscle relaxants (non-depolarizing) ---> SmPC of [1] of eMC

In patients treated with systemic corticosteroids, use of non-depolarising muscle relaxants can result in prolonged relaxation and acute myopathy.

Deflazacort [1], non-potassium-sparing diuretics ---> SmPC of [1] of eMC

Corticosteroids may exacerbate the hypokalaemia associated with thiazide use.

Deflazacort [1], oral contraceptives ---> SmPC of [1] of eMC

In patients taking estrogens, corticosteroid requirements may be reduced.

Deflazacort [1], phenobarbital ---> SmPC of [1] of eMC

Phenobarbital enhances the corticosteroid metabolism and its therapeutic effects may be reduced. Therefore it may be necessary to adjust the dose of corticosteroid accordingly

Deflazacort [1], phenytoin ---> SmPC of [1] of eMC

Deflazacort is metabolised in the liver. It is recommended to increase the maintenance dose of deflazacort if drugs which are liver enzyme inducers are co-administered

Deflazacort [1], pregnancy ---> SmPC of [1] of eMC

Deflazacort does cross the placenta. As with all drugs, corticosteroids should only be prescribed when the benefits to the mother and child outweigh the risks.

Deflazacort [1], primidone ---> SmPC of [1] of eMC

Deflazacort is metabolised in the liver. It is recommended to increase the maintenance dose of deflazacort if drugs which are liver enzyme inducers are co-administered

Deflazacort [1], rifampicin ---> SmPC of [1] of eMC

Deflazacort is metabolised in the liver. It is recommended to increase the maintenance dose of deflazacort if drugs which are liver enzyme inducers are co-administered

Deflazacort [1], salicylates ---> SmPC of [1] of eMC

The renal clearance of salicylates is increased by corticosteroids and steroid withdrawal may result in salicylate intoxication.

Deflazacort [1], thiazides ---> SmPC of [1] of eMC

Corticosteroids may exacerbate the hypokalaemia associated with thiazide use.

Deflazacort [1], vaccinations ---> SmPC of [1] of eMC

The antibody response to vaccines may be diminished.

Deflazacort [1], vaccinations with live organism vaccines ---> SmPC of [1] of eMC

Live vaccines should not be given to individuals with impaired responsiveness.

Deflazacort, digital glycosides

Increased cardiac glycoside effect by hypokaliemia

Deflazacort, ephedrine

Increased glucocorticoid metabolism and decreased effect

Deflazacort, glimepiride [2] ---> SmPC of [2] of eMC

Weakening of the blood-glucose-lowering effect and possible hyperglycaemia

Deflazacort, hydantoins

The strong CYP3A4 induction may decrease the plasma concentrations of glucocorticoid

Deflazacort, hydroxychloroquine

The co-administration of hydroxychloroquine and corticoids may increase the risk of myopathies and cardiomyopathies

Deflazacort, indometacin

Increased risk of gastrointestinal haemorrhage

Deflazacort, itraconazol

The strong CYP3A4 inhibition may increase the plasma concentrations of glucocorticoid

Deflazacort, ketoconazole

The strong CYP3A4 inhibition may increase the plasma concentrations of glucocorticoid

Deflazacort, laxatives

Increased potassium elimination

Deflazacort, magnesium hydroxide

Decreased bioavailability of glucocorticoid in chronic liver desease

Deflazacort, mefloquine

Increased risk of myopathies and cardiomyopathies

Deflazacort, natriuretic agents

Increased potassium elimination

Deflazacort, NSAID

Increased risk of gastrointestinal haemorrhage

Deflazacort, praziquantel

Decreased plasma concentration of praziquantel

Deflazacort, protirelin

Reduction of TSH-increase

Deflazacort, somatorelin [2] ---> SmPC of [2] of eMC

High levels of glucocorticoids as well as somatostatin or its analogues may inhibit the growth hormone release.

Deflazacort, somatropin

Decreased effect of somatropin

Deflazacort, strong CYP3A4 inductors

The strong CYP3A4 induction may decrease the plasma concentrations of glucocorticoid

Deflazacort, strong CYP3A4 inhibitors

The strong CYP3A4 inhibition may increase the plasma concentrations of glucocorticoid

Deflazacort, sulfonylureas

Weakening of the blood-glucose-lowering effect and, thus raised blood glucose levels may occur

Deflazacort, tipranavir

Increased plasma levels of glucocorticoid metabolized by CYP3A4 with risk of systemic corticosteroid effects. Concomitant use not recommended

Deflazacort, tipranavir/ritonavir

Increased plasma levels of glucocorticoid metabolized by CYP3A4 with risk of systemic corticosteroid effects. Concomitant use not recommended

Deflazacort, vitamin D

Functional antagonism. The D vitamin analog promotes the calcium absorption and the glucocorticoid inhibits it.

Deflazacort, xanthines

Hypokalaemic effects of xanthines are enhanced by corticosteroids.

Glucocorticoids, loop diuretics ---> SmPC of [deflazacort] of eMC

Hypokalaemic effects of loop diuretics are enhanced by corticosteroids.

Glucocorticoids, phenytoin ---> SmPC of [deflazacort] of eMC

Phenytoin enhances the corticosteroid metabolism and its therapeutic effects may be reduced. Therefore it may be necessary to adjust the dose of corticosteroid accordingly

Glucocorticoids, salicylates ---> SmPC of [deflazacort] of eMC

The renal clearance of salicylates is increased by corticosteroids and steroid withdrawal may result in salicylate intoxication.

Glucocorticoids, thiazides ---> SmPC of [deflazacort] of eMC

Corticosteroids may exacerbate the hypokalaemia associated with thiazide use.

Glucocorticoids, vaccinations with live organism vaccines

Increased toxicity of vaccine due to the immunosuppressive effect of corticosteroid

CONTRAINDICATIONS of Deflazacort

- Systemic infection unless specific anti-infective therapy is employed.

- Hypersensitivity to deflazacort or any of the ingredients.

- Patients receiving live virus immunisation.

http://www.medicines.org.uk/emc/

Degarelix (Firmagon)

Ability to drive, degarelix [2] ---> SmPC of [2] of EMA

Fatigue and dizziness are common adverse reactions that might influence the ability to drive and use machines.

Amiodarone, degarelix [2] ---> SmPC of [2] of EMA

The combination of degarelix with medicinal products known to prolong the QTc interval or medicinal products able to induce torsades de pointes should be carefully evaluated

Breast-feeding, degarelix [2] ---> SmPC of [2] of EMA

There is no relevant indication for use in women

Cisapride, degarelix [2] ---> SmPC of [2] of EMA

The combination of degarelix with medicinal products known to prolong the QTc interval or medicinal products able to induce torsades de pointes should be carefully evaluated

Class IA antiarrhythmic agents, degarelix [2] ---> SmPC of [2] of EMA

The combination of degarelix with medicinal products known to prolong the QTc interval or medicinal products able to induce torsades de pointes should be carefully evaluated

Class III antiarrhythmic agents, degarelix [2] ---> SmPC of [2] of EMA

The combination of degarelix with medicinal products known to prolong the QTc interval or medicinal products able to induce torsades de pointes should be carefully evaluated

Degarelix [1], disopyramide ---> SmPC of [1] of EMA

The combination of degarelix with medicinal products known to prolong the QTc interval or medicinal products able to induce torsades de pointes should be carefully evaluated

Degarelix [1], dofetilide ---> SmPC of [1] of EMA

The combination of degarelix with medicinal products known to prolong the QTc interval or medicinal products able to induce torsades de pointes should be carefully evaluated

Degarelix [1], fertility ---> SmPC of [1] of EMA

FIRMAGON may inhibit male fertility as long as the testosterone is suppressed.

Degarelix [1], ibutilide ---> SmPC of [1] of EMA

The combination of degarelix with medicinal products known to prolong the QTc interval or medicinal products able to induce torsades de pointes should be carefully evaluated

Degarelix [1], methadone ---> SmPC of [1] of EMA

The combination of degarelix with medicinal products known to prolong the QTc interval or medicinal products able to induce torsades de pointes should be carefully evaluated

Degarelix [1], moxifloxacin ---> SmPC of [1] of EMA

The combination of degarelix with medicinal products known to prolong the QTc interval or medicinal products able to induce torsades de pointes should be carefully evaluated

Degarelix [1], neuroleptics ---> SmPC of [1] of EMA

The combination of degarelix with medicinal products known to prolong the QTc interval or medicinal products able to induce torsades de pointes should be carefully evaluated

Degarelix [1], pregnancy ---> SmPC of [1] of EMA

There is no relevant indication for use in women

Degarelix [1], QT interval prolonging drugs ---> SmPC of [1] of EMA

The combination of degarelix with medicinal products known to prolong the QTc interval or medicinal products able to induce torsades de pointes should be carefully evaluated

Degarelix [1], quinidine ---> SmPC of [1] of EMA

The combination of degarelix with medicinal products known to prolong the QTc interval or medicinal products able to induce torsades de pointes should be carefully evaluated

Degarelix [1], sotalol ---> SmPC of [1] of EMA

The combination of degarelix with medicinal products known to prolong the QTc interval or medicinal products able to induce torsades de pointes should be carefully evaluated

Degarelix [1], substrate for the CYP450 system ---> SmPC of [1] of EMA

Degarelix is not a substrate for the human CYP450 system and has not been shown to induce/inhibit CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4/5 to any great extent in vitro. Clinically significant pharmacokinetic interactions are unlikely.

Degarelix [1], torsades de pointes inducing drugs ---> SmPC of [1] of EMA

The combination of degarelix with medicinal products known to prolong the QTc interval or medicinal products able to induce torsades de pointes should be carefully evaluated

CONTRAINDICATIONS of Degarelix (Firmagon)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/firmagon-epar-product-information_en.pdf 30/03/2022

Delafloxacin (Quofenix)

Ability to drive, delafloxacin [2] ---> SmPC of [2] of EMA

Some adverse drug reactions (e.g. dizziness, headache, visual disorders) may impair the patient's ability to concentrate and react

Antacids, delafloxacin [2] ---> SmPC of [2] of EMA

Oral administration of delafloxacin with antacids containing aluminium or magnesium may substantially interfere with the absorption of delafloxacin. Delafloxacin should be taken at least 2 hours before or 6 hours after this agent.

Breast-feeding, delafloxacin [2] ---> SmPC of [2] of EMA

Breast-feeding is contraindicated during treatment with delafloxacin.

Delafloxacin [1], didanosine ---> SmPC of [1] of EMA

Oral administration of delafloxacin with didanosine buffered tablets may substantially interfere with the absorption of delafloxacin. Delafloxacin should be taken at least 2 hours before or 6 hours after this didanosine.

Delafloxacin [1], divalent cations ---> SmPC of [1] of EMA

Oral dosing of delafloxacin with this agent may substantially interfere with the absorption of delafloxacin, resulting in systemic levels considerably lower than desired. Delafloxacin should be taken at least 2 hours before or 6 hours after this agent.

Delafloxacin [1], fertility ---> SmPC of [1] of EMA

The effects of delafloxacin on fertility in humans have not been studied. Nonclinical studies conducted with delafloxacin in rats do not indicate harmful effects with respect to fertility or reproductive performance (see section 5.3).

Delafloxacin [1], interactions ---> SmPC of [1] of EMA

There are no available data concerning specific effects of other medicinal products on delafloxacin. Known fluoroquinolones-associated possible interactions shall be considered.

Delafloxacin [1], iron ---> SmPC of [1] of EMA

Delafloxacin [1], magnesium ---> SmPC of [1] of EMA

Delafloxacin should not be co-administered with any solution containing multivalent cations, e.g. magnesium, through the same intravenous line

Delafloxacin [1], pregnancy ---> SmPC of [1] of EMA

Delafloxacin is contraindicated during pregnancy and in women of childbearing potential not using contraception

Delafloxacin [1], sucralfate ---> SmPC of [1] of EMA

Delafloxacin [1], trivalent cations ---> SmPC of [1] of EMA

Delafloxacin [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential have to use effective contraception during treatment with delafloxacin.

Delafloxacin [1], zinc ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Delafloxacin (Quofenix)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Hypersensitivity to any fluoroquinolone or quinolone antibacterial medicinal product.

- Previous history of tendon disorders related to fluoroquinolone administration.

- Pregnancy, women of childbearing potential not using contraception and breast-feeding

- Children or growing adolescents below 18 years of age

https://www.ema.europa.eu/en/documents/product-information/quofenix-epar-product-information_en.pdf 05/03/2025

Delamanid (Deltyba)

Ability to drive, delamanid [2] ---> SmPC of [2] of EMA

Patients should be advised not to drive or use machines if they experience any adverse reaction with a potential impact on the ability to perform these activities (e.g. headache and tremor are very common).

Amiodarone, delamanid [2] ---> SmPC of [2] of EMA

Treatment with delamanid should not be initiated in patients with risk factors like taking medicinal products that are known to prolong the QTc interval, unless the possible benefit is considered to outweigh the potential risks.

Anti-HIV medicinal products, delamanid [2] ---> SmPC of [2] of EMA

Delamanid exposure remained unchanged (< 25% difference) with anti-HIV medicinal products tenofovir disoproxil and efavirenz but was slightly increased with the combination anti-HIV medicinal products containing lopinavir/ritonavir.

Arsenic trioxide, delamanid [2] ---> SmPC of [2] of EMA

Astemizole, delamanid [2] ---> SmPC of [2] of EMA

Azole antifungals, delamanid [2] ---> SmPC of [2] of EMA

Bepridil, delamanid [2] ---> SmPC of [2] of EMA

Breast-feeding, delamanid [2] ---> SmPC of [2] of EMA

A risk to the newborns/infants cannot be excluded. It is recommended that women should not breastfeed during treatment with Deltyba.

Carbamazepine, delamanid [2] ---> SmPC of [2] of EMA

Taking medicinal products that are strong inducers of CYP3A4 (e.g. carbamazepine) with delamanid is contraindicated

Chlorpromazine, delamanid [2] ---> SmPC of [2] of EMA

Cisapride, delamanid [2] ---> SmPC of [2] of EMA

Clarithromycin, delamanid [2] ---> SmPC of [2] of EMA

CYP450 isozymes, delamanid [2] ---> SmPC of [2] of EMA

In-vitro studies showed that delamanid did not inhibit CYP450 isozymes. However, there is a potential for delamanid to have an effect on these transporters.

Delamanid [1], diphemanil ---> SmPC of [1] of EMA

Delamanid [1], disopyramide ---> SmPC of [1] of EMA

Delamanid [1], dofetilide ---> SmPC of [1] of EMA

Delamanid [1], domperidone ---> SmPC of [1] of EMA

Delamanid [1], droperidol ---> SmPC of [1] of EMA

Delamanid [1], efavirenz ---> SmPC of [1] of EMA

No clinically relevant reduction in delamanid exposure was observed with the weak inducer efavirenz when administered at a dose of 600 mg daily for 10 days in combination with delamanid 100 mg twice daily.

Delamanid [1], electrolyte imbalance ---> SmPC of [1] of EMA

Treatment with delamanid should not be initiated in patients with risk factors like electrolyte disturbances, particularly hypokalaemia, hypocalcaemia or hypomagnesaemia unless the possible benefit is considered to outweigh the potential risks.

Delamanid [1], erythromycin ---> SmPC of [1] of EMA

Delamanid [1], ethambutol ---> SmPC of [1] of EMA

Co-administration with delamanid significantly increased steady state plasma concentrations of ethambutol by approximately 25%, the clinical relevance is unknown.

Delamanid [1], fertility ---> SmPC of [1] of EMA

Deltyba had no effect on male or female fertility in animals (see section 5.3). There are no clinical data on the effects of delamanid on fertility in humans.

Delamanid [1], haloperidol ---> SmPC of [1] of EMA

Delamanid [1], hydroquinidine ---> SmPC of [1] of EMA

Delamanid [1], hypocalcemia ---> SmPC of [1] of EMA

Delamanid [1], hypokalemia ---> SmPC of [1] of EMA

Delamanid [1], hypomagnesemia ---> SmPC of [1] of EMA

Delamanid [1], ibutilide ---> SmPC of [1] of EMA

Delamanid [1], lopinavir/ritonavir ---> SmPC of [1] of EMA

Co-administration of delamanid with a strong inhibitor of CYP3A (lopinavir/ritonavir) was associated with 30% higher exposure to the metabolite M-6705, which has been associated with QTc prolongation.

Delamanid [1], mesoridazine ---> SmPC of [1] of EMA

Delamanid [1], methadone ---> SmPC of [1] of EMA

Delamanid [1], mizolastine ---> SmPC of [1] of EMA

Delamanid [1], moxifloxacin ---> SmPC of [1] of EMA

Co-administration of moxifloxacin and delamanid in MDR-TB patients has not been studied. Moxifloxacin is not recommended for use in patients treated with delamanid.

Delamanid [1], pentamidine ---> SmPC of [1] of EMA

Delamanid [1], phenothiazines ---> SmPC of [1] of EMA

Delamanid [1], pimozide ---> SmPC of [1] of EMA

Delamanid [1], pregnancy ---> SmPC of [1] of EMA

Studies in animals have shown reproductive toxicity (see section 5.3). Deltyba is not recommended during pregnancy and in women of childbearing potential not using contraception.

Delamanid [1], probucol ---> SmPC of [1] of EMA

Delamanid [1], procainamide ---> SmPC of [1] of EMA

Delamanid [1], QT interval prolonging drugs ---> SmPC of [1] of EMA

Care must be taken in using delamanid in patients already receiving medicinal products associated with QT prolongation (see section 4.4).

Delamanid [1], quinidine ---> SmPC of [1] of EMA

Delamanid [1], quinolones ---> SmPC of [1] of EMA

All QTcF prolongations above 60 ms were associated with concomitant fluoroquinolone use

Delamanid [1], rifampicin ---> SmPC of [1] of EMA

Clinical drug interactions studies in healthy subjects indicated a reduced exposure to delamanid, of up to 45% following 15 days of co-administration of the strong inducer of CYP3A4 (rifampicin 300 mg daily) with delamanid (200 mg daily).

Delamanid [1], rifampicin/isoniazid/pyrazinamide ---> SmPC of [1] of EMA

Exposure of concomitant anti-TB drugs (rifampicin [R]/ isoniazid [H]/ pyrazinamide [Z]) was not affected.

Delamanid [1], saquinavir ---> SmPC of [1] of EMA

Delamanid [1], sertindole ---> SmPC of [1] of EMA

Delamanid [1], sotalol ---> SmPC of [1] of EMA

Delamanid [1], sparfloxacin ---> SmPC of [1] of EMA

Delamanid [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Taking medicinal products that are strong inducers of CYP3A4 (e.g. carbamazepine) with delamanid is contraindicated

Delamanid [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Delamanid [1], sultopride ---> SmPC of [1] of EMA

Delamanid [1], terfenadine ---> SmPC of [1] of EMA

Delamanid [1], thioridazine ---> SmPC of [1] of EMA

Delamanid [1], transporters ---> SmPC of [1] of EMA

In-vitro studies showed that delamanid and metabolites did not have any effect on the transporters MDR1(pgp), BCRP, OATP1, OATP3, OCT1, OCT2, OATP1B1, OATP1B3 and BSEP, at concentrations of approximately 5 to 20 fold greater than the Cmax at steady state

Delamanid [1], vinca alkaloids ---> SmPC of [1] of EMA

Delamanid, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Due to the risk of QTc prolongation associated with DM-6705, if coadministration is considered necessary, very frequent ECG monitoring throughout the full delamanid treatment period is recommended

Delamanid, ritonavir [2] ---> SmPC of [2] of EMA

Co-administration of delamanid with a strong inhibitor of CYP3A (ritonavir) may increase exposure to delamanid metabolite, which has been associated with QTc prolongation.

CONTRAINDICATIONS of Delamanid (Deltyba)

- Hypersensitivity to the active substance or to any of the excipients

- Serum albumin < 2.8 g/dL (see section 4.4 regarding use in patients with serum albumin ≥ 2.8 g/dL)

- Taking medicinal products that are strong inducers of CYP3A4 (e.g. carbamazepine).

https://www.ema.europa.eu/en/documents/product-information/deltyba-epar-product-information_en.pdf 29/02/2024

Delapril

Ability to drive, delapril

As with other antihypertensives, the ability to drive and use machines may be reduced

Alcohol, delapril

Alcohol increases the hypotensive effect

Allopurinol, delapril [2] ---> SmPC of [2] of eMC

Concomitant administration of allopurinol with ACE inhibitors may lead to an increased risk for leucopenia especially when the latter are used at higher than currently recommended doses.

Amiloride, delapril

Concomitant administration of potassium-sparing diuretics or potassium salts may increase the risk of hypercaliemia

Anaesthetics, delapril

Concomitant use of certain anaesthetic medicinal products with ACE inhibitors may result in further reduction of blood pressure

Antacids, delapril

Antacids induce decreased bioavailability of ACE inhibitors.

Antihypertensives, delapril [2] ---> SmPC of [2] of EMA

The co-administration may enhance the hypotensive effect

Breast-feeding, delapril

Delapril is contraindicated during breastfeeding

Corticosteroids, delapril [2] ---> SmPC of [2] of eMC

Concomitant administration of systemic corticosteroids with ACE inhibitors may lead to an increased risk for leucopenia.

Cytostatics, delapril [2] ---> SmPC of [2] of eMC

Concomitant administration of cytostatics with ACE inhibitors may lead to an increased risk for leucopenia especially when the latter are used at higher than currently recommended doses.

Delapril [1], diuretics ---> SmPC of [1] of eMC

Excessive reductions in blood pressure, especially in patients in whom diuretic therapy was recently instituted, have been reported with ACE inhibitors.

Delapril [1], insulin ---> SmPC of [1] of eMC

Concomitant treatment with ACE inhibitors and antidiabetic agents may cause a pronounced hypoglycaemic effect with the risk of hypoglycaemia.

Delapril [1], neuroleptics ---> SmPC of [1] of eMC

Concomitant use of antipsychotics with ACE inhibitors may result in further reduction of blood pressure

Delapril [1], oral antidiabetics ---> SmPC of [1] of eMC

Concomitant treatment with ACE inhibitors and antidiabetic agents may cause a pronounced hypoglycaemic effect with the risk of hypoglycaemia.

Delapril [1], potassium ---> SmPC of [1] of eMC

Concomitant administration of potassium-sparing diuretics or potassium salts may increase the risk of hypercaliemia

Delapril [1], procainamide ---> SmPC of [1] of eMC

Concomitant administration of procainamide with ACE inhibitors may lead to an increased risk for leucopenia especially when the latter are used at higher than currently recommended doses.

Delapril [1], sympathomimetics ---> SmPC of [1] of eMC

Sympathomimetics may reduce the antihypertensive effects of ACE inhibitors.

Delapril, hyperkalemia

Increased risk of hyperkalemia, particularly in renal failure

Delapril, immunosuppressives

Concomitant administration of immunosuppressive agents with ACE inhibitors may lead to an increased risk for leucopenia especially when the latter are used at higher than currently recommended doses.

Delapril, lithium

Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors.

Delapril, NSAID

The co-administration of ACE inhibitors with long-term NSAIDs may decrease the antihypertensive effect, increase the risk of renal failure and cause hypercaliemia.

Delapril, potassium-sparing diuretics

Concomitant administration of potassium-sparing diuretics or potassium salts may increase the risk of hypercaliemia

Delapril, pregnancy

The use of ACE inhibitors is not recommended during the first trimester of pregnancy. The use of ACE inhibitors is contra-indicated during the 2nd and 3rd trimester of pregnancy

Delapril, thiazides

Delapril treatment may reduce the potassium loss caused by thiazide diuretics

Delapril, triamterene

Concomitant administration of potassium-sparing diuretics or potassium salts may increase the risk of hypercaliemia

Delapril, tricyclic antidepressant

Concomitant use of tricyclic antidepressants with ACE inhibitors may result in further reduction of blood pressure

Dengue tetravalent vaccine (Dengvaxia)

Ability to drive, dengue tetravalent vaccine [2] ---> SmPC of [2] of EMA

Dengvaxia has minor influence on the ability to drive and use machines.

Blood products, dengue tetravalent vaccine [2] ---> SmPC of [2] of EMA

It is recommended to wait for at least 6 weeks, and preferably for 3 months, following the end of treatment before administering Dengvaxia, in order to avoid neutralization of the attenuated viruses contained in the vaccine.

Breast-feeding, dengue tetravalent vaccine [2] ---> SmPC of [2] of EMA

Considering that Dengvaxia is a live attenuated vaccine and that there is very limited experience from post marketing data with Dengvaxia in lactating women, the vaccine is contraindicated during lactation

Chemotherapy, dengue tetravalent vaccine [2] ---> SmPC of [2] of EMA

Dengvaxia should not be administered to subjects receiving immunosuppressive therapies such as chemotherapy or high doses of systemic corticosteroids within 4 weeks prior to vaccination

Corticosteroids, dengue tetravalent vaccine [2] ---> SmPC of [2] of EMA

Dengvaxia should not be administered to subjects receiving immunosuppressive therapies such as chemotherapy or high doses of systemic corticosteroids within 4 weeks prior to vaccination

Dengue tetravalent vaccine [1], fertility ---> SmPC of [1] of EMA

No specific studies have been performed on fertility. Animal studies did not indicate any harmful effects with respect to female fertility

Dengue tetravalent vaccine [1], immunoglobulins ---> SmPC of [1] of EMA

Dengue tetravalent vaccine [1], immunosuppressives ---> SmPC of [1] of EMA

Dengvaxia should not be administered to subjects receiving immunosuppressive therapies such as chemotherapy or high doses of systemic corticosteroids within 4 weeks prior to vaccination (see section 4.3).

Dengue tetravalent vaccine [1], pregnancy ---> SmPC of [1] of EMA

Dengvaxia is a live attenuated vaccine, therefore Dengvaxia is contraindicated during pregnancy

Dengue tetravalent vaccine [1], vaccinations ---> SmPC of [1] of EMA

If Dengvaxia is to be given at the same time as another injectable vaccine, the vaccines should always be administered at different injection sites.

Dengue tetravalent vaccine [1], women of childbearing potential ---> SmPC of [1] of EMA

As with other live attenuated vaccines, women of childbearing potential have to use effective contraception during at least one month after each dose.

CONTRAINDICATIONS of Dengue tetravalent vaccine (Dengvaxia)

- Hypersensitivity to the active substance, to any of the excipients listed in section 6.1, or after prior administration of Dengvaxia or a vaccine containing the same components.

- Individuals with congenital or acquired cell-mediated immune deficiency, including immunosuppressive therapies such as chemotherapy or high doses of systemic corticosteroids (e.g. 20 mg or 2 mg/kg of prednisone for 2 weeks or more) within 4 weeks prior to vaccination.

- Individuals with symptomatic HIV infection or with asymptomatic HIV infection when accompanied by evidence of impaired immune function.

- Pregnant women (see section 4.6).

- Breast-feeding women (see section 4.6).

https://www.ema.europa.eu/en/documents/product-information/dengvaxia-epar-product-information_en.pdf 04/12/2025 (withdrawn)

Dengue tetravalent vaccine (Qdenga)

Ability to drive, Dengue tetravalent vaccine [2] ---> SmPC of [2] of EMA

Qdenga has minor influence on the ability to drive and use machines.

Blood products, Dengue tetravalent vaccine [2] ---> SmPC of [2] of EMA

For patients receiving treatment with immunoglobulins or blood products containing immunoglobulins, such as blood or plasma, it is recommended to wait for at least 6 weeks, and preferably for 3 months, following the end of treatment

Breast-feeding, Dengue tetravalent vaccine [2] ---> SmPC of [2] of EMA

It is unknown whether Qdenga is excreted in human milk. A risk to the newborns/infants cannot be excluded. Qdenga is contraindicated during breast-feeding (see section 4.3).

Corticosteroids, Dengue tetravalent vaccine [2] ---> SmPC of [2] of EMA

Qdenga should not be administered to subjects receiving immunosuppressive therapies such as chemotherapy or high doses of systemic corticosteroids within 4 weeks prior to vaccination

Dengue tetravalent vaccine [1], immunoglobulins ---> SmPC of [1] of EMA

Dengue tetravalent vaccine [1], immunosuppressives ---> SmPC of [1] of EMA

Qdenga should not be administered to subjects receiving immunosuppressive therapies such as chemotherapy or high doses of systemic corticosteroids within 4 weeks prior to vaccination

Dengue tetravalent vaccine [1], pregnancy ---> SmPC of [1] of EMA

Qdenga is a live attenuated vaccine, therefore Qdenga is contraindicated during pregnancy

Dengue tetravalent vaccine [1], vaccinations ---> SmPC of [1] of EMA

Qdenga may be administered concomitantly with an hepatitis A vaccine. Coadministration has been studied in adults.

Dengue tetravalent vaccine [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should avoid pregnancy for at least one month following vaccination. Women who intend to become pregnant should be advised to delay vaccination (see sections 4.4 and 4.3).

Dengue tetravalent vaccine [1], yellow fever vaccine ---> SmPC of [1] of EMA

Qdenga may be administered concomitantly with a yellow fever vaccine.

CONTRAINDICATIONS of Dengue tetravalent vaccine (Qdenga)

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1 or hypersensitivity to a previous dose of Qdenga.

- Individuals with congenital or acquired immune deficiency, including immunosuppressive therapies such as chemotherapy or high doses of systemic corticosteroids (e.g. 20 mg/day or 2 mg/kg body weight/day of prednisone for 2 weeks or more) within 4 weeks prior to vaccination, as with other live attenuated vaccines.

- Individuals with symptomatic HIV infection or with asymptomatic HIV infection when accompanied by evidence of impaired immune function.

- Pregnant women (see section 4.6).

- Breast-feeding women (see section 4.6).

https://www.ema.europa.eu/en/documents/product-information/qdenga-epar-product-information_en.pdf 19/08/2025

Delgocitinib (Anzupgo)

Breast-feeding, delgocitinib [2] ---> SmPC of [2] of EMA

As a precautionary measure, care should be taken to avoid direct skin contact when taking care of an infant immediately after applying Anzupgo to the hands and/or wrists.

Delgocitinib [1], fertility ---> SmPC of [1] of EMA

No human data on the effect of delgocitinib on fertility are available. Based on findings in female rats, oral administration of delgocitinib resulted in reduced fertility at exposures considered sufficiently in excess of the human exposure

Delgocitinib [1], males ---> SmPC of [1] of EMA

Animal studies did not indicate effects with respect to fertility in males.

Delgocitinib [1], medicinal products ---> SmPC of [1] of EMA

Delgocitinib has not been evaluated in combination with other topical medicinal products and coapplication on the same skin area is not recommended.

Delgocitinib [1], pregnancy ---> SmPC of [1] of EMA

As a precautionary measure, it is preferable to avoid the use of Anzupgo during pregnancy.

CONTRAINDICATIONS of Delgocitinib (Anzupgo)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/anzupgo-epar-product-information_en.pdf 18/06/2025

Denosumab (Xgeva)

Biphosphonates, denosumab [2] ---> SmPC of [2] of EMA

There were no clinically-relevant alterations in trough serum concentration and pharmacodynamics of denosumab by concomitant chemotherapy and/or hormone therapy or by previous intravenous bisphosphonate exposure.

Breast-feeding, denosumab [2] ---> SmPC of [2] of EMA

A decision must be made on whether to abstain from breast-feeding or to abstain from XGEVA therapy taking into account the benefit of breast-feeding to the newborn/infant and the benefit of therapy for the woman.

Denosumab [1], fertility ---> SmPC of [1] of EMA

No data are available on the effect of denosumab on human fertility. Animal studies do not indicate direct or indirect harmful effects with respect to fertility (see section 5.3).

Denosumab [1], pregnancy ---> SmPC of [1] of EMA

XGEVA is not recommended for use in pregnant women and women of childbearing potential not using contraception.

Denosumab [1], pregnancy ---> SmPC of [1] of EMA

Women should be advised not to become pregnant during and for at least 5 months after treatment with XGEVA.

Denosumab [1], vitamin D ---> SmPC of [1] of EMA

Supplementation with calcium and vitamin D is required in all patients unless hypercalcaemia is present (see section 4.2).

Denosumab, etelcalcetide [2] ---> SmPC of [2] of EMA

Concurrent administration of other medicinal products known to reduce serum calcium (e.g. cinacalcet and denosumab) and etelcalcetide may result in an increased risk of hypocalcaemia (see section 4.4).

Denosumab, imlifidase [2] ---> SmPC of [2] of EMA

Recommended time interval after administration of 0.25 mg/kg imlifidase: 4 days

Denosumab, palopegteriparatide [2] ---> SmPC of [2] of EMA

Other medicinal products can exert effects on serum calcium and may alter the therapeutic response to Yorvipath. Patients should be monitored for changes in serum calcium when treated concomitantly with these medicinal products.

CONTRAINDICATIONS of Denosumab (Xgeva)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Severe, untreated hypocalcaemia

- Unhealed lesions from dental or oral surgery.

https://www.ema.europa.eu/en/documents/product-information/xgeva-epar-product-information_en.pdf 29/07/2025

Other trade names: Bomyntra, Conexxence, Evfraxy, Jubbonti, Jubereq, Junod, Obodence, Osenvelt, Osvyrti, Prolia, Stoboclo, Xbryk, Vevzuo, Wyost, Yaxwer,

Depreotide (NeoSpect)

Breast-feeding, depreotide [2] ---> SmPC of [2] of EMA

Depreotide is contraindicated during breast-feeding

Depreotide [1], pregnancy ---> SmPC of [1] of EMA

Depreotide is contraindicated in pregnancy

CONTRAINDICATIONS of Depreotide (NeoSpect)

- History of hypersensitivity reaction to depreotide, any of the excipients of NeoSpect or sodium pertechnetate (99mTc) solution for injection.

- Pregnancy and lactation.

https://www.ema.europa.eu/en/documents/product-information/neospect-epar-product-information_en.pdf 18/11/2010 (withdrawn)

Dequalinium

Breast-feeding, dequalinium [2] ---> SmPC of [2] of eMC

The safety of this product during lactation has not been established, but it is not considered to constitute a hazard.

Dequalinium [1], pregnancy ---> SmPC of [1] of eMC

The safety of this product during pregnancy has not been established, but it is not considered to constitute a hazard.

Dequalinium, soap

Decreased antimicrobial activity of dequalinium

Dequalinium, spermicide

Decreased antimicrobial activity of dequalinium

Dequalinium, vaginal douche

Decreased antimicrobial activity of dequalinium

CONTRAINDICATIONS of Dequalinium

Hypersensitivity to any of the ingredients.

http://www.medicines.org.uk/emc/

Desflurane

Ability to drive, desflurane

Patients should be advised that the ability to perform tasks such as driving or operation of machinery may be impaired after general anaesthesia, and it is advisable to avoid such tasks for a period of 24 hours.

ACE inhibitors, desflurane

Desflurane may potentiate the hypotensive effect when is administered with other antihypertensive drugs

Antihypertensives, desflurane

Desflurane may potentiate the hypotensive effect when is administered with other antihypertensive drugs

Benzodiazepines, desflurane

Patients receiving benzodiazepines showed a marked reduction in the anaesthetic requirements or MAC.

Betablockers, desflurane

Desflurane may potentiate the hypotensive effect when is administered with other antihypertensive drugs

Breast-feeding, desflurane

There are no adequate data from the use of desflurane in lactating women, therefore desflurane is not indicated for use during lactation

CNS depressants, desflurane

The co-administration of anesthetic agents with CNS depressants may have synergistic effects

Desflurane, esketamine

Enhancement of anesthetic effect

Desflurane, IMAOs

Desflurane may potentiate the hypotensive effect when is administered with other antihypertensive drugs

Desflurane, muscle relaxants

Commonly used muscle relaxants are potentiated by desflurane.

Desflurane, neuroleptics

Desflurane may potentiate the hypotensive effect when is administered with other antihypertensive drugs

Desflurane, nitrous oxide

The MAC for desflurane is reduced by concomitant N2O administration.

Desflurane, opiates

Patients receiving opioids showed a marked reduction in the anaesthetic requirements or MAC.

Desflurane, pregnancy

There are no adequate data from the use of desflurane in pregnant women, therefore desflurane is not indicated for use during pregnancy

Desflurane, sedatives

Patients receiving sedative drugs showed a marked reduction in the anaesthetic requirements or MAC.

Desflurane, suxamethonium [2] ---> SmPC of [2] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Desflurane, tricyclic antidepressant

Desflurane may potentiate the hypotensive effect when is administered with other antihypertensive drugs

A disintegrin and metalloproteinase (Adzynma)

A disintegrin and metalloproteinase [1], administration ---> SmPC of [1] of EMA

For intravenous use after reconstitution only.

A disintegrin and metalloproteinase [1], breast-feeding ---> SmPC of [1] of EMA

The decision either to discontinue breast-feeding or discontinue ADZYNMA should take into account the importance of this medicinal product to the mother.

A disintegrin and metalloproteinase [1], drive ---> SmPC of [1] of EMA

Recombinant ADAMTS13 may have a minor influence on the ability to drive and use machines. Dizziness and somnolence may occur following the administration of ADZYNMA (see section 4.8).

A disintegrin and metalloproteinase [1], fertility ---> SmPC of [1] of EMA

No human data are available on the effects of rADAMTS13 on male and female fertility. Animal data do not indicate direct or indirect harmful effects with respect to male or female fertility (see section 5.3).

A disintegrin and metalloproteinase [1], pregnancy ---> SmPC of [1] of EMA

The use of ADZYNMA during pregnancy may only be considered after a thorough individual risk benefit analysis by the treating physician before and during treatment.

CONTRAINDICATIONS of A disintegrin and metalloproteinase (Adzynma)

- Life-threatening hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/adzynma-epar-product-information_en.pdf 07/08/2024

Desirudin (Revasc)

Abciximab, desirudin [2] ---> SmPC of [2] of EMA

Desirudin should be used with caution in conjunction with medicinal products which affect platelet function

Acetylsalicylic acid, desirudin [2] ---> SmPC of [2] of EMA

Desirudin should be used with caution in conjunction with medicinal products which affect platelet function

Apixaban [1], desirudin ---> SmPC of [1] of EMA

Due to an increased bleeding risk, concomitant treatment of apixaban with any other anticoagulants is contraindicated

Breast-feeding, desirudin [2] ---> SmPC of [2] of EMA

It is not known whether desirudin is excreted in human milk. However, lactating mothers should be advised to avoid breast feeding or alternative medicinal products used.

Clopidogrel, desirudin [2] ---> SmPC of [2] of EMA

Desirudin should be used with caution in conjunction with medicinal products which affect platelet function

Dabigatran etexilate [1], desirudin ---> SmPC of [1] of EMA

The co-administration may increase the risk of bleeding

Dabigatran, desirudin ---> SmPC of [dabigatran etexilate] of EMA

The co-administration may increase the risk of bleeding

Desirudin [1], dextran ---> SmPC of [1] of EMA

During prophylaxis, concomitant use of medicinal products containing heparins and dextrans is not recommended. The effects of desirudin and unfractionated heparins on prolongation of aPTT have been shown to be additive (see section 4.4).

Desirudin [1], eptifibatide ---> SmPC of [1] of EMA

Desirudin should be used with caution in conjunction with medicinal products which affect platelet function

Desirudin [1], GP IIb/IIIa inhibitors ---> SmPC of [1] of EMA

Desirudin should be used with caution in conjunction with medicinal products which affect platelet function

Desirudin [1], heparins ---> SmPC of [1] of EMA

Desirudin [1], iloprost ---> SmPC of [1] of EMA

Desirudin should be used with caution in conjunction with medicinal products which affect platelet function

Desirudin [1], medicinal products ---> SmPC of [1] of EMA

Any agent which may enhance the risk of haemorrhage should be discontinued prior to initiation of desirudin therapy. If co-administration cannot be avoided, close clinical and laboratory monitoring should be conducted (see section 4.4).

Desirudin [1], NSAID ---> SmPC of [1] of EMA

Desirudin should be used with caution in conjunction with medicinal products which affect platelet function

Desirudin [1], oral anticoagulants ---> SmPC of [1] of EMA

If a patient is switched from oral anticoagulants to desirudin therapy or from desirudin to oral anticoagulants, the anticoagulant activity should continue to be closely monitored with appropriate methods.

Desirudin [1], pregnancy ---> SmPC of [1] of EMA

. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Revasc is contraindicated in pregnancy (see section 4.3).

Desirudin [1], ticlopidine ---> SmPC of [1] of EMA

Desirudin should be used with caution in conjunction with medicinal products which affect platelet function

Desirudin [1], tirofiban ---> SmPC of [1] of EMA

Desirudin should be used with caution in conjunction with medicinal products which affect platelet function

Desirudin, fondaparinux [2] ---> SmPC of [2] of EMA

Agents that may enhance the risk of haemorrhage should not be administered concomitantly with fondaparinux.

CONTRAINDICATIONS of Desirudin (Revasc)

Desirudin is contraindicated in patients:

- with hypersensitivity to the active substance or to any of the excipients

- with active bleeding and/or irreversible coagulation disorders

- with severe renal and hepatic impairment

- during pregnancy

- with severe uncontrolled hypertension and subacute bacterial endocarditis.

https://www.ema.europa.eu/en/documents/product-information/revasc-epar-product-information_en.pdf 26/09/2017 (withdrawn)

Desloratadine (Dasselta)

Ability to drive, desloratadine [2] ---> SmPC of [2] of EMA

Nevertheless, as there is individual variation in response to all medicinal products, it is recommended that patients are advised not to engage in activities requiring mental alertness, such as driving a car or using machines

Alcohol, desloratadine [2] ---> SmPC of [2] of EMA

Cases of alcohol intolerance and intoxication have been reported during post marketing use. Therefore, caution is recommended if alcohol is taken concomitantly.

Breast-feeding, desloratadine [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from desloratadine therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Desloratadine [1], erythromycin ---> SmPC of [1] of EMA

No clinically relevant interactions were observed in clinical trials with desloratadine in which erythromycin were co-administered.

Desloratadine [1], fertility ---> SmPC of [1] of EMA

There are no data available on male and female fertility.

Desloratadine [1], ketoconazole ---> SmPC of [1] of EMA

No clinically relevant interactions were observed in clinical trials with desloratadine in which ketoconazole were co-administered.

Desloratadine [1], pregnancy ---> SmPC of [1] of EMA

As a precautionary measure, it is preferable to avoid the use of desloratadine during pregnancy.

CONTRAINDICATIONS of Desloratadine (Dasselta)

- Hypersensitivity to the active substance, to any of the excipients listed in section 6.1 or to loratadine.

https://www.ema.europa.eu/en/documents/product-information/dasselta-epar-product-information_en.pdf 09/06/2022

Other trade names: Aerius, Allex, Azomyr, Desloratadine Actavis, Desloratadine ratiopharm, Desloratadine Teva, Lodesdineta, Neoclarityn, Opulis,

Desloratadine/pseudoephedrine (Aerinaze)

Ability to drive, desloratadine/pseudoephedrine [2] ---> SmPC of [2] of EMA

It is recommended that patients are advised not to engage in activities requiring mental alertness, until they have established their own response to the medicinal product.

Alcohol, desloratadine/pseudoephedrine [2] ---> SmPC of [2] of EMA

In a clinical pharmacology trial desloratadine taken concomitantly with alcohol did not potentiate the performance impairing effects of alcohol. Alcohol use should be avoided during Aerinaze treatment.

Alpha-methyldopa, desloratadine/pseudoephedrine [2] ---> SmPC of [2] of EMA

Sympathomimetic medicines reduce the antihypertensive effect of alfa-methyldopa

Amphetamine, desloratadine/pseudoephedrine [2] ---> SmPC of [2] of EMA

Concurrent administration with other sympathomimetics may result in critical hypertension reactions

Anorexogenic, desloratadine/pseudoephedrine [2] ---> SmPC of [2] of EMA

Concurrent administration with other sympathomimetics may result in critical hypertension reactions

Antacids, desloratadine/pseudoephedrine [2] ---> SmPC of [2] of EMA

The antacid increases the rate of pseudoephedrine absorption

Antihypertensive, desloratadine/pseudoephedrine [2] ---> SmPC of [2] of EMA

Concurrent administration with other sympathomimetics may result in critical hypertension reactions

Breast-feeding, desloratadine/pseudoephedrine [2] ---> SmPC of [2] of EMA

Aerinaze should not be used during breast-feeding.

Bromocriptine, desloratadine/pseudoephedrine [2] ---> SmPC of [2] of EMA

The combination is not recommended

Cabergoline, desloratadine/pseudoephedrine [2] ---> SmPC of [2] of EMA

The combination is not recommended

Decongestants, desloratadine/pseudoephedrine [2] ---> SmPC of [2] of EMA

Concurrent administration with other sympathomimetics may result in critical hypertension reactions

Desloratadine/pseudoephedrine [1], digital glycosides ---> SmPC of [1] of EMA

The combination is not recommended

Desloratadine/pseudoephedrine [1], digoxin ---> SmPC of [1] of EMA

The following combination is not recommended

Desloratadine/pseudoephedrine [1], dihydroergotamine ---> SmPC of [1] of EMA

Dihydroergotamine, ergotamine, methylergometrine: risk of vasoconstriction and increase in blood pressure.

Desloratadine/pseudoephedrine [1], ephedrine ---> SmPC of [1] of EMA

Risk of vasoconstriction

Desloratadine/pseudoephedrine [1], ergotamine ---> SmPC of [1] of EMA

Dihydroergotamine, ergotamine, methylergometrine: risk of vasoconstriction and increase in blood pressure.

Desloratadine/pseudoephedrine [1], erythromycin ---> SmPC of [1] of EMA

No clinically relevant interactions were observed in clinical trials with desloratadine in which erythromycin were co-administered.

Desloratadine/pseudoephedrine [1], fertility ---> SmPC of [1] of EMA

There are no data available on male and female fertility.

Desloratadine/pseudoephedrine [1], guanethidine ---> SmPC of [1] of EMA

Sympathomimetic medicines reduce the antihypertensive effect of guanethidine

Desloratadine/pseudoephedrine [1], IMAOs ---> SmPC of [1] of EMA

As Aerinaze contains pseudoephedrine sulphate, it is also contraindicated in patients who are receiving monoamine oxidase (MAO) inhibitor therapy or during the 2 weeks following the stopping of such treatment.

Desloratadine/pseudoephedrine [1], kaolin ---> SmPC of [1] of EMA

The kaolin decreases the rate of pseudoephedrine absorption

Desloratadine/pseudoephedrine [1], ketoconazole ---> SmPC of [1] of EMA

No clinically relevant interactions were observed in clinical trials with desloratadine in which ketoconazole were co-administered.

Desloratadine/pseudoephedrine [1], lisuride ---> SmPC of [1] of EMA

Risk of vasoconstriction and increase in blood pressure. The combination is not recommended

Desloratadine/pseudoephedrine [1], mecamylamine ---> SmPC of [1] of EMA

Sympathomimetic medicines reduce the antihypertensive effect of mecamylamine

Desloratadine/pseudoephedrine [1], methylergometrine ---> SmPC of [1] of EMA

Dihydroergotamine, ergotamine, methylergometrine: risk of vasoconstriction and increase in blood pressure.

Desloratadine/pseudoephedrine [1], naphazoline ---> SmPC of [1] of EMA

Risk of vasoconstriction

Desloratadine/pseudoephedrine [1], nasal decongestants ---> SmPC of [1] of EMA

Risk of vasoconstriction

Desloratadine/pseudoephedrine [1], oxymetazoline ---> SmPC of [1] of EMA

Risk of vasoconstriction

Desloratadine/pseudoephedrine [1], pergolide ---> SmPC of [1] of EMA

Risk of vasoconstriction and increase in blood pressure. The combination is not recommended

Desloratadine/pseudoephedrine [1], phenylephrine ---> SmPC of [1] of EMA

Risk of vasoconstriction

Desloratadine/pseudoephedrine [1], phenylpropanolamine ---> SmPC of [1] of EMA

Risk of vasoconstriction. Concomitant use should be avoided

Desloratadine/pseudoephedrine [1], pregnancy ---> SmPC of [1] of EMA

As a precautionary measure, it is preferable to avoid the use of Aerinaze during pregnancy.

Desloratadine/pseudoephedrine [1], reserpine ---> SmPC of [1] of EMA

Sympathomimetic medicines reduce the antihypertensive effect of reserpine

Desloratadine/pseudoephedrine [1], sympathomimetics ---> SmPC of [1] of EMA

Concurrent administration with other sympathomimetics may result in critical hypertension reactions

Desloratadine/pseudoephedrine [1], tricyclic antidepressant ---> SmPC of [1] of EMA

Concurrent administration with other sympathomimetics may result in critical hypertension reactions

Desloratadine/pseudoephedrine [1], veratrum alkaloids ---> SmPC of [1] of EMA

Sympathomimetic medicines reduce the antihypertensive effect of veratrum alkaloids

Pergolide, pseudoephedrine ---> SmPC of [desloratadine/pseudoephedrine] of EMA

Risk of vasoconstriction and increased blood pressure. Concomitant use not recommended

CONTRAINDICATIONS of Desloratadine/pseudoephedrine (Aerinaze)

- Hypersensitivity to the active substances, to any of the excipients listed in section 6.1, or to adrenergic medicinal products or to loratadine.

- As Aerinaze contains pseudoephedrine sulphate, it is also contraindicated in patients who are receiving monoamine oxidase (MAO) inhibitor therapy or during the 2 weeks following the stopping of such treatment.

- Aerinaze is also contraindicated in patients with:

. narrow-angle glaucoma,

. urinary retention,

. cardiovascular diseases such as ischaemic heart disease, tachyarrhythmia and severe hypertension,

. hyperthyroidism,

. a history of haemorrhagic stroke or with risk factors which could increase the risk of haemorrhagic stroke. This is due to the alpha-mimetic activity of pseudoephedrine sulphate in combination with other vasoconstrictors such as bromocriptine, pergolide, lisuride, cabergoline, ergotamine, dihydroergotamine or any other decongestant medicinal product used as a nasal decongestant, either by oral route or by nasal route (phenylpropanolamine, phenylephrine, ephedrine, oxymetazoline, naphazoline…).

https://www.ema.europa.eu/en/documents/product-information/aerinaze-epar-product-information_en.pdf 07/12/2022

Desmopressin

Antihypertensives, desmopressin

Desmopressin may weaken the hypotensive effect

Breast-feeding, desmopressin [2] ---> SmPC of [2] of eMC

The amounts of desmopressin that may be transferred to the child are considerably less than the amounts required to influence diuresis.

Carbamazepine, desmopressin [2] ---> SmPC of [2] of eMC

Substances which are known to induce SIADH may cause an additive antidiuretic effect leading to an increased risk of water retention and/or hyponatraemia.

Chlorpromazine, desmopressin [2] ---> SmPC of [2] of eMC

Substances which are known to induce SIADH may cause an additive antidiuretic effect leading to an increased risk of water retention and/or hyponatraemia.

Desmopressin [1], loperamide ---> SmPC of [1] of eMC

Concomitant treatment with loperamide may result in a 3-fold increase of desmopressin plasma concentrations, which may lead to an increased risk of water retention and/or hyponatraemia.

Desmopressin [1], NSAID ---> SmPC of [1] of eMC

NSAIDs may induce water retention and/or hyponatraemia.

Desmopressin [1], pregnancy ---> SmPC of [1] of eMC

Caution should be exercised when prescribing to pregnant women.

Desmopressin [1], SIADH inductors ---> SmPC of [1] of eMC

Substances which are known to induce SIADH may cause an additive antidiuretic effect leading to an increased risk of water retention and/or hyponatraemia.

Desmopressin [1], SSRI ---> SmPC of [1] of eMC

Substances which are known to induce SIADH may cause an additive antidiuretic effect leading to an increased risk of water retention and/or hyponatraemia.

Desmopressin [1], tricyclic antidepressant ---> SmPC of [1] of eMC

Substances which are known to induce SIADH may cause an additive antidiuretic effect leading to an increased risk of water retention and/or hyponatraemia.

Desmopressin, dimethicone

The co-administration of dimethicone may decrease the absorption of desmopressin

Desmopressin, fibrates

The co-administration may increase the antidiuretic effect

Desmopressin, foods

A fat meal significantly decreased the absorption of desmopressin

Desmopressin, glibenclamide

The co-administration may shorten the antidiuretic effect

Desmopressin, hypertensive drugs

Desmopressin may increase the hypertensive effect

Desmopressin, lithium

The co-administration may shorten the antidiuretic effect

Desmopressin, noradrenaline

Decreased antidiuretic effect

Desmopressin, norepinephrine

Decreased antidiuretic effect

Desmopressin, oxytocin

The co-administration may increase the antidiuretic effect

Desmopressin, ticagrelor [2] ---> SmPC of [2] of EMA

Co-administration of ticagrelor with desmopressin did not have any effect on ADP-induced platelet aggregation. If clinically indicated, medicinal products that alter haemostasis should be used with caution in combination with ticagrelor

Desmopressin, tolvaptan [2] ---> SmPC of [2] of EMA

The effect of vasopressin analogues such as desmopressin may be attenuated in patients using such analogues to prevent or control bleeding when co-administered with tolvaptan.

CONTRAINDICATIONS of Desmopressin

- Desmopressin tablets are contraindicated in cases of cardiac insufficiency and other conditions requiring treatment with diuretic agents.

- Desmopressin tablets should only be used in patients with normal blood pressure.

- Before prescribing desmopressin tablets the diagnoses of psychogenic polydipsia and alcohol abuse should be excluded.

- Desmopressin should not be prescribed to patients over the age of 65 for the treatment of primary nocturnal enuresis.

http://www.medicines.org.uk/emc/

Desogestrel

Activated charcoal, desogestrel [2] ---> SmPC of [2] of eMC

During treatment with medical charcoal, the absorption of the steroid may be reduced and thereby the contraceptive efficacy.

Barbiturates, desogestrel [2] ---> SmPC of [2] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones

Breast-feeding, desogestrel [2] ---> SmPC of [2] of eMC

Based on the available data desogestrel may be used during lactation. The development and growth of a nursing infant, whose mother uses desogestrel, should, however, be carefully observed.

Carbamazepine, desogestrel [2] ---> SmPC of [2] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones

Desogestrel [1], enzyme inductors ---> SmPC of [1] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones

Desogestrel [1], felbamate ---> SmPC of [1] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones

Desogestrel [1], griseofulvin ---> SmPC of [1] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones

Desogestrel [1], hydantoins ---> SmPC of [1] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones

Desogestrel [1], nelfinavir ---> SmPC of [1] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones

Desogestrel [1], oxcarbazepine ---> SmPC of [1] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones

Desogestrel [1], phenobarbital ---> SmPC of [1] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones

Desogestrel [1], phenytoin ---> SmPC of [1] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones

Desogestrel [1], pregnancy ---> SmPC of [1] of eMC

Extensive epidemiological studies have revealed neither an increased risk of birth defects in children born to women who used COCs before pregnancy, nor a teratogenic effect when COCs were taken inadvertently during early pregnancy.

Desogestrel [1], primidone ---> SmPC of [1] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones

Desogestrel [1], rifabutin ---> SmPC of [1] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones

Desogestrel [1], rifampicin ---> SmPC of [1] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones

Desogestrel [1], ritonavir ---> SmPC of [1] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones

Desogestrel [1], St. John's wort ---> SmPC of [1] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones

Desogestrel [1], topiramate ---> SmPC of [1] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones

CONTRAINDICATIONS of Desogestrel

- Known or suspected pregnancy.

- Active venous thromboembolic disorder.

- Presence or history of severe hepatic disease as long as liver function values have not returned to normal.

- Known or suspected sex-steroid sensitive malignancies.

- Undiagnosed vaginal bleeding.

- Hypersensitivity to the active substance or to any of the excipients

http://www.medicines.org.uk/emc/

Desoximetason

Desoximetason, Schwangerschaft

Die Anwendung während der Schwangerschaft ist kontraindiziert.

Desoximetason, Stillzeit

Andere Glukokortikoide gehen in die Muttermilch über. Bei einer großflächigen oder langfristigen Anwendung soll nicht während der Stillzeit angewendet werden.

Deucravacitinib (Sotyktu)

Breast-feeding, deucravacitinib [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from deucravacitinib therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman

Cyclosporine, deucravacitinib [2] ---> SmPC of [2] of EMA

Medicinal products that are inhibitors or inducers of CYP enzymes or transporters do not meaningfully affect plasma deucravacitinib exposures (see section 5.2).

Deucravacitinib [1], diflunisal ---> SmPC of [1] of EMA

Medicinal products that are inhibitors or inducers of CYP enzymes or transporters do not meaningfully affect plasma deucravacitinib exposures (see section 5.2).

Deucravacitinib [1], famotidine ---> SmPC of [1] of EMA

Medicinal products that are inhibitors or inducers of CYP enzymes or transporters do not meaningfully affect plasma deucravacitinib exposures (see section 5.2).

Deucravacitinib [1], fertility ---> SmPC of [1] of EMA

Animal studies do not indicate direct or indirect harmful effects with respect to fertility (see section 5.3).

Deucravacitinib [1], fluvoxamine ---> SmPC of [1] of EMA

Medicinal products that are inhibitors or inducers of CYP enzymes or transporters do not meaningfully affect plasma deucravacitinib exposures (see section 5.2).

Deucravacitinib [1], methotrexate ---> SmPC of [1] of EMA

Deucravacitinib does not meaningfully impact plasma exposures

Deucravacitinib [1], mycophenolate mofetil ---> SmPC of [1] of EMA

Deucravacitinib does not meaningfully impact plasma exposures

Deucravacitinib [1], norethisterone/ethinylestradiol ---> SmPC of [1] of EMA

Deucravacitinib does not meaningfully impact plasma exposures

Deucravacitinib [1], oral contraceptives ---> SmPC of [1] of EMA

Deucravacitinib does not meaningfully impact plasma exposures

Deucravacitinib [1], pregnancy ---> SmPC of [1] of EMA

As a precautionary measure, it is preferable to avoid the use of deucravacitinib during pregnancy.

Deucravacitinib [1], pyrimethamine ---> SmPC of [1] of EMA

Medicinal products that are inhibitors or inducers of CYP enzymes or transporters do not meaningfully affect plasma deucravacitinib exposures (see section 5.2).

Deucravacitinib [1], rabeprazole ---> SmPC of [1] of EMA

Medicinal products that are inhibitors or inducers of CYP enzymes or transporters do not meaningfully affect plasma deucravacitinib exposures (see section 5.2).

Deucravacitinib [1], rosuvastatin ---> SmPC of [1] of EMA

Deucravacitinib does not meaningfully impact plasma exposures

Deucravacitinib [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

Use of live vaccines in patients being treated with deucravacitinib should be avoided. The response to live or non-live vaccines has not been evaluated.

CONTRAINDICATIONS of Deucravacitinib (Sotyktu)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Clinically important active infections (e.g. active tuberculosis, see section 4.4).

https://www.ema.europa.eu/en/documents/product-information/sotyktu-epar-product-information_en.pdf 04/07/2024

Dexamethasone (attention to only Ozurdex)

Ability to drive, dexamethasone [2] ---> SmPC of [2] of EMA

Patients may experience temporarily reduced vision after receiving OZURDEX by intravitreal injection (see section 4.8). They should not drive or use machines until this has resolved.

Absorption, dexamethasone [2] ---> SmPC of [2] of EMA

Systemic absorption is minimal and no interactions are anticipated.

Albendazole, dexamethasone

The co-administration may increase the plasma concentrations of active albendazole metabolite

Alizapride, dexamethasone

The co-administration may enhance the extrapyramidal motor effects

Anticholinergics, dexamethasone

Additional increase in the intraocular pressure

Aprepitant [1], dexamethasone ---> SmPC of [1] of EMA

The usual oral dexamethasone dose should be reduced by approximately 50 % when co-administered with EMEND 125 mg/80 mg regimen

Atazanavir/cobicistat [1], dexamethasone ---> SmPC of [1] of EMA

Concomitant use of EVOTAZ and corticosteroids that are metabolised by CYP3A may increase the risk of development of systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression.

Atropine, dexamethasone

Additional increase in the intraocular pressure

Avapritinib [1], dexamethasone ---> SmPC of [1] of EMA

Co-administration with strong or moderate CYP3A inducers should be avoided because it may decrease the plasma concentrations of avapritinib

Axitinib [1], dexamethasone ---> SmPC of [1] of EMA

Co-administration of axitinib with strong CYP3A4/5 inducers may decrease axitinib plasma concentrations. Selection of concomitant medicinal products with no or minimal CYP3A4/5 induction potential is recommended.

Bexarotene [1], dexamethasone ---> SmPC of [1] of EMA

On the basis of the oxidative metabolism of bexarotene by cytochrome P450 3A4 (CYP3A4). Co-administration with CYP3A4 inducers may theoretically cause a reduction in plasma bexarotene concentrations.

Bortezomib [1], dexamethasone ---> SmPC of [1] of EMA

In the same drug-drug interaction study assessing the effect of dexamethasone, a weaker CYP3A4 inducer, on the pharmacokinetics of bortezomib (injected intravenously), there was no significant effect on the pharmacokinetics of bortezomib

Breast-feeding, dexamethasone [2] ---> SmPC of [2] of EMA

OZURDEX is not recommended during breast feeding unless clearly necessary.

Carbamazepine [1], dexamethasone ---> SmPC of [1] of eMC

Carbamazepine may decrease the plasma levels of dexamethasone

Carmustine [1], dexamethasone ---> SmPC of [1] of EMA

In combination with chemotherapeutic medicinal products reduced activity of antiepileptic medicinal products must be anticipated.

Caspofungin [1], dexamethasone ---> SmPC of [1] of EMA

When co-administering inducers of metabolic enzymes, an increase in the daily dose of caspofungin to 70 mg, following the 70 mg loading dose, should be considered in adult patients (see section 4.2).

Cyclophosphamide, dexamethasone

The previous or concomitant treatment of dexamethasone may increase the metabolism and thus enhance the effect of cyclophosphamide due to increasing formation of active alkylating metabolites of cyclophosphamide

Dabrafenib [1], dexamethasone ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Daclatasvir [1], dexamethasone ---> SmPC of [1] of EMA

Daclatasvir is contraindicated in combination with medicinal products that strongly induce CYP3A4 and P-gp, and thus may lead to lower exposure and loss of efficacy of daclatasvir.

Daratumumab [1], dexamethasone ---> SmPC of [1] of EMA

Clinical pharmacokinetic assessments of daratumumab in combination with lenalidomide, pomalidomide, thalidomide, bortezomib and dexamethasone indicated no clinically-relevant drug-drug interaction

Darunavir/cobicistat [1], dexamethasone ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], dexamethasone ---> SmPC of [1] of EMA

Based on theoretical considerations (systemic) dexamethasone is expected to decrease darunavir and/or cobicistat plasma concentrations. CYP3A induction

Darunavir/ritonavir, dexamethasone ---> SmPC of [darunavir] of EMA

Systemic dexamethasone may decrease plasma concentrations of darunavir. (CYP3A induction). Systemic dexamethasone should be used with caution when combined with boosted darunavir.

Dasatinib [1], dexamethasone ---> SmPC of [1] of EMA

Daunorubicin, dexamethasone

Incompatibility

Dexamethasone [1], fertility ---> SmPC of [1] of EMA

There are no fertility data available.

Dexamethasone [1], pregnancy ---> SmPC of [1] of EMA

OZURDEX is not recommended during pregnancy unless the potential benefit justifies the potential risk to the foetus.

Dexamethasone, docetaxel [2] ---> SmPC of [2] of EMA

Dexamethasone did not affect protein binding of docetaxel

Dexamethasone, dolutegravir/rilpivirine ---> SmPC of [rilpivirine] of EMA

The CYP3A4 induction by dexamethasone may decrease the plasma concentrations and the therapeutic effect of rilpivirine. Contra-indicated (except as a single dose)

Dexamethasone, emtricitabine/rilpivirine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Significant dose dependent decreases in rilpivirine plasma concentrations are expected (induction of CYP3A). Co-administration is contraindicated.

Dexamethasone, emtricitabine/rilpivirine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

The strong CYP3A4 induction by dexamethasone may decrease the plasma concentrations and the therapeutic effect of rilpivirine. Contra-indicated (except as a single dose)

Dexamethasone, enzalutamide [2] ---> SmPC of [2] of EMA

Enzalutamide, enzymatic inductor, may increase the metabolism of dexamethasone and decrease its plasma levels and effect

Dexamethasone, ephedrine [2] ---> SmPC of [2] of eMC

Ephedrine has been shown to increase the clearance of dexamethasone.

Dexamethasone, etravirine [2] ---> SmPC of [2] of EMA

Dexamethasone is expected to decrease plasma concentrations of etravirine. Systemic dexamethasone should be used with caution or alternatives should be considered, particularly for chronic use.

Dexamethasone, everolimus [2] ---> SmPC of [2] of EMA

Decreased exposure of everolimus expected. Avoid the use of concomitant potent CYP3A4 inducers.

Dexamethasone, fosaprepitant [2] ---> SmPC of [2] of EMA

The CYP3A4 inhibition may increase the plasma levels of dexamethasone. The usual oral dexamethasone dose should be reduced

Dexamethasone, imatinib [2] ---> SmPC of [2] of EMA

Substances that are inducers of CYP3A4 activity may significantly reduce exposure to imatinib, potentially increasing the risk of therapeutic failure. Concomitant use of strong CYP3A4 inducers and imatinib should be avoided.

Dexamethasone, indinavir [2] ---> SmPC of [2] of EMA

The CYP3A4 inhibition/induction may increase/decrease the plasma concentrations of dexamethasone/indinavir. Careful monitoring is recommended

Dexamethasone, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

The CYP3A4 inhibition/induction may increase/decrease the plasma concentrations of dexamethasone/indinavir. Careful monitoring is recommended

Dexamethasone, itraconazol

The co-administration may increase the plasma levels of dexamethasone. The dosage should be reduced if necessary

Dexamethasone, ixabepilone

The strong CYP3A4 induction may reduce plasma concentrations of ixabepilone

Dexamethasone, ixazomib [2] ---> SmPC of [2] of EMA

When ixazomib is administered together with dexamethasone, which is known to be a weak to moderate inducer of CYP3A4 as well as other enzymes and transporters, the risk for reduced efficacy of oral contraceptives needs to be considered.

Dexamethasone, ketoconazole [2] ---> SmPC of [2] of EMA

Potential increase in plasma concentrations of dexamethasone. Careful monitoring. Dose adjustment of dexamethasone may be required.

Dexamethasone, lenacapavir [2] ---> SmPC of [2] of EMA

Plasma concentrations of corticosteroids may be increased when co-administered with lenacapavir.

Dexamethasone, lenalidomide [2] ---> SmPC of [2] of EMA

Co-administration of single or multiple doses of dexamethasone (40 mg once daily) has no clinically relevant effect on the multiple dose pharmacokinetics of lenalidomide (25 mg once daily).

Dexamethasone, lopinavir/ritonavir [2] ---> SmPC of [2] of EMA

Lopinavir concentrations may be decreased due to CYP3A induction by dexamethasone. Clinical monitoring of antiviral efficacy is recommended when these medicines are concomitantly administered with Kaletra.

Dexamethasone, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Glycaemic control should be carefully assessed when saxagliptin is used concomitantly with a potent CYP3A4/5 inducer.

Dexamethasone, mifepristone [2] ---> SmPC of [2] of eMC

CYP3A4 inductors may induce mifepristone metabolism (lowering serum levels of mifepristone).

Dexamethasone, nalmefene [2] ---> SmPC of [2] of EMA

Concomitant administration with a UGT inducer may potentially lead to subtherapeutic nalmefene plasma concentrations.

Dexamethasone, neratinib [2] ---> SmPC of [2] of EMA

Concurrent use of neratinib with moderate CYP3A4/P-gp inducers is not recommended as it may also lead to loss of efficacy

Dexamethasone, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

Co-administration of a single dose of 300 mg netupitant with a dexamethasone regimen (20 mg on Day 1, followed by 8 mg twice daily from Day 2 to Day 4) significantly increased the exposure to dexamethasone in a time and dose dependent manner.

Dexamethasone, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir inhibits CYP3A and as a result is expected to increase the plasma concentrations of dexamethasone. Careful monitoring of therapeutic and adverse effects is recommended when dexamethasone is concomitantly administered with ritonavir.

Dexamethasone, palonosetron [2] ---> SmPC of [2] of EMA

In a population pharmacokinetic analysis, it has been shown that there was no significant effect on palonosetron clearance when co-administered with CYP2D6 inducers and inhibitors

Dexamethasone, panobinostat [2] ---> SmPC of [2] of EMA

When panobinostat is administered together with dexamethasone, which is known to be a weak to moderate inducer of CYP3A4 as well as other enzymes and transporters, the risk for reduced efficacy of hormonal contraceptives needs to be considered.

Dexamethasone, parecoxib [2] ---> SmPC of [2] of EMA

The metabolism of valdecoxib may increase when co-administered with enzyme inducers

Dexamethasone, pomalidomide [2] ---> SmPC of [2] of EMA

Co-administration of pomalidomide with dexamethasone (an inducer of CYP3A) had no effect on the pharmacokinetics of pomalidomide

Dexamethasone, pomalidomide [2] ---> SmPC of [2] of EMA

Caution should be exercised when pomalidomide in combination with dexamethasone is used in patients previously infected with HBV, including patients who are anti-HBc positive but HBsAg negative.

Dexamethasone, praziquantel

The co-administration may decrease the plasma levels of praziquantel

Dexamethasone, protirelin

Reduction of TSH-increase

Dexamethasone, remdesivir [2] ---> SmPC of [2] of EMA

Dexamethasone is a substrate of CYP3A4 and although remdesivir inhibits CYP3A4, due to remdesivir's rapid clearance after I.V administration, remdesivir is unlikely to have a significant effect on dexamethasone exposure.

Dexamethasone, rilpivirine [2] ---> SmPC of [2] of EMA

The CYP3A4 induction by dexamethasone may decrease the plasma concentrations and the therapeutic effect of rilpivirine. Contra-indicated (except as a single dose)

Dexamethasone, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent inhibits CYP3A and as a result is expected to increase the plasma concentrations of dexamethasone.

Dexamethasone, rolapitant [2] ---> SmPC of [2] of EMA

Rolapitant had no significant effects on the pharmacokinetics of dexamethasone when oral dexamethasone was administered on Days 1 to 3 after a single 180 mg dose of rolapitant was co-administered on Day 1.

Dexamethasone, saquinavir [2] ---> SmPC of [2] of EMA

Dexamethasone induces CYP3A4 and may decrease saquinavir concentrations. Use with caution.

Dexamethasone, saxagliptin [2] ---> SmPC of [2] of EMA

The co-administration of saxagliptin and CYP3A4/5 inducers may result in decreased plasma concentration of saxagliptin and increased concentration of its major metabolite. Glycaemic control should be carefully assessed

Dexamethasone, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Glycaemic control should be carefully assessed when saxagliptin is used concomitantly with a potent CYP3A4/5 inducer.

Dexamethasone, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Dexamethasone, sibutramine [2] ---> SmPC of [2] of eMC

Rifampicin, phenytoin, carbamazepine, phenobarbital and dexamethasone are CYP3A4 enzyme inducers and may accelerate sibutramine metabolism, although this has not been studied experimentally.

Dexamethasone, simeprevir [2] ---> SmPC of [2] of EMA

The moderate CYP3A4 enzyme induction by dexamethasone may decrease the plasma concentrations of simeprevir. It is not recommended to co-administer simeprevir with systemic dexamethasone

Dexamethasone, sorafenib [2] ---> SmPC of [2] of EMA

Inducers of CYP3A4 activity and/or glucuronidation may increase metabolism of sorafenib and thus decrease sorafenib concentrations.

Dexamethasone, sparsentan [2] ---> SmPC of [2] of EMA

Concomitant use with a moderate or strong CYP3A inducer decreases sparsentan exposure, which may reduce the efficacy of sparsentan. Therefore, co-administration with a moderate or strong CYP3A inducer is not recommended.

Dexamethasone, sunitinib [2] ---> SmPC of [2] of EMA

Administration of sunitinib with potent CYP3A4 inducers may decrease sunitinib concentrations. Combination with CYP3A4 inducers should therefore be avoided

Dexamethasone, telaprevir [2] ---> SmPC of [2] of EMA

Dexamethasone (systemic), CYP3A4 inductor, may decrease the plasma levels of telaprevir. The combination should be used with caution or alternatives should be considered.

Dexamethasone, temozolomide [2] ---> SmPC of [2] of EMA

Co-administration of dexamethasone, prochlorperazine, phenytoin, carbamazepine, ondansetron, H2 receptor antagonists, or phenobarbital did not alter the clearance of TMZ.

Dexamethasone, tetracosactide

Decreased release of cortisol

Dexamethasone, valdecoxib [2] ---> SmPC of [2] of EMA

The enzymatic inductor may increase the metabolism of valdecoxib and decrease its plasma levels

CONTRAINDICATIONS of Dexamethasone (attention to only Ozurdex)

- Hypersensitivity to the active substance or to any of the excipients as listed in section 6.1.

- Active or suspected ocular or periocular infection including most viral diseases of the cornea and conjunctiva, including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases.

- Advanced glaucoma which cannot be adequately controlled by medicinal products alone.

- Aphakic eyes with ruptured posterior lens capsule.

- Eyes with Anterior Chamber Intraocular Lens (ACIOL), iris or transscleral fixated intraocular lens and ruptured posterior lens capsule.

https://www.ema.europa.eu/en/documents/product-information/ozurdex-epar-product-information_en.pdf 24/10/2025

Other trade names: Neofordex,

Dexchlorpheniramine

Ability to drive, dexchlorpheniramine

Somnolence may occur

Alcohol, dexchlorpheniramine

The combination of dexchlorpheniramine with other CNS depressants may enhance the CNS depressant effect

Anticholinergics, dexchlorpheniramine

Additive anticholinergic effects

Antiparkinsonian agents, dexchlorpheniramine

Additive anticholinergic effects

Anxiolytics, dexchlorpheniramine

The combination of dexchlorpheniramine with other CNS depressants may enhance the CNS depressant effect

Atropine, dexchlorpheniramine

Additive anticholinergic effects

Barbiturates, dexchlorpheniramine

The combination of dexchlorpheniramine with other CNS depressants may enhance the CNS depressant effect

Benzodiazepines, dexchlorpheniramine

The combination of dexchlorpheniramine with other CNS depressants may enhance the CNS depressant effect

Breast-feeding, dexchlorpheniramine

The lactation is not recommended

CNS depressants, dexchlorpheniramine

The combination of dexchlorpheniramine with other CNS depressants may enhance the CNS depressant effect

Clonidine, dexchlorpheniramine

The combination of dexchlorpheniramine with other CNS depressants may enhance the CNS depressant effect

Dexchlorpheniramine, hypnotics

The combination of dexchlorpheniramine with other CNS depressants may enhance the CNS depressant effect

Dexchlorpheniramine, methadone

The combination of dexchlorpheniramine with other CNS depressants may enhance the CNS depressant effect

Dexchlorpheniramine, monoamine oxidase inhibitors

The co-administration of dexchlorpheniramine mit MAOI and within 2 weeks after MAOI discontinuation is contraindicated

Dexchlorpheniramine, neuroleptics

The combination of dexchlorpheniramine with other CNS depressants may enhance the CNS depressant effect

Dexchlorpheniramine, oral anticoagulants

The antihistaminic agent may decrease the effect of oral anticoagulant

Dexchlorpheniramine, phenothiazines

Additive anticholinergic effects

Dexchlorpheniramine, pregnancy

Strict indication in the first and second trimester. Contraindicated in the third trimester

Dexchlorpheniramine, tricyclic antidepressants

The combination of dexchlorpheniramine with other CNS depressants may enhance the CNS depressant effect. Additive anticholinergic effects

Dexibuprofen

Ability to drive, dexibuprofen [2] ---> SmPC of [2] of eMC

During treatment with dexibuprofen the patient's reaction capacity may be reduced when dizziness or fatigue appear as side effects.

ACE inhibitors, dexibuprofen [2] ---> SmPC of [2] of eMC

As with other NSAIDs, concomitant treatment with drugs increasing potassium plasma levels, may be associated with increased serum potassium levels and may increase the risk of renal failure

Acetylsalicylic acid, dexibuprofen [2] ---> SmPC of [2] of eMC

The combination may inhibit the effect of low dose acetylsalicylic acid on platelet aggregation. Caution should be exercised

AIIRA, dexibuprofen [2] ---> SmPC of [2] of eMC

As with other NSAIDs, concomitant treatment with drugs increasing potassium plasma levels, may be associated with increased serum potassium levels and may increase the risk of renal failure

Alcohol, NSAID

Enhancement of the adverse effects of the NSAID, especially those of the gastrointestinal tract

Aminoglycoside antibiotics, dexibuprofen

Co-administration of aminoglycoside antibiotics with NSAIDs may increase the risk of nephrotoxicity on account of reduced synthesis of prostaglandins in the kidney. During combination treatment renal function must be closely monitored

Aminoglycoside antibiotics, NSAID

Anticoagulants, dexibuprofen [2] ---> SmPC of [2] of eMC

The effects of anticoagulants on bleeding time can be potentiated by NSAIDs.

Betablockers, dexibuprofen [2] ---> SmPC of [2] of eMC

NSAIDs may reduce the efficacy of beta-blockers, possibly due to inhibition of the formation of vasodilatory prostaglandins.

Breast-feeding, dexibuprofen [2] ---> SmPC of [2] of eMC

Ibuprofen is slightly excreted in human milk. Breast-feeding is possible with dexibuprofen if dosage is low and the treatment period is short.

Cardiac glycosides, dexibuprofen

NSAID may exacerbate cardiac failure, reduce the glomerular filtration rate and increase plasma levels of the cardiac glycoside

Corticosteroids, dexibuprofen [2] ---> SmPC of [2] of eMC

The risk of gastrointestinal ulceration may be increased by the concomitant administration of NSAIDs and corticosteroids.

Coxibs, dexibuprofen [2] ---> SmPC of [2] of eMC

The concomitant use with other NSAIDs should be avoided, since simultaneous administration of different NSAIDs can increase the risk of gastrointestinal ulceration and haemorrhage.

Cyclosporine, dexibuprofen [2] ---> SmPC of [2] of eMC

As with other NSAIDs, concomitant treatment with drugs increasing potassium plasma levels, may be associated with increased serum potassium levels and may increase the risk of renal failure

CYP2C8 inductors, dexibuprofen

The CYP2C8 induction may decrease the dexibuprofen effect

CYP2C9 inductors, dexibuprofen

The CYP2C9 induction may decrease the dexibuprofen effect

Dexibuprofen [1], digoxin ---> SmPC of [1] of eMC

NSAIDs can increase the plasma levels of digoxin and increase the risk of digoxin toxicity.

Dexibuprofen [1], heparin ---> SmPC of [1] of eMC

As with other NSAIDs, concomitant treatment with drugs increasing potassium plasma levels, may be associated with increased serum potassium levels and may increase the risk of renal failure

Dexibuprofen [1], hyperkalemia ---> SmPC of [1] of eMC

As with other NSAIDs, concomitant treatment with drugs increasing potassium plasma levels, may be associated with increased serum potassium levels and may increase the risk of renal failure

Dexibuprofen [1], lithium ---> SmPC of [1] of eMC

NSAIDs can increase the plasma levels of lithium, by reducing its renal clearance.

Dexibuprofen [1], loop diuretics ---> SmPC of [1] of eMC

Concurrent use of an NSAID and a diuretic may increase the risk of renal failure secondary to a reduction in renal blood flow.

Dexibuprofen [1], methotrexate ---> SmPC of [1] of eMC

If NSAIDs and methotrexate are given within 24 hours of each other plasma levels of methotrexate may increase, via a reduction in its renal clearance thus increasing the potential for methotrexate toxicity.

Dexibuprofen [1], NSAID ---> SmPC of [1] of eMC

The concomitant use with other NSAIDs should be avoided, since simultaneous administration of different NSAIDs can increase the risk of gastrointestinal ulceration and haemorrhage.

Dexibuprofen [1], phenytoin ---> SmPC of [1] of eMC

Ibuprofen may displace phenytoin from protein-binding sites, possibly leading to increased phenytoin serum levels and toxicity.

Dexibuprofen [1], platelet aggregation inhibitors ---> SmPC of [1] of eMC

Dexibuprofen inhibits platelet aggregation via platelet cyclooxygenase inhibition. Caution is required when dexibuprofen is combined with other antiplatelet agents, because of the risk of increased antiplatelet effect.

Dexibuprofen [1], potassium-sparing diuretics ---> SmPC of [1] of eMC

As with other NSAIDs, concomitant treatment with drugs increasing potassium plasma levels, may be associated with increased serum potassium levels and may increase the risk of renal failure

Dexibuprofen [1], pregnancy ---> SmPC of [1] of eMC

Like other drugs of this class, dexibuprofen should only be administered in the first 5 months of pregnancy if clearly needed. From the beginning of the 6th month of pregnancy onward dexibuprofen is contraindicated.

Dexibuprofen [1], salicylates ---> SmPC of [1] of eMC

Concomitant use of several NSAIDs should be avoided due to an increased risk of adverse effects, particularly upper gastrointestinal disorders.

Dexibuprofen [1], thiazides ---> SmPC of [1] of eMC

Concurrent use of an NSAID and a diuretic may increase the risk of renal failure secondary to a reduction in renal blood flow.

Dexibuprofen [1], thrombolytics ---> SmPC of [1] of eMC

Dexibuprofen inhibits platelet aggregation via platelet cyclooxygenase inhibition. Caution is required when dexibuprofen is combined with thrombolytics because of the risk of increased antiplatelet effect.

Dexibuprofen [1], ticlopidine ---> SmPC of [1] of eMC

Dexibuprofen inhibits platelet aggregation via platelet cyclooxygenase inhibition. Caution is required when dexibuprofen is combined with ticlopidine because of the risk of increased antiplatelet effect.

Dexibuprofen [1], trimethoprim ---> SmPC of [1] of eMC

As with other NSAIDs, concomitant treatment with drugs increasing potassium plasma levels, may be associated with increased serum potassium levels and may increase the risk of renal failure

Dexibuprofen [1], warfarin ---> SmPC of [1] of eMC

The effects of anticoagulants on bleeding time can be potentiated by NSAIDs.

Dexibuprofen, hydantoins

The co-administration may increase the toxic effects of hydantoin and is not recommended

Dexibuprofen, mifepristone

The NSAID should not be used for 8-12 days after mifepristone administration as NSAID can reduce the effect of mifepristone.

Dexibuprofen, pentoxifylline

Increased risk of bleeding. Increase clinical monitoring and check bleeding time more often

Dexibuprofen, phenobarbital

The CYP2C8 induction may decrease the dexibuprofen effect

Dexibuprofen, quinolones

The NSAID can increase the risk of convulsions associated with quinolone antibiotic.

Dexibuprofen, rifampicin

The CYP2C9 induction may decrease the dexibuprofen effect

Dexibuprofen, sirolimus

Concomitant administration of sirolimus with NSAIDs may increase the risk of nephrotoxicity on account of reduced synthesis of prostaglandins in the kidney. During combination treatment renal function must be closely monitored

Dexibuprofen, SSRI

The co-administration can increase the risk of gastrointestinal bleeding

Dexibuprofen, strong CYP2C8 inductors

The strong CYP2C8 induction may decrease the dexibuprofen effect

Dexibuprofen, strong CYP2C8 inductors

The CYP2C8 induction may decrease the dexibuprofen effect

Dexibuprofen, sulfonylureas

NSAIDs can increase the hypoglycaemic effect of sulfonylureas by displacement from plasma protein binding sites. Caution is recommended

Dexibuprofen, sulphonamides

The co-administration may increase the toxic effects of sulfonamide and is not recommended

Dexibuprofen, tacrolimus

Concomitant administration of tacrolimus with NSAIDs may increase the risk of nephrotoxicity on account of reduced synthesis of prostaglandins in the kidney. During combination treatment renal function must be closely monitored

Dexibuprofen, zidovudine

Increased risk of haematological toxicity. Caution is recommended

Digoxin, NSAID ---> SmPC of [dexibuprofen] of eMC

NSAID may exacerbate cardiac failure, reduce the glomerular filtration rate and increase plasma levels of the cardiac glycoside

Hyperkalemia, NSAID ---> SmPC of [dexibuprofen] of eMC

As with other NSAIDs, concomitant treatment with drugs increasing potassium plasma levels, may be associated with increased serum potassium levels and may increase the risk of renal failure

NSAID, sirolimus

CONTRAINDICATIONS of Dexibuprofen

Dexibuprofen must not be administered in the following cases:

- Patients previously sensitive to dexibuprofen, to any other NSAID, or to any of the excipients of the product.

- Patients in whom substances with a similar action (e.g. aspirin or other NSAIDs) precipitate attacks of asthma, bronchospasm, acute rhinitis, or cause nasal polyps, urticaria or angioneurotic oedema.

- Patients with active or suspected gastrointestinal ulcer or history of recurrent gastrointestinal ulcer.

- Patients who have gastrointestinal bleeding or other active bleedings or bleeding disorders.

- Patients with active Crohn's disease or active ulcerative colitis.

- Patients with severe heart failure.

- Patients with severe renal dysfunction (GFR < 30 ml/min).

- Patients with severely impaired hepatic function.

- Patients with haemorrhagic diathesis and other coagulation disorders, or patients receiving anticoagulant therapy.

- From the beginning of 6th month of pregnancy

http://www.medicines.org.uk/emc/

Dexketoprofen

Ability to drive, dexketoprofen [2] ---> SmPC of [2] of eMC

Dizziness or drowsiness may occur

ACE inhibitors, dexketoprofen [2] ---> SmPC of [2] of eMC

In some patients with compromised renal function, the coadministration may result in further deterioration of renal function, which is usually reversible.

AIIRA, dexketoprofen [2] ---> SmPC of [2] of eMC

In some patients with compromised renal function, the coadministration may result in further deterioration of renal function, which is usually reversible.

Aminoglycoside antibiotics, dexketoprofen [2] ---> SmPC of [2] of eMC

In some patients with compromised renal function, the coadministration may result in further deterioration of renal function, which is usually reversible.

Betablockers, dexketoprofen [2] ---> SmPC of [2] of eMC

Treatment with a NSAID may decrease their antihypertensive effect via inhibition of prostaglandin synthesis.

Breast-feeding, dexketoprofen [2] ---> SmPC of [2] of eMC

It is not known whether dexketoprofen is excreted in human milk. It is contraindicated during breastfeeding

Cardiac glycosides, dexketoprofen [2] ---> SmPC of [2] of eMC

NSAID may exacerbate cardiac failure, reduce the glomerular filtration rate and increase plasma levels of the cardiac glycoside

Corticosteroids, dexketoprofen [2] ---> SmPC of [2] of eMC

There is an increased risk of gastrointestinal ulceration or bleeding with corticosteroids

Coumarin anticoagulants, dexketoprofen [2] ---> SmPC of [2] of eMC

NSAIDs may enhance the effects of anti-coagulants, such as warfarin, due to the high plasma protein binding of dexketoprofen and the inhibition of platelet function and damage to the gastroduodenal mucosa.

Coxibs, dexketoprofen [2] ---> SmPC of [2] of eMC

Concomitant use of several NSAIDs should be avoided due to an increased risk of adverse effects, particularly upper gastrointestinal disorders.

Cyclosporine, dexketoprofen [2] ---> SmPC of [2] of eMC

Nephrotoxicity may be enhanced by NSAIDs via renal prostaglandin mediated effects. During combination therapy, renal function has to be measured.

Dexketoprofen [1], diuretics ---> SmPC of [1] of eMC

Dexketoprofen may reduce the effect of diuretics

Dexketoprofen [1], heparin ---> SmPC of [1] of eMC

Increased risk of haemorrhage (due to the inhibition of platelet function and damage to the gastroduodenal mucosa).

Dexketoprofen [1], hydantoins ---> SmPC of [1] of eMC

The toxic effects of hydantoins may be increased.

Dexketoprofen [1], lithium ---> SmPC of [1] of eMC

NSAIDs increase blood lithium levels, which may reach toxic values (decreased renal excretion of lithium).

Dexketoprofen [1], methotrexate ---> SmPC of [1] of eMC

Methotrexate, used at high doses of 15 mg/week or more: increased haematological toxicity of methotrexate via a decrease in its renal clearance by antiinflammatory agents in general

Dexketoprofen [1], mifepristone ---> SmPC of [1] of eMC

Because of a theoretical risk that prostaglandin synthetase inhibitors may alter the efficacy of mifepristone, NSAIDS should not be used for 8-12 days after mifepristone administration.

Dexketoprofen [1], NSAID ---> SmPC of [1] of eMC

Concomitant use of several NSAIDs should be avoided due to an increased risk of adverse effects, particularly upper gastrointestinal disorders.

Dexketoprofen [1], pentoxifylline ---> SmPC of [1] of eMC

Increased risk of bleeding. Increase clinical monitoring and check bleeding time more often

Dexketoprofen [1], platelet aggregation inhibitors ---> SmPC of [1] of eMC

The co-administration may increase the risk of gastrointestinal bleeding

Dexketoprofen [1], pregnancy ---> SmPC of [1] of eMC

During the first and second trimester of pregnancy, dexketoprofen trometamol should not be given unless clearly necessary. During the thirds trimester of pregnancy is contraindicated

Dexketoprofen [1], probenecide ---> SmPC of [1] of eMC

Plasma concentrations of dexketoprofen may be increased; this interaction can be due to an inhibitory mechanism at the site of renal tubular secretion and of glucuronoconjugation and requires adjustment of the dose of dexketoprofen.

Dexketoprofen [1], quinolones ---> SmPC of [1] of eMC

Animal data indicate that high doses of quinolones in combination with NSAIDS can increase the risk of developing convulsions.

Dexketoprofen [1], salicylates ---> SmPC of [1] of eMC

Concomitant use of several NSAIDs should be avoided due to an increased risk of adverse effects, particularly upper gastrointestinal disorders.

Dexketoprofen [1], SSRI ---> SmPC of [1] of eMC

The co-administration can increase the risk of gastrointestinal bleeding

Dexketoprofen [1], sulfonylureas ---> SmPC of [1] of eMC

NSAIDs can increase the hypoglycaemic effect of sulfonylureas by displacement from plasma protein binding sites.

Dexketoprofen [1], sulphonamides ---> SmPC of [1] of eMC

The toxic effects of sulphonamides may be increased.

Dexketoprofen [1], tacrolimus ---> SmPC of [1] of eMC

Nephrotoxicity may be enhanced by NSAIDs via renal prostaglandin mediated effects. During combination therapy, renal function has to be measured.

Dexketoprofen [1], thrombolytics ---> SmPC of [1] of eMC

Increased bleeding risk

Dexketoprofen [1], warfarin ---> SmPC of [1] of eMC

Dexketoprofen [1], zidovudine ---> SmPC of [1] of eMC

Risk of increased red cell line toxicity via action on reticulocytes, with severe anaemia occurring one week after the NSAID is started

Dexketoprofen, potassium-sparing diuretics

The co-administration may decrease the diuretic effect, increase the risk of renal failure due to a reduction in renal blood flow and cause hypercaliemia.

CONTRAINDICATIONS of Dexketoprofen

KERAL tablets must not be administered in the following cases:

- patients hypersensitive to dexketoprofen, to any other NSAID, or to any of the excipients of the product.

- patients in whom substances with a similar action (e.g. acetylsalicylic acid, or other NSAIDs) precipitate attacks of asthma, bronchospasm, acute rhinitis, or cause nasal polyps, urticaria or angioneurotic oedema.

- patients with active or suspected peptic ulcer/haemorrhage or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding) or chronic dyspepsia.

- patients with history of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy

- patients who have gastrointestinal bleeding or other active bleedings or bleeding disorders.

- patients with Crohn's disease or ulcerative colitis.

- patients with a history of bronchial asthma.

- patients with severe heart failure.

- patients with moderate to severe renal dysfunction (creatinine clearance <50 ml/min).

- patients with severely impaired hepatic function (Child-Pugh score 10 - 15).

- patients with haemorrhagic diathesis and other coagulation disorders.

- during the third trimester of pregnancy and lactation period.

http://www.medicines.org.uk/emc/

Dexmedetomidine (Dexdor)

Ability to drive, dexmedetomidine [2] ---> SmPC of [2] of EMA

Patients should be advised to refrain from driving or other hazardous tasks for a suitable period of time after receiving Dexdor for procedural sedation.

Alfentanyl, dexmedetomidine [2] ---> SmPC of [2] of EMA

Specific studies have confirmed enhanced effects with isoflurane, propofol, alfentanil, and midazolam.

Anaesthetics, dexmedetomidine [2] ---> SmPC of [2] of EMA

Co-administration of dexmedetomidine with anaesthetics, sedatives, hypnotics, and opioids is likely to lead to an enhancement of effects, including sedative, anaesthetic and cardiorespiratory effects.

Antihypertensives, dexmedetomidine [2] ---> SmPC of [2] of EMA

The possibility of enhanced hypotensive and bradycardic effects should be considered in patients receiving other medicinal products causing these effects, for example beta blockers

Betablockers, dexmedetomidine [2] ---> SmPC of [2] of EMA

The possibility of enhanced hypotensive and bradycardic effects should be considered in patients receiving other medicinal products causing these effects, for example beta blockers

Breast-feeding, dexmedetomidine [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breastfeeding or to discontinue dexmedetomidine therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

CYP2B6 substrates, dexmedetomidine [2] ---> SmPC of [2] of EMA

In vitro study suggests that interaction potential in vivo exists between dexmedetomidine and substrates with dominant CYP2B6 metabolism.

Cytochrome P450, dexmedetomidine [2] ---> SmPC of [2] of EMA

Inhibition of CYP enzymes including CYP2B6 by dexmedetomidine has been studied in human liver microsome incubations.

Dexmedetomidine [1], drugs inducing bradycardia ---> SmPC of [1] of EMA

The possibility of enhanced hypotensive and bradycardic effects should be considered in patients receiving other medicinal products causing these effects, for example beta blockers

Dexmedetomidine [1], drugs primarily metabolised by CYP2B6 ---> SmPC of [1] of EMA

In vitro study suggests that interaction potential in vivo exists between dexmedetomidine and substrates with dominant CYP2B6 metabolism.

Dexmedetomidine [1], esmolol ---> SmPC of [1] of EMA

Additional effects in an interaction study with esmolol were modest.

Dexmedetomidine [1], fertility ---> SmPC of [1] of EMA

In the rat fertility study, dexmedetomidine had no effect on male or female fertility. No human data on fertility are available.

Dexmedetomidine [1], hypnotics ---> SmPC of [1] of EMA

Dexmedetomidine [1], induction ---> SmPC of [1] of EMA

Induction of dexmedetomidine in vitro was observed on CYP1A2, CYP2B6, CYP2C8, CYP2C9 and CYP3A4, and induction in vivo cannot be excluded. The clinical significance is unknown.

Dexmedetomidine [1], isoflurane ---> SmPC of [1] of EMA

Specific studies have confirmed enhanced effects with isoflurane, propofol, alfentanil, and midazolam.

Dexmedetomidine [1], midazolam ---> SmPC of [1] of EMA

Specific studies have confirmed enhanced effects with isoflurane, propofol, alfentanil, and midazolam.

Dexmedetomidine [1], opiates ---> SmPC of [1] of EMA

Dexmedetomidine [1], pharmacodynamics ---> SmPC of [1] of EMA

However, due to possible pharmacodynamic interactions, when co-administered with dexmedetomidine, a reduction in dosage of dexmedetomidine or the concomitant anaesthetic, sedative, hypnotic or opioid may be required.

Dexmedetomidine [1], pregnancy ---> SmPC of [1] of EMA

Studies in animals have shown reproductive toxicity (see section 5.3). Dexdor should not be used during pregnancy unless the clinical condition of the woman requires treatment with dexmedetomidine.

Dexmedetomidine [1], propofol ---> SmPC of [1] of EMA

Specific studies have confirmed enhanced effects with isoflurane, propofol, alfentanil, and midazolam.

Dexmedetomidine [1], sedatives ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Dexmedetomidine (Dexdor)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Advanced heart block (grade 2 or 3) unless paced

- Uncontrolled hypotension

- Acute cerebrovascular conditions.

https://www.ema.europa.eu/en/documents/product-information/dexdor-epar-product-information_en.pdf 11/06/2025

Other trade names: Dexmedetomidine Accord, Dexdomitor, Sedadex,

Dexrazoxane (Savene)

Ability to drive, dexrazoxane [2] ---> SmPC of [2] of EMA

Dizziness, somnolence and syncope have been reported in a few patients included in Savene studies TT01 and TT02. Dexrazoxane has minor influence on the ability to drive and use machines.

Antineoplastics, dexrazoxane [2] ---> SmPC of [2] of EMA

Dexrazoxane may add to the toxicity induced by the chemotherapy cycle during which the accident took place, requiring careful monitoring of haematological parameters

Breast-feeding, dexrazoxane [2] ---> SmPC of [2] of EMA

It is not known whether dexrazoxane is excreted in human milk. Because of the potential for serious adverse reactions in breast-fed infants exposed to dexrazoxane, breast-feeding is contraindicated during Savene therapy (see section 4.3).

Chemotherapy, dexrazoxane [2] ---> SmPC of [2] of EMA

Dexrazoxane may add to the toxicity induced by the chemotherapy cycle during which the accident took place, requiring careful monitoring of haematological parameters (see section 4.4).

Cyclosporine, dexrazoxane [2] ---> SmPC of [2] of EMA

Excessive immunosuppression with risk of lymphoproliferative disease

Dexrazoxane [1], dimethylsulfoxide ---> SmPC of [1] of EMA

Dimethylsulfoxide (DMSO) should not be used in patients who are administered dexrazoxane to treat anthracycline extravasation

Dexrazoxane [1], doxorubicine ---> SmPC of [1] of EMA

Co-administration of doxorubicin (50 to 60 mg/m2) or epirubicin (60 to 100 mg/m2) did not affect dexrazoxane pharmacokinetics significantly

Dexrazoxane [1], epirubicin ---> SmPC of [1] of EMA

Co-administration of doxorubicin (50 to 60 mg/m2) or epirubicin (60 to 100 mg/m2) did not affect dexrazoxane pharmacokinetics significantly

Dexrazoxane [1], fertility ---> SmPC of [1] of EMA

There are limited fertility data from animal studies available, but testicular changes were observed in rats and rabbits following repeat dosing (see section 5.3).

Dexrazoxane [1], inactivated vaccines ---> SmPC of [1] of EMA

Use an inactivated vaccine where this exists (poliomyelitis).

Dexrazoxane [1], interactions ---> SmPC of [1] of EMA

When tested in five major cytochrome P450 isoenzymes CYP1A, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, none of these were inhibited by dexrazoxane.

Dexrazoxane [1], men ---> SmPC of [1] of EMA

Sexually active men and women of childbearing potential should be advised not to father a child/become pregnant and must use effective contraceptive measures during and up to 6 months after treatment.

Dexrazoxane [1], oral anticoagulants ---> SmPC of [1] of EMA

Patients treated with anticoagulants should be monitored more frequently as cytotoxic agents may interact with oral anticoagulants.

Dexrazoxane [1], pharmacokinetics ---> SmPC of [1] of EMA

Co-administration of doxorubicin (50 to 60 mg/m2) or epirubicin (60 to 100 mg/m2) did not affect dexrazoxane pharmacokinetics significantly.

Dexrazoxane [1], phenytoin ---> SmPC of [1] of EMA

Concomitant use of cytotoxic medicinal products may reduce the absorption of phenytoin leading to an exacerbation of convulsions. Co-administration is not recommended

Dexrazoxane [1], pregnancy ---> SmPC of [1] of EMA

Dexrazoxane should not be administered to pregnant women unless clearly necessary.

Dexrazoxane [1], tacrolimus ---> SmPC of [1] of EMA

Excessive immunosuppression with risk of lymphoproliferative disease

Dexrazoxane [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

Risk of systemic, possible fatal disease. This risk is increased in subjects who are already immunosuppressed by their underlying disease or by concomitant chemotherapy.

Dexrazoxane [1], women of childbearing potential ---> SmPC of [1] of EMA

Women must inform their doctor immediately if they become pregnant (see section 4.3).

Dexrazoxane [1], yellow fever vaccine ---> SmPC of [1] of EMA

Risk of fatal generalised vaccinial disease. The co-administration is contraindicated

Dexrazoxane, epirubicin [2] ---> SmPC of [2] of eMC

Increase of myelosuppression may occur in patients receiving combination therapy of anthracycline and dexrazoxane.

Dexrazoxane, radiotherapy

Possible enhancement of toxicity induced by the radiotherapy, requiring careful monitoring of haematological parameters

CONTRAINDICATIONS of Dexrazoxane (Savene)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Women of childbearing potential not using contraceptive measures

- Breast-feeding

- Concomitant vaccination with yellow fever vaccine

https://www.ema.europa.eu/en/documents/product-information/savene-epar-product-information_en.pdf 06/09/2024

Other trade names: Cardioxane,

Dextromethorphan

Ability to drive, dextromethorphan [2] ---> SmPC of [2] of eMC

Unlikely to produce an effect.

Abiraterone [1], dextromethorphan ---> SmPC of [1] of EMA

Abiraterone, CYP2D6 inhibitor, may increase the systemic exposure (AUC) of dextromethorphan. Caution is advised

Alcohol, dextromethorphan

Alcohol intake during the treatment with dextromethorphan may increase the adverse reactions. It should not be taken together with alcoholic drinks

Amiodarone, dextromethorphan

The CYP2D6 inhibition may increase the plasma concentrations of dextromethorphan

Anticholinergics, dextromethorphan

The anticholinergic effects may be enhanced

Antihistamines, dextromethorphan

The co-administration of dextromethorphan with CNS depressants can result in mutual potentiation of effects

Aripiprazole [1], dextromethorphan ---> SmPC of [1] of EMA

When aripiprazole was administered concomitantly with dextromethorphan, there was no clinically important change in concentrations of dextromethorphan. Thus, no dosage adjustment is required

Barbiturates, dextromethorphan

The co-administration of dextromethorphan with CNS depressants can result in mutual potentiation of effects

Breast-feeding, dextromethorphan [2] ---> SmPC of [2] of eMC

It should only be used when the potential benefit of treatment to the mother exceeds any possible hazards to suckling infant.

Buprenorphine [1], dextromethorphan ---> SmPC of [1] of eMC

This combination increases central nervous system depression

Celecoxib, dextromethorphan

Treatment with celecoxib produced an increase in plasma concentrations of dextromethorphan (CYP2D6 substrate)

Cimetidine, dextromethorphan

The CYP2D6 inhibition may increase the plasma concentrations of dextromethorphan

Cinacalcet [1], dextromethorphan ---> SmPC of [1] of EMA

Clobazam [1], dextromethorphan ---> SmPC of [1] of eMC

Clobazam is a weak CYP2D6 inhibitor. Dose adjustment of drugs metabolized by CYP2D6 may be necessary.

CNS depressants, dextromethorphan

The co-administration of dextromethorphan with CNS depressants can result in mutual potentiation of effects

Cobimetinib [1], dextromethorphan ---> SmPC of [1] of EMA

A clinical drug-drug interaction (DDI) study in cancer patients showed that plasma concentrations of midazolam (a sensitive CYP3A substrate) and dextromethorphan (a sensitive CYP2D6 substrate) were not altered in the presence of cobimetinib.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, dextromethorphan ---> SmPC of [dasabuvir] of EMA

CYP2D6 substrates (e.g. desipramine, metoprolol and dextromethorphan) are not expected to require dose adjustments.

Dextromethorphan [1], IMAOs ---> SmPC of [1] of eMC

Dextromethorphan is contraindicated in individuals who are taking, or have taken, monoamine oxidase inhibitors within the preceding 2 weeks

Dextromethorphan [1], moclobemide ---> SmPC of [1] of eMC

Dextromethorphan is contraindicated in individuals who are taking, or have taken, monoamine oxidase inhibitors within the preceding 2 weeks

Dextromethorphan [1], phenelzine ---> SmPC of [1] of eMC

Phenelzine should not be used in combination with dextromethorphan

Dextromethorphan [1], pregnancy ---> SmPC of [1] of eMC

It should only be used when the potential benefit of treatment to the mother exceeds any possible hazards to the developing foetus

Dextromethorphan [1], tranylcypromine ---> SmPC of [1] of eMC

Dextromethorphan is contraindicated in individuals who are taking, or have taken, monoamine oxidase inhibitors within the preceding 2 weeks

Dextromethorphan, dopamine agonists

The effects of dopaminergic agonist may be enhanced

Dextromethorphan, eliglustat [2] ---> SmPC of [2] of EMA

Concomitant administration of eliglustat with CYP2D6 substrates may increase the exposition of these substrates. Lower doses of medicinal products that are CYP2D6 substrates may be required.

Dextromethorphan, expectorants

The cough reflex inhibition may cause secretion congestion

Dextromethorphan, fluoxetine

The CYP2D6 inhibition may increase the plasma concentrations of dextromethorphan

Dextromethorphan, grapefruit juice

The CYP3A4 inhibition may increase the plasma levels of dextromethorphan

Dextromethorphan, haloperidol

The CYP2D6 inhibition may increase the plasma concentrations of dextromethorphan

Dextromethorphan, ibuprofen

Concomitant use may cause a serotoninergic syndrome. Concomitant use should be avoided within 14 day after taking ibuprofen

Dextromethorphan, isavuconazole [2] ---> SmPC of [2] of EMA

No CRESEMBA dose adjustment necessary. Dextromethorphan: no dose adjustment required.

Dextromethorphan, levomepromazine [2] ---> SmPC of [2] of eMC

Co-administration of levomepromazine and drugs primarily metabolised by the CYP2D6 may result in increased plasma concentrations of the drugs that could increase or prolong both therapeutic or adverse effects of those drugs.

Dextromethorphan, linezolid [2] ---> SmPC of [2] of eMC

There has been one report of a patient experiencing serotonin syndrome-like effects while taking linezolid and dextromethorphan which resolved on discontinuation of both medications.

Dextromethorphan, memantin [2] ---> SmPC of [2] of EMA

Concomitant use should be avoided, owing to the risk of pharmacotoxic psychosis

Dextromethorphan, methylnaltrexone [2] ---> SmPC of [2] of EMA

In a clinical drug interaction study in healthy adult male subjects, a subcutaneous dose of 0.3 mg/kg of methylnaltrexone bromide did not significantly affect the metabolism of dextromethorphan, a CYP2D6 substrate.

Dextromethorphan, mucolytics

The cough reflex inhibition may cause secretion congestion

Dextromethorphan, neuroleptics

The co-administration of dextromethorphan with CNS depressants can result in mutual potentiation of effects

Dextromethorphan, non-selective MAO-inhibitors ---> SmPC of [safinamide] of EMA

There have been reports of medicinal product interactions with the concomitant use of dextromethorphan and non-selective MAO inhibitors.

Dextromethorphan, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

Viekirax administered with or without dasabuvir. CYP2D6 substrates (e.g. desipramine, metoprolol and dextromethorphan) are not expected to require dose adjustments.

Dextromethorphan, panobinostat [2] ---> SmPC of [2] of EMA

Panobinostat increased the Cmax and the AUC of dextromethorphan (a substrate of CYP2D6) by 1.8- and 1.6-fold, respectively, and it cannot be excluded that the effect may be larger on a more sensitive CYP2D6 substrate.

Dextromethorphan, parecoxib [2] ---> SmPC of [2] of EMA

Treatment with valdecoxib produced a 3-fold increase in plasma concentrations of dextromethorphan (CYP2D6 substrate)

Dextromethorphan, paroxetine

The CYP2D6 inhibition may increase the plasma concentrations of dextromethorphan

Dextromethorphan, procarbazine

Concomitant use may cause a serotoninergic syndrome. Concomitant use should be avoided within 14 day after taking procarbazine

Dextromethorphan, propafenone

The CYP2D6 inhibition may increase the plasma concentrations of dextromethorphan

Dextromethorphan, quinidine

The CYP2D6 inhibition may increase the plasma concentrations of dextromethorphan

Dextromethorphan, rasagiline [2] ---> SmPC of [2] of EMA

In view of the MAO inhibitory activity of rasagiline, the concomitant administration of rasagiline and dextromethorphan is not recommended

Dextromethorphan, ritonavir

The CYP2D6 inhibition may increase the plasma concentrations of dextromethorphan

Dextromethorphan, rolapitant [2] ---> SmPC of [2] of EMA

Caution should be taken when rolapitant is combined with a medicinal product metabolised by CYP2D6, notably those having a narrow therapeutic margin

Dextromethorphan, safinamide [2] ---> SmPC of [2] of EMA

There have been reports of medicinal product interactions with the concomitant use of dextromethorphan and non-selective MAO inhibitors. In view of the MAO inhibitory activity of safinamide, the concomitant administration is not recommended,

Dextromethorphan, selegiline

Concomitant use may cause a serotoninergic syndrome. Concomitant use should be avoided within 14 day after taking selegiline

Dextromethorphan, Seville orange

The CYP3A4 inhibition may increase the plasma levels of dextromethorphan

Dextromethorphan, sibutramine [2] ---> SmPC of [2] of eMC

As sibutramine inhibits serotonin reuptake (among other effects), sibutramine should not be used concomitantly with other drugs which also raise serotonin levels in the brain (serotonin syndrome)

Dextromethorphan, simeprevir [2] ---> SmPC of [2] of EMA

No dose adjustment is required

Dextromethorphan, SSRI

The co-administration increases the risk of serotonin syndrome and of neuroleptic malignant syndrome. The combination should be avoided

Dextromethorphan, stiripentol [2] ---> SmPC of [2] of EMA

Stiripentol is an inhibitor of the enzymes CYP2D6 and may markedly increase the plasma concentrations of substances metabolised by these enzymes and increase the risk of adverse reactions

Dextromethorphan, strong CYP2D6 inhibitors

The strong CYP2D6 inhibition may increase the plasma concentrations of dextromethorphan

Dextromethorphan, thioridazine

The CYP2D6 inhibition may increase the plasma concentrations of dextromethorphan

Dextromethorphan, valdecoxib [2] ---> SmPC of [2] of EMA

Valdecoxib, CYP2D6 inhibitor, may increase the plasma concentrations of dextromethorphan

CONTRAINDICATIONS of Dextromethorphan

- BENYLIN DRY COUGHS (NON DROWSY) is contraindicated in individuals with known hypersensitivity to the product or any of its components.

- BENYLIN DRY COUGHS (NON DROWSY) is contraindicated in individuals who are taking, or have taken, monoamine oxidase inhibitors within the preceding two weeks.

The concomitant use of a dextromethorphan-containing product and monoamine oxidase inhibitors, can occasionally result in symptoms such as hyperpyrexia, hallucinations, gross excitation or coma.

- Dextromethorphan, in common with other centrally acting antitussive agents, should not be given to subjects in, or at risk of developing respiratory failure.

- Not to be used in children under the age of 12 years.

http://www.medicines.org.uk/emc/

Dextromethorphan/quinidine (Nuedexta)

Ability to drive, dextromethorphan/quinidine [2] ---> SmPC of [2] of EMA

Patients should be warned about the potential for CNS-related effects like somnolence, dizziness and syncope or impaired vision

Alcohol, dextromethorphan/quinidine [2] ---> SmPC of [2] of EMA

Caution should be used when this medicinal product is taken in combination with alcohol or other centrally acting medicinal products that might increase the risk of adverse reactions such as somnolence and dizziness.

Amitriptyline, dextromethorphan/quinidine [2] ---> SmPC of [2] of EMA

Quinidine is a potent inhibitor of CYP2D6. Treatment with dextromethorphan/quinidine may therefore result in elevated plasma levels and accumulation of co-administered medicinal products that undergo extensive CYP2D6 metabolism.

Amprenavir, dextromethorphan/quinidine [2] ---> SmPC of [2] of EMA

Concomitant administration of medicines that inhibit CYP3A4 can be expected to increase plasma levels of quinidine, which could increase risk relating to QTc prolongation. Strong and moderate CYP3A4 inhibitors should be avoided during treatment.

Anticholinergics, dextromethorphan/quinidine [2] ---> SmPC of [2] of EMA

Patients should be monitored for worsening clinical condition in myasthenia gravis and other conditions that may be adversely affected by anticholinergic effects.

Aprepitant, dextromethorphan/quinidine [2] ---> SmPC of [2] of EMA

Atazanavir, dextromethorphan/quinidine [2] ---> SmPC of [2] of EMA

Atomoxetine, dextromethorphan/quinidine [2] ---> SmPC of [2] of EMA

Breast-feeding, dextromethorphan/quinidine [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from NUEDEXTA therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Carbamazepine, dextromethorphan/quinidine [2] ---> SmPC of [2] of EMA

Potent CYP3A4 inducers may accelerate the metabolism of quinidine, resulting in lower plasma concentrations and hence decreased inhibition of CYP2D6. This may lead to decreased efficacy of dextromethorphan/quinidine.

Chlorpromazine, dextromethorphan/quinidine [2] ---> SmPC of [2] of EMA

Concomitant use of dextromethorphan/quinidine and chlorpromazine, CYP2D6 substrate that also prolongs QT interval, requires caution

Clarithromycin, dextromethorphan/quinidine [2] ---> SmPC of [2] of EMA

CNS depressants, dextromethorphan/quinidine [2] ---> SmPC of [2] of EMA

Caution should be used when dextromethorphan/quinidine is taken in combination with other centrally acting medicinal products that might increase the risk of adverse reactions such as somnolence and dizziness.

Codeine, dextromethorphan/quinidine [2] ---> SmPC of [2] of EMA

In the case of pro-drugs whose actions are mediated by the CYP2D6-produced metabolites, efficacy may be substantially reduced by dextromethorphan/quinidine due to inhibition of CYP2D6 and hence impaired formation of the active metabolite.

Dabigatran, dextromethorphan/quinidine [2] ---> SmPC of [2] of EMA

Quinidine is an inhibitor of P-glycoprotein. Concomitant administration of quinidine with dabigatran, a P-glycoprotein substrate, could increase dabigatran plasma concentrations

Desipramine, dextromethorphan/quinidine [2] ---> SmPC of [2] of EMA

Given the pharmacodynamic and pharmacokinetic interactions, concomitant use of dextromethorphan/quinidine and tricyclic antidepressants is not recommended due to the elevated risk of serotonin syndrome

Dextromethorphan/quinidine [1], digoxin ---> SmPC of [1] of EMA

Quinidine is an inhibitor of P-glycoprotein. Concomitant administration of quinidine with digoxin, a P-glycoprotein substrate, results in serum digoxin levels that may be as much as doubled.

Dextromethorphan/quinidine [1], diltiazem ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], drugs primarily metabolised by CYP2D6 ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], drugs primarily metabolised by CYP2D6 and prolong the QT interval ---> SmPC of [1]

Concomitant medicinal products that both prolong the QT interval and are primarily metabolised by CYP2D6 are of particular potential concern.

Dextromethorphan/quinidine [1], drugs primarily metabolised by CYP2D6 with narrow therapeutic index ---> SmPC of [

Medicinal products that are dependent on CYP2D6 metabolism, especially those with a relatively narrow therapeutic index, should generally be avoided during treatment with dextromethorphan/quinidine

Dextromethorphan/quinidine [1], erythromycin ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], fertility ---> SmPC of [1] of EMA

In pre-clinical studies no effect on fertility was observed in male and female rats (see section 5.3).

Dextromethorphan/quinidine [1], flecainide ---> SmPC of [1] of EMA

Concomitant use of dextromethorphan/quinidine and flecainide, CYP2D6 substrate that also prolongs QT interval, requires caution

Dextromethorphan/quinidine [1], fluconazole ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], fosamprenavir ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], grapefruit juice ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], haloperidol ---> SmPC of [1] of EMA

Concomitant use of dextromethorphan/quinidine and haloperidol, CYP2D6 substrate that also prolongs QT interval, requires caution

Dextromethorphan/quinidine [1], hydrocodone ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], IMAOs ---> SmPC of [1] of EMA

Nuedexta must not be used with MAOIs, or in patients who have taken MAOIs within the preceding 14 days due to the risk of serotonin syndrome

Dextromethorphan/quinidine [1], imipramine ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], indinavir ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], itraconazol ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], ketoconazole ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], mefloquine ---> SmPC of [1] of EMA

Dextromethorphan/quinidine is contraindicated in patients receiving concomitant treatment with mefloquine

Dextromethorphan/quinidine [1], memantin ---> SmPC of [1] of EMA

Dextromethorphan and memantine are antagonists of the N-D-aspartate (NMDA) receptor which could theoretically result in an additive effect at NMDA receptors and potentially an increased incidence of adverse reactions.

Dextromethorphan/quinidine [1], metoprolol ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], moclobemide ---> SmPC of [1] of EMA

Nuedexta must not be used with MAOIs, or in patients who have taken MAOIs within the preceding 14 days due to the risk of serotonin syndrome

Dextromethorphan/quinidine [1], moderate CYP3A4 inhibitors ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], nefazodone ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], nelfinavir ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], nortriptyline ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], paroxetine ---> SmPC of [1] of EMA

Paroxetine exposure (AUC0-24) increased by 1.7 fold and Cmax increased by 1.5 fold. If NUEDEXTA and paroxetine are prescribed concomitantly, the initial dose of paroxetine should be reduced.

Dextromethorphan/quinidine [1], perphenazine ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], phenelzine ---> SmPC of [1] of EMA

Nuedexta must not be used with MAOIs, or in patients who have taken MAOIs within the preceding 14 days due to the risk of serotonin syndrome

Dextromethorphan/quinidine [1], phenobarbital ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], phenytoin ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], pregnancy ---> SmPC of [1] of EMA

As this medicinal product may cause foetal harm, it is not recommended during pregnancy and in women of childbearing potential not using contraception.

Dextromethorphan/quinidine [1], QT interval prolonging drugs ---> SmPC of [1] of EMA

When initiating treatment with dextromethorphan/quinidine in patients at risk of QT prolongation, ECG evaluation of the QT interval should be conducted at baseline and at 2 hours after the first dose administered in the fasted state

Dextromethorphan/quinidine [1], quinidine ---> SmPC of [1] of EMA

Dextromethorphan/quinidine is contraindicated in patients receiving concomitant treatment with quinidine

Dextromethorphan/quinidine [1], quinine ---> SmPC of [1] of EMA

Dextromethorphan/quinidine is contraindicated in patients receiving concomitant treatment with quinine

Dextromethorphan/quinidine [1], rifampicin ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], ritonavir ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], saquinavir ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], serotonergic medicines ---> SmPC of [1] of EMA

When dextromethorphan/quinidine is used with other serotoninergic medicines, the risk of "serotonin syndrome" may be increased due to pharmacodynamic interaction.

Dextromethorphan/quinidine [1], SSRI ---> SmPC of [1] of EMA

Caution should be exercised if patients are treated with concomitant selective serotonin reuptake inhibitors (SSRIs).

Dextromethorphan/quinidine [1], St. John's wort ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], tamoxifen ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], telithromycin ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], thioridazine ---> SmPC of [1] of EMA

Thioridazine, a CYP2D6 substrate that also prolong the QT interval is contraindicated

Dextromethorphan/quinidine [1], ticagrelor ---> SmPC of [1] of EMA

Quinidine is an inhibitor of P-glycoprotein. Concomitant administration of quinidine with ticagrelor, a P-glycoprotein substrate, could increase ticagrelor plasma concentrations

Dextromethorphan/quinidine [1], tricyclic antidepressant ---> SmPC of [1] of EMA

Dextromethorphan/quinidine [1], verapamil ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Dextromethorphan/quinidine (Nuedexta)

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

- Patients with a history of quinidine-, quinine-, mefloquine-induced thrombocytopenia, hepatitis, bone marrow depression or lupus-like syndrome

- Patients receiving concomitant treatment with quinidine, quinine, or mefloquine

- Patients with a prolonged QT interval, congenital long QT syndrome or a history suggestive of torsades de pointes ventricular tachycardia

- Patients receiving concomitant treatment with thioridazine, a medicinal product that both significantly prolongs QT interval and is primarily metabolized by CYP2D6. Interaction with NUEDEXTA may result in an increased effect on QT interval

- Patients with complete atrioventricular (AV) block without implanted pacemakers, or in patients who are at high risk of complete AV block

- Patients taking monoamine oxidase inhibitors (MAOIs) or who have taken MAOIs within the preceding 14 days due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Treatment with an MAOI should not be initiated until at least 14 days after stopping NUEDEXTA

https://www.ema.europa.eu/en/documents/product-information/nuedexta-epar-product-information_en.pdf 11/03/2016 (withdrawn)

Dextropropoxyphene

Ability to drive, dextropropoxyphene

The opioid analgesic may cause somnolence, decreased psychic alertness and vertigo

Ability to drive, opioid analgesics

The opioid analgesic may cause somnolence, decreased psychic alertness and vertigo

Alprazolam, dextropropoxyphene

Increased plasma levels of alprazolam

Amphetamine, dextropropoxyphene

Possible enhancement of stimulant effect on the CNS of amphetamine

Betablockers, dextropropoxyphene

Increased bioavailability and decreased clearance of betablocker

Breast-feeding, dextropropoxyphene

Dextropropoxyphene is excreted in human milk in small quantities.

Buprenorphine [1], dextropropoxyphene ---> SmPC of [1] of eMC

This combination increases central nervous system depression

Carbamazepine [1], dextropropoxyphene ---> SmPC of [1] of eMC

The plasma concentrations of carbamazepine may be increased

Dextropropoxyphene, drugs primarily metabolised by CYP2D6

Dextropropoxyphene, CYP2D6 inhibitor, may increase the plasma concentrations of the medicinal products metabolized by CYP2D6

Dextropropoxyphene, drugs primarily metabolised by CYP3A4

Dextropropoxyphene, CYP3A4 inhibitor, may increase the plasma concentrations of the medicinal products metabolized by CYP3A4

Dextropropoxyphene, IMAOs

Possible enhancement of effect and toxicity of dextropropoxyphene

Dextropropoxyphene, nalbuphine

Pure µ agonists decrease the analgetic effect due to competitive blockade of receptors. Concomitant use is contraindicated.

Dextropropoxyphene, nicotine

Decreased analgetic effect of dextropropoxyphene

Dextropropoxyphene, orphenadrine

The co-administration may cause tremor, confusion and anxiety states

Dextropropoxyphene, oxcarbazepine [2] ---> SmPC of [2] of eMC

Dextropropoxyphene had no effect on the pharmacokinetics of MHD.

Dextropropoxyphene, pregnancy

Dextropropoxyphene should be avoided during pregnancy unless essential.

Dextropropoxyphene, ritonavir

The co-administration may increase the plasma levels and toxicity of dextropropoxyphene

Dextropropoxyphene, tricyclic antidepressant

Increase of plasma levels of the tricyclic antidepressant. The co-administration is not recommended

Dextropropoxyphene, warfarin

Enhancement of anticoagulant effect and increase of prothrombin time

Diacerein

Aluminium, diacerein

Decreased absorption of diacerein. Separate administration by at least 2 hours

Antacids, diacerein

Decreased absorption of diacerein. Separate administration by at least 2 hours

Breast-feeding, diacerein

Diacerein is contraindicated in lactating women.

Calcium, diacerein

Decreased absorption of diacerein. Separate administration by at least 2 hours

Diacerein, magnesium

Decreased absorption of diacerein. Separate administration by at least 2 hours

Diacerein, pregnancy

Diacerein is contraindicated in pregnancy

Diazepam

Ability to drive, diazepam [2] ---> SmPC of [2] of eMC

Sedation, amnesia, impaired concentration, and impaired muscular function may adversely affect the ability to drive or use machines.

ACE inhibitors [1], diazepam ---> SmPC of [1] of eMC

Enhanced hypotensive effect

AIIRA, diazepam [2] ---> SmPC of [2] of eMC

Enhanced hypotensive effect

Ajmaline, diazepam

The co-administration of ajmaline with diazepam increases the frequency of long-lasting cholestasis

Alcohol, diazepam [2] ---> SmPC of [2] of eMC

Diazepam should not be used together with alcohol (enhanced sedative effects)

Alfa-adrenergic receptor blockers, diazepam

Enhanced hypotensive and sedative effect

Anaesthetics, diazepam [2] ---> SmPC of [2] of eMC

Enhancement of the central depressive effect may occur

Antidepressants, diazepam [2] ---> SmPC of [2] of eMC

Enhancement of the central depressive effect may occur

Antiepileptics, diazepam [2] ---> SmPC of [2] of eMC

Enhancement of the central depressive effect may occur

Antihypertensives [1], diazepam ---> SmPC of [1] of eMC

Enhanced hypotensive effect

Anxiolytics, diazepam [2] ---> SmPC of [2] of eMC

Enhancement of the central depressive effect may occur

Atazanavir/cobicistat [1], diazepam ---> SmPC of [1] of EMA

Concentrations of the sedative/hypnotic may be increased when co-administered with EVOTAZ. The mechanism is inhibition of CYP3A4 by cobicistat. For the sedative/hypnotic, dose reduction may be necessary and concentration monitoring is recommended.

Bazedoxifene, diazepam ---> SmPC of [conjugated oestrogens/bazedoxifene] of EMA

Based on in vitro bazedoxifene plasma protein-binding characteristics, interactions with warfarin, digoxin or diazepam are unlikely.

Betablockers, diazepam [2] ---> SmPC of [2] of eMC

Enhanced hypotensive effect

Breast-feeding, diazepam [2] ---> SmPC of [2] of eMC

Since benzodiazepines are found in the breast milk, benzodiazepines should not be given to breast feeding mothers.

Brivaracetam [1], diazepam ---> SmPC of [1] of EMA

Brivaracetam may increase plasma concentrations of medicinal products metabolised by CYP2C19 (e.g. lansoprazole, omeprazole, diazepam).

Buspirone [1], diazepam ---> SmPC of [1] of eMC

After addition of buspirone to the diazepam dose regimen, no statistically significant differences in the steady-state pharmacokinetic parameters (Cmax , AUC, and C min ) were observed for diazepam

Caffeine, diazepam [2] ---> SmPC of [2] of eMC

Concurrent use of diazepam and caffeine may result in reduced sedative and anxiolytic effects of diazepam.

Calcium antagonists, diazepam [2] ---> SmPC of [2] of eMC

Enhanced hypotensive effect

Carbamazepine, diazepam

Carbamazepine, strong CYP3A4 inductor, may decrease the plasma levels of diazepam. The co-administration is not recommended

Cimetidine [1], diazepam ---> SmPC of [1] of eMC

Cimetidine can prolong the elimination of drugs metabolised by oxidation in the liver.

Ciprofloxacin, diazepam

The co-administration may decrease diazepam clearance and prolong its half life

Clozapine, diazepam

Pharmacodynamic synergism: severe hypotension, respiratory depression, unconsciousness and potentially fatal respiratory and/or cardiac arrest. The combination should be avoided

CNS depressants, diazepam [2] ---> SmPC of [2] of eMC

Enhancement of the central depressive effect may occur

Cobicistat [1], diazepam ---> SmPC of [1] of EMA

Concentrations of this sedative/hypnotic may be increased when co-administered with cobicistat.

Conjugated oestrogens/bazedoxifene [1], diazepam ---> SmPC of [1] of EMA

Based on in vitro bazedoxifene plasma protein-binding characteristics, interactions with warfarin, digoxin or diazepam are unlikely.

Corticosteroids, diazepam

The enzymatic induction may decrease the plasma levels of diazepam.

Dabrafenib [1], diazepam ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Darunavir/cobicistat [1], diazepam ---> SmPC of [1] of EMA

Darunavir/ritonavir, diazepam ---> SmPC of [darunavir] of EMA

Sedative/hypnotics are extensively metabolised by CYP3A. Co-administration with boosted darunavir may cause a large increase in the concentration of these medicines.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, diazepam ---> SmPC of [dasabuvir] of EMA

CYP2C19 induction by ritonavir. No dose adjustment required for diazepam; increase dose if clinically indicated.

Diazepam [1], disulfiram ---> SmPC of [1] of eMC

Enhancing of the sedative effect of diazepam

Diazepam [1], diuretics ---> SmPC of [1] of eMC

Enhanced hypotensive effect

Diazepam [1], erythromycin ---> SmPC of [1] of eMC

The enzymatic inhibitor reduces clearance and may potentiate the action of benzodiazepines

Diazepam [1], estrogens ---> SmPC of [1] of eMC

Possible inhibition of hepatic metabolism of diazepam.

Diazepam [1], fluoxetine ---> SmPC of [1] of eMC

The CYP 2C19 inhibition may increase the plasma levels of diazepam

Diazepam [1], general anesthetics ---> SmPC of [1] of eMC

Enhancement of the central depressive effect may occur

Diazepam [1], grapefruit juice ---> SmPC of [1] of eMC

The CYP3A4 inhibition may increase the plasma levels of diazepam.

Diazepam [1], hydralazine ---> SmPC of [1] of eMC

Enhanced hypotensive effect

Diazepam [1], hypnotics ---> SmPC of [1] of eMC

Enhancement of the central depressive effect may occur

Diazepam [1], itraconazol ---> SmPC of [1] of eMC

The CYP3A4 inhibition may increase the plasma levels of diazepam.

Diazepam [1], ketoconazole ---> SmPC of [1] of eMC

The CYP3A4 and CYP 2C19 inhibition may increase the plasma levels of diazepam

Diazepam [1], levodopa ---> SmPC of [1] of eMC

There have been rare reports of possible antagonism of levodopa by diazepam.

Diazepam [1], moxonidine ---> SmPC of [1] of eMC

Enhanced hypotensive and sedative effect

Diazepam [1], neuroleptics ---> SmPC of [1] of eMC

Enhancement of the central depressive effect may occur

Diazepam [1], nitroprussiate ---> SmPC of [1] of eMC

Enhanced hypotensive effect

Diazepam [1], organic nitrates ---> SmPC of [1] of eMC

Enhanced hypotensive effect

Diazepam [1], pregnancy ---> SmPC of [1] of eMC

If diazepam is prescribed to a woman of childbearing potential, she should be warned to contact her physician regarding discontinuance of diazepam if she intends to become, or suspects that she is pregnant.

Diazepam [1], sedating antihistamines ---> SmPC of [1] of eMC

Enhancement of the central depressive effect may occur

Diazepam [1], sedatives ---> SmPC of [1] of eMC

Enhancement of the central depressive effect may occur

Diazepam [1], sodium valproate ---> SmPC of [1] of eMC

Diazepam has been reported to be displaced from protein-binding sites by sodium valproate (increased serum levels: increased risk of drowsiness).

Diazepam [1], vasodilators ---> SmPC of [1] of eMC

Enhanced hypotensive effect

Diazepam [1], zidovudine ---> SmPC of [1] of eMC

Increased zidovudine clearance by diazepam

Diazepam, diltiazem

The co-administration may decrease the plasma levels of diltiazem

Diazepam, elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Concentrations of other benzodiazepines, including diazepam, may be increased when administered with Genvoya. With other sedatives/hypnotics, dose reduction may be necessary and concentration monitoring is recommended.

Diazepam, elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

The co-administration may increase the plasma concentrations of sedative. Dose reduction may be necessary and concentration monitoring is recommended.

Diazepam, enzalutamide [2] ---> SmPC of [2] of EMA

Enzalutamide, enzymatic inductor, may increase the metabolism of diazepam and decrease its plasma levels and effect

Diazepam, enzyme inhibitors

Known inhibitors of hepatic enzymes, particularly cytochrome P450 have been shown to reduce the clearance of benzodiazepines and may potentiate their action

Diazepam, esketamine

Increased pharmacodynamic effect of esketamine

Diazepam, esomeprazole [2] ---> SmPC of [2] of EMA

Esomeprazole inhibits CYP2C19, the major esomeprazole metabolising enzyme. Thus, when esomeprazole is combined with medicinal products metabolised by CYP2C19, the plasma concentrations of these medicinal products may be increased

Diazepam, ethinylestradiol/chlormadinone

Ethinylestradiol may inhibit the hepatic microsomal enzymes and increase plasma concentrations of diazepam

Diazepam, etravirine [2] ---> SmPC of [2] of EMA

Etravirine is expected to increase plasma concentrations of diazepam. Alternatives to diazepam should be considered.

Diazepam, fluvoxamine [2] ---> SmPC of [2] of eMC

The plasma levels of oxidatively metabolised benzodiazepines are likely to be increased when co-administered with fluvoxamine. The dosage of these benzodiazepines should be reduced during co-administration with fluvoxamine.

Diazepam, fosaprepitant

The CYP3A4 and CYP2C19 inhibition may increase the plasma levels of diazepam

Diazepam, fosphenytoin [2] ---> SmPC of [2] of eMC

Diazepam may increase or decrease phenytoin serum levels

Diazepam, hydroxycobalamin

Physical incompatibility (particle formation). These medicinal products must not be administered simultaneously through the same intravenous line as hydroxocobalamine

Diazepam, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with diazepam may increase the serum concentrations of diazepam. Concentration monitoring of diazepam is recommended and dose reduction may be considered.

Diazepam, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir should not be administered with diazepam

Diazepam, ivacaftor [2] ---> SmPC of [2] of EMA

Administration of ivacaftor may increase systemic exposure of medicinal products which are substrates of CYP3A, which may increase or prolong their therapeutic effect and adverse reactions.

Diazepam, ketamine

Increased pharmacodynamic effect of ketamine

Diazepam, letermovir [2] ---> SmPC of [2] of EMA

Letermovir has the potential to decrease the exposure of CYP2C9 and/or CYP2C19 substrates potentially resulting in subtherapeutic levels.

Diazepam, mephenytoin

Increased hydantoin plasma levels

Diazepam, modafinil [2] ---> SmPC of [2] of eMC

Substances that are largely eliminated via CYP2C19 metabolism may have reduced clearance upon co-administration of modafinil and may thus require dosage reduction.

Diazepam, muscle relaxants

Possible pharmacodynamic antagonism. Modified intensity of neuromuscular blockage. Special caution is recommended.

Diazepam, nelfinavir [2] ---> SmPC of [2] of EMA

Co-administration of nelfinavir with inhibitors of CYP2C19 may be expected to reduce the conversion of nelfinavir to its major active metabolite M8 (tert-butyl hydroxy nelfinavir) with a concomitant increase in plasma nelfinavir levels

Diazepam, nicotine

The clearance of diazepam can be accelerated by smokers

Diazepam, nilutamide

Nilutamide may inhibit the hepatic metabolism of diazepam and increase its plasma levels

Diazepam, olanzapine [2] ---> SmPC of [2] of EMA

Olanzapine does not inhibit the main CYP450 isoenzymes in vitro (e.g. 1A2, 2D6, 2C9, 2C19, 3A4). Thus no particular interaction is expected as verified through in vivo studies where no inhibition of metabolism was found

Diazepam, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

CYP2C19 induction by ritonavir. No dose adjustment required for diazepam; increase dose if clinically indicated.

Diazepam, omeprazole [2] ---> SmPC of [2] of eMC

As omeprazole is metabolised in the liver through cytochrome P450, it can prolong the elimination of diazepam

Diazepam, opioid analgesics

The co-administration may enhance the depressive effect on the CNS and an enhancement of the euphoria, leading to an increase in psychic dependence

Diazepam, oral contraceptives

The co-administration may increase the plasma levels of diazepam and cause intermenstrual bleeding

Diazepam, pancuronium [2] ---> SmPC of [2] of eMC

Potentiation of the duration of action of pancuronium and the intensity of neuromuscular block.

Diazepam, parecoxib [2] ---> SmPC of [2] of EMA

Caution should be observed when administering parecoxib with medicinal products known to be substrates of CYP2C19

Diazepam, phenytoin

Diazepam may increase phenytoin serum levels

Diazepam, posaconazole

Posaconazole, strong CYP3A4 inhibitor, may increase the plasma levels of diazepam

Diazepam, prajmalium

The co-administration of prajmalium with diazepam increases the frequency of long-lasting cholestasis

Diazepam, primidone

Chronic administration of primidone may stimulate the metabolism of diazepam and reduces its levels. It has been also reported in isolated cases inhibition of the metabolism

Diazepam, rifabutin

Rifabutin has a similar structure as rifampicin. Concomitant use of rifabutin and diazepam may decrease the diazepam effects

Diazepam, rifampicin [2] ---> SmPC of [2] of eMC

The enzymatic inductor may increase clearance of benzodiazepines

Diazepam, riluzole [2] ---> SmPC of [2] of EMA

In vitro studies suggest that CYP1A2 is the principal isozyme involved in the initial oxidative metabolism of riluzole. Inhibitors of CYP1A2 could potentially decrease the rate of riluzole elimination

Diazepam, ritonavir [2] ---> SmPC of [2] of EMA

Increased plasma concentrations of diazepam, increasing the risk of extreme sedation and respiratory depression and is therefore contraindicated

Diazepam, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Increased benzodiazepine plasma concentrations. Careful monitoring of patients with regard to sedative effects is warranted.

Diazepam, stiripentol [2] ---> SmPC of [2] of EMA

The CYP3A4 and CYP2C19 inhibition may increase the plasma levels of diazepam with potential risk of overdose.

Diazepam, strong CYP2C19 inhibitors

The strong CYP2C19 inhibition may increase the plasma concentrations of diazepam

Diazepam, strong CYP3A4 inductors

The strong CYP3A4 induction may decrease the plasma levels of diazepam. The co-administration is not recommended

Diazepam, strong CYP3A4 inhibitors

The strong CYP3A4 inhibition may increase the plasma concentrations of diazepam

Diazepam, succinylcholine

Possible pharmacodynamic antagonism. Modified intensity of neuromuscular blockage. Special caution is recommended.

Diazepam, sultiame

The co-administration may increase the plasma levels of diazepam. Adjustment of the dose may be required

Diazepam, suxamethonium

Possible pharmacodynamic antagonism. Modified intensity of neuromuscular blockage. Special caution is recommended.

Diazepam, telithromycin

The CYP3A4 inhibition may increase the plasma levels of diazepam. Oral coadministration should be avoided

Diazepam, theophylline

Counteraction of the pharmacodynamic effects of diazepam, e.g. reduction of sedation and psychomotor effects. Special caution is recommended

Diazepam, topiramate [2] ---> SmPC of [2] of eMC

Topiramate inhibits the enzyme CYP 2C19 and may interfere with other substances metabolized via this enzyme

Diazepam, tubocuranine

Possible pharmacodynamic antagonism. Modified intensity of neuromuscular blockage. Special caution is recommended.

Diazepam, valdecoxib [2] ---> SmPC of [2] of EMA

Valdecoxib, CYP2C19 inhibitor, may increase the plasma concentrations of diazepam

Diazepam, valproic acid

Valproate displaces diazepam from its protein binding and inhibits its metabolism.

Diazepam, venlafaxine [2] ---> SmPC of [2] of eMC

Venlafaxine has no effects on the pharmacokinetics and pharmacodynamics of diazepam and its active metabolite, desmethyldiazepam. It is unknown whether a pharmacokinetic and/or pharmacodynamic interaction with other benzodiazepines exists.

CONTRAINDICATIONS of Diazepam

- Known hypersensitivity to diazepam, benzodiazepines or any of the excipients

- Phobic or obsessional states; chronic psychosis, hyperkinesis (paradoxical reactions may occur)

- Acute pulmonary insufficiency; respiratory depression, acute or chronic severe respiratory insufficiency (ventilatory failure may be exacerbated)

- Myasthenia gravis (condition may be exacerbated)

- Sleep apnoea (condition may be exacerbated)

- Severe hepatic insufficiency (elimination half-life of diazepam may be prolonged)

- Acute porphyria

- Diazepam should not be used as monotherapy in patients with depression or those with anxiety and depression as suicide may be precipitated in such patients.

- Hypersensitivity to egg or soyabean as egg phospholipid and soyabean oil are included in the preparation.

- Planning a pregnancy

- Pregnancy (unless there are compelling reasons

http://www.medicines.org.uk/emc/

Dibotermin alfa (InductOs)

Breast-feeding, dibotermin alfa [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to abstain from InductOs therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Dibotermin alfa [1], fertility ---> SmPC of [1] of EMA

No impact on fertility was detected in non-clinical studies. No clinical data are available; potential risk for human is unknown.

Dibotermin alfa [1], glucocorticoids ---> SmPC of [1] of EMA

In non-clinical studies, concurrent administration of glucocorticoids depressed bone repair (measured as a % change from control), but the effects of InductOs were not altered.

Dibotermin alfa [1], hemostatic agents ---> SmPC of [1] of EMA

The use of these products in close proximity to InductOs is not recommended as this may lead to bone formation at the site of implant of the fibrin-based haemostatic agent or sealant (see section 4.2).

Dibotermin alfa [1], NSAID ---> SmPC of [1] of EMA

Although patient outcome was not affected, an interaction between NSAIDs and InductOs cannot be excluded.

Dibotermin alfa [1], pharmacokinetics ---> SmPC of [1] of EMA

As dibotermin alfa is a protein and has not been identified in the general circulation, it is an unlikely candidate for pharmacokinetic drug-drug interactions.

Dibotermin alfa [1], pregnancy ---> SmPC of [1] of EMA

InductOs is not recommended during pregnancy and in women of childbearing potential not using contraception (see section 4.4).

CONTRAINDICATIONS of Dibotermin alfa (InductOs)

InductOs is contraindicated for patients with:

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1

- Skeletal immaturity

- Any active malignancy or patient undergoing treatment for a malignancy

- An active infection at the operative site

- Persistent compartment syndrome or neurovascular residua of compartment syndrome

- Pathological fractures such as those observed in (but not limited to) Paget's disease or in metastatic bone

https://www.ema.europa.eu/en/documents/product-information/inductos-epar-product-information_en.pdf 18/10/2021

Diclofenac

Ability to drive, diclofenac [2] ---> SmPC of [2] of eMC

Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.

ACE inhibitors, diclofenac [2] ---> SmPC of [2] of eMC

Reduced antihypertensive effect

Algeldrate/magnesium hydroxide, diclofenac

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Aluminium hydroxide, diclofenac

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Anticoagulants, diclofenac

Caution is recommended as concomitant use may increase bleeding risk

Antidiabetics, diclofenac [2] ---> SmPC of [2] of eMC

There have been isolated reports of hypoglycaemic and hyperglycaemic effects which have required adjustment to the dosage of hypoglycaemic agents.

Antihypertensives, diclofenac [2] ---> SmPC of [2] of eMC

Reduced antihypertensive effect

Betablockers, diclofenac [2] ---> SmPC of [2] of eMC

NSAIDs (especially indometacin) may reduce the antihypertensive effects of beta-blockers possibly by inhibiting renal prostaglandin synthesis and/or causing sodium and fluid retention.

Bile-acid sequestrants, diclofenac

Decreased absorption of diclofenac

Breast-feeding, diclofenac [2] ---> SmPC of [2] of eMC

NSAIDs can appear in breast milk in very low concentrations. NSAIDs should, if possible, be avoided when breastfeeding.

Calcium antagonists, diclofenac

Diclofenac may increase the elimination of the calcium channel blocker

Carbaldrate, diclofenac

The aluminium salt decreases the absorption of the co-administered active principle. Separate administration by at least 2 hours

Cardiac glycosides [1], diclofenac ---> SmPC of [1] of eMC

NSAID may exacerbate cardiac failure, reduce the glomerular filtration rate and increase plasma levels of the cardiac glycoside

Ceftriaxone, diclofenac

Diclofenac may increase the elimination of ceftriaxone

Certoparin, diclofenac

The co-administration may enhance the pharmacological effects of certoparin

Cholestyramine, diclofenac

Decreased absorption of diclofenac.

Clodronate, diclofenac

Patients receiving NSAIDs in addition to sodium clodronate have developed renal dysfunction.

Colestipol, diclofenac

Decreased absorption of diclofenac

Corticosteroids, diclofenac [2] ---> SmPC of [2] of eMC

lncreased risk of gastrointestinal ulceration or bleeding

Coumarin anticoagulants, diclofenac

The NSAID may enhance the effects of anti-coagulant.

Coxibs, diclofenac [2] ---> SmPC of [2] of eMC

Concomitant use of several NSAIDs should be avoided due to an increased risk of adverse effects, particularly upper gastrointestinal disorders.

Cyclosporine [1], diclofenac ---> SmPC of [1] of eMC

lncreased risk of nephrotoxicity.

Diclofenac [1], digoxin ---> SmPC of [1] of eMC

NSAID may exacerbate cardiac failure, reduce the glomerular filtration rate and increase plasma levels of the cardiac glycoside

Diclofenac [1], diuretics ---> SmPC of [1] of eMC

Reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity of NSAIDs

Diclofenac [1], lithium ---> SmPC of [1] of eMC

Decreased elimination of lithium

Diclofenac [1], methotrexate ---> SmPC of [1] of eMC

Decreased elimination of methotrexate.

Diclofenac [1], NSAID ---> SmPC of [1] of eMC

Concomitant use of several NSAIDs should be avoided due to an increased risk of adverse effects, particularly upper gastrointestinal disorders.

Diclofenac [1], platelet aggregation inhibitors ---> SmPC of [1] of eMC

lncreased risk of gastrointestinal bleeding

Diclofenac [1], pregnancy ---> SmPC of [1] of eMC

NSAIDs should not be used during the first two trimesters of pregnancy or labour unless the potential benefit to the patient outweighs the potential risk to the foetus. The use in the last trimester of pregnancy is contraindicated.

Diclofenac [1], quinolones ---> SmPC of [1] of eMC

Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.

Diclofenac [1], SSRI ---> SmPC of [1] of eMC

lncreased risk of gastrointestinal bleeding

Diclofenac [1], zidovudine ---> SmPC of [1] of eMC

Increased risk of haematological toxicity when NSAIDs are given with zidovudine.

Diclofenac, drospirenone

Risk of hyperkalaemia

Diclofenac, erlotinib

Possible increased risk of bleeding

Diclofenac, fluconazole [2] ---> SmPC of [2] of eMC

Fluconazole has the potential to increase the systemic exposure of NSAIDs that are metabolized by CYP2C9. Frequent monitoring for adverse events and toxicity related to NSAIDs is recommended. Adjustment of dose of NSAIDs may be needed.

Diclofenac, fossil tree

Additive anticoagulant effects may increase bleed risk.

Diclofenac, isradipine [2] ---> SmPC of [2] of eMC

The peak plasma concentration of isradipine increases by about 20% during co-administration with diclofenac but this is not expected to be clinically significant, as steady state exposure remained unchanged.

Diclofenac, leflunomide [2] ---> SmPC of [2] of EMA

A771726 displaced diclofenac from its plasma protein binding, but the unbound fraction is only increased by 10% to 50%. There is no indication that these effects are of clinical relevance.

Diclofenac, metildigoxin

Increased plasma levels of metildigoxin

Diclofenac, mifepristone

NSAIDs should not be used for 8-12 days after mifepristone administration as NSAlDs can reduce the effect of mifepristone.

Diclofenac, nalmefene [2] ---> SmPC of [2] of EMA

Co-administration with medicinal products that are potent inhibitors of the UGT2B7 enzyme may significantly increase the exposure to nalmefene.

Diclofenac, penicillamine

Possible increased risk of nephrotoxicity

Diclofenac, pentazocine

Seizures may occur with nonsteroidal anti-inflamatory drugs

Diclofenac, pentoxifylline

Possible increased risk of bleeding

Diclofenac, phenytoin

The co-administration of phenytoin and diclofenac may increase plasma levels of phenytoin. It is recommended to control the plasma levels of phenytoin

Diclofenac, potassium-sparing diuretics

The co-administration may decrease the diuretic effect, increase the risk of renal failure due to a reduction in renal blood flow and cause hypercaliemia.

Diclofenac, probenecide

The co-administration may delay the elimination of diclofenac and increase its plasma levels, effects and adverse reactions

Diclofenac, rifampicin

Rifampicin, enzymatic inductor, may increase the metabolism of diclofenac and decrease its plasma levels and effect

Diclofenac, riluzole [2] ---> SmPC of [2] of EMA

Diclofenac, ritonavir

Plasma concentration of NSAID possibly increased

Diclofenac, safinamide [2] ---> SmPC of [2] of EMA

Safinamide may transiently inhibit BCRP in vitro. No precautions are necessary when safinamide is taken with medicinal products that are BCRP substrates (e.g., pitavastatin, pravastatin, ciprofloxacin, methotrexate, topotecan, diclofenac or glyburide).

Diclofenac, sodium oxybate [2] ---> SmPC of [2] of EMA

Co-administration of sodium oxybate and diclofenac in healthy volunteers reduced the attention deficit caused by the administration of Xyrem alone as measured by psychometric tests.

Diclofenac, strong CYP2C9 inhibitors

The strong CYP2C9 inhibition may increase the plasma concentrations of diclofenac

Diclofenac, sulfinpyrazone

The strong CYP2C9 inhibition may increase the plasma concentrations of diclofenac

Diclofenac, sultiame

The co-administration may increase the plasma levels of diclofenac. Adjustment of the dose may be required

Diclofenac, tamsulosin [2] ---> SmPC of [2] of eMC

Diclofenac may increase the elimination rate of tamsulosin

Diclofenac, telmisartan

The co-administration may increase the risk of acute renal failure and hyperkalemia.

Diclofenac, triamterene/hydrochlorothiazide

Salicylates and NSAIDs may decrease the antihypertensive and diuretic effect of triamterene/hydrochlorothiazide

Diclofenac, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole, CYP2C9 inhibitor, may increase the plasma concentrations of diclofenac. Frequent monitoring for adverse reactions and toxicity related to NSAIDs is recommended. Dose reduction of NSAIDs may be needed.

Diclofenac, warfarin [2] ---> SmPC of [2] of eMC

Possible increase of plasma concentration and anticoagulant effect of warfarin due to displacement from plasma proteins

CONTRAINDICATIONS of Diclofenac

- Hypersensitivity to diclofenac or any of the excipients.

- Active, or history of recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or bleeding).

- NSAIDs are contraindicated in patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema, or urticaria) in response to ibuprofen, aspirin, or other non-steroidal anti-inflammatory drugs.

- Established congestive heart failure (NYHA II-IV), ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease.

- Severe heart failure, hepatic failure and renal failure

- History of gastro-intestinal bleeding or perforation, relating to previous NSAID therapy.

- During the last trimester of pregnancy

- This product contains soya. If you are allergic to peanut or soya, do not use this medicinal product.

http://www.medicines.org.uk/emc/

Didanosine

Abacavir [1], didanosine ---> SmPC of [1] of EMA

Nucleoside and nucleotide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine.

Abacavir/lamivudine [1], didanosine ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Abacavir/lamivudine/zidovudine [1], didanosine ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Allopurinol, didanosine [2] ---> SmPC of [2] of eMC

Inhibitors of xanthine oxidase may increase exposure to didanosine when administered concomitantly and thus increase the potential for didanosine associated undesirable effects.

Allopurinol/lesinurad [1], didanosine ---> SmPC of [1] of EMA

Plasma didanosine Cmax and AUC values were approximately doubled with concomitant allopurinol treatment (300 mg daily) without affecting terminal half-life. Co- administration of these 2 active substances is generally not recommended.

Aluminium, didanosine

The antacid with aluminium should be administered 2 hours before didanosine

Amprenavir [1], didanosine ---> SmPC of [1] of EMA

It is recommended that didanosine and amprenavir should be administered at least 1 hour apart

Atazanavir/cobicistat [1], didanosine ---> SmPC of [1] of EMA

No significant effect on atazanavir concentrations was observed when administered with enteric-coated didanosine, but administration with food decreased didanosine concentrations.

Atazanavir/ritonavir, didanosine ---> SmPC of [atazanavir] of EMA

Didanosine should be taken at the fasted state 2 hours after atazanavir/ritonavir taken with food.

Atovaquone [1], didanosine ---> SmPC of [1] of eMC

There was a 24% decrease in the AUC for ddI when co-administered with atovaquone which is unlikely to be of clinical significance.

Azithromycin [1], didanosine ---> SmPC of [1] of eMC

Coadministration of 1200 mg/day azithromycin with 400 mg/day didanosine in 6 HIV-positive subjects did not appear to affect the steady-state pharmacokinetics of didanosine as compared with placebo.

Breast-feeding, didanosine [2] ---> SmPC of [2] of eMC

It is recommended that women taking didanosine do not breast-feed because of the potential for serious adverse reactions in nursing infants.

Ciprofloxacin, didanosine [2] ---> SmPC of [2] of eMC

The co-administration should be avoided because absorption of ciprofloxacin may be reduced.

Daclatasvir [1], didanosine ---> SmPC of [1] of EMA

No dose adjustment of Daklinza or the NRTI is required.

Darunavir/cobicistat [1], didanosine ---> SmPC of [1] of EMA

Darunavir/ritonavir, didanosine ---> SmPC of [darunavir] of EMA

Didanosine [1], foods ---> SmPC of [1] of eMC

To minimise the impact of food on the didanosine pharmacokinetics, didanosine should be administered on an empty stomach at least 2 hours before or 2 hours after a meal

Didanosine [1], ganciclovir ---> SmPC of [1] of eMC

Los pacientes que tomen didanosina en combinación con ganciclovir y valganciclovir deben ser cuidadosamente monitorizados por las toxicidades asociadas a didanosina.

Didanosine [1], methadone ---> SmPC of [1] of eMC

If didanosine is used in combination with methadone, patients should be closely monitored for adequate clinical response.

Didanosine [1], pancreatitis ---> SmPC of [1] of eMC

Co-administration of didanosine with medicines that are known to cause peripheral neuropathy or pancreatitis may increase the risk of these toxicities.

Didanosine [1], peripheral neuropathy ---> SmPC of [1] of eMC

Co-administration of didanosine with medicines that are known to cause peripheral neuropathy or pancreatitis may increase the risk of these toxicities. Patients who receive these medicines should be carefully observed.

Didanosine [1], pregnancy ---> SmPC of [1] of eMC

The use of didanosine during pregnancy should be considered only if clearly indicated, and only when the potential benefit outweighs the possible risk.

Didanosine [1], ribavirin/stavudin ---> SmPC of [1] of eMC

Fatal hepatic failure, as well as peripheral neuropathy, pancreatitis and symptomatic hyperlactatemia/lactic acidosis have been reported in patients receiving didanosine and ribavirin with or without stavudine. Co-administration is not recommended

Didanosine [1], valganciclovir ---> SmPC of [1] of eMC

Los pacientes que tomen didanosina en combinación con ganciclovir y valganciclovir deben ser cuidadosamente monitorizados por las toxicidades asociadas a didanosina.

Didanosine [1], xanthine oxidase inhibitors ---> SmPC of [1] of eMC

Inhibitors of xanthine oxidase may increase exposure to didanosine when administered concomitantly and thus increase the potential for didanosine associated undesirable effects.

Didanosine [1], zidovudine ---> SmPC of [1] of eMC

No dosage adjustment necessary.

Didanosine, efavirenz/emtricitabine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

The combination increases the systemic exposition to didanosine. Co-administration is not recommended

Didanosine, elvitegravir [2] ---> SmPC of [2] of EMA

Didanosine (on an empty stomach) should be administered at least 1 hour before or 2 hours after elvitegravir (with food). Clinical monitoring is recommended.

Didanosine, elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Nucleos(t)ide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine.

Didanosine, elvitegravir/ritonavir ---> SmPC of [elvitegravir] of EMA

Didanosine (on an empty stomach) should be administered at least 1 hour before or 2 hours after elvitegravir (with food). Clinical monitoring is recommended.

Didanosine, emtricitabine [2] ---> SmPC of [2] of EMA

Nucleos(t)ide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine

Didanosine, emtricitabine/rilpivirine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Combination is not recommended since exposure to didanosine is significantly increased following co-administration with tenofovir disoproxil fumarate that may increase the risk of didanosine-related adverse reactions

Didanosine, emtricitabine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Co-administration is not recommended because it results in a 40-60% increase in systemic exposure to didanosine that may increase the risk of didanosine-related adverse reactions

Didanosine, etravirine [2] ---> SmPC of [2] of EMA

No significant effect on didanosine and etravirine PK parameters is seen. INTELENCE and didanosine can be used without dose adjustments.

Didanosine, fosamprenavir/ritonavir ---> SmPC of [fosamprenavir] of EMA

No clinically significant interaction is observed. No dose separation or dosage adjustment necessary

Didanosine, foscarnet [2] ---> SmPC of [2] of eMC

There is no pharmacokinetic interaction between foscarnet and didanosine

Didanosine, indinavir [2] ---> SmPC of [2] of EMA

Indinavir and didanosine formulations containing buffer should be administered at least 1 hour apart on an empty stomach.

Didanosine, itraconazol

Itraconazol should be administered 2 hours before didanosine

Didanosine, ketoconazole

Ketoconazole should be administered 2 hours before didanosine

Didanosine, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

No dosage adjustment necessary.

Didanosine, loperamide

No dosage adjustment necessary.

Didanosine, magnesium

The antacid with magnesium should be administered 2 hours before didanosine

Didanosine, metoclopramide

No dosage adjustment necessary.

Didanosine, minocycline

Due to increased pH value in stomach (didanosine tablets contain an antacid) there is a decreased gastrointestinal absorption of tetracyclines. Dosages should be maximally separated.

Didanosine, mitochondrial function ---> SmPC of [abacavir/lamivudine/zidovudine] of EMA

Nucleoside and nucleotide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine.

Didanosine, moxifloxacin [2] ---> SmPC of [2] of eMC

An interval of about 6 hours should be left between administration of agents containing bivalent or trivalent cations and administration of moxifloxacin.

Didanosine, nelfinavir [2] ---> SmPC of [2] of EMA

Nelfinavir should be administered (with food) 1 hour after or more than 2 hours before didanosine.

Didanosine, nevirapine [2] ---> SmPC of [2] of EMA

Didanosine and Viramune can be coadministered without dose adjustments.

Didanosine, norfloxacin

Decreased absorption of norfloxacin. Separate administration at least 2 hours

Didanosine, peginterferon alfa-2a/ribavirin ---> SmPC of [peginterferon alfa-2a] of EMA

Co-administration of ribavirin and didanosine is not recommended. Reports of fatal hepatic failure as well as peripheral neuropathy, pancreatitis, and symptomatic hyperlactataemia/lactic acidosis have been reported with use of ribavirin.

Didanosine, peginterferon alfa-2b/ribavirin ---> SmPC of [peginterferon alfa-2b] of EMA

Co-administration of ribavirin and didanosine is not recommended. Reports of mitochondrial toxicity, in particular lactic acidosis and pancreatitis, of which some fatal, have been reported

Didanosine, pentamidine

The co-administration may increase the risk or pancreatitis

Didanosine, ranitidine

No dosage adjustment necessary.

Didanosine, ribavirin [2] ---> SmPC of [2] of EMA

Pharmacologically, Rebetol increases phosphorylated metabolites of purine nucleosides in vitro. This activity could potentiate the risk of lactic acidosis induced by purine nucleoside analogs (e.g. didanosine or abacavir).

Didanosine, rifabutin

No dosage adjustment necessary.

Didanosine, rilpivirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required. Didanosine should be administered at least 2 hours before or at least 4 hours after rilpivirine.

Didanosine, ritonavir [2] ---> SmPC of [2] of EMA

As ritonavir is recommended to be taken with food and didanosine should be taken on an empty stomach, dosing should be separated by 2.5 h.

Didanosine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Decreased saquinavir exposition. No dosage adjustment necessary.

Didanosine, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required.

Didanosine, stavudine [2] ---> SmPC of [2] of EMA

The combination of stavudine with didanosine is contraindicated given that both drugs exhibits high risk of mitochondrial toxicity

Didanosine, sulfamethoxazol

No dosage adjustment necessary.

Didanosine, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Nucleos(t)ide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine. Co-administration of tenofovir disoproxil fumarate and didanosine is not recommended

Didanosine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Tipranavir may decrease the plasma levels of didanosine. The combination should be separated by at least 2 hours to avoid formulation incompatibility

Didanosine, trimethoprim

No dosage adjustment necessary.

CONTRAINDICATIONS of Didanosine

- Hypersensitivity to the active substance or to any of the excipients

- Paediatric patients younger than 6 years (risk of inadvertent aspiration).

http://www.medicines.org.uk/emc/

Dienogest

Azole antifungals, dienogest

The CYP3A4 inhibition may increase the plasma levels of dienogest

Barbiturates, dienogest

The enzymatic induction may decrease the plasma levels of dienogest

Breast-feeding, dienogest

Dienogest is not recommended during breastfeeding

Dienogest, enzyme inductors

The enzymatic induction may decrease the plasma levels of dienogest

Dienogest, erythromycin

The moderate CYP3A4 inhibition may increase the plasma levels of dienogest

Dienogest, felbamate

The enzymatic induction may decrease the plasma levels of dienogest

Dienogest, griseofulvin

The enzymatic induction may decrease the plasma levels of dienogest

Dienogest, ketoconazole

The CYP3A4 inhibition may increase the plasma levels of dienogest

Dienogest, nevirapine

The enzymatic induction may decrease the plasma levels of dienogest

Dienogest, phenytoin

The enzymatic induction may decrease the plasma levels of dienogest

Dienogest, pregnancy

Dienogest should not be given to pregnant women due to it is not necessary to treat a endometriosis during pregnancy

Dienogest, primidone

The enzymatic induction may decrease the plasma levels of dienogest

Dienogest, protease inhibitors

The CYP3A4 inhibition may increase the plasma levels of dienogest

Dienogest, rifampicin

The enzymatic induction may decrease the plasma levels of dienogest

Dienogest, strong CYP3A4 inductors

The strong CYP3A4 induction may decrease the plasma levels of dienogest

Dienogest, strong CYP3A4 inhibitors

The strong CYP3A4 inhibition may increase the plasma levels of dienogest

Dienogest, topiramate

The enzymatic induction may decrease the plasma levels of dienogest

St. John's wort, dienogest

The enzymatic induction may decrease the plasma levels of dienogest

Difelikefalin (Kapruvia)

Ability to drive, difelikefalin [2] ---> SmPC of [2] of EMA

Somnolence and/or dizziness have been reported in patients receiving difelikefalin. Dizziness occurred within the first 9 weeks of treatment and was generally transient.

Alprazolam, difelikefalin [2] ---> SmPC of [2] of EMA

Concurrent administration of medicinal products such as sedating antihistamines, opioid analgesics or other CNS depressants may increase the likelihood of dizziness and somnolence (see section 4.4).

Breast-feeding, difelikefalin [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Kapruvia therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Clonidine, difelikefalin [2] ---> SmPC of [2] of EMA

Concurrent administration of medicinal products such as sedating antihistamines, opioid analgesics or other CNS depressants may increase the likelihood of dizziness and somnolence (see section 4.4).

CNS depressants, difelikefalin [2] ---> SmPC of [2] of EMA

Concurrent administration of medicinal products such as sedating antihistamines, opioid analgesics or other CNS depressants may increase the likelihood of dizziness and somnolence (see section 4.4).

CYP450, difelikefalin [2] ---> SmPC of [2] of EMA

Interactions of difelikefalin with other medicinal products are unlikely.

Difelikefalin [1], fertility ---> SmPC of [1] of EMA

There are no data on the effect of difelikefalin on fertility in humans. In rat studies with difelikefalin, there was no effect on fertility (see section 5.3).

Difelikefalin [1], gabapentin ---> SmPC of [1] of EMA

Concurrent administration of medicinal products such as sedating antihistamines, opioid analgesics or other CNS depressants may increase the likelihood of dizziness and somnolence (see section 4.4).

Difelikefalin [1], hyperkalemia ---> SmPC of [1] of EMA

Hyperkalaemia frequently occurs in chronic kidney disease patients on haemodialysis. Frequent monitoring of potassium levels is recommended.

Difelikefalin [1], ondansetron ---> SmPC of [1] of EMA

Concurrent administration of medicinal products such as sedating antihistamines, opioid analgesics or other CNS depressants may increase the likelihood of dizziness and somnolence (see section 4.4).

Difelikefalin [1], opioid analgesics ---> SmPC of [1] of EMA

Concurrent administration of medicinal products such as sedating antihistamines, opioid analgesics or other CNS depressants may increase the likelihood of dizziness and somnolence (see section 4.4).

Difelikefalin [1], pregabalin ---> SmPC of [1] of EMA

Concurrent administration of medicinal products such as sedating antihistamines, opioid analgesics or other CNS depressants may increase the likelihood of dizziness and somnolence (see section 4.4).

Difelikefalin [1], pregnancy ---> SmPC of [1] of EMA

As a precautionary measure, it is preferable to avoid the use of Kapruvia during pregnancy.

Difelikefalin [1], sedating antihistamines ---> SmPC of [1] of EMA

Concurrent administration of medicinal products such as sedating antihistamines, opioid analgesics or other CNS depressants may increase the likelihood of dizziness and somnolence (see section 4.4).

Difelikefalin [1], sertraline ---> SmPC of [1] of EMA

Concurrent administration of medicinal products such as sedating antihistamines, opioid analgesics or other CNS depressants may increase the likelihood of dizziness and somnolence (see section 4.4).

Difelikefalin [1], trazodone ---> SmPC of [1] of EMA

Concurrent administration of medicinal products such as sedating antihistamines, opioid analgesics or other CNS depressants may increase the likelihood of dizziness and somnolence (see section 4.4).

Difelikefalin [1], zolpidem ---> SmPC of [1] of EMA

Concurrent administration of medicinal products such as sedating antihistamines, opioid analgesics or other CNS depressants may increase the likelihood of dizziness and somnolence (see section 4.4).

CONTRAINDICATIONS of Difelikefalin (Kapruvia)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/kapruvia-epar-product-information_en.pdf 14/10/2024

Diflunisal (Attrogy)

ACE inhibitors, diflunisal [2] ---> SmPC of [2] of EMA

The antihypertensive effects of some antihypertensive medicinal products, including ACE inhibitors, beta-blocking agents and diuretics, may be reduced when used concomitantly with NSAIDs.

Acemetacine, diflunisal

Diflunisal may delay the elimination of acemetacine

Acenocoumarol [1], diflunisal ---> SmPC of [1] of eMC

Drugs altering haemostasis may potentiate the anticoagulant activity and increase the risk of haemorrhage. The use concomitant is not recommended

Acetazolamide, diflunisal [2] ---> SmPC of [2] of EMA

Experimental studies show that salicylic acid derivatives, such as diflunisal, increase the free pharmacologically active concentration of acetazolamide.

Acetylsalicylic acid, diflunisal [2] ---> SmPC of [2] of EMA

The concomitant use of diflunisal and other NSAIDs (including cyclooxygenase-2 selective inhibitors) is not recommended owing to the increased possibility of gastro-intestinal toxicity.

Algeldrate/magnesium hydroxide, diflunisal

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Aluminium hydroxide, diflunisal

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Aluminium hydroxide, diflunisal [2] ---> SmPC of [2] of EMA

Co-administration of aluminium hydroxide decreases the absorption of diflunisal. The medicinal products should be taken with a 2-hour interval.

Aluminium oxide/magnesium hydroxide, diflunisal

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Anticoagulants, diflunisal [2] ---> SmPC of [2] of EMA

Those receiving diflunisal who have pre-existing coagulation disorders or who are on concomitant anticoagulant therapy, should be carefully monitored.

Antihypertensive, diflunisal [2] ---> SmPC of [2] of EMA

The antihypertensive effects of some antihypertensive medicinal products, including ACE inhibitors, beta-blocking agents and diuretics, may be reduced when used concomitantly with NSAIDs.

Antiplatelet therapy, diflunisal [2] ---> SmPC of [2] of EMA

There is an increased risk of gastro-intestinal bleeding when used concomitantly with NSAIDs.

Betablockers, diflunisal [2] ---> SmPC of [2] of EMA

The antihypertensive effects of some antihypertensive medicinal products, including ACE inhibitors, beta-blocking agents and diuretics, may be reduced when used concomitantly with NSAIDs.

Boceprevir [1], diflunisal ---> SmPC of [1] of EMA

Boceprevir is primarily metabolized by aldo-keto reductase (AKR). In medicine interaction trials conducted with AKR inhibitors, boceprevir exposure did not increase to a clinically significant extent. Boceprevir may be co-administered with AKR inhibitors

Breast-feeding, diflunisal [2] ---> SmPC of [2] of EMA

Diflunisal is excreted in human milk to such an extent that effects on the breastfed newborn / infant are likely. Diflunisal is contraindicated during breast-feeding (see section 4.3).

Corticosteroids, diflunisal [2] ---> SmPC of [2] of EMA

The risk of gastro-intestinal bleeding and ulceration associated with NSAIDs is increased when used with corticosteroids.

Cyclosporine, diflunisal [2] ---> SmPC of [2] of EMA

Administration of NSAIDs concomitantly with ciclosporin has been associated with an increase in ciclosporin-induced toxicity, possibly due to decreased synthesis of renal prostacyclin.

Deucravacitinib [1], diflunisal ---> SmPC of [1] of EMA

Medicinal products that are inhibitors or inducers of CYP enzymes or transporters do not meaningfully affect plasma deucravacitinib exposures (see section 5.2).

Diflunisal [1], diuretics ---> SmPC of [1] of EMA

The antihypertensive effects of some antihypertensive medicinal products, including ACE inhibitors, beta-blocking agents and diuretics, may be reduced when used concomitantly with NSAIDs.

Diflunisal [1], diuretics ---> SmPC of [1] of EMA

NSAIDs may reduce the effect of diuretics. Diuretics can increase the risk of nephrotoxicity of NSAIDs.

Diflunisal [1], fertility ---> SmPC of [1] of EMA

The use of diflunisal may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation in infertility, withdrawal of diflunisal should be considered.

Diflunisal [1], heparin ---> SmPC of [1] of EMA

Those receiving diflunisal who have pre-existing coagulation disorders or who are on concomitant anticoagulant therapy, should be carefully monitored.

Diflunisal [1], indometacin ---> SmPC of [1] of EMA

Diflunisal reduces renal clearance and glucuronidation of indomethacin which results in a substantial increase of the plasma levels of indomethacin.

Diflunisal [1], lithium ---> SmPC of [1] of EMA

As a consequence, when an NSAID and lithium are given concomitantly, the patient should be observed carefully for signs of lithium toxicity.

Diflunisal [1], methotrexate ---> SmPC of [1] of EMA

Diflunisal can produce renal dysfunction resulting in reduced excretion of methotrexate. Diflunisal may also compete for drug transporters responsible for excreting methotrexate (e.g. OAT1 and OAT3).

Diflunisal [1], NSAID ---> SmPC of [1] of EMA

The concomitant use of diflunisal and other NSAIDs (including cyclooxygenase-2 selective inhibitors) is not recommended owing to the increased possibility of gastro-intestinal toxicity.

Diflunisal [1], oligohydramnios ---> SmPC of [1] of EMA

Diflunisal must be discontinued if oligohydramnios or ductus arteriosus constriction are found.

Diflunisal [1], pregnancy ---> SmPC of [1] of EMA

Therefore, during the first and second trimester of pregnancy, diflunisal should not be given unless clearly necessary. Consequently, diflunisal is contraindicated during the third trimester of pregnancy (see section 4.3).

Diflunisal [1], rivaroxaban ---> SmPC of [1] of EMA

Those receiving diflunisal who have pre-existing coagulation disorders or who are on concomitant anticoagulant therapy, should be carefully monitored.

Diflunisal [1], SSRI ---> SmPC of [1] of EMA

There is an increased risk of gastro-intestinal bleeding when used concomitantly with NSAIDs.

Diflunisal [1], tacrolimus ---> SmPC of [1] of EMA

There is a possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.

Diflunisal [1], vitamin K antagonists ---> SmPC of [1] of EMA

Those receiving diflunisal who have pre-existing coagulation disorders or who are on concomitant anticoagulant therapy, should be carefully monitored.

Diflunisal [1], warfarin ---> SmPC of [1] of EMA

Those receiving diflunisal who have pre-existing coagulation disorders or who are on concomitant anticoagulant therapy, should be carefully monitored.

Diflunisal, indometacin [2] ---> SmPC of [2] of EMA

Co-administration of diflunisal with indometacin increases the plasma level of indomethacin by about a third, with a concomitant decrease in renal clearance. Fatal GI haemorrhage has occurred. The combination should not be used.

Diflunisal, proglumetacine

Diflunisal, regorafenib [2] ---> SmPC of [2] of EMA

Co-administration of a strong UGT1A9 inhibitor during regorafenib treatment should be avoided, as their influence on the steady-state exposure of regorafenib and its metabolites has not been studied.

CONTRAINDICATIONS of Diflunisal (Attrogy)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Previous acute asthmatic attacks, urticaria, rhinitis or angioedema precipitated by acetylsalicylic acid or other NSAIDs, due to risk of cross-reaction.

- Active gastro-intestinal bleeding.

- Severe heart failure (see section 4.4).

- Severe renal impairment (GFR ≤30 ml/min) (see section 4.4).

- Severe hepatic impairment (Child-Pugh C; see section 4.4).

- Use during the third trimester of pregnancy and in breast-feeding mothers (see section 4.6).

https://www.ema.europa.eu/en/documents/product-information/attrogy-epar-product-information_en.pdf 28/08/2025

Digoxin

Abemaciclib [1], digoxin ---> SmPC of [1] of EMA

Ability to drive, digoxin [2] ---> SmPC of [2] of eMC

Since central nervous system and visual disturbances have been reported, patients should exercise caution before driving, using machinery or participating in dangerous activities.

Acarbose [1], digoxin ---> SmPC of [1] of eMC

In individual cases acarbose may affect digoxin bioavailability, which may require dose adjustment of digoxin

Acebutolol, digoxin

Concurrent use of digoxin and acebutolol may occasionally induce serious bradycardia.

Aceclofenac [1], digoxin ---> SmPC of [1] of eMC

NSAIDs may exacerbate cardiac failure, reduce GFR (glomerular filtration rate) and inhibit the renal clearance of glycosides, resulting in increased plasma glycoside levels.

Acemetacine, digoxin

Acemetacine may increase the plasma levels of digoxin

Acetylsalicylic acid [1], digoxin ---> SmPC of [1] of eMC

NSAIDs increase the digoxin plasma levels which may reach toxic values. The combination of digoxin and NSAIDs is not recommended

Activated charcoal, digoxin

Decreased digoxin absorption or increased elimination due to enterohepatic circulation interruption. Digoxin should be administered 2 hours before.

Adrenaline, digoxin [2] ---> SmPC of [2] of eMC

Serum levels of digoxin may be reduced by concomitant administration of adrenaline

Albiglutide [1], digoxin ---> SmPC of [1] of EMA

Albiglutide did not meaningfully alter the pharmacokinetics of a single-dose of digoxin (0.5 mg) when coadministered with steady-state albiglutide (50 mg weekly).

Alectinib [1], digoxin ---> SmPC of [1] of EMA

When Alecensa is co-administered with P-gp substrates (e.g., digoxin, dabigatran etexilate, topotecan, sirolimus, everolimus, nilotinib and lapatinib), appropriate monitoring is recommended.

Algeldrate/magnesium hydroxide, digoxin

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Aliskiren [1], digoxin ---> SmPC of [1] of EMA

Digoxin bioavailability may be slightly decreased by aliskiren.

Aliskiren/amlodipine [1], digoxin ---> SmPC of [1] of EMA

Digoxin bioavailability may be slightly decreased by aliskiren.

Aliskiren/amlodipine/hydrochlorothiazide [1], digoxin ---> SmPC of [1] of EMA

Thiazide induced hypokalaemia/hypomagnaesemia favour the onset of digitalis-induced cardiac arrhythmias. Periodic monitoring of serum potassium and ECG is recommended

Aliskiren/hydrochlorothiazide [1], digoxin ---> SmPC of [1] of EMA

Digoxin bioavailability may be slightly decreased by aliskiren.

Almasilate, digoxin

There are studies which describe an absorption reduction of the active principle co-administered with almasilate

Alprazolam [1], digoxin ---> SmPC of [1] of eMC

Serum levels of digoxin may be increased by concomitant administration of alprazolam

Aluminium hydroxide, digoxin

The aluminium hydroxide may decrease the absorption of digoxin. Separate administration by at least 2 hours

Aluminium oxide/magnesium hydroxide, digoxin

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Ambrisentan [1], digoxin ---> SmPC of [1] of EMA

Steady-state administration of ambrisentan in healthy volunteers had no clinically relevant effects on the single-dose pharmacokinetics of digoxin, a substrate for Pgp

Amiloride, digoxin

The co-administration may decrease the positive inotrope effect of digoxin and promote heart rhythm disorders

Amiodarone [1], digoxin ---> SmPC of [1] of eMC

The co-administration will bring about an increase in the plasma digoxin concentration and thus precipitate symptoms and signs associated with high digoxin levels.

Amlodipine/valsartan [1], digoxin ---> SmPC of [1] of EMA

In clinical interaction studies, amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin, warfarin or ciclosporin.

Amoxicillin [1], digoxin ---> SmPC of [1] of eMC

An increase in the absorption of digoxin is possible on concurrent administration with amoxicillin. A dose adjustment of digoxin may be necessary.

Amphotericin B, digoxin [2] ---> SmPC of [2] of eMC

Agents causing hypokalaemia or intracellular potassium deficiency may cause increased sensitivity to digoxin

Amphotericin, digoxin [2] ---> SmPC of [2] of eMC

Agents causing hypokalaemia or intracellular potassium deficiency may cause increased sensitivity to digoxin

Anagrelide [1], digoxin ---> SmPC of [1] of EMA

In vivo interaction studies in humans have demonstrated that digoxin and warfarin do not affect the pharmacokinetic properties of anagrelide.

Antacids, digoxin

Decreased digoxin absorption or increased elimination due to enterohepatic circulation interruption. Digoxin should be administered 2 hours before.

Aprepitant [1], digoxin ---> SmPC of [1] of EMA

Aprepitant does not seem to interact with the P-glycoprotein transporter, as suggested by the lack of interaction of aprepitant with digoxin.

Atazanavir/cobicistat [1], digoxin ---> SmPC of [1] of EMA

Plasma concentrations of digoxin may be increased when coadministered with EVOTAZ. The mechanism of interaction is inhibition of P-gp by cobicistat. The lowest dose of digoxin should initially be prescribed.

Atenolol/nifedipine, digoxin ---> SmPC of [nifedipine] of eMC

The administration of nifedipine and digoxin concurrently may lead to reduced digoxin clearance and therefore, bring about an increase in the plasma digoxin level.

Atorvastatin [1], digoxin ---> SmPC of [1] of eMC

When multiple doses of digoxin and 10 mg atorvastatin were co-administered, steady-state digoxin concentrations increased slightly. Patients taking digoxin should be monitored appropriately.

Atorvastatin, digoxin ---> SmPC of [ezetimibe/atorvastatin] of eMC

When multiple doses of digoxin and 10 mg atorvastatin were coadministered, steady-state digoxin concentrations increased slightly. Patients taking digoxin should be monitored appropriately.

Atropine, digoxin

The decrease of the gut motility caused by atropine increases the absorption of the co-administrated digoxin

Axitinib [1], digoxin ---> SmPC of [1] of EMA

In vitro studies indicated that axitinib inhibits P-glycoprotein. The co-administration of axitinib is not expected to increase the plasma concentration of digoxin, or other P-glycoprotein substrates, in vivo.

Azilsartan medoxomil [1], digoxin ---> SmPC of [1] of EMA

No clinically significant interactions have been reported in studies of azilsartan medoxomil or azilsartan given with amlodipine, antacids, chlortalidone, digoxin, fluconazole, glyburide, ketoconazole, metformin, and warfarin.

Azithromycin [1], digoxin ---> SmPC of [1] of eMC

Concomitant administration azithromycin with digoxin may result in increased serum levels of the digoxin.

Balsalazide, digoxin

Digoxin uptake has been impaired in some individuals co-treated with sulphasalazine. Even if it is not known whether this would occur also during treatment with balsalazide, it is recommended that digoxin plasma levels should be monitored

Bazedoxifene, digoxin ---> SmPC of [conjugated oestrogens/bazedoxifene] of EMA

Based on in vitro bazedoxifene plasma protein-binding characteristics, interactions with warfarin, digoxin or diazepam are unlikely.

Betablockers, digoxin ---> SmPC of [carvedilol] of eMC

Digoxin, in association with beta-adrenoceptor blocking drugs, may increase atrio-ventricular conduction time.

Bisacodyl [1], digoxin ---> SmPC of [1] of eMC

Electrolyte imbalance may lead to increased sensitivity to cardiac glycosides.

Bleomycin, digoxin

Decreased bioavailibility of digoxin

Boceprevir [1], digoxin ---> SmPC of [1] of EMA

No dose adjustment of digoxin or Victrelis is recommended. Patients receiving digoxin should be monitored appropriately

Bosentan [1], digoxin ---> SmPC of [1] of EMA

Co-administration of bosentan with digoxin decreased the AUC, Cmax and Cmin of digoxin. The mechanism for this interaction may be induction of P-glycoprotein. This interaction is unlikely to be of clinical relevance.

Breast-feeding, digoxin [2] ---> SmPC of [2] of eMC

Although digoxin is excreted in breast milk, the quantities are minute and breast feeding is not contra-indicated.

Bulk producers, digoxin

Decreased digoxin absorption or increased elimination due to enterohepatic circulation interruption. Digoxin should be administered 2 hours before.

Buspirone [1], digoxin ---> SmPC of [1] of eMC

Buspirone may displace digoxin from its plasma protein binding

Butylscopolamine, digoxin

Butylscopolamine may impair the effect from other medicinal products as digoxine

Cabozantinib [1], digoxin ---> SmPC of [1] of EMA

Calcifediol, digoxin

Calcifediol may cause hypercalcemia, which may enhance the inotropic effects and toxicity of digoxin

Calcium antagonists, digoxin [2] ---> SmPC of [2] of eMC

Serum levels of digoxin may be increased by concomitant administration of calcium antagonists

Calcium, digoxin [2] ---> SmPC of [2] of eMC

Calcium, particularly if administered rapidly by the intravenous route, may produce serious arrhythmias in digitalized patients.

Canagliflozin [1], digoxin ---> SmPC of [1] of EMA

Canagliflozin has been observed to inhibit P-gp in vitro. Patients taking digoxin or other cardiac glycosides (e.g., digitoxin) should be monitored appropriately.

Canagliflozin/metformin [1], digoxin ---> SmPC of [1] of EMA

The inhibition of P-glycoprotein by canagliflozin may increase the exposure to digoxin

Captopril, digoxin

Serum levels of digoxin may be increased by concomitant administration of captopril

Carbaldrate, digoxin

The aluminium salt decreases the absorption of the co-administered active principle. Separate administration by at least 2 hours

Carbamazepine [1], digoxin ---> SmPC of [1] of eMC

Carbamazepine may decrease the plasma levels of digoxine.

Carbenoxolone, digoxin [2] ---> SmPC of [2] of eMC

Agents causing hypokalaemia or intracellular potassium deficiency may cause increased sensitivity to digoxin

Carfilzomib [1], digoxin ---> SmPC of [1] of EMA

Carfilzomib is a P-glycoprotein (P-gp) but not a BCRP substrate. Caution should be observed when carfilzomib is combined with substrates of P-gp (e.g. digoxin, colchicine).

Cariprazine [1], digoxin ---> SmPC of [1] of EMA

Cariprazine is a P-gp inhibitor in vitro at its theoretical maximum intestinal concentration. The use of P-gp substrates with narrow therapeutic index such as dabigatran and digoxin could require extra monitoring and dose adjustment.

Carmustine [1], digoxin ---> SmPC of [1] of EMA

Concomitant use with digoxin leads to delayed, moderate, suspected, decreased effect of digoxin (due to the decreased digoxin absorption).

Carvedilol [1], digoxin ---> SmPC of [1] of eMC

An increase of steady state digoxin levels by approximately 16% and of digitoxin by approximately 13% has been seen in hypertensive patients in connection with the concomitant use of carvedilol and digoxin.

Ceritinib [1], digoxin ---> SmPC of [1] of EMA

Based on in vitro data, ceritinib is predicted to inhibit intestinal P-gp. Therefore, ceritinib may have the potential to increase plasma concentrations of co-administered medicinal products transported by P-gp.

Chloroquine [1], digoxin ---> SmPC of [1] of eMC

Hydroxychloroquine and possibly chloroquine increase plasma concentration of digoxin.

Cholestyramine, digoxin

Decreased digoxin absorption or increased elimination due to enterohepatic circulation interruption. Digoxin should be administered 2 hours before.

Cinitapride, digoxin

Cinitapride can reduce the absorption of digoxin

Clarithromycin [1], digoxin ---> SmPC of [1] of eMC

When clarithromycin and digoxin are administered together, inhibition of Pgp by clarithromycin may lead to increased exposure to digoxin.

Clebopride, digoxin

Clebopride decreases the effects of cimetidine and digoxine

Clopidogrel [1], digoxin ---> SmPC of [1] of EMA

The pharmacokinetics of digoxin or theophylline were not modified by the co-administration of clopidogrel.

Clopidogrel/acetylsalicylic acid [1], digoxin ---> SmPC of [1] of EMA

The pharmacokinetics of digoxin or theophylline were not modified by the co-administration of clopidogrel.

Clozapine [1], digoxin ---> SmPC of [1] of eMC

Clozapine may increase the plasma concentrations of digoxin due to displacement from plasma proteins.

Cobicistat [1], digoxin ---> SmPC of [1] of EMA

The co-administration may increase the plasma levels of digoxin

Colesevelam [1], digoxin ---> SmPC of [1] of EMA

In interaction studies in healthy volunteers, colesevelam had no effect on the bioavailability of digoxin

Colestilan [1], digoxin ---> SmPC of [1] of EMA

BindRen lowered the bioavailability of digoxin by 16% and Cmax by 17%

Colestipol, digoxin

Decreased digoxin absorption or increased elimination due to enterohepatic circulation interruption. Digoxin should be administered 2 hours before.

Conjugated oestrogens/bazedoxifene [1], digoxin ---> SmPC of [1] of EMA

Based on in vitro bazedoxifene plasma protein-binding characteristics, interactions with warfarin, digoxin or diazepam are unlikely.

Corticosteroids, digoxin [2] ---> SmPC of [2] of eMC

Agents causing hypokalaemia or intracellular potassium deficiency may cause increased sensitivity to digoxin

Cotrimoxazole [1], digoxin ---> SmPC of [1] of eMC

The co-administration of trimethoprim and digoxin increases digoxin levels in a proportion of elderly patients

Crizotinib [1], digoxin ---> SmPC of [1] of EMA

Administration of crizotinib (intestinal P-gp inhibitor) with medicinal products that are substrates of P-gp may increase their therapeutic effect and adverse reactions. Close clinical surveillance is recommended

Cyclophosphamide, digoxin

Decreased absorption of digoxin

Cyclosporine [1], digoxin ---> SmPC of [1] of eMC

Ciclosporin may reduce the clearance of digoxin

Cytostatics, digoxin [2] ---> SmPC of [2] of eMC

Serum levels of digoxin may be reduced by concomitant administration of some cytostatics

Dabigatran etexilate [1], digoxin ---> SmPC of [1] of EMA

When dabigatran was co-administered with digoxin, no changes on digoxin and no clinical relevant changes on dabigatran exposure have been observed.

Dabigatran [1], digoxin ---> SmPC of [1] of EMA

When dabigatran was co-administered with digoxin, no changes on digoxin and no clinical relevant changes on dabigatran exposure have been observed.

Dabrafenib [1], digoxin ---> SmPC of [1] of EMA

Concomitant administration of dabrafenib with digoxin may result in decreased digoxin exposure. Caution should be exercised and additional monitoring of digoxin is recommended

Daclatasvir [1], digoxin ---> SmPC of [1] of EMA

P-gp inhibition by daclatasvir may increase the serum digoxin concentrations

Dalbavancin [1], digoxin ---> SmPC of [1] of EMA

Darifenacin [1], digoxin ---> SmPC of [1] of EMA

Darifenacin co-administered with digoxin at steady state resulted in a small increase in digoxin exposure

Darunavir/cobicistat [1], digoxin ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (P-glycoprotein inhibition) is expected to increase digoxin plasma concentrations.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], digoxin ---> SmPC of [1] of EMA

Darunavir/ritonavir, digoxin ---> SmPC of [darunavir] of EMA

The possible inhibition of P-glycoprotein may increase the digoxin exposition

Dasabuvir with ombitasvir/paritaprevir/ritonavir, digoxin ---> SmPC of [dasabuvir] of EMA

While dasabuvir is an in vitro inhibitor of P-gp, no significant change was observed in the exposure of the P-gp substrate, digoxin, when administered with dasabuvir with ombitasvir/paritaprevir/ritonavir.

Deferasirox [1], digoxin ---> SmPC of [1] of EMA

No interaction was observed between deferasirox and digoxin in healthy adult volunteers.

Dexibuprofen [1], digoxin ---> SmPC of [1] of eMC

NSAIDs can increase the plasma levels of digoxin and increase the risk of digoxin toxicity.

Dextromethorphan/quinidine [1], digoxin ---> SmPC of [1] of EMA

Quinidine is an inhibitor of P-glycoprotein. Concomitant administration of quinidine with digoxin, a P-glycoprotein substrate, results in serum digoxin levels that may be as much as doubled.

Diclofenac [1], digoxin ---> SmPC of [1] of eMC

NSAID may exacerbate cardiac failure, reduce the glomerular filtration rate and increase plasma levels of the cardiac glycoside

Digoxin [1], diltiazem ---> SmPC of [1] of eMC

Serum levels of digoxin may be increased by concomitant administration of calcium antagonists

Digoxin [1], diuretics ---> SmPC of [1] of eMC

Agents causing hypokalaemia or intracellular potassium deficiency may cause increased sensitivity to digoxin

Digoxin [1], epoprostenol ---> SmPC of [1] of eMC

Serum levels of digoxin may be increased by concomitant administration of epoprostenol

Digoxin [1], erythromycin ---> SmPC of [1] of eMC

The co-administration of drugs metabolised by the cytochrome P450 system may be associated with elevated serum levels if administered concomitantly with erythromycin.

Digoxin [1], flecainide ---> SmPC of [1] of eMC

Serum levels of digoxin may be increased by concomitant administration of flecainide

Digoxin [1], gentamicin ---> SmPC of [1] of eMC

Serum levels of digoxin may be increased by concomitant administration of gentamicin

Digoxin [1], hypokalemia ---> SmPC of [1] of eMC

Agents causing hypokalaemia or intracellular potassium deficiency may cause increased sensitivity to digoxin

Digoxin [1], hypomagnesemia ---> SmPC of [1] of eMC

Agents causing hypokalaemia or intracellular potassium deficiency may cause increased sensitivity to digoxin

Digoxin [1], indometacin ---> SmPC of [1] of eMC

Serum levels of digitoxin may be increased by concomitant administration of indometacin

Digoxin [1], isradipine ---> SmPC of [1] of eMC

Isradipine causes no change in serum digoxin levels.

Digoxin [1], kaliuretic medicines ---> SmPC of [1] of eMC

Agents causing hypokalaemia or intracellular potassium deficiency may cause increased sensitivity to digoxin

Digoxin [1], laxatives ---> SmPC of [1] of eMC

Agents causing hypokalaemia or intracellular potassium deficiency may cause increased sensitivity to digoxin

Digoxin [1], lithium ---> SmPC of [1] of eMC

Agents causing hypokalaemia or intracellular potassium deficiency may cause increased sensitivity to digoxin

Digoxin [1], loop diuretics ---> SmPC of [1] of eMC

Agents causing hypokalaemia or intracellular potassium deficiency may cause increased sensitivity to digoxin

Digoxin [1], macrolide antibiotics ---> SmPC of [1] of eMC

Serum levels of digoxin may be increased by concomitant administration of macrolide antibiotics

Digoxin [1], manidipine ---> SmPC of [1] of eMC

Serum levels of digoxin may be increased by concomitant administration of calcium antagonists

Digoxin [1], minocycline ---> SmPC of [1] of eMC

Serum levels of digoxin may be increased by concomitant administration of tetracyclines

Digoxin [1], neomycin ---> SmPC of [1] of eMC

Serum levels of digoxin may be reduced by concomitant administration of neomycin

Digoxin [1], P-gp inhibitors ---> SmPC of [1] of eMC

Digoxin is a substrate of P-glycoprotein. Thus, inhibitors of P-glycoprotein may increase blood concentrations of digoxin by enhancing its absorption and/or by reducing its renal clearance

Digoxin [1], penicillamine ---> SmPC of [1] of eMC

Oral absorption of digoxin may be reduced by concomitant administration of penicillamine

Digoxin [1], penicillins ---> SmPC of [1] of eMC

Agents causing hypokalaemia or intracellular potassium deficiency may cause increased sensitivity to digoxin

Digoxin [1], phenothiazines ---> SmPC of [1] of eMC

Phenothiazines may enhance the absorption of digoxin

Digoxin [1], phenytoin ---> SmPC of [1] of eMC

Serum levels of digoxin may be reduced by concomitant administration of phenytoin

Digoxin [1], prazosin ---> SmPC of [1] of eMC

Serum levels of digoxin may be increased by concomitant administration of prazosin

Digoxin [1], pregnancy ---> SmPC of [1] of eMC

As with all drugs, use should be considered only when the expected clinical benefit of treatment to the mother outweighs any possible risk to the developing foetus.

Digoxin [1], propantheline ---> SmPC of [1] of eMC

Serum levels of digoxin may be increased by concomitant administration of propantheline

Digoxin [1], quinine ---> SmPC of [1] of eMC

Serum levels of digoxin may be increased by concomitant administration of quinine

Digoxin [1], rifampicin ---> SmPC of [1] of eMC

Serum levels of digoxin may be reduced by concomitant administration of rifampicin

Digoxin [1], salbutamol ---> SmPC of [1] of eMC

Serum levels of digoxin may be reduced by concomitant administration of salbutamol

Digoxin [1], salicylates ---> SmPC of [1] of eMC

Agents causing hypokalaemia or intracellular potassium deficiency may cause increased sensitivity to digoxin

Digoxin [1], strong P-gp inhibitors ---> SmPC of [1] of eMC

Digoxin is a substrate of P-glycoprotein. Thus, inhibitors of P-glycoprotein may increase blood concentrations of digoxin by enhancing its absorption and/or by reducing its renal clearance

Digoxin [1], succinylcholine ---> SmPC of [1] of eMC

Patients receiving digoxin are more susceptible to the effects of suxamethonium-exacerbated hyperkalaemia.

Digoxin [1], suxamethonium ---> SmPC of [1] of eMC

Patients receiving digoxin are more susceptible to the effects of suxamethonium-exacerbated hyperkalaemia.

Digoxin [1], tetracyclines ---> SmPC of [1] of eMC

Serum levels of digoxin may be increased by concomitant administration of tetracyclines

Digoxin [1], thiazides ---> SmPC of [1] of eMC

Agents causing hypokalaemia or intracellular potassium deficiency may cause increased sensitivity to digoxin

Digoxin [1], trimethoprim ---> SmPC of [1] of eMC

Serum levels of digoxin may be increased by concomitant administration of trimethoprim

Digoxin, diphenoxylate

Diphenoxylate decreases intestinal motility and increases the absorption of digoxine

Digoxin, docetaxel [2] ---> SmPC of [2] of EMA

Docetaxel did not influence the binding of digitoxin

Digoxin, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Digoxin, doxorubicine [2] ---> SmPC of [2] of eMC

Doxorubicin may reduce oral bioavailability of digoxin.

Digoxin, dronedarone [2] ---> SmPC of [2] of EMA

The P-glycoprotein inhibition by dronedarone increases the plasma concentrations of digoxin. Clinical, ECG and biological monitoring is recommended and digoxin dosage should be halved

Digoxin, dulaglutide [2] ---> SmPC of [2] of EMA

No dose adjustment of digoxin is necessary when administered with dulaglutide.

Digoxin, edoxaban [2] ---> SmPC of [2] of EMA

No dose modification is necessary when Lixiana is administered with digoxin.

Digoxin, elbasvir/grazoprevir [2] ---> SmPC of [2] of EMA

Elbasvir has minimal intestinal P-gp inhibition in humans, and does not result in clinically relevant increases in concentrations of digoxin (a P-gp substrate), with an 11% increase in plasma AUC. No dose adjustment is required.

Digoxin, eliglustat [2] ---> SmPC of [2] of EMA

Concomitant administration of eliglustat with P-gp substrates may increase the exposition of the P-gp substrates. Lower doses of substances which are P-gp substrates may be required.

Digoxin, elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

It is recommended that digoxin levels be monitored when digoxin is combined with Genvoya.

Digoxin, elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

The co-administration may increase the Cmax of digoxin. It is recommended that digoxin levels be monitored when digoxin is combined with Stribild.

Digoxin, empagliflozin [2] ---> SmPC of [2] of EMA

Co-administration of digoxin, a P-gp substrate, with empagliflozin resulted in a 6% increase in AUC and 14% increase in Cmax of digoxin. These changes were not considered to be clinically meaningful.

Digoxin, empagliflozin/linagliptin [2] ---> SmPC of [2] of EMA

Linagliptin is a P-glycoprotein substrate, and inhibits P-glycoprotein mediated transport of digoxin with low potency.

Digoxin, empagliflozin/metformin [2] ---> SmPC of [2] of EMA

Co-administration of digoxin, a P-gp substrate, with empagliflozin resulted in a 6% increase in AUC and 14% increase in Cmax of digoxin. These changes were not considered to be clinically meaningful.

Digoxin, emtricitabine/rilpivirine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Digoxin, emtricitabine/rilpivirine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

No dosage adjustment necessary.

Digoxin, enzalutamide [2] ---> SmPC of [2] of EMA

Digoxin, eplerenone [2] ---> SmPC of [2] of eMC

Systemic exposure (AUC) to digoxin increases when co-administered with eplerenone. Caution is warranted when digoxin is dosed near the upper limit of therapeutic range.

Digoxin, eslicarbazepine [2] ---> SmPC of [2] of EMA

A study in healthy subjects showed no effect of eslicarbazepine acetate 1,200 mg once daily on digoxin pharmacokinetics, suggesting that eslicarbazepine acetate has no effect on the transporter P-glycoprotein.

Digoxin, esmolol [2] ---> SmPC of [2] of eMC

When digoxin and Esmolol hydrochloride 10 mg/ml solution for injection were concomitantly administered intravenously to normal volunteers, there was a 10-20% increase in digoxin blood levels at some time points.

Digoxin, esomeprazole [2] ---> SmPC of [2] of EMA

Esomeprazole may increase the absorption of digoxin.

Digoxin, etoricoxib [2] ---> SmPC of [2] of eMC

Increased plasma concentrations of digoxin. This increase is not generally important for most patients.

Digoxin, etravirine [2] ---> SmPC of [2] of EMA

Etravirine and digoxin can be used without dose adjustments. It is recommended that digoxin levels be monitored when digoxin is combined with etravirine.

Digoxin, exenatide [2] ---> SmPC of [2] of EMA

In interaction studies of the effect of immediate-release exenatide on digoxin and lisinopril there were no clinical relevant effects on Cmax or AUC, however, a delay in tmax of about 2 h was observed.

Digoxin, felodipine [2] ---> SmPC of [2] of eMC

The co-administration increases the plasma levels of digoxin

Digoxin, fidaxomicin [2] ---> SmPC of [2] of EMA

Fidaxomicin had a small but not clinically relevant effect on digoxin exposure.

Digoxin, fingolimod [2] ---> SmPC of [2] of EMA

Treatment with Gilenya should not be initiated in patients receiving beta blockers, or other substances which may decrease heart rate because of the potential additive effects on heart rate

Digoxin, flucloxacillin

Increased plasma levels of digoxin

Digoxin, fluvastatin [2] ---> SmPC of [2] of eMC

No clinically significant pharmacokinetic interactions occur when fluvastatin is concomitantly administered with digoxin.

Digoxin, fluvoxamine [2] ---> SmPC of [2] of eMC

Fluvoxamine does not influence plasma concentrations of digoxin.

Digoxin, fosphenytoin [2] ---> SmPC of [2] of eMC

Blood levels and/or effects of digoxine may be altered by phenytoin

Digoxin, galantamine [2] ---> SmPC of [2] of eMC

As expected with cholinomimetics, a pharmacodynamic interaction is possible with medicinal products that significantly reduce the heart rate. Therapeutic doses of galantamine 24 mg/day had no effect on the kinetics of digoxin

Digoxin, gastric pH increasing medication

Increased bioavailability of digoxin

Digoxin, ginseng

It has been reported increased digoxin levels

Digoxin, glecaprevir/pibrentasvir [2] ---> SmPC of [2] of EMA

Inhibition of P-gp. Caution and therapeutic concentration monitoring of digoxin is recommended.

Digoxin, gonadorelin [2] ---> SmPC of [2] of eMC

Digoxin may decrease the gonadotropine secretion

Digoxin, hydrochlorothiazide ---> SmPC of [aliskiren/hydrochlorothiazide] of EMA

Thiazide induced hypokalaemia/hypomagnaesemia favour the onset of digitalis-induced cardiac arrhythmias. Periodic monitoring of serum potassium and ECG is recommended

Digoxin, hydroquinidine

Digoxine (and by extrapolation deslanoside). There is increased digoxinemia due to decreased renal clearance of digoxin. There is also rhythm disorders (excessive bradycardia and AV conduction disorders)

Digoxin, hydrotalcite

The co-administration of hydrotalcite with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 1-2 hours

Digoxin, hydroxychloroquine [2] ---> SmPC of [2] of eMC

Hydroxychloroquine may increase the plasma concentrations of digoxin.

Digoxin, hypercalcemia

Hypercalcemia predisposes to digitalis toxicity

Digoxin, hyperkalemia

The co-administration may decrease the positive inotrope effect of digoxin and promote heart rhythm disorders

Digoxin, ibrutinib [2] ---> SmPC of [2] of EMA

To minimise the potential for an interaction in the GI tract, oral narrow therapeutic range, P-gp or BCRP substrates such as digoxin or methotrexate should be taken at least 6 hours before or after IMBRUVICA.

Digoxin, idebenone [2] ---> SmPC of [2] of EMA

Idebenone may inhibit P-glycoprotein (p-gp) with possible exposure increases of e.g. dabigatran etexilate, digoxin or aliskiren. Idebenone is not a substrate for p-gp in vitro.

Digoxin, indinavir [2] ---> SmPC of [2] of EMA

The P-glycoprotein inhibition by ritonavir may increase the plasma concentrations of digoxin. Careful monitoring is recommended

Digoxin, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Ritonavir may increase digoxin levels due to modification of P-glycoprotein mediated digoxin efflux. Careful monitoring of digoxin levels is recommended when digoxin is concomitantly administered with indinavir/ritonavir.

Digoxin, insulin degludec/liraglutide [2] ---> SmPC of [2] of EMA

A single dose administration of digoxin 1 mg with liraglutide resulted in a reduction of digoxin AUC by 16%. No adjustment of digoxin dose is required

Digoxin, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

No dose adjustment for digoxin is required when co-administered with lixisenatide.

Digoxin, interferon

Caution should be used when administering interferon with medicines mainly metabolised by hepatic cytochrome P450 and have a narrow therapeutic window

Digoxin, irbesartan [2] ---> SmPC of [2] of EMA

The pharmacokinetic of digoxin was not altered by coadministration of irbesartan.

Digoxin, isavuconazole [2] ---> SmPC of [2] of EMA

No CRESEMBA dose adjustment necessary. Digoxin (P-gp substrate): serum digoxin concentrations should be monitored and used for titration of the digoxin dose.

Digoxin, itraconazol [2] ---> SmPC of [2] of eMC

Itraconazole may increase the plasma concentrations of digoxin. Use with caution

Digoxin, ivabradine [2] ---> SmPC of [2] of EMA

Specific drug-drug interaction studies have shown no clinically significant effect of the digoxine on pharmacokinetics and pharmacodynamics of ivabradine

Digoxin, ivacaftor [2] ---> SmPC of [2] of EMA

Based on in vitro results, ivacaftor and its M1 metabolite have the potential to inhibit CYP3A and P-gp. Co-administration with digoxin, a sensitive P-gp-substrate, increased digoxin exposure

Digoxin, kaolin

Decreased digoxin absorption or increased elimination due to enterohepatic circulation interruption. Digoxin should be administered 2 hours before.

Digoxin, ketoconazole [2] ---> SmPC of [2] of EMA

Potential increase in plasma concentrations of digoxine. Careful monitoring of digoxin levels is recommended.

Digoxin, ketoprofen

The co-administration of ketoprofen with digoxin may increase the plasma levels of digoxin

Digoxin, ketorolac [2] ---> SmPC of [2] of eMC

Ketorolac does not alter digoxin protein binding.

Digoxin, lacosamide [2] ---> SmPC of [2] of EMA

Interaction trials showed that lacosamide had no effect on the pharmacokinetics of digoxin.

Digoxin, lansoprazole [2] ---> SmPC of [2] of eMC

Co-administration of Lansoprazole and digoxin may lead to increased digoxin plasma levels.

Digoxin, lapatinib [2] ---> SmPC of [2] of EMA

Caution should be exercised when dosing lapatinib (P-gp inhibitor) concurrently with medicinal products with narrow therapeutic windows that are substrates of P-gp

Digoxin, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

Co-administration of ledipasvir/sofosbuvir (inhibition of P-gp) with digoxin may increase the concentration of digoxin.

Digoxin, lenalidomide [2] ---> SmPC of [2] of EMA

The monitoring of the digoxin concentration is advised

Digoxin, lercanidipine [2] ---> SmPC of [2] of eMC

Patients on concomitant digoxin treatment should be closely monitored clinically for signs of digoxin toxicity.

Digoxin, letermovir [2] ---> SmPC of [2] of EMA

No dose adjustment required.

Digoxin, levetiracetam [2] ---> SmPC of [2] of EMA

Levetiracetam 2,000 mg daily did not influence the pharmacokinetics of digoxin and warfarin; prothrombin times were not modified.

Digoxin, levofloxacin [2] ---> SmPC of [2] of EMA

Clinical pharmacology studies have shown that the pharmacokinetics of levofloxacin were not affected to any clinically relevant extent when levofloxacin was administered together with digoxine

Digoxin, light paraffin

Agents causing hypokalaemia or intracellular potassium deficiency may cause increased sensitivity to digoxin

Digoxin, linagliptin [2] ---> SmPC of [2] of EMA

Linagliptin is a P-glycoprotein substrate, and inhibits P-glycoprotein mediated transport of digoxin with low potency.

Digoxin, linagliptin/metformin [2] ---> SmPC of [2] of EMA

Co-administration of multiple daily doses of 5 mg linagliptin with multiple doses of 0.25 mg digoxin had no effect on the pharmacokinetics of digoxin in healthy subjects. Linagliptin is not an inhibitor of P-glycoprotein-mediated transport in vivo.

Digoxin, liraglutide [2] ---> SmPC of [2] of EMA

A single dose administration of digoxin 1 mg with liraglutide resulted in a reduction of digoxin AUC by 16%. No adjustment of digoxin dose is required

Digoxin, lixisenatide [2] ---> SmPC of [2] of EMA

No dose adjustment for digoxin is required when co-administered with lixisenatide

Digoxin, lomitapide [2] ---> SmPC of [2] of EMA

Lomitapide, P-glycoprotein inhibitor, may increase the absorption of the P-glycoprotein substrate

Digoxin, lopinavir/ritonavir [2] ---> SmPC of [2] of EMA

Plasma concentrations of digoxin may be increased due to P-glycoprotein inhibition by lopinavir/ritonavir. The increased digoxin level may lessen over time as Pgp induction develops.

Digoxin, lornoxicam

Decreased renal elimination of digoxin

Digoxin, losartan/hydrochlorothiazide [2] ---> SmPC of [2] of eMC

Thiazide-induced hypokalaemia or hypomagnesaemia may favour the onset of digitalis-induced cardiac arrhythmias.

Digoxin, lovastatine

Concomitant use of lovastatin and digoxin in patients with hypercholesterinemia had no effects on the digoxin plasma concentration

Digoxin, lumacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

In vitro studies indicated that lumacaftor has the potential to both inhibit and induce P-gp. Therefore, concomitant use of lumacaftor/ivacaftor with P-gp substrates (e.g., digoxin) may alter the exposure of these substrates.

Digoxin, lumiracoxib

NSAID may exacerbate cardiac failure, reduce the glomerular filtration rate and increase plasma levels of the cardiac glycoside

Digoxin, lurasidone [2] ---> SmPC of [2] of EMA

Coadministration of lurasidone with digoxin (a P-gp substrate) did not increase the exposure to digoxin and only slightly increased Cmax (1.3 -fold)

Digoxin, magaldrate

The co-administration may decrease the absorption of digoxin. It is recommended to administer the two substances at least 2 hours apart.

Digoxin, magnesium hydroxide

The magnesium hydroxide may decrease the absorption of digoxine. Separate administration by 2-3 hours

Digoxin, maraviroc [2] ---> SmPC of [2] of EMA

Maraviroc does not significantly affect the pharmacokinetics of digoxin

Digoxin, methyldopa

The co-administration may cause sinus bradycardia

Digoxin, metoclopramide

Serum levels of digoxin may be reduced by concomitant administration of metoclopramide

Digoxin, midostaurin [2] ---> SmPC of [2] of EMA

Medicinal products with a narrow therapeutic range that are substrates of P-gp should be used with caution when administered concomitantly with midostaurin and may need dose adjustment to maintain optimal exposure

Digoxin, miglitol

Decreased bioavailability of digoxin

Digoxin, mirabegron [2] ---> SmPC of [2] of EMA

The inhibition of P-glycoprotein by mirabegron may increase the exposure to digoxin

Digoxin, moxifloxacin [2] ---> SmPC of [2] of eMC

After repeated dosing in healthy volunteers, moxifloxacin increased Cmax of digoxin by approximately 30% without affecting AUC or trough levels. No precaution is required for use with digoxin.

Digoxin, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

NSAIDs may increase plasma cardiac glycoside levels when co-administered with cardiac glycosides such as digoxin.

Digoxin, nebivolol [2] ---> SmPC of [2] of eMC

Nebivolol does not influence the kinetics of digoxin

Digoxin, nefazodone

Serum levels of digoxin may be increased by concomitant administration of nefazodone

Digoxin, neratinib [2] ---> SmPC of [2] of EMA

This pre-systemic interaction of neratinib with digoxin might be clinically relevant for P-gp substrates with a narrow therapeutic window (e.g. dabigatran, digoxin, and fexofenadine).

Digoxin, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

In vitro data show that netupitant is a P-gp inhibitor. Caution is recommended when netupitant is combined with digoxin or with other P-gp substrates such as dabigatran, or colchicine.

Digoxin, nicardipine [2] ---> SmPC of [2] of eMC

Careful monitoring of serum digoxin levels is advised in patients also receiving nicardipine as levels may be increased.

Digoxin, nifedipine [2] ---> SmPC of [2] of eMC

The administration of nifedipine and digoxin concurrently may lead to reduced digoxin clearance and therefore, bring about an increase in the plasma digoxin level.

Digoxin, nitrendipine

The co-administration may increase the plasma levels of digoxin

Digoxin, NSAID ---> SmPC of [dexibuprofen] of eMC

NSAID may exacerbate cardiac failure, reduce the glomerular filtration rate and increase plasma levels of the cardiac glycoside

Digoxin, octreotide [2] ---> SmPC of [2] of eMC

Drugs mainly metabolised by CYP3A4 and which have a low therapeutic index should be only used with octreotide with caution.

Digoxin, olaparib [2] ---> SmPC of [2] of EMA

In vitro, olaparib inhibits the efflux transporter P-gp (IC50 = 76 µM), therefore it cannot be excluded that olaparib may cause clinically relevant drug interactions with substrates of P-gp

Digoxin, olmesartan medoxomil [2] ---> SmPC of [2] of eMC

Olmesartan medoxomil had no significant effect on the pharmacokinetics of digoxin.

Digoxin, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

Olmesartan medoxomil had no significant effect on the pharmacokinetics of digoxin.

Digoxin, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

P-gp inhibition by paritaprevir, ritonavir and dasabuvir. Decrease digoxin dose by 30-50%. Appropriate monitoring of serum digoxin levels is recommended.

Digoxin, omeprazole [2] ---> SmPC of [2] of eMC

Simultaneous treatment with omeprazole and digoxin in healthy subjects lead to a 10% increase in the bioavailability of digoxin as a consequence of the increased intragastric pH.

Digoxin, P-gp inductors ---> SmPC of [bosentan] of EMA

The induction of P-glycoprotein reduces the exposition of digoxin

Digoxin, palbociclib [2] ---> SmPC of [2] of EMA

Administration of palbociclib with medicinal products that are substrates of P-gp (e.g., digoxin, dabigatran, colchicine, pravastatin) may increase their therapeutic effect and adverse reactions.

Digoxin, pancuronium

Pancuronium may increase the risk of cardiac arrhythmias

Digoxin, pantoprazole [2] ---> SmPC of [2] of EMA

No clinically significant interactions were observed

Digoxin, para-aminosalicylic acid [2] ---> SmPC of [2] of EMA

Para-aminosalicylic acid may decrease the gastrointestinal absorption of digoxin, by inhibiting the absorption function of intestinal cells.

Digoxin, parathyroid hormone [2] ---> SmPC of [2] of EMA

The combined use of parathyroid hormone and digital glycosides may predispose to digitalis toxicity if hypercalcemia develops.

Digoxin, paromomycin

The co-administration may alter the gastrointestinal absorption of digitalic agent. Caution is recommended

Digoxin, perphenazine [2] ---> SmPC of [2] of eMC

Phenothiazines may enhance the absorption of digoxin

Digoxin, phenylbutazone

Serum levels of digoxin may be reduced by concomitant administration of phenylbutazone (induction of hepatic metabolism of digoxin)

Digoxin, phosphodiesterase inhibitors

Phosphodiesterase inhibitors may increase the risk of cardiac arrhythmias

Digoxin, pioglitazone [2] ---> SmPC of [2] of EMA

Interaction studies have shown that pioglitazone has no relevant effect on either the pharmacokinetics or pharmacodynamics of digoxin

Digoxin, piroxicam [2] ---> SmPC of [2] of eMC

Concurrent therapy with piroxicam and digoxin did not affect the plasma levels of either drug.

Digoxin, pitavastatin

Digoxin, a glycoprotein-P substrate, showed no interaction with pitavastatin

Digoxin, pitolisant [2] ---> SmPC of [2] of EMA

With other CYP3A4, CYP2B6 (e.g. efavirenz, bupropion), CYP2C (e.g. repaglinide, phenytoin, warfarin), P-gp (e.g. dabigatran, digoxin) and UGT (e.g. morphine, paracetamol, irinotecan) substrates, caution should be made

Digoxin, ponatinib [2] ---> SmPC of [2] of EMA

In vitro, ponatinib is an inhibitor of P-gp. Therefore, ponatinib may have the potential to increase plasma concentrations of co-administered substrates of P-gp and may increase their therapeutic effect and adverse reactions.

Digoxin, posaconazole [2] ---> SmPC of [2] of EMA

Administration of other azoles has been associated with increases in digoxin levels. Therefore, posaconazole may increase plasma concentration of digoxin

Digoxin, potassium

The co-administration may decrease the positive inotrope effect of digoxin and promote heart rhythm disorders

Digoxin, potassium canrenoate

The co-administration of digoxin with potassium canreonate may increase plasma levels of digoxin

Digoxin, potassium chloride

Hypercaliemia may be dangerous in digitalized patients

Digoxin, potassium-sparing diuretics

The co-administration may decrease the positive inotrope effect of digoxin and promote heart rhythm disorders

Digoxin, prasugrel [2] ---> SmPC of [2] of EMA

Efient can be concomitantly administered with ASA, heparin, digoxin, and medicinal products that elevate gastric pH, including proton pump inhibitors and H2 blockers.

Digoxin, propafenone [2] ---> SmPC of [2] of eMC

During the treatment with propafenone there have been reports of increased plasma and/or blood levels of digoxin

Digoxin, proton pump inhibitors ---> SmPC of [lansoprazole] of eMC

For patients expected to be on prolonged treatment or who take PPIs with digoxin or drugs that may cause hypomagnesaemia, health care professionals should consider measuring magnesium levels before starting PPI treatment and periodically during treatment

Digoxin, quinidine ---> SmPC of [dextromethorphan/quinidine] of EMA

Quinidine is an inhibitor of P-glycoprotein. Concomitant administration of quinidine with digoxin, a P-glycoprotein substrate, results in serum digoxin levels that may be as much as doubled.

Digoxin, rabeprazole

Increased bioavailability of digoxin

Digoxin, ranolazine [2] ---> SmPC of [2] of EMA

An increase in plasma digoxin concentrations by an average of 1.5-fold has been reported when Ranexa and digoxin are co-administered. Therefore, digoxin levels should be monitored following initiation and termination of Ranexa therapy.

Digoxin, regorafenib [2] ---> SmPC of [2] of EMA

Clinical data indicate that regorafenib has no effect on digoxin pharmacokinetics, therefore can be given concomitantly with p-glycoprotein substrates, such as digoxin, without a clinically meaningful drug interaction.

Digoxin, reserpine

Increased risk of rhythm disorders

Digoxin, retigabine [2] ---> SmPC of [2] of EMA

There was no meaningful change in digoxin Cmax. No dose adjustment of digoxin is needed.

Digoxin, ribociclib [2] ---> SmPC of [2] of EMA

Caution and monitoring for toxicity are advised during concomitant treatment with sensitive substrates of this transporter which exhibit a narrow therapeutic index

Digoxin, rilpivirine [2] ---> SmPC of [2] of EMA

No dosage adjustment necessary.

Digoxin, ritonavir [2] ---> SmPC of [2] of EMA

Increased plasma concentrations of digoxin that may lessen over time as induction of P-gp develops

Digoxin, rivaroxaban [2] ---> SmPC of [2] of EMA

No clinically significant pharmacokinetic or pharmacodynamic interactions were observed when rivaroxaban was co-administered with digoxin

Digoxin, rolapitant [2] ---> SmPC of [2] of EMA

Digoxin, rosuvastatin [2] ---> SmPC of [2] of eMC

Based on data from specific interaction studies no clinically relevant interaction with digoxin is expected

Digoxin, roxithromycin

Roxitromycin may increase the absorption and the plasma levels of digoxin

Digoxin, rufinamide [2] ---> SmPC of [2] of EMA

It is recommended that patients treated with substances that are metabolised by the CYP3A4 enzyme system are to be carefully monitored for two weeks at the start of, or after the end of treatment with rufinamide, or after any marked change in the dose.

Digoxin, ruxolitinib [2] ---> SmPC of [2] of EMA

Ruxolitinib may inhibit P-glycoprotein and breast cancer resistance protein (BCRP) in the intestine. This may result in increased systemic exposure of substrates of these transporters

Digoxin, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Large increments of digoxin may be expected when saquinavir/ritonavir is introduced in patients already treated with digoxin.

Digoxin, scopolamine

Scopolamine may change the effect of digoxin

Digoxin, semaglutide [2] ---> SmPC of [2] of EMA

Semaglutide did not change the overall exposure or Cmax of digoxin following a single dose of digoxin (0.5 mg).

Digoxin, sevelamer carbonate [2] ---> SmPC of [2] of EMA

In interaction studies in healthy volunteers, sevelamer hydrochloride, which contains the same active moiety as sevelamer carbonate, had no effect on the bioavailability of digoxin, warfarin, enalapril or metoprolol.

Digoxin, sevelamer hydrochloride [2] ---> SmPC of [2] of EMA

In interaction studies in healthy volunteers, sevelamer hydrochloride had no effect on the bioavailability of digoxin

Digoxin, silodosin [2] ---> SmPC of [2] of EMA

Steady state levels of digoxin, a substrate of P-glycoprotein, were not significantly affected. No dose adjustment is required.

Digoxin, simeprevir [2] ---> SmPC of [2] of EMA

Inhibition of P-gp transporter. Concentrations of digoxin should be monitored and used for titration of digoxin dose to obtain the desired clinical effect.

Digoxin, sitagliptin [2] ---> SmPC of [2] of EMA

Increased AUC and Cmax of digoxin. Patients at risk of digoxin toxicity should be monitored

Digoxin, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

Sitagliptin had a small effect on plasma digoxin concentrations. Patients at risk of digoxin toxicity should be monitored for this when sitagliptin and digoxin are administered concomitantly

Digoxin, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Inhibition of P-gp. Co-administration of Epclusa with digoxin may increase the concentration of digoxin. Caution is warranted and therapeutic concentration monitoring of digoxin is recommended when co-administered with Epclusa.

Digoxin, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Inhibition of P-gp. Co-administration of Vosevi with digoxin may increase the concentration of digoxin. Caution is warranted and therapeutic concentration monitoring of digoxin is recommended.

Digoxin, solifenacin [2] ---> SmPC of [2] of eMC

Intake of solifenacin showed no effect on the pharmacokinetics of digoxin.

Digoxin, sorafenib [2] ---> SmPC of [2] of EMA

Increased plasma concentrations of P-gp substrates such as digoxin cannot be excluded with concomitant treatment with sorafenib.

Digoxin, spironolactone [2] ---> SmPC of [2] of eMC

Spironolactone has been reported to increase serum digoxin concentration

Digoxin, St. John's wort

St. John's wort, inductor of transporters of P-glycoprotein, may decrease the exposure to digoxin. St. John's Wort should be avoided

Digoxin, sterculia

Agents causing hypokalaemia may cause increased sensitivity to digoxin

Digoxin, sucralfate [2] ---> SmPC of [2] of eMC

Concomitant administration of sucralfate may reduce the bioavailability of digoxin. The bioavailability may be restored by separating the administration from sucralfate by 2 hours.

Digoxin, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

Drug-drug interaction studies have been conducted in healthy subjects with losartan, furosemide, digoxin, warfarin, and omeprazole. Co-administration of Velphoro did not affect the bioavailability of these products as measured by the AUC.

Digoxin, sulfasalazine [2] ---> SmPC of [2] of eMC

Reduced absorption of digoxin, resulting in non-therapeutic serum levels, has been reported when used concomitantly with oral sulfasalazine.

Digoxin, sympathomimetics

Sympathomimetics may increase the risk of provoking arrhythmias

Digoxin, telaprevir [2] ---> SmPC of [2] of EMA

The intestinal P-glycoprotein inhibition may increase the exposition of digoxin

Digoxin, telithromycin [2] ---> SmPC of [2] of EMA

Digoxin, telmisartan [2] ---> SmPC of [2] of EMA

When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma concentration (49%) and in trough concentration (20%) were observed.

Digoxin, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma concentration (49%) and in trough concentration (20%) were observed

Digoxin, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma concentration (49%) and in trough concentration (20%) were observed.

Digoxin, temsirolimus [2] ---> SmPC of [2] of EMA

When temsirolimus is co-administered with medicinal products which are P-gp substrates close monitoring for adverse events related to the co-administered medicinal products should be observed.

Digoxin, terbinafine [2] ---> SmPC of [2] of eMC

Terbinafine does not interfere with the clearance of digoxin.

Digoxin, teriparatide [2] ---> SmPC of [2] of EMA

Sporadic case reports have suggested that hypercalcaemia may predispose patients to digitalis toxicity. Because FORSTEO transiently increases serum calcium, FORSTEO should be used with caution in patients taking digitalis.

Digoxin, tetrabenazine

Tetrabenazin has no effect on the bioavailability of digoxin

Digoxin, thalidomide [2] ---> SmPC of [2] of EMA

Thalidomide does not interact with digoxin. It is not known whether the effect will be different in multiple myeloma patients.

Digoxin, theophylline

Phosphodiesterase inhibitors may increase the risk of cardiac arrhythmias

Digoxin, tiagabine [2] ---> SmPC of [2] of eMC

Tiagabine does not have any clinically significant effect on the plasma concentrations of digoxine

Digoxin, tiaprofenic acid

The co-administration of tiaprofenic acid with digoxin may increase the plasma concentrations of digoxin

Digoxin, ticagrelor [2] ---> SmPC of [2] of EMA

Appropriate clinical and/or laboratory monitoring is recommended when giving narrow therapeutic index P-gp dependent medicinal products like digoxin concomitantly with ticagrelor

Digoxin, ticlopidine

Concomitant use of ticlopidine and digoxin reduces the plasma concentrations of digoxin (ca. 15 %). Changing of digoxin effects are not expected

Digoxin, tigecycline [2] ---> SmPC of [2] of EMA

No dosage adjustment is necessary when tigecycline is administered with digoxin.

Digoxin, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Transient inhibition of P-gp by tipranavir/ritonavir, followed by induction of P-gp by tipranavir/ritonavir at steady-state. Monitoring of digoxin serum concentrations is recommended

Digoxin, tizanidine

The co-administration may enhance the antihypertensive effect and a bradycardia. Caution is recommended

Digoxin, tolvaptan [2] ---> SmPC of [2] of EMA

Increased steady state digoxin concentrations. Patients should be evaluated for excessive digoxin effects

Digoxin, topiramate [2] ---> SmPC of [2] of eMC

In a single-dose study, serum digoxin area under plasma concentration curve (AUC) decreased 12% due to concomitant administration of topiramate.

Digoxin, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of digoxine thus increasing risk of toxicity

Digoxin, trazodone [2] ---> SmPC of [2] of eMC

Concurrent use with trazodone may result in elevated serum levels of digoxin

Digoxin, triamterene

The co-administration may decrease the positive inotrope effect of digoxin and promote heart rhythm disorders

Digoxin, tricyclic antidepressant

Tricyclic antidepressants may increase the risk of cardiac arrhythmias

Digoxin, trimethoprim/sulfamethoxazol ---> SmPC of [cotrimoxazole] of eMC

The co-administration of trimethoprim and digoxin increases digoxin levels in a proportion of elderly patients

Digoxin, tubular secretion

The co-administration may increase the serum levels of either one and/or both principle actives due to competition for the active tubular secretion.

Digoxin, ulipristal [2] ---> SmPC of [2] of EMA

In vitro data indicate that ulipristal may be an inhibitor of P-gp in the gastrointestinal wall during absorption. It is recommended that co-administration of ulipristal acetate and P-gp substrates should be separated in time by at least 1.5 hours.

Digoxin, valsartan [2] ---> SmPC of [2] of eMC

In drug interaction studies with valsartan, no interactions of clinical significance have been found with valsartan and digoxine

Digoxin, vandetanib [2] ---> SmPC of [2] of EMA

Vandetanib, P-glycoprotein inhibitor, may increase the plasma levels of digoxin. The bradycardiac effect of digoxin may increase the risk of vandetanib QTc interval prolongation and Torsade de Pointes. Increased clinical and biological surveillance

Digoxin, vardenafil [2] ---> SmPC of [2] of EMA

The pharmacokinetics of vardenafil (20 mg) was not affected by co-administration with digoxine

Digoxin, varenicline [2] ---> SmPC of [2] of EMA

Varenicline did not alter the steady-state pharmacokinetics of digoxin.

Digoxin, vemurafenib [2] ---> SmPC of [2] of EMA

Digoxin, venetoclax [2] ---> SmPC of [2] of EMA

Digoxin, verapamil [2] ---> SmPC of [2] of eMC

Verapamil has been shown to increase the serum concentration of digoxin and caution should be exercised with regard to digitalis toxicity.

Digoxin, vildagliptin ---> SmPC of [vildagliptin/metformin] of EMA

Drug-drug interaction studies with digoxin (P-glycoprotein substrate) and warfarin (CYP2C9 substrate) in healthy subjects have shown no clinically relevant pharmacokinetic interactions after coadministration with vildagliptin.

Digoxin, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Digoxin, vincristine

The co-administration may decrease the absorption of digoxin

Digoxin, vorapaxar [2] ---> SmPC of [2] of EMA

Vorapaxar is a weak inhibitor of the intestinal P-glycoprotein (P-gp) transporter. Co-administration of vorapaxar and digoxin increased digoxin Cmax and AUC. No dosage adjustment is recommended.

Digoxin, voriconazole [2] ---> SmPC of [2] of EMA

No dosage adjustment necessary.

Digoxin, zonisamide [2] ---> SmPC of [2] of EMA

Caution is advised when starting or stopping zonisamide treatment or changing the zonisamide dose in patients who are also receiving medicinal products which are P-gp substrates (e.g. digoxin, quinidine).

CONTRAINDICATIONS of Digoxin

- Lanoxin is contra-indicated in intermittent complete heart block or second degree atrioventricular block, especially if there is a history of Stokes-Adams attacks.

- Lanoxin is contra-indicated in arrhythmias caused by cardiac glycoside intoxication.

- Lanoxin is contra-indicated in supraventricular arrhythmias associated with an accessory atrioventricular pathway, as in the Wolff-Parkinson-White syndrome, unless the electrophysiological characteristics of the accessory pathway and any possible deleterious effect of digoxin on these characteristics has been evaluated. If an accessory pathway is known or suspected to be present and there is no history of previous supraventricular arrhythmias, Lanoxin is similarly contraindicated.

- Lanoxin is contra-indicated in ventricular tachycardia or ventricular fibrillation.

- Lanoxin is contra-indicated in hypertrophic obstructive cardiomyopathy, unless there is concomitant atrial fibrillation and heart failure but even then caution should be exercised if Lanoxin is to be used.

- Lanoxin is contra-indicated in patients known to be hypersensitive to digoxin, other digitalis glycosides, or to any component of the preparation.

http://www.medicines.org.uk/emc/

Dihydrocodeine

Ability to drive, dihydrocodeine [2] ---> SmPC of [2] of eMC

Dihydrocodeine produces sedation and may also cause changes in vision, including blurred or double vision. If affected, patients should not drive or operate machinery.

Alcohol, dihydrocodeine [2] ---> SmPC of [2] of eMC

The hypotensive, sedative and respiratory depressive effects of alcohol may be enhanced; alcohol should be avoided.

Amitriptyline, dihydrocodeine [2] ---> SmPC of [2] of eMC

Opiates potentiate the effects of CNS depressants

Analgesics, dihydrocodeine

Possible mutual potentiation of the analgetic effect

Antihypertensives, dihydrocodeine

The co-administration may enhance the sedative and respiratory depressor effect

Antitussives, dihydrocodeine

The co-administration of dihydrocodeine and cough-relieving agents may enhance the effect of the cough-relieving agent

Breast-feeding, dihydrocodeine [2] ---> SmPC of [2] of eMC

It is not known if dihydrocodeine is excreted into breast milk and use should be avoided during breast-feeding unless the potential benefit outweighs the risk.

Cimetidine, dihydrocodeine [2] ---> SmPC of [2] of eMC

Cimetidine may inhibit the metabolism of dihydrocodeine resulting in increased plasma concentrations.

CNS depressants, dihydrocodeine [2] ---> SmPC of [2] of eMC

Opiates potentiate the effects of CNS depressants

Dihydrocodeine [1], IMAOs ---> SmPC of [1] of eMC

The use of dihydrocodeine should be avoided while the patient is taking MAOIs and for 2 weeks after MAOI discontinuation.

Dihydrocodeine [1], imipramine ---> SmPC of [1] of eMC

Opiates potentiate the effects of CNS depressants

Dihydrocodeine [1], mexiletine ---> SmPC of [1] of eMC

Dihydrocodeine may delay absorption of mexiletine.

Dihydrocodeine [1], opipramol ---> SmPC of [1] of eMC

Opiates potentiate the effects of CNS depressants

Dihydrocodeine [1], pregnancy ---> SmPC of [1] of eMC

A possible association with respiratory and cardiac malformations has been reported following first trimester exposure to codeine. Dihydrocodeine may cause respiratory depression in the neonate.

Dihydrocodeine [1], tricyclic antidepressant ---> SmPC of [1] of eMC

Opiates potentiate the effects of CNS depressants

Dihydrocodeine, indocyanine green

Extinction attenuation

Dihydrocodeine, muscle relaxants

The co-administration may cause additive depression of CNS and additive respiratory depression

Dihydrocodeine, nalbuphine

Pure µ agonists decrease the analgetic effect due to competitive blockade of receptors. Concomitant use is contraindicated.

Dihydrocodeine, opioid agonist/antagonists

Possible weakening of effects

Dihydrocodeine, paracetamol

Possible mutual potentiation of the analgetic effect

Dihydrocodeine, pentazocine

Possible weakening of effects

Dihydrocodeine, secretolytics

The cough reflex inhibition may cause secretion congestion

CONTRAINDICATIONS of Dihydrocodeine

- Acute respiratory depression.

- Obstructive airways disease

- Known hypersensitivity to dihydrocodeine, or other opioid analgesics, or to any of the excipients

- Acute alcoholism

- Severe hepatic dysfunction

- Head injury or raised intracranial pressure (in addition to the risk of respiratory depression and increased intracranial pressure, may affect papillary and other responses vital for neurological assessment).

- Children under 4 years of age.

- Dihydrocodeine should not be given to comatose patients.

- Dihydrocodeine is also contraindicated where there is a risk of paralytic ileus, or in acute diarrhoeal conditions such as acute ulcerative colitis or antibiotic associated colitis (e.g. pseudomembranous colitis) or diarrhoea caused by poisoning.

http://www.medicines.org.uk/emc/

Diltiazem

Ability to drive, diltiazem [2] ---> SmPC of [2] of eMC

On the basis of reported adverse drug reactions, i.e. dizziness (common), malaise (common), the ability to drive and use machines could be altered. However, no studies have been performed.

Acamprosate, diltiazem

The co-administration may deteriorate an angina pectoris

Alfa-adrenergic receptor blockers, diltiazem [2] ---> SmPC of [2] of eMC

Concomitant treatment of diltiazem with alpha-antagonists may produce or aggravate hypotension. The combination of diltiazem with an alpha-antagonist should be considered only with the strict monitoring of the blood pressure.

Alfentanyl [1], diltiazem ---> SmPC of [1] of eMC

Available human pharmacokinetic data indicate that the metabolism of alfentanil is inhibited by known cytochrome P450 3A4 enzyme inhibitors. This could increase the risk of prolonged or delayed respiratory depression.

Aliskiren/amlodipine [1], diltiazem ---> SmPC of [1] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure. Clinical monitoring and dose adjustment may thus be required.

Aliskiren/amlodipine/hydrochlorothiazide [1], diltiazem ---> SmPC of [1] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure. Clinical monitoring and dose adjustment may thus be required.

Alprazolam, diltiazem

Concomitant use of alprazolam and strong CYP3A4 inhibitors should be done with caution a significant dose reduction should be considered

Aminophylline [1], diltiazem ---> SmPC of [1] of eMC

Calcium channel blockers may decrease aminophylline clearance resulting in increased plasma theophylline concentrations and the potential for increased toxicity

Amiodarone [1], diltiazem ---> SmPC of [1] of eMC

Certain calcium channel inhibitors (diltiazem, verapamil); potentiation of negative chronotropic properties and conduction slowing effects may occur. Combined therapy is not recommended

Amisulpride, diltiazem

Concomitant use of amisulpride with drugs inducing bradycardia is not recommended

Amitriptyline [1], diltiazem ---> SmPC of [1] of eMC

Diltiazem may possibly increase the plasma concentration of amitriptyline.

Amlodipine, diltiazem ---> SmPC of [aliskiren/amlodipine] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure. Clinical monitoring and dose adjustment may thus be required.

Amlodipine/valsartan [1], diltiazem ---> SmPC of [1] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure. Clinical monitoring and dose adjustment may thus be required.

Amlodipine/valsartan/hydrochlorothiazide [1], diltiazem ---> SmPC of [1] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure.

Anaesthetics, diltiazem [2] ---> SmPC of [2] of eMC

Depression of cardiac contractility, conductivity and automaticity, as well as the vascular dilatation associated with anaesthetics may be potentiated by calcium channel blockers.

Antiarrhythmics, diltiazem [2] ---> SmPC of [2] of eMC

Concomitant prescription of diltiazem with other antiarrhythmic agents is not recommended (additive risk of increased cardiac adverse effects).

Antihypertensives, diltiazem

Diltiazem may enhance the effect of co-administered antihypertensive agents

Apixaban [1], diltiazem ---> SmPC of [1] of EMA

Active substances which are not considered strong inhibitors of both CYP3A4 and P-gp are expected to increase apixaban plasma concentration to a lesser extent. No dose adjustment for apixaban is required

Aripiprazole [1], diltiazem ---> SmPC of [1] of EMA

When weak inhibitors of CYP3A4 (e.g., diltiazem) or CYP2D6 (e.g., escitalopram) are used concomitantly with this medicinal product, modest increases in plasma aripiprazole concentrations may be expected.

Atazanavir [1], diltiazem ---> SmPC of [1] of EMA

The co-administration of atazanavir (strong CYP3A4 inhibitor) may increase the plasma concentrations of diltiazem and desacetyl-diltiazem. Caution is warranted

Atazanavir/cobicistat [1], diltiazem ---> SmPC of [1] of EMA

Exposure to diltiazem is increased when diltiazem is coadministered with atazanavir, a component of EVOTAZ. An initial dose reduction of diltiazem by 50% should be considered, and electrocardiogram monitoring is recommended.

Atazanavir/ritonavir, diltiazem ---> SmPC of [atazanavir] of EMA

The co-administration of atazanavir/ritonavir (strong CYP3A4 inhibitors) may increase the plasma concentrations of diltiazem and desacetyl-diltiazem. Caution is warranted

Atenolol [1], diltiazem ---> SmPC of [1] of eMC

Combination should be used with caution in patients with impaired ventricular function, and not at all in patients with conduction abnormalities. May result in severe hypotension, bradycardia and cardiac failure.

Atenolol/chlortalidone [1], diltiazem ---> SmPC of [1] of eMC

Combined use of beta-blockers and calcium channel blockers with negative inotropic effects can lead to an exaggeration of these effects. This may result in severe hypotension, bradycardia and cardiac failure.

Atenolol/nifedipine, diltiazem ---> SmPC of [atenolol] of eMC

Atenolol/nifedipine must not be used in conjunction with calcium channel blockers with negative inotropic effects since this can lead to an exaggeration of these effects. It may result in severe hypotension, bradycardia and cardiac failure

Atorvastatin [1], diltiazem ---> SmPC of [1] of eMC

Moderate CYP3A4 inhibitors may increase plasma concentrations of atorvastatin. Appropriate clinical monitoring of the patient is recommended when concomitantly used of atorvastatin with moderate CYP3A4 inhibitors.

Avanafil [1], diltiazem ---> SmPC of [1] of EMA

Avanafil is predominantly metabolised by CYP3A4. The moderate CYP3A4 inhibitors may increase the exposition of avanafil. The maximum recommended dose of avanafil is 100 mg, not to exceed once every 48 hours

Benzodiazepine primarily metabolised by CYP3A4, diltiazem [2] ---> SmPC of [2] of eMC

Special care should be taken when prescribing short-acting benzodiazepines metabolized by the CYP3A4 pathway in patients using diltiazem.

Betablockers, diltiazem [2] ---> SmPC of [2] of eMC

Betablockers: Possibility of rhythm disturbances (pronounced bradycardia, sinus arrest), sino-atrial and atrio-ventricular conduction disturbances and heart failure (synergistic effect).

Bilastine [1], diltiazem ---> SmPC of [1] of eMC

Concomitant intake of bilastine, substrate for P-gp, may likewise have the potential to increase plasma concentrations of bilastine.

Bisoprolol [1], diltiazem ---> SmPC of [1] of eMC

Negative influence on contractility and atrio-ventricular conduction.

Boceprevir [1], diltiazem ---> SmPC of [1] of EMA

Boceprevir, CYP3A4 inhibitor, may increase the plasma concentrations of calcium channel blocker. Caution is warranted and clinical monitoring of patients is recommended.

Bosutinib [1], diltiazem ---> SmPC of [1] of EMA

Breast-feeding, diltiazem [2] ---> SmPC of [2] of eMC

Diltiazem is excreted in breast milk at low concentrations. Breast-feeding while taking this drug should be avoided. If use of diltiazem is considered medically essential, an alternative method of infant feeding should be instituted.

Buspirone [1], diltiazem ---> SmPC of [1] of eMC

Concomitant administration of buspirone and a CYP3A4 inhibitor increased the plasma concentrations of buspirone. A low dose of buspirone is recommended.

Calcium, diltiazem

Hypercalcemia may decrease the effect of diltiazem

Carbamazepine, diltiazem [2] ---> SmPC of [2] of eMC

Increase in circulating carbamazepine levels. It is recommended that the plasma carbamazepine concentrations be assayed and that the dose should be adjusted if necessary.

Cariprazine [1], diltiazem ---> SmPC of [1] of EMA

Metabolism of cariprazine and its major active metabolites is mediated mainly by CYP3A4. The co-administration of cariprazine with strong or moderate inhibitors of CYP3A4 is contraindicated

Carteolol [1], diltiazem ---> SmPC of [1] of eMC

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic beta-blockers solution is administered concomitantly with oral calcium channel blockers

Carvedilol [1], diltiazem ---> SmPC of [1] of eMC

Isolated cases of conduction disturbance (rarely compromised haemodynamics) have been reported, if oral carvedilol and oral diltiazem are given concomitantly. The intravenous co-administration is contraindicated

Celiprolol [1], diltiazem ---> SmPC of [1] of eMC

Calcium channel antagonists such as verapamil (and to a lesser extent diltiazem) and beta blockers both slow A-V conduction and depress myocardial contractility through different mechanisms.

Cerivastatin, diltiazem

The risk of myopathy and rhabdomyolysis due to statins metabolised by CYP3A4 may be increased with concomitant use of diltiazem.

Cilostazol [1], diltiazem ---> SmPC of [1] of EMA

The overall pharmacological activity of cilostazol increases 19% when co-administered with diltiazem. No dose adjustment is necessary.

Cimetidine, diltiazem [2] ---> SmPC of [2] of eMC

Increase in plasma diltiazem concentrations. Patients currently receiving diltiazem therapy should be carefully monitored when initiating or discontinuing therapy with H2 antagonists. An adjustment in diltiazem daily dose may be necessary.

Cobicistat [1], diltiazem ---> SmPC of [1] of EMA

Concentrations of calcium channel blockers may be increased when co-administered with cobicistat. Clinical monitoring of therapeutic effect and adverse events is recommended when these medicinal products are co-administered with Tybost.

Cobimetinib [1], diltiazem ---> SmPC of [1] of EMA

Caution should be exercised if cobimetinib is coadministered with moderate CYP3A inhibitors. When cobimetinib is co-administered with a moderate CYP3A inhibitor, patients should be carefully monitored for safety.

Crizotinib [1], diltiazem ---> SmPC of [1] of EMA

Bradycardia has been reported during clinical studies; therefore, use crizotinib with caution due to the risk of excessive bradycardia when used in combination with other bradycardic agents

Curare-type muscle relaxants, diltiazem

Diltiazem may enhance the neuromuscular blockade

Cyclosporine [1], diltiazem ---> SmPC of [1] of eMC

Inhibitors of CYP3A4 may lead to increased levels of cyclosporine.

Dabrafenib [1], diltiazem ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Daclatasvir [1], diltiazem ---> SmPC of [1] of EMA

Administration of daclatasvir with diltiazem (CYP3A4 inhibitor) may result in increased concentrations of daclatasvir. Caution is advised.

Dantrolene, diltiazem [2] ---> SmPC of [2] of eMC

Dapoxetine [1], diltiazem ---> SmPC of [1] of eMC

Concomitant treatment of dapoxetine with moderate CYP3A4 inhibitors may give rise to significantly increased exposure of dapoxetine and desmethyldapoxetine, especially in CYP2D6 poor metabolizers.

Darunavir/cobicistat [1], diltiazem ---> SmPC of [1] of EMA

Darunavir/cobicistat is expected to increase the calcium channel blocker plasma concentrations. (CYP3A and/or CYP2D6 inhibition)

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], diltiazem ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase this calcium channel blocker plasma concentrations. CYP3A inhibition

Darunavir/ritonavir, diltiazem ---> SmPC of [darunavir] of EMA

Boosted darunavir can be expected to increase the plasma concentrations of calcium channel blocker. (CYP3A and/or CYP2D6 inhibition)

Dasabuvir with ombitasvir/paritaprevir/ritonavir, diltiazem ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EM

Dextromethorphan/quinidine [1], diltiazem ---> SmPC of [1] of EMA

Diazepam, diltiazem

The co-administration may decrease the plasma levels of diltiazem

Digitoxin, diltiazem

The CYP3A4 inhibition may increase the plasma levels of digitoxin

Digoxin [1], diltiazem ---> SmPC of [1] of eMC

Serum levels of digoxin may be increased by concomitant administration of calcium antagonists

Diltiazem [1], drugs primarily metabolised by CYP3A4 ---> SmPC of [1] of eMC

Diltiazem is also a CYP3A4 isoform inhibitor. Co-administration with other CYP3A4 substrates may result in an increase in plasma concentration of either co-administered drug.

Diltiazem [1], H2 antagonists ---> SmPC of [1] of eMC

Diltiazem [1], lithium ---> SmPC of [1] of eMC

Risk of increase in lithium-induced neurotoxicity

Diltiazem [1], lovastatine ---> SmPC of [1] of eMC

Diltiazem is an inhibitor of CYP3A4 and has been shown to significantly increase the AUC of some statins. The risk of myopathy and rhabdomyolysis due to statins metabolised by CYP3A4 may be increased with concomitant use of diltiazem.

Diltiazem [1], organic nitrates ---> SmPC of [1] of eMC

Increased hypotensive effects and faintness (additive vasodilating effects)

Diltiazem [1], phenobarbital ---> SmPC of [1] of eMC

Drugs that increase hepatic microsomal activity (eg phenobarbital, phenytoin) lead to decreased plasma diltiazem levels.

Diltiazem [1], pregnancy ---> SmPC of [1] of eMC

Diltiazem is not recommended during pregnancy, as well as in women of child-bearing potential not using effective contraception.

Diltiazem [1], ranitidine ---> SmPC of [1] of eMC

Diltiazem [1], rifampicin ---> SmPC of [1] of eMC

Risk of decrease of diltiazem plasma levels after initiating therapy with rifampicin

Diltiazem [1], St. John's wort ---> SmPC of [1] of eMC

Co-administration of diltiazem with a CYP3A4 inducer may result in a decrease of diltiazem plasma concentrations.

Diltiazem [1], statins metabolised by CYP3A4 ---> SmPC of [1] of eMC

Diltiazem [1], strong CYP3A4 inductors ---> SmPC of [1] of eMC

Co-administration of diltiazem with a CYP3A4 inducer may result in a decrease of diltiazem plasma concentrations.

Diltiazem [1], strong CYP3A4 inhibitors ---> SmPC of [1] of eMC

A moderate (less than 2-fold) increase of diltiazem plasma concentration in cases of co-administration with a stronger CYP3A4 inhibitor has been documented.

Diltiazem [1], triazolam ---> SmPC of [1] of eMC

Diltiazem significantly increases plasma concentrations of triazolam and prolongs its half-life.

Diltiazem, disopyramide [2] ---> SmPC of [2] of eMC

Antiarrhythmic combination should be avoided except under certain circumstances

Diltiazem, diuretics

Diltiazem may enhance the effect of co-administered antihypertensive agents

Diltiazem, dronedarone [2] ---> SmPC of [2] of EMA

Calcium antagonists with depressant effects on sinus and atrio-ventricular node such as verapamil and diltiazem should be used with caution when associated with dronedarone.

Diltiazem, droperidol [2] ---> SmPC of [2] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzyme CYP3A4 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Diltiazem, dutasteride [2] ---> SmPC of [2] of eMC

Dutasteride serum levels were on average 1.6 to 1.8 times greater, respectively, in a small number of patients treated concurrently with verapamil or diltiazem (moderate inhibitors of CYP3A4 and inhibitors of P-glycoprotein) than in other patients

Diltiazem, efavirenz [2] ---> SmPC of [2] of EMA

The CYP3A4 induction by efavirenz may decrease the diltiazem concentration

Diltiazem, efavirenz/emtricitabine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Dose adjustments of diltiazem when co-administered with Atripla should be guided by clinical response

Diltiazem, eliglustat [2] ---> SmPC of [2] of EMA

Diltiazem, elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Concentrations of calcium channel blocker may be increased when co-administered with cobicistat.

Diltiazem, elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Concentrations of calcium channel blockers may be increased when co-administered with cobicistat.

Diltiazem, encorafenib [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inhibitors should be co-administered with caution. When encorafenib is co-administered with a moderate CYP3A inhibitor, patients should be carefully monitored for safety.

Diltiazem, enzalutamide [2] ---> SmPC of [2] of EMA

Enzalutamide, enzymatic inductor, may increase the metabolism of diltiazem and decrease its plasma levels and effect

Diltiazem, enzyme inductors

Drugs that increase hepatic microsomal activity (eg phenobarbital, phenytoin) lead to decreased plasma diltiazem levels.

Diltiazem, eplerenone [2] ---> SmPC of [2] of eMC

Moderate CYP3A4 inhibitors may increase the AUC of eplerenone. Eplerenone dosing should not exceed 25 mg when moderate inhibitors of CYP3A4 are co-administered with eplerenone

Diltiazem, esmolol [2] ---> SmPC of [2] of eMC

Calcium antagonists such as verapamil and to a lesser extent diltiazem have a negative influence on contractility and AV-conduction. This combination should be used with caution with verapamil in patients with impaired ventricular function

Diltiazem, everolimus [2] ---> SmPC of [2] of EMA

Increase in everolimus concentration is expected. Use caution when co-administration of moderate CYP3A4 inhibitors or PgP inhibitors cannot be avoided.

Diltiazem, ezetimibe/atorvastatin [2] ---> SmPC of [2] of eMC

Moderate CYP3A4 inhibitors may increase plasma concentrations of atorvastatin. Appropriate clinical monitoring of the patient is recommended when concomitantly used with moderate CYP3A4 inhibitors.

Diltiazem, ezetimibe/simvastatine [2] ---> SmPC of [2] of eMC

The risk of myopathy and rhabdomyolysis is increased by concomitant administration of diltiazem with simvastatin 80 mg

Diltiazem, felodipine/metoprolol

Metoprolol should not be given in combination with calcium channel blockers of diltiazem type since this may cause bradycardia, hypotension, heart failure and asystole and may increase auriculo-ventricular conduction time.

Diltiazem, fenofibrate/simvastatin [2] ---> SmPC of [2] of EMA

Caution should be exercised when combining fenofibrate/simvastatine with certain other less potent CYP 3A4 inhibitors. The risk of myopathy and rhabdomyolysis is increased by concomitant use of diltiazem with simvastatin 40 mg per day.

Diltiazem, fentanyl [2] ---> SmPC of [2] of EMA

The concomitant use of fentanyl with moderate CYP3A4 inhibitors may result in increased fentanyl plasma concentrations, potentially causing serious adverse drug reactions including fatal respiratory depression.

Diltiazem, fesoterodine [2] ---> SmPC of [2] of EMA

Caution should be exercised when prescribing fesoterodine to patients in whom an increased exposure to the active metabolite is expected, e. g. coadministration of moderate CYP3A4 inhibitors. No dosing adjustments are recommended

Diltiazem, fingolimod [2] ---> SmPC of [2] of EMA

Treatment with Gilenya should not be initiated in patients receiving beta blockers, or other substances which may decrease heart rate because of the potential additive effects on heart rate

Diltiazem, fosaprepitant [2] ---> SmPC of [2] of EMA

In patients with mild to moderate hypertension, infusion of fosaprepitant over 15 minutes with diltiazem resulted in a 1.4-fold increase in diltiazem AUC and a small but clinically meaningful decrease in blood pressure

Diltiazem, fosphenytoin

Co-administration of diltiazem with a CYP3A4 inducer may result in a decrease of diltiazem plasma concentrations.

Diltiazem, guanfacin [2] ---> SmPC of [2] of EMA

Co-administration of Intuniv with moderate and strong CYP3A4/5 inhibitors elevates plasma guanfacine concentrations and increases the risk of adverse reactions such as hypotension, bradycardia, and sedation.

Diltiazem, hydroquinidine

Concomitant use of hydroquinidine and bradycardiac agents increases the risk of heart rhythm disorders (torsades de pointes)

Diltiazem, hypercalcemia

Hypercalcemia may decrease the effect of diltiazem

Diltiazem, ibrutinib [2] ---> SmPC of [2] of EMA

Ibrutinib is primarily metabolised by cytochrome P450 enzyme 3A4. Concomitant use of ibrutinib and medicinal products that moderately inhibit CYP3A4 can increase ibrutinib exposure and should be avoided.

Diltiazem, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with diltiazem may increase the serum concentrations of diltiazem. Clinical monitoring of therapeutic effect and adverse reactions is recommended.

Diltiazem, imipramine [2] ---> SmPC of [2] of eMC

Blood levels of imipramine may be increased by calcium channel blockers

Diltiazem, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Dose modification of calcium channel blocker should be considered when coadministered with indinavir/ritonavir as it may result in an increased response.

Diltiazem, ivabradine [2] ---> SmPC of [2] of EMA

The combination of ivabradine with the heart rate reducing agent diltiazem (moderate CYP3A4 inhibitor) resulted in an increase in ivabradine exposure. The concomitant use of ivabradine with diltiazem is contraindicated

Diltiazem, lomitapide [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase lomitapide AUC. The combination of lomitapide with strong CYP3A4 inhibitors is contra-indicated

Diltiazem, lurasidone [2] ---> SmPC of [2] of EMA

Coadministration of lurasidone with medicinal products that moderately inhibit CYP3A4 may increase exposure to lurasidone.

Diltiazem, methylprednisolone

Inhibition of methylprednisolone metabolism (CYP3A4) and inhibition of P-glycoprotein: The patient should be monitored when initiating methylprednisolone treatment. An adjustment in the dose of methylprednisolone may be necessary.

Diltiazem, metildigoxin

Increased plasma levels of metildigoxin

Diltiazem, metoprolol [2] ---> SmPC of [2] of eMC

Diltiazem, midazolam [2] ---> SmPC of [2] of EMA

Diltiazem has been shown to reduce the clearance of midazolam and other benzodiazepines and may potentiate their actions.

Diltiazem, nadolol

Diltiazem can cause altered automaticity (excessive bradycardia, sinus arrest), sino-atrial and AV conduction disorders, and heart failure due to synergistic effects

Diltiazem, naloxegol [2] ---> SmPC of [2] of EMA

Concomitant use of naloxegol with CYP3A4 inhibitors increases naloxegol exposition. A dose adjustment of naloxegol is recommended when co-administered with moderate CYP3A4 inhibitors

Diltiazem, nebivolol [2] ---> SmPC of [2] of eMC

Negative influence on contractility and atrio-ventricular conduction. Concomitant treatment is not recommended

Diltiazem, neratinib [2] ---> SmPC of [2] of EMA

Co-administration of neratinib with moderate CYP3A4/P-gp inhibitors is contraindicated

Diltiazem, neuroleptics

Increased hypotensive effect. Caution is recommended

Diltiazem, nifedipine

Diltiazem decreases the clearance of nifedipine

Diltiazem, olaparib [2] ---> SmPC of [2] of EMA

Known strong or moderate CYP3A inhibitors are not recommended with olaparib

Diltiazem, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure.

Diltiazem, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

Diltiazem, oxprenolol [2] ---> SmPC of [2] of eMC

Calcium antagonists may enhance bradycardia, myocardial depression and hypotension; particularly after i.v. use of verapamil in patients taking oral betablockers, the possibility of hypotension and cardiac arrhythmias cannot be excluded

Diltiazem, pasireotide [2] ---> SmPC of [2] of EMA

Clinical monitoring of heart rate, notably at the beginning of treatment, is recommended in patients receiving pasireotide concomitantly with bradycardic medicinal products

Diltiazem, penbutolol

The co-administration of calcium antagonists of verapamil- and diltiazem type with penbutolol may increase the tendency to cardiac conduction and rhythm disorders and cause strong hypotension

Diltiazem, phenazone

Concomitant use of phenazone and calcium antagonists delays the elimination of phenazone. There is the possibility of an accumulation

Diltiazem, phenytoin

Co-administration of diltiazem with a CYP3A4 inducer may result in a decrease of diltiazem plasma concentrations.

Diltiazem, posaconazole [2] ---> SmPC of [2] of EMA

Concomitant use of posaconazole with calcium channel blockers metabolised through CYP3A4 increases plasma concentrations of the calcium channel blocker.

Diltiazem, prasugrel [2] ---> SmPC of [2] of EMA

CYP3A inhibitors are not anticipated to have a significant effect on the pharmacokinetics of the prasugrel active metabolite.

Diltiazem, propranolol [2] ---> SmPC of [2] of EMA

Co-administration of diltiazem with propranolol can cause altered automaticity (excessive bradycardia, sinus arrest), sino-atrial and AV conduction disorders, and increased risk of ventricular arrhythmias along with heart failure.

Diltiazem, quinidine

Hypotension. Pulmonary edema with obstructive hypertrophic cardiomyopathy

Diltiazem, ranolazine [2] ---> SmPC of [2] of EMA

Careful dose titration of ranolazine is recommended in patients treated with moderately potent CYP3A4 inhibitors. Down-titration of ranolazine may be required

Diltiazem, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir, CYP3A4 inhibitor, may increase the plasma concentrations of diltiazem. Careful monitoring of therapeutic and adverse effects is recommended.

Diltiazem, rupatadine [2] ---> SmPC of [2] of eMC

The concomitant administration of rupatadine with inhibitors of the isozyme CYP3A4 increases the systemic exposure to rupatadine. Rupatadine should be used with caution when it is administered concomitantly with inhibitors of CYP3A4.

Diltiazem, ruxolitinib [2] ---> SmPC of [2] of EMA

Mild or moderate CYP3A4 inhibitors may increase ruxolitinib exposition. No dose adjustment is recommended when ruxolitinib is co-administered with mild or moderate CYP3A4 inhibitors

Diltiazem, saquinavir

Careful monitoring of therapeutic and adverse effects is recommended.

Diltiazem, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Possible increase in the plasma concentrations of calcium channel antagonist. Careful monitoring of therapeutic and adverse effects is recommended.

Diltiazem, saxagliptin [2] ---> SmPC of [2] of EMA

Coadministration of saxagliptin with the moderate inhibitor of CYP3A4/5 diltiazem, increased the Cmax and AUC of saxagliptin by 63% and 2.1-fold, respectively, and the corresponding values for the active metabolite were decreased by 44% and 34%.

Diltiazem, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Concomitant administration of saxagliptin with the moderate inhibitor of CYP3A4/5 diltiazem. The pharmacokinetic effects are not clinically meaningful and do not require dose adjustment.

Diltiazem, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Co-administration of saxagliptin with the moderate inhibitor of CYP3A4/5 diltiazem, increased the Cmax and AUC of saxagliptin by 63% and 2.1-fold, respectively, and the corresponding values for the active metabolite were decreased by 44% and 34%.

Diltiazem, sertindole

The concomitant administration of CYP3A inhibitors and sertindole is contraindicated, as this may lead to significant increases in sertindole levels

Diltiazem, silodosin [2] ---> SmPC of [2] of EMA

When silodosin was co-administered with a CYP3A4 inhibitor of moderate potency such as diltiazem, an increase in silodosin AUC of approximately 30 % was observed, but Cmax and half-life were not affected.

Diltiazem, simeprevir [2] ---> SmPC of [2] of EMA

The intestinal CYP3A4 enzyme and P-gp transporter inhibition by simeprevir may increase the plasma concentrations of orally administered calcium channel blocker. Diltiazem, CYP3A4 inhibitor, may increase the plasma levels of simeprevir

Diltiazem, simvastatine [2] ---> SmPC of [2] of eMC

The risk of myopathy and rhabdomyolysis is increased by concomitant administration of diltiazem with simvastatin 80 mg. The dose of simvastatin should not exceed 20 mg daily in patients receiving concomitant medication with diltiazem.

Diltiazem, sirolimus [2] ---> SmPC of [2] of EMA

The simultaneous oral administration of sirolimus and diltiazem significantly affected the bioavailability of sirolimus. Sirolimus Cmax, tmax, and AUC were increased 1.4-fold, 1.3-fold, and 1.6-fold, respectively.

Diltiazem, solifenacin [2] ---> SmPC of [2] of eMC

Since solifenacin is metabolised by CYP3A4, pharmacokinetic interactions are possible with other CYP3A4 substrates with higher affinity (e.g. verapamil, diltiazem)

Diltiazem, sotalol [2] ---> SmPC of [2] of eMC

Beta-blockers should be avoided in combination with cardiodepressant calcium-channel blockers such as verapamil and diltiazem because of the additive effects on atrioventricular conduction, and ventricular function.

Diltiazem, sulfinpyrazone

The co-administration may decrease the plasma levels of sulfinpyrazone

Diltiazem, sulpiride [2] ---> SmPC of [2] of eMC

The combination of sulpiride with bradycardia-inducing medications is not recommended

Diltiazem, tacrolimus [2] ---> SmPC of [2] of EMA

Concomitant use of substances known to inhibit CYP3A4 may affect the metabolism of tacrolimus and thereby increase tacrolimus blood levels.

Diltiazem, talinolol

Combined use of beta-adrenoceptor blocking drugs and calcium channel blockers with negative inotropic effects can lead to prolongation of SA and AV conduction. This may result in severe hypotension, bradycardia and cardiac failure.

Diltiazem, telaprevir [2] ---> SmPC of [2] of EMA

Inhibition of CYP3A and/or effect on P-gp transport in the gut increases plasma concentration of calcium channel blocker. Caution is warranted and clinical monitoring of patients is recommended.

Diltiazem, temsirolimus [2] ---> SmPC of [2] of EMA

Concomitant treatment with moderate CYP3A4 inhibitors should only be administered with caution in patients receiving 25 mg and should be avoided in patients receiving temsirolimus doses higher than 25 mg.

Diltiazem, tetracyclic antidepressant

Increased hypotensive effect. Caution is recommended

Diltiazem, theophylline [2] ---> SmPC of [2] of eMC

Calcium antagonists reduce clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Diltiazem, ticagrelor [2] ---> SmPC of [2] of EMA

Co-administration of diltiazem with ticagrelor increased the ticagrelor Cmax by 69% and AUC to 2.7 fold. Other moderate CYP3A4 inhibitors would be expected to have a similar effect and can as well be co-administered with ticagrelor.

Diltiazem, tolvaptan [2] ---> SmPC of [2] of EMA

Tolvaptan plasma concentrations have been increased by up to 5.4-fold area under time-concentration curve (AUC) after the administration of strong CYP3A4 inhibitors. Caution should be exercised in co-administering CYP3A4 inhibitors with tolvaptan

Diltiazem, tricyclic antidepressant

Increased hypotensive effect. Caution is recommended

Diltiazem, venetoclax [2] ---> SmPC of [2] of EMA

At initiation and during the dose-titration phase, concomitant use of venetoclax with moderate CYP3A inhibitors should be avoided. Alternative treatments should be considered.

Diltiazem, vitamin D

Hypercalcemia may decrease the effect of diltiazem

CONTRAINDICATIONS of Diltiazem

- Sick sinus syndrome except in the presence of a functioning ventricular pacemaker

- pregnancy; women of child-bearing potential

- congestive heart failure

- severe aortic stenosis

- cardiogenic shock

- severe hypotension (systolic Blood Pressure less than 90 mmHg)

- Second- or third-degree AV block except in the presence of a functioning ventricular pacemaker

- Severe bradycardia (below 40 bpm)

- Left ventricular failure with pulmonary congestion

- Hypersensitivity to diltiazem or to any of the excipients

- Concomitant use of dantrolene infusion

http://www.medicines.org.uk/emc/

Dimenhydrinate

Ability to drive, dimenhydrinate

Somnolence, memory disorders and decreased concentration ability may occur

Alcohol, dimenhydrinate

Dimenhydrinate may increase the effects of other CNS depressors and enhance the sedative effects

Aminoglycoside antibiotics, dimenhydrinate

The co-administration may mask the symptome of ototoxicity

Anaesthetics, dimenhydrinate

Dimenhydrinate may increase the effects of other CNS depressors and enhance the sedative effects

Anticholinergics, dimenhydrinate

The co-administration of dimenhydrinate with other anticholinergic drugs may enhance or prolong the anticholinergic effect

Antihypertensives, dimenhydrinate

The co-administration may enhance the hypotensive effect

Antimalarial agents, dimenhydrinate

The concurrent use of dimenhydrinate and drugs that also prolong the QT interval should be avoided

Antiparkinsonian agents, dimenhydrinate

The co-administration of dimenhydrinate with other anticholinergic drugs may enhance or prolong the anticholinergic effect

Barbiturates, dimenhydrinate

Dimenhydrinate may increase the effects of other CNS depressors and enhance the sedative effects

Benzodiazepines, dimenhydrinate

Dimenhydrinate may increase the effects of other CNS depressors and enhance the sedative effects

Breast-feeding, dimenhydrinate

Dimenhydrinate passes into the mother milk. Breast-feeding should be avoided during therapy

CNS depressants, dimenhydrinate

Dimenhydrinate may increase the effects of other CNS depressors and enhance the sedative effects

Cisplatin, dimenhydrinate

The co-administration may mask the symptome of ototoxicity

Class IA antiarrhythmic agents, dimenhydrinate

The concurrent use of dimenhydrinate and drugs that also prolong the QT interval should be avoided

Class III antiarrhythmic agents, dimenhydrinate

The concurrent use of dimenhydrinate and drugs that also prolong the QT interval should be avoided

Dimenhydrinate, disulfiram

Increased risk of spasms

Dimenhydrinate, drugs inducing hypokaliemia

The concurrent use of dimenhydrinate and drugs that can cause hypokaliemia should be avoided

Dimenhydrinate, hypnotics

Dimenhydrinate may increase the effects of other CNS depressors and enhance the sedative effects

Dimenhydrinate, monoamine oxidase inhibitors

The co-administration of dimenhydrinate and MAOIs may cause life-threatening enteroparesis, urinary retention, increased intraocular tension, hypotension, impaired function of CNS and respiration. The coadministration is contraindicated

Dimenhydrinate, neuroleptics

The co-administration of dimenhydrinate with other anticholinergic drugs may enhance or prolong the anticholinergic effect

Dimenhydrinate, non-potassium-sparing diuretics

The concurrent use of dimenhydrinate and drugs that can cause hypokaliemia should be avoided

Dimenhydrinate, opioid analgesics

Dimenhydrinate may increase the effects of other CNS depressors and enhance the sedative effects

Dimenhydrinate, ototoxic agents

The co-administration of dimenhydrinate with other ototoxic drugs may mask the symptome of ototoxicity

Dimenhydrinate, photosensitizing agents

Dimenhydrinate may enhance the photosensitizer effect of other drugs

Dimenhydrinate, pregnancy

Strict indication in the 1st and 2nd trimester. Contraindicated in the last weeks of pregnancy

Dimenhydrinate, seizure-threshold lowering drugs

Increased risk of spasms

Dimenhydrinate, tricyclic antidepressants

The co-administration of dimenhydrinate with other anticholinergic drugs may enhance or prolong the anticholinergic effect

QT interval prolonging drugs, dimenhydrinate

The concurrent use of dimenhydrinate and drugs that also prolong the QT interval should be avoided

Dimethyl fumarate (Tecfidera)

Acetylsalicylic acid, dimethyl fumarate [2] ---> SmPC of [2] of EMA

In 2 healthy volunteer studies, the administration of 325 mg (or equivalent) non-enteric coated acetylsalicylic acid, 30 minutes prior to Tecfidera, dosing over 4 days and over 4 weeks, respectively, did not alter the pharmacokinetic profile of Tecfidera

Alcohol, dimethyl fumarate [2] ---> SmPC of [2] of EMA

Consumption of moderate amounts of alcohol did not alter exposure to dimethyl fumarate and was not associated with an increase in adverse reactions. Consumption of large amounts of strong alcoholic drinks should be avoided within 1 h of taking Tecfidera

Aminoglycoside antibiotics, dimethyl fumarate [2] ---> SmPC of [2] of EMA

El tratamiento simultáneo con medicamentos nefrotóxicos (como los aminoglucósidos, diuréticos, antiinflamatorios no esteroideos o litio) puede aumentar el potencial de reacciones adversas renales (por ejemplo, proteinuria, ver sección 4.8)

Antineoplastics, dimethyl fumarate [2] ---> SmPC of [2] of EMA

Tecfidera has not been studied in combination with anti-neoplastic or immunosuppressive therapies and caution should, therefore, be used during concomitant administration.

Breast-feeding, dimethyl fumarate [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue Tecfidera therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Combination oral contraceptives, dimethyl fumarate

In an in vivo study, co-administration of dimethyl fumarate with a combined oral contraceptive (norgestimate and ethinyl estradiol) did not elicit any relevant change in oral contraceptive exposure.

Corticosteroids, dimethyl fumarate [2] ---> SmPC of [2] of EMA

In multiple sclerosis clinical studies, the concomitant treatment of relapses with a short course of intravenous corticosteroids was not associated with a clinically relevant increase of infection.

Cytochrome P450, dimethyl fumarate [2] ---> SmPC of [2] of EMA

In humans, dimethyl fumarate is extensively metabolised by esterases before it reaches the systemic circulation and further metabolism occurs through the tricarboxylic acid cycle, with no involvement of the cytochrome P450 (CYP) system.

Dimethyl fumarate [1], diuretics ---> SmPC of [1] of EMA

Dimethyl fumarate [1], drug interaction risks ---> SmPC of [1] of EMA

Dimethyl fumarate [1], fertility ---> SmPC of [1] of EMA

There are no data on the effects of dimethyl fumarate on human fertility. Data from preclinical studies do not suggest that dimethyl fumarate would be associated with an increased risk of reduced fertility (see section 5.3).

Dimethyl fumarate [1], foods ---> SmPC of [1] of EMA

Tecfidera should be taken with food (see section 5.2). For those patients who may experience flushing or gastrointestinal adverse reactions, taking Tecfidera with food may improve tolerability (see sections 4.4, 4.5 and 4.8).

Dimethyl fumarate [1], fumaric acid ---> SmPC of [1] of EMA

During treatment with Tecfidera, simultaneous use of other fumaric acid derivatives (topical or systemic) should be avoided.

Dimethyl fumarate [1], glatiramer ---> SmPC of [1] of EMA

Commonly used medicinal products in patients with multiple sclerosis were clinically tested for potential interactions with dimethyl fumarate and did not alter the pharmacokinetic profile of dimethyl fumarate.

Dimethyl fumarate [1], immunosuppressives ---> SmPC of [1] of EMA

Tecfidera has not been studied in combination with anti-neoplastic or immunosuppressive therapies and caution should, therefore, be used during concomitant administration.

Dimethyl fumarate [1], inactivated vaccines ---> SmPC of [1] of EMA

Concomitant administration of non-live vaccines according to national vaccination schedules may be considered during Tecfidera therapy.

Dimethyl fumarate [1], interferon beta-1a ---> SmPC of [1] of EMA

Dimethyl fumarate [1], lithium ---> SmPC of [1] of EMA

Dimethyl fumarate [1], nephrotoxic substances ---> SmPC of [1] of EMA

Dimethyl fumarate [1], NSAID ---> SmPC of [1] of EMA

Dimethyl fumarate [1], oral contraceptives ---> SmPC of [1] of EMA

In an in vivo study, co-administration of Tecfidera with a combined oral contraceptive (norgestimate and ethinyl oestradiol) did not elicit any relevant change in oral contraceptive exposure.

Dimethyl fumarate [1], pregnancy ---> SmPC of [1] of EMA

Tecfidera should be used during pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the foetus.

Dimethyl fumarate [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

Live vaccines might carry an increased risk of clinical infection and should not be given to patients treated with Tecfidera unless, in exceptional cases, this potential risk is considered to be outweighed by the risk to the individual of not vaccinating

CONTRAINDICATIONS of Dimethyl fumarate (Tecfidera)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Suspected or confirmed progressive multifocal leukoencephalopathy (PML).

https://www.ema.europa.eu/en/documents/product-information/tecfidera-epar-product-information_en.pdf 06/01/2025

Other trade names: Dimethyl fumarate Accord, Dimethyl fumarate Mylan, Skilarence,

Dinoprostone

Breast-feeding, dinoprostone [2] ---> SmPC of [2] of eMC

It is not indicated during lactation

Dinoprostone [1], oxytocic agents ---> SmPC of [1] of eMC

Prostaglandins potentiate the uterotonic effect of oxytocic drugs. Therefore, dinoprostone should not be used concurrently with the use of oxytocic drugs.

Dinoprostone [1], pregnancy ---> SmPC of [1] of eMC

The product is for the initiation of cervical ripening in pregnant patients at term only where labour induction is indicated. It is not indicated for use during early or other phases of pregnancy

Dinoprostone, methylergometrine

Prostaglandin potentiates the uterotonic effect of oxytocic drugs. Co-administration is not recommended

Dinoprostone, NSAID

NSAID decreases the endogen prostaglandin synthesis and decreases its effect

CONTRAINDICATIONS of Dinoprostone

PROPESS should not be used or left in place:

1. When labour has started.

2. When oxytocic drugs are being given.

3. When strong prolonged uterine contractions would be inappropriate such as in patients:

a. who have had previous major uterine surgery, e.g. caesarean section, myomectomy etc.

b. with cephalopelvic disproportion

c. with fetal malpresentation

d. with suspicion or evidence of fetal distress

e. who have had more than three full term deliveries

f. previous surgery or rupture of the cervix

4. When there is current pelvic inflammatory disease, unless adequate prior treatment has been instituted.

5. When there is hypersensitivity to dinoprostone or to any of the excipients.

6. When there is placenta previa or unexplained vaginal bleeding during the current pregnancy.

http://www.medicines.org.uk/emc/

Dinutuximab beta (Qarziba)

Ability to drive, dinutuximab beta [2] ---> SmPC of [2] of EMA

Dinutuximab beta has major influence on the ability to drive and use machines. Patients should not use or drive machines during treatment with dinutuximab beta.

Breast-feeding, dinutuximab beta [2] ---> SmPC of [2] of EMA

There are no data on lactating women. It is unknown whether dinutuximab beta is excreted in human milk. Breast-feeding should be discontinued during treatment with Qarziba and for 6 months after the last dose.

Corticosteroids beta, dinutuximab [2] ---> SmPC of [2] of EMA

Due to their immunosuppressive activity, concomitant treatment with corticosteroids is not recommended within 2 weeks prior to the first treatment course until 1 week after the last treatment course with dinutuximab beta, except for life-threatening cond

CYP450, dinutuximab beta [2] ---> SmPC of [2] of EMA

A risk for indirect reduction of CYP activity due to higher TNF-? and IL-6 levels and, therefore, interactions with concomitantly used medicinal products, cannot be excluded.

Dinutuximab beta [1], fertility ---> SmPC of [1] of EMA

In animals, dedicated fertility studies have not been conducted, but no adverse effects on reproductive organs were observed in toxicity studies performed in Guinea pig and cynomolgous monkey.

Dinutuximab beta [1], immunoglobulins ---> SmPC of [1] of EMA

Concomitant use of intravenous immunoglobulins is not recommended as they may interfere with dinutuximab beta-dependent cellular cytotoxicity.

Dinutuximab beta [1], pregnancy ---> SmPC of [1] of EMA

Qarziba may cause fetal harm when administered to pregnant women. Qarziba should not be used during pregnancy.

Dinutuximab beta [1], vaccinations ---> SmPC of [1] of EMA

Vaccinations should be avoided during administration of dinutuximab beta until 10 weeks after the last treatment course, due to immune stimulation through dinutuximab beta and possible risk for rare neurological toxicities.

Dinutuximab beta [1], women of childbearing potential ---> SmPC of [1] of EMA

Qarziba should not be used in women of childbearing potential not using contraception. It is recommended that women of childbearing potential use contraception for 6 months after discontinuation of treatment with dinutuximab beta.

CONTRAINDICATIONS of Dinutuximab beta (Qarziba)

- Hypersensitivity (Grade 4) to the active substance or to any of the excipients listed in section 6.1.

- Acute grade 3 or 4, or extensive chronic graft-versus-host disease (GvHD)

https://www.ema.europa.eu/en/documents/product-information/qarziba-epar-product-information_en.pdf. 27/10/2023

Diosmin

Breast-feeding, diosmin

It use is not recommended during breastfeeding

Diosmin, pregnancy

Caution is warranted when prescribing diosmin to pregnant women

Diphenhydramine

Ability to drive, diphenhydramine [2] ---> SmPC of [2] of eMC

Diphenhydramine has a major influence on the ability to drive and use machines. It is a hypnotic and will produce drowsiness or sedation soon after the dose has been taken.

Adrenaline, diphenhydramine

The effects of adrenaline may be potentiated by diphenhydramine

Alcohol, diphenhydramine [2] ---> SmPC of [2] of eMC

Diphenhydramine has additive effects with alcohol

Aminosalicyclic acid, diphenhydramine

Diphenhydramine decreases the plasma levels of aminosalicyclic acid

Anaesthetics, diphenhydramine

Mutual enhancement of CNS-depressant effect

Anticholinergics, diphenhydramine [2] ---> SmPC of [2] of eMC

As diphenhydramine has some antimuscarinic activity, the effects of anticholinergic drugs may be potentiated therefore medical advice should be sought before taking diphenhydramine with such medicines.

Antimalarial agents, diphenhydramine

The co-administration is contraindicated

Anxiolytics, diphenhydramine

Mutual enhancement of CNS-depressant effect

Atropine, diphenhydramine [2] ---> SmPC of [2] of eMC

Biperiden, diphenhydramine [2] ---> SmPC of [2] of eMC

Breast-feeding, diphenhydramine [2] ---> SmPC of [2] of eMC

Diphenhydramine hydrochloride is not recommended for use during lactation in nursing mothers.

Centrally-acting antihypertensives, diphenhydramine

Concomitant use of diphenhydramine with central antihypertensive drugs may potentiate the fatigue

Class IA antiarrhythmic agents, diphenhydramine

The co-administration is contraindicated

Class III antiarrhythmic agents, diphenhydramine

The co-administration is contraindicated

CNS depressants, diphenhydramine [2] ---> SmPC of [2] of eMC

Diphenhydramine has additive effects with other CNS depressants resulting in increased antimuscarinic and sedative effects.

Diphenhydramine [1], IMAOs ---> SmPC of [1] of eMC

Diphenhydramine [1], pregnancy ---> SmPC of [1] of eMC

Diphenhydramine crosses the placental barrier. This drug is not recommended during pregnancy.

Diphenhydramine [1], tricyclic antidepressant ---> SmPC of [1] of eMC

Diphenhydramine, epinephrine

The effects of adrenaline may be potentiated by diphenhydramine

Diphenhydramine, felodipine/metoprolol

CYP2D6 inhibitors may increase the plasma levels of metoprolol

Diphenhydramine, hypokalemia

The co-administration is contraindicated

Diphenhydramine, metoprolol [2] ---> SmPC of [2] of eMC

Enzyme inhibitors may increase plasma concentrations of hepatically metabolised beta-blockers.

Diphenhydramine, opioid analgesics

Mutual enhancement of CNS-depressant effect

Diphenhydramine, ototoxic agents

Concomitant use of diphenhydramine with ototoxic drugs may mask the ototoxic symptoms

Diphenhydramine, para-aminosalicylic acid [2] ---> SmPC of [2] of EMA

Diphenylhydramine decreases the gastrointestinal absorption of para-aminosalicylic acid, and should not be administered concomitantly.

Diphenhydramine, photosensitizing agents

Diphenhydramine may potentiate the photosensibility of other drugs

Diphenhydramine, pitolisant [2] ---> SmPC of [2] of EMA

Anti-histamines (H1-receptor antagonists) crossing the haemato-encephalic barrier (e.g. pheniramine maleate, chlorpheniramine, diphenhydramine, promethazine, mepyramine) may impair the efficacy of pitolisant.

Diphenhydramine, QT interval prolonging drugs

The co-administration is contraindicated

Diphenhydramine, succinylcholine [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Diphenhydramine, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Diphenhydramine, sympathomimetics

Increased sympathomimetic effect

CONTRAINDICATIONS of Diphenhydramine

- Contra-indicated in patients who are hypersensitive to diphenhydramine or to any ingredients of the tablets, and in those with the following conditions:

- asthma,

- narrow angle glaucoma,

- prostatic hypertrophy,

- stenosing peptic ulcer,

- pyloroduodenal obstruction or bladder neck obstruction and

- porphyria.

http://www.medicines.org.uk/emc/

Dipotassium clorazepate

Ability to drive, dipotassium clorazepate

The sedative effect affects the ability to drive or use machines

Alcohol, dipotassium clorazepate

The sedative effect can be enhanced

Anaesthetics, dipotassium clorazepate

The combination of CNS depressors may mutually potentiate the depressor effect on the CNS

Antacids, dipotassium clorazepate

The co-administration may decrease the bioavailibility of clorazepate

Antidepressants, dipotassium clorazepate

The combination of CNS depressors may mutually potentiate the depressor effect on the CNS

Antiepileptics, dipotassium clorazepate

The combination of CNS depressors may mutually potentiate the depressor effect on the CNS

Anxiolytics, dipotassium clorazepate

The combination of CNS depressors may mutually potentiate the depressor effect on the CNS

Barbiturates, dipotassium clorazepate

The combination of CNS depressors may mutually potentiate the depressor effect on the CNS

Benzodiazepines, dipotassium clorazepate

The co-administration may increase the risk of developing dependency

Benzodiazepines, muscle relaxants

The co-administration may have an additive muscle relaxant effect

Betablockers, dipotassium clorazepate

The combination of CNS depressors may mutually potentiate the depressor effect on the CNS

Breast-feeding, dipotassium clorazepate

Contraindicated

Cimetidine, dipotassium clorazepate

The co-administration may enhance and prolong the clorazepate effect

Cisapride, dipotassium clorazepate

The co-administration may increase the absorption and the sedative effect of clorazepate

Clonidine, dipotassium clorazepate

The combination of CNS depressors may mutually potentiate the depressor effect on the CNS

Clozapine, dipotassium clorazepate

The co-administration may increase the risk of respiratory and/or circulatory failure

CNS depressants, dipotassium clorazepate

The combination of CNS depressors may mutually potentiate the depressor effect on the CNS

Curare-type muscle relaxants, dipotassium clorazepate

The co-administration may have an additive muscle relaxant effect

Darunavir/cobicistat [1], dipotassium clorazepate ---> SmPC of [1] of EMA

Darunavir/ritonavir, dipotassium clorazepate ---> SmPC of [darunavir] of EMA

Sedative/hypnotics are extensively metabolised by CYP3A. Co-administration with boosted darunavir may cause a large increase in the concentration of these medicines.

Dipotassium clorazepate, disulfiram

The co-administration may enhance and prolong the clorazepate effect

Dipotassium clorazepate, elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

The co-administration may increase the plasma concentrations of sedative. Dose reduction may be necessary and concentration monitoring is recommended.

Dipotassium clorazepate, enzyme inhibitors

The co-administration may enhance the benzodiazepine activity

Dipotassium clorazepate, erythromycin

The co-administration may enhance the benzodiazepine activity

Dipotassium clorazepate, fluconazole

Fluconazole may increase the effect of the clorazepate

Dipotassium clorazepate, H2 antagonists

The co-administration may decrease the bioavailibility of clorazepate

Dipotassium clorazepate, hypnotics

The combination of CNS depressors may mutually potentiate the depressor effect on the CNS

Dipotassium clorazepate, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with clorazepate may increase the serum concentrations of clorazepate. Concentration monitoring of clorazepate is recommended and dose reduction may be considered.

Dipotassium clorazepate, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir should not be administered with clorazepate

Dipotassium clorazepate, lithium

The combination of CNS depressors may mutually potentiate the depressor effect on the CNS

Dipotassium clorazepate, muscle relaxants

The co-administration may have an additive muscle relaxant effect

Dipotassium clorazepate, narcotics

The combination of CNS depressors may mutually potentiate the depressor effect on the CNS

Dipotassium clorazepate, neuroleptics

The combination of CNS depressors may mutually potentiate the depressor effect on the CNS

Dipotassium clorazepate, omeprazole

The co-administration may enhance and prolong the clorazepate effect

Dipotassium clorazepate, opiates

The co-administration may cause a mutual potentiation of the depressor effect on the CNS, enhance the euphoric effect and promote a psychic dependency

Dipotassium clorazepate, pregnancy

Strict indication

Dipotassium clorazepate, ritonavir [2] ---> SmPC of [2] of EMA

Increased plasma concentrations of clorazepate, increasing the risk of extreme sedation and respiratory depression and is therefore contraindicated

Dipotassium clorazepate, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Increased benzodiazepine plasma concentrations. Careful monitoring of patients with regard to sedative effects is warranted.

Dipotassium clorazepate, sedating antihistamines

The combination of CNS depressors may mutually potentiate the depressor effect on the CNS

Dipotassium clorazepate, sedatives

The combination of CNS depressors may mutually potentiate the depressor effect on the CNS

Dipyridamole

Acenocoumarol, dipyridamole [2] ---> SmPC of [2] of eMC

It is possible that dipyridamole may enhance the effects of oral anti-coagulants.

Acetylsalicylic acid, dipyridamole [2] ---> SmPC of [2] of eMC

Addition of dipyridamole to acetylsalicylic acid does not increase the incidence of bleeding events.

Adenosine [1], dipyridamole ---> SmPC of [1] of eMC

Dipyridamole inhibits adenosine cellular uptake and metabolism, and potentiates the action of adenosine. The co-administration is contraindicated

Antacids, dipyridamole

The administration of antacids may reduce the efficacy of dipyridamole

Anticholinesterase, dipyridamole [2] ---> SmPC of [2] of eMC

Dipyridamole may counteract the anticholinesterase effect of cholinesterase inhibitors thereby potentially aggravating myasthenia gravis.

Anticoagulants, dipyridamole [2] ---> SmPC of [2] of eMC

When dipyridamole is used in combination with any substances impacting coagulation such as anticoagulants and antiplatelets the safety profile for these medications must be observed.

Antihypertensives, dipyridamole [2] ---> SmPC of [2] of eMC

Dipyridamole may increase the hypotensive effect of drugs which reduce blood pressure

Apixaban [1], dipyridamole ---> SmPC of [1] of EMA

Agents associated with serious bleeding are not recommended concomitantly with apixaban

Asparaginase [1], dipyridamole ---> SmPC of [1] of EMA

Concomitant use of glucocorticoids and/ or anticoagulants with asparaginase may increase the risk of a change in coagulation parameters (see section 4.4). This can promote tendency to bleeding (anticoagulants) or thrombosis (glucocorticoids).

Breast-feeding, dipyridamole [2] ---> SmPC of [2] of eMC

Dipyridamole should only be used during lactation if considered essential by the physician.

Caffeine, dipyridamole

Xanthines may weaken the vasodilator efect of dipyridamole

Carteolol, dipyridamole

Increased hypotensive effect of IV dipyridamole

Certoparin, dipyridamole

The co-administration may enhance the pharmacological effects of certoparin

Citalopram [1], dipyridamole ---> SmPC of [1] of eMC

Caution is warranted for patients who are being treated simultaneously with anticoagulants, medicinal products that affect platelet function, or other medicines that can increase the risk of haemorrhage

Dalteparin [1], dipyridamole ---> SmPC of [1] of eMC

Enhancement of the anticoagulant effect of dalteparin by anticoagulant/antiplatelet agents

Dipyridamole [1], pregnancy ---> SmPC of [1] of eMC

Medicines should not be used in pregnancy, especially the first trimester unless the expected benefit is thought to outweigh the possible risk to the foetus

Dipyridamole [1], warfarin ---> SmPC of [1] of eMC

When dipyridamole was administered concomitantly with warfarin, bleeding was no greater in frequency or severity than that observed when warfarin was administered alone.

Dipyridamole, distigmine

Dipyridamole may counteract the anticholinesterase effect of cholinesterase inhibitors

Dipyridamole, doubutamine

In an echocardiography, the administration of dipyridamole may cause a potential dangerous hypotension

Dipyridamole, enoxaparin [2] ---> SmPC of [2] of eMC

The co-administration may enhance the pharmacologic effect and increase the bleeding risk. A close clinical and laboratory monitoring is recommended

Dipyridamole, eptifibatide [2] ---> SmPC of [2] of EMA

Eptifibatid did not appear to increase the risk of major and minor bleeding associated with concomitant use of dipyridamole.

Dipyridamole, fludarabine [2] ---> SmPC of [2] of eMC

Dipyridamole and other inhibitors of adenosine uptake may reduce the therapeutic efficacy of fludarabine.

Dipyridamole, fondaparinux [2] ---> SmPC of [2] of EMA

Other antiplatelet medicinal products and NSAIDs should be used with caution. If co-administration is essential, close monitoring is necessary.

Dipyridamole, fossil tree

Additive anticoagulant effects may increase the bleed risk. Concomitant therapy should be avoided.

Dipyridamole, melagatran

The co-administration may significantly increase the bleeding risk

Dipyridamole, nadroparin

The co-administration may increase the nadroparin effect

Dipyridamole, oxybutynine [2] ---> SmPC of [2] of EMA

The anticholinergic activity of oxybutynin is increased by concurrent use of other anticholinergics or medicinal products with anticholinergic activity

Dipyridamole, P-gp inhibitors

Inhibitor of the P-glycoprotein can increase the bioavailability of dipyridamole

Dipyridamole, parnaparin

Increased risk of bleeding (inhibition of platelet function)

Dipyridamole, pegaspargase [2] ---> SmPC of [2] of EMA

The use of Oncaspar can lead to fluctuating coagulation factors. This can promote the tendency to bleeding and/or thrombosis. Caution is therefore needed when anticoagulants are given concomitantly.

Dipyridamole, phenindione

The co-administration is not recommended since it may increase the intensity of bleedings

Dipyridamole, regadenoson [2] ---> SmPC of [2] of EMA

Dipyridamole increases blood adenosine levels and the response to regadenoson may be altered when blood adenosine levels are increased. When possible, dipyridamole should be withheld for at least 2 days prior to regadenoson administration

Dipyridamole, reteplase [2] ---> SmPC of [2] of EMA

Caution should be employed when used reteplase with other medicinal products affecting haemostasis

Dipyridamole, sildenafil [2] ---> SmPC of [2] of EMA

There are no data on the interaction of sildenafil and non-specific phosphodiesterase inhibitors such as theophylline or dipyridamole.

Dipyridamole, theophylline

Xanthines may weaken the vasodilator efect of dipyridamole

Dipyridamole, treprostinil

The co-administration may increase the risk of bleeding. Additive hypotensive effect.

Dipyridamole, vardenafil [2] ---> SmPC of [2] of EMA

There are no data on the interaction of vardenafil and non-specific phosphodiesterase inhibitors such as theophylline or dipyridamole.

Dipyridamole, xanthines

Xanthines may weaken the vasodilator efect of dipyridamole

Dipyridamole, ximelagatran

The co-administration may significantly increase the bleeding risk

CONTRAINDICATIONS of Dipyridamole

- Hypersensitivity to any of the components of the product.

- In case of rare hereditary conditions that may be incompatible with an excipient of the product the use of the product is contraindicated.

http://www.medicines.org.uk/emc/

Diroximel fumarate (Vumerity)

Acetylsalicylic acid, diroximel fumarate [2] ---> SmPC of [2] of EMA

Potential risks associated with acetylsalicylic acid therapy should be considered prior to co-administration with Vumerity in patients with relapsing remitting MS.

Aminoglycoside antibiotics, diroximel fumarate [2] ---> SmPC of [2] of EMA

Concurrent therapy with nephrotoxic medicinal products may increase the potential of renal adverse reactions (e.g. proteinuria see section 4.8) in patients taking Vumerity

Antineoplastics, diroximel fumarate [2] ---> SmPC of [2] of EMA

Diroximel fumarate has not been studied in combination with anti-neoplastic or immunosuppressive therapies and caution should, therefore, be used during concomitant administration.

Breast-feeding, diroximel fumarate [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue Vumerity therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Combination oral contraceptives, dimethyl fumarate ---> SmPC of [dimethyl fumarate] of EMA

In an in vivo study, co-administration of dimethyl fumarate with a combined oral contraceptive (norgestimate and ethinyl estradiol) did not elicit any relevant change in oral contraceptive exposure.

Corticosteroids, diroximel fumarate [2] ---> SmPC of [2] of EMA

In MS clinical studies, the concomitant treatment of relapses with a short course of intravenous corticosteroids was not associated with a clinically relevant increase of infection.

Diroximel fumarate [1], diuretics ---> SmPC of [1] of EMA

Concurrent therapy with nephrotoxic medicinal products may increase the potential of renal adverse reactions (e.g. proteinuria see section 4.8) in patients taking Vumerity

Diroximel fumarate [1], fertility ---> SmPC of [1] of EMA

There are no data on the effects of Vumerity on human fertility. Data from animal studies with diroximel fumarate showed no impairment of male or female fertility (see section 5.3).

Diroximel fumarate [1], foods ---> SmPC of [1] of EMA

For those patients who may experience flushing or gastrointestinal adverse reactions, taking with food may improve tolerability

Diroximel fumarate [1], immunosuppressives ---> SmPC of [1] of EMA

Diroximel fumarate has not been studied in combination with anti-neoplastic or immunosuppressive therapies and caution should, therefore, be used during concomitant administration.

Diroximel fumarate [1], lithium ---> SmPC of [1] of EMA

Concurrent therapy with nephrotoxic medicinal products may increase the potential of renal adverse reactions (e.g. proteinuria see section 4.8) in patients taking Vumerity

Diroximel fumarate [1], nephrotoxic substances ---> SmPC of [1] of EMA

Concurrent therapy with nephrotoxic medicinal products may increase the potential of renal adverse reactions (e.g. proteinuria see section 4.8) in patients taking Vumerity

Diroximel fumarate [1], NSAID ---> SmPC of [1] of EMA

Concurrent therapy with nephrotoxic medicinal products may increase the potential of renal adverse reactions (e.g. proteinuria see section 4.8) in patients taking Vumerity

Diroximel fumarate [1], oral contraceptives ---> SmPC of [1] of EMA

Although not studied with diroximel fumarate, in vitro CYP induction studies did not demonstrate an interaction between dimethyl fumarate and oral contraceptives.

Diroximel fumarate [1], pregnancy ---> SmPC of [1] of EMA

Vumerity should be used during pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the foetus.

Diroximel fumarate [1], vaccinations ---> SmPC of [1] of EMA

Concomitant administration of non-live vaccines according to national vaccination schedules may be considered during Vumerity therapy.

Diroximel fumarate, vaccinations with live organism vaccines [2] ---> SmPC of [2] of EMA

Live vaccines might carry an increased risk of clinical infection and should not be given to patients unless, in exceptional cases, this potential risk is considered to be outweighed by the risk to the individual of not vaccinating.

Fumaric acid esters, fumaric acid esters ---> SmPC of [dimethyl fumarate] of EMA

During treatment, simultaneous use of other fumaric acid esters (topical or systemic) should be avoided. Vumerity should not be administered concomitantly with dimethyl fumarate.

CONTRAINDICATIONS of Diroximel fumarate (Vumerity)

- Hypersensitivity to the active substance, to any of the excipients listed in section 6.1 or other fumaric acid esters

- Suspected or confirmed Progressive Multifocal Leukoencephalopathy (PML).

https://www.ema.europa.eu/en/documents/product-information/vumerity-epar-product-information_en.pdf 05/02/2025

Disopyramide

Ability to drive, disopyramide [2] ---> SmPC of [2] of eMC

Some adverse reactions may impair the patient's ability to concentrate and react, and hence the ability to drive or operate machinery.

Abiraterone [1], disopyramide ---> SmPC of [1] of EMA

Since androgen deprivation treatment may prolong the QT interval, caution is advised when administering ZYTIGA with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes

Amantadine, disopyramide

The co-administration of amantadine with drugs that prolong the QT interval is contraindicated

Amifampridine [1], disopyramide ---> SmPC of [1] of EMA

The concomitant use of amifampridine with medicinal products known to cause QT prolongation is contraindicated as this combination may lead to an enhanced risk of ventricular tachycardia, notably torsade de pointes

Amiodarone [1], disopyramide ---> SmPC of [1] of eMC

The combined therapy of amiodarone with drugs which prolong the QT interval is contra-indicated due to the increased risk of torsades de pointes

Amisulpride [1], disopyramide ---> SmPC of [1] of eMC

Caution is advised when prescribing amisulpride with medicines known to prolong the QT interval

Amphotericin B, disopyramide [2] ---> SmPC of [2] of eMC

Concomitant use of disopyramide with drugs can induce hypokalaemia may reduce the action of the drug, or potentiate proarrhythmic effects

Antiarrhythmics, disopyramide

Concomitant administration of disopyramide with other anti-arrhythmic drugs is contra-indicated except under certain circumstances

Antiarrhythmics, disopyramide [2] ---> SmPC of [2] of eMC

Concomitant administration of disopyramide with other anti-arrhythmic drugs is contra-indicated except under certain circumstances

Anticholinergics, disopyramide [2] ---> SmPC of [2] of eMC

Atropine and other anticholinergic drugs, including phenothiazines, may potentiate the atropine-like effects of disopyramide.

Astemizole, disopyramide [2] ---> SmPC of [2] of eMC

Concomitant administration of disopyramide with other drugs liable to provoke ventricular arrythmias, especially Torsade de Pointes is contra-indicated

Atazanavir/cobicistat [1], disopyramide ---> SmPC of [1] of EMA

Concentrations of the antiarrhythmic may be increased when co-administered with EVOTAZ. The mechanism is CYP3A inhibition by atazanavir and cobicistat. Co-administration has the potential to produce serious and/or life-threatening adverse reactions.

Atenolol [1], disopyramide ---> SmPC of [1] of eMC

Class I anti-arrhythmic drugs with atenolol may have a potentiating effect on atrial-conduction time and induce negative inotropic effect.

Atenolol/chlortalidone [1], disopyramide ---> SmPC of [1] of eMC

Class I anti-arrhythmic drugs with atenolol may have a potentiating effect on atrial-conduction time and induce negative inotropic effect.

Atropine, disopyramide [2] ---> SmPC of [2] of eMC

Atropine and other anticholinergic drugs, including phenothiazines, may potentiate the atropine-like effects of disopyramide.

Azole antifungals, disopyramide [2] ---> SmPC of [2] of eMC

There is evidence that phosphodiesterase Type 5 inhibitors may be potentially associated with a risk of QT prolongation. Concomitant administration of disopyramide with such drugs may potentially enhance this QT prolongation effect and is not recommended

Beclometasone/formoterol/glycopyrronium [1], disopyramide ---> SmPC of [1] of EMA

Concomitant treatment with quinidine, disopyramide, procainamide, antihistamines, monoamine oxidase inhibitors, tricyclic antidepressants and phenothiazines can prolong the QT interval and increase the risk of ventricular arrhythmias.

Bendroflumethiazide [1], disopyramide ---> SmPC of [1] of eMC

The cardiac toxicity of disopyramide is increased if hypokalaemia occurs.

Bepridil, disopyramide [2] ---> SmPC of [2] of eMC

Antiarrhythmic combination should be avoided except under certain circumstances

Betablockers, disopyramide [2] ---> SmPC of [2] of eMC

Antiarrhythmic combination should be avoided except under certain circumstances

Betaxolol, disopyramide

The combination may cause alterations of contractibility and stimulus conduction by suppression of sympathetic compensatory mechanisms

Bosutinib [1], disopyramide ---> SmPC of [1] of EMA

Bosutinib should be used with caution in patients who have or may develop prolongation of QT, including those patients taking anti-arrhythmic medicinal products or other medicinal products that may lead to QT prolongation

Breast-feeding, disopyramide [2] ---> SmPC of [2] of eMC

If the drug is considered essential, an alternative method of feeding should be used.

Bretylium, disopyramide [2] ---> SmPC of [2] of eMC

Antiarrhythmic combination should be avoided except under certain circumstances

Budesonide/formoterol [1], disopyramide ---> SmPC of [1] of EMA

Concomitant treatment of formoterol with disopyramide can prolong the QTc-interval and increase the risk of ventricular arrhythmias.

Budipine, disopyramide

The co-administration of budipine with drugs known to prolong QT interval is contraindicated

Butylscopolamine [1], disopyramide ---> SmPC of [1] of eMC

The anticholinergic effect may be intensified by hyoscine butylbromide

Carteolol [1], disopyramide ---> SmPC of [1] of eMC

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic beta-blockers solution is administered concomitantly with antiarrhythmics (including amiodarone)

Celiprolol [1], disopyramide ---> SmPC of [1] of eMC

Care should be taken in prescribing beta-adrenoceptor blockers with Class I antiarrhythmic agents, since these agents may potentiate the negative effects on A-V conduction and myocardial contractility.

Ceritinib [1], disopyramide ---> SmPC of [1] of EMA

Ceritinib should be used with caution in patients taking other medicinal products that may lead to QT prolongation. Monitoring of the QT interval is indicated in the event of combinations of such medicinal products

Chlorpromazine, disopyramide

The co-administration causes addition of atropinic adverse effects e. g. retention of urine, dry mouth, obstipation

Cisapride, disopyramide [2] ---> SmPC of [2] of eMC

Concomitant administration of disopyramide with other drugs liable to provoke ventricular arrythmias, especially Torsade de Pointes is contra-indicated

Clarithromycin [1], disopyramide ---> SmPC of [1] of eMC

There have been post-marketed reports of torsade de points occurring with the concurrent use of clarithromycin and disopyramide. Electrocardiograms should be monitored for QTc prolongation during co-administration

Class I antiarrhythmic agents, disopyramide [2] ---> SmPC of [2] of eMC

Antiarrhythmic combination should be avoided except under certain circumstances

Class II antiarrhythmic agents, disopyramide [2] ---> SmPC of [2] of eMC

Antiarrhythmic combination should be avoided except under certain circumstances

Class III antiarrhythmic agents, disopyramide [2] ---> SmPC of [2] of eMC

Antiarrhythmic combination should be avoided except under certain circumstances

Class IV antiarrhythmic agents, disopyramide [2] ---> SmPC of [2] of eMC

Antiarrhythmic combination should be avoided except under certain circumstances

Clomipramine [1], disopyramide ---> SmPC of [1] of eMC

The risk of QTc prolongation and Torsade de Pointes is likely to be increased if clomipramine is co-administered with other drugs that can cause QTc prolongation. Therefore concomitant use is not recommended

Cobicistat [1], disopyramide ---> SmPC of [1] of EMA

The co-administration with cobicistat may increase the concentrations of antiarrhythmic

Corticosteroids, disopyramide [2] ---> SmPC of [2] of eMC

Concomitant use of disopyramide with drugs can induce hypokalaemia may reduce the action of the drug, or potentiate proarrhythmic effects

Crizotinib [1], disopyramide ---> SmPC of [1] of EMA

Concomitant use of crizotinib (prolongs QT interval) with medicinal products known to prolong QT interval or medicinal products able to induce Torsades de pointes should be carefully considered.

Cyclosporine, disopyramide [2] ---> SmPC of [2] of eMC

When prescribing a drug metabolised by CYP3A it should be kept in mind that disopyramide is probably also a substrate of this isozyme and thus competitive inhibition of metabolism might occur, possibly increasing serum levels of these drugs.

Daclatasvir [1], disopyramide ---> SmPC of [1] of EMA

No clinically relevant effects on the pharmacokinetics of either medicinal product are expected when daclatasvir is coadministered with the other medicinal product

Darunavir/cobicistat [1], disopyramide ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase the antiarrhythmic plasma concentrations. Caution is warranted

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], disopyramide ---> SmPC of [1] of EMA

Degarelix [1], disopyramide ---> SmPC of [1] of EMA

The combination of degarelix with medicinal products known to prolong the QTc interval or medicinal products able to induce torsades de pointes should be carefully evaluated

Delamanid [1], disopyramide ---> SmPC of [1] of EMA

Diltiazem, disopyramide [2] ---> SmPC of [2] of eMC

Antiarrhythmic combination should be avoided except under certain circumstances

Disopyramide [1], diuretics ---> SmPC of [1] of eMC

Concomitant use of disopyramide with drugs can induce hypokalaemia may reduce the action of the drug, or potentiate proarrhythmic effects

Disopyramide [1], drugs primarily metabolised by CYP3A4 ---> SmPC of [1] of eMC

Disopyramide [1], hypokalemia ---> SmPC of [1] of eMC

Concomitant use of disopyramide with drugs can induce hypokalaemia may reduce the action of the drug, or potentiate proarrhythmic effects

Disopyramide [1], ibutilide ---> SmPC of [1] of eMC

Antiarrhythmic combination should be avoided except under certain circumstances

Disopyramide [1], lidoflazine ---> SmPC of [1] of eMC

Antiarrhythmic combination should be avoided except under certain circumstances

Disopyramide [1], macrolide antibiotics ---> SmPC of [1] of eMC

Disopyramide [1], PDE5 inhibitors ---> SmPC of [1] of eMC

There is evidence that phosphodiesterase Type 5 inhibitors may be associated with a risk of QT prolongation. Co-administration of disopyramide with such drugs may potentially enhance this QT prolongation effect and is not recommended.

Disopyramide [1], phenothiazines ---> SmPC of [1] of eMC

Atropine and other anticholinergic drugs, including phenothiazines, may potentiate the atropine-like effects of disopyramide.

Disopyramide [1], phenytoin ---> SmPC of [1] of eMC

Inducers of CYP3A may reduce disopyramide and increase MN-disopyramide serum levels. Since the magnitude of such potential effects is not foreseeable, such drug combinations are not recommended.

Disopyramide [1], pregnancy ---> SmPC of [1] of eMC

The drug should only be used during pregnancy if benefits clearly outweigh the possible risks to the mother and foetus.

Disopyramide [1], rifampicin ---> SmPC of [1] of eMC

Inducers of CYP3A may reduce disopyramide and increase MN-disopyramide serum levels. Since the magnitude of such potential effects is not foreseeable, such drug combinations are not recommended.

Disopyramide [1], sparfloxacin ---> SmPC of [1] of eMC

Concomitant administration of disopyramide with other drugs liable to provoke ventricular arrythmias, especially Torsade de Pointes is contra-indicated

Disopyramide [1], stimulant laxatives ---> SmPC of [1] of eMC

Stimulant laxatives are not recommended to be given concomitantly with disopyramide, due to their potassium lowering potential.

Disopyramide [1], strong CYP3A4 inductors ---> SmPC of [1] of eMC

Inducers of CYP3A may reduce disopyramide and increase MN-disopyramide serum levels. Since the magnitude of such potential effects is not foreseeable, such drug combinations are not recommended.

Disopyramide [1], strong CYP3A4 inhibitors ---> SmPC of [1] of eMC

Disopyramide [1], sultopride ---> SmPC of [1] of eMC

Concomitant administration of disopyramide with other drugs liable to provoke ventricular arrythmias, especially Torsade de Pointes is contra-indicated

Disopyramide [1], terfenadine ---> SmPC of [1] of eMC

Concomitant administration of disopyramide with other drugs liable to provoke ventricular arrythmias, especially Torsade de Pointes is contra-indicated

Disopyramide [1], tetracosactide ---> SmPC of [1] of eMC

Concomitant use of disopyramide with drugs can induce hypokalaemia may reduce the action of the drug, or potentiate proarrhythmic effects

Disopyramide [1], tetracyclic antidepressant ---> SmPC of [1] of eMC

Concomitant administration of disopyramide with other drugs liable to provoke ventricular arrythmias, especially Torsade de Pointes is contra-indicated

Disopyramide [1], theophylline ---> SmPC of [1] of eMC

Disopyramide [1], torsades de pointes inducing drugs ---> SmPC of [1] of eMC

Concomitant administration of disopyramide with other drugs liable to provoke ventricular arrythmias, especially Torsade de Pointes is contra-indicated

Disopyramide [1], tricyclic antidepressant ---> SmPC of [1] of eMC

Concomitant administration of disopyramide with other drugs liable to provoke ventricular arrythmias, especially Torsade de Pointes is contra-indicated

Disopyramide [1], verapamil ---> SmPC of [1] of eMC

Antiarrhythmic combination should be avoided except under certain circumstances

Disopyramide [1], vincamine ---> SmPC of [1] of eMC

Concomitant administration of disopyramide with other drugs liable to provoke ventricular arrythmias, especially Torsade de Pointes is contra-indicated

Disopyramide [1], warfarin ---> SmPC of [1] of eMC

Disopyramide, droperidol [2] ---> SmPC of [2] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Disopyramide, elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Concentrations of this antiarrhythmic drug may be increased when co-administered with cobicistat.

Disopyramide, elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

The co-administration with cobicistat may increase the concentrations of antiarrhythmic

Disopyramide, enzalutamide [2] ---> SmPC of [2] of EMA

The concomitant use of enzalutamide with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes should be carefully evaluated

Disopyramide, eribulin [2] ---> SmPC of [2] of EMA

The inhibition of hepatic transport proteins may increase the plasma concentrations of eribulin. Co-administration is not recommended

Disopyramide, esmolol [2] ---> SmPC of [2] of eMC

Concomitant use of esmolol and class I antiarrhythmic agents can increase the action of both on the AV-conductance time and induce negative inotropic effect.

Disopyramide, etravirine [2] ---> SmPC of [2] of EMA

Etravirine is expected to decrease plasma concentrations of this antiarrhythmic. Caution is warranted and therapeutic concentration monitoring, if available, is recommended for antiarrhythmics when co-administered with etravirine.

Disopyramide, fluphenazine [2] ---> SmPC of [2] of eMC

The effect of fluphenazine on the QT interval is likely to be potentiated by concurrent use of other drugs that also prolong the QT interval. Therefore, concurrent use of these drugs and fluphenazine is contraindicated.

Disopyramide, formoterol [2] ---> SmPC of [2] of eMC

Caution should be observed in patients treated with drugs that may be associated with QT-interval prolongation and an increased risk of ventricular arrhythmia

Disopyramide, glibenclamide [2] ---> SmPC of [2] of EMA

The co-administration may enhance the hypoglycemic effect

Disopyramide, glimepiride [2] ---> SmPC of [2] of eMC

Potentiation of the blood-sugar-lowering effect and possible hypoglycaemia

Disopyramide, gliquidone

Hypoglycemic reactions may occur as expression of enhancement effect of gliquidone with gliquidone is co-administered with disopyramide

Disopyramide, haloperidol [2] ---> SmPC of [2] of eMC

Concomitant use of haloperidol with drugs known to prolong the QT interval may increase the risk of ventricular arrhythmias, including torsade de pointes. Therefore concomitant use of these products is not recommended

Disopyramide, hydrochlorothiazide ---> SmPC of [losartan/hydrochlorothiazide] of eMC

Periodic monitoring of serum potassium and ECG is recommended, when hydrochlorothiazide is administered with drugs which may induce torsades de pointes

Disopyramide, hydroquinidine

Concomitant use of hydroquinidine with drugs that can induce torsades de pointes is contraindicated due to increased risk of heart rhythm disorders (torsades de pointes)

Disopyramide, hydroxyzine [2] ---> SmPC of [2] of eMC

Co-administration of hydroxyzine with drugs known to prolong the QT interval and/or induce Torsade de Pointes increase the risk of cardiac arrhythmia. Therefore, the combination is contra-indicated

Disopyramide, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with disopyramide may increase the serum concentrations of disopyramide. Clinical monitoring is recommended.

Disopyramide, indapamide [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Disopyramide, indinavir [2] ---> SmPC of [2] of EMA

Indinavir with or without ritonavir should not be administered with medicinal products with narrow therapeutic ranges and which are CYP3A4 substrates. The elevated plasma concentrations of these medicines may cause serious or life-threatening reactions.

Disopyramide, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Disopyramide, insulin glargin [2] ---> SmPC of [2] of EMA

Enhanced blood-glucose-lowering effect and increased susceptibility to hypoglycaemia

Disopyramide, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

This substance may enhance the blood-glucose-lowering effect and increase susceptibility to hypoglycaemia.

Disopyramide, insulin glulisin [2] ---> SmPC of [2] of EMA

Possible enhancement of blood-glucose-lowering activity and increased susceptibility to hypoglycaemia

Disopyramide, interferon

Caution should be used when administering interferon with medicines mainly metabolised by hepatic cytochrome P450 and have a narrow therapeutic window

Disopyramide, itraconazol [2] ---> SmPC of [2] of eMC

Itraconazole may increase the plasma concentrations of disopyramide. Coadministration is contraindicated

Disopyramide, ivabradine [2] ---> SmPC of [2] of EMA

The concomitant use of cardiovascular and non-cardiovascular QT prolonging medicinal products with ivabradine should be avoided since QT prolongation may be exacerbated by heart rate reduction.

Disopyramide, ketoconazole [2] ---> SmPC of [2] of EMA

Concomitant therapy of ketoconazole with substances that may have their plasma concentrations increased and have QT prolonging potential is contraindicated

Disopyramide, levomepromazine [2] ---> SmPC of [2] of eMC

There is an increased risk of arrhythmias when neuroleptics are used with drugs that prolong the QT interval

Disopyramide, lithium ---> SmPC of [lithium carbonate] of eMC

As a precautionary measure, lithium should be avoided in patients concomitantly treated with drugs that are known to prolong the QT interval

Disopyramide, losartan/hydrochlorothiazide [2] ---> SmPC of [2] of eMC

Periodic monitoring of serum potassium and ECG is recommended when losartan/hydrochlorothiazide is administered with torsades de pointes-inducing medicinal products

Disopyramide, lurasidone [2] ---> SmPC of [2] of EMA

Caution is advised when prescribing lurasidone with medicinal products known to prolong the QT interval

Disopyramide, mequitazine

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Disopyramide, moxifloxacin [2] ---> SmPC of [2] of eMC

The co-administration may have an additive effect on the QT interval prolongation. This might lead to an increased risk of ventricular arrhythmias, including torsade de pointes. The combination is contraindicated.

Disopyramide, nadolol [2] ---> SmPC of [2] of eMC

Additive or antagonistic effects may occur with nadolol and antiarrhythmic agents.

Disopyramide, nebivolol [2] ---> SmPC of [2] of eMC

Combination not recommended as the effect on atrio-ventricular conduction time may be potentiated and the negative inotropic effect increased

Disopyramide, nilotinib [2] ---> SmPC of [2] of EMA

Significant prolongation of the QT interval may occur when nilotinib is inappropriately taken with medicinal products with a known potential to prolong QT. Prolongation of the QT interval may expose patients to the risk of fatal outcome.

Disopyramide, oxprenolol [2] ---> SmPC of [2] of eMC

Class I anti-arrhythmic drugs may increase atrial-conduction time and induce negative inotropic effect when administered concomitantly with beta-blockers.

Disopyramide, paliperidone [2] ---> SmPC of [2] of EMA

Caution is advised when prescribing paliperidone with medicines known to prolong the QT interval

Disopyramide, panobinostat [2] ---> SmPC of [2] of EMA

Based on preclinical and clinical data, panobinostat has the potential to prolong the QT interval. Concomitant use of panobinostat and other substances that are known to prolong the QT interval is not recommended.

Disopyramide, pasireotide [2] ---> SmPC of [2] of EMA

Pasireotide should be used with caution in patients who are concomitantly receiving medicinal products that prolong the QT interval

Disopyramide, pentamidine [2] ---> SmPC of [2] of eMC

Caution is advised when pentamidine isetionate is concomitantly used with drugs that are known to prolong the QT interval

Disopyramide, phenobarbital

Inducers of CYP3A may reduce disopyramide and increase MN-disopyramide serum levels. Since the magnitude of such potential effects is not foreseeable, such drug combinations are not recommended.

Disopyramide, pimozide [2] ---> SmPC of [2] of eMC

Concomitant use of pimozide with drugs known to prolong the QT interval is contra-indicated

Disopyramide, pioglitazone/glimepiride [2] ---> SmPC of [2] of EMA

Potentiation of the blood-glucose-lowering effect and, thus, in some instances hypoglycaemia may occur

Disopyramide, piperaquine ---> SmPC of [piperaquine/artenimol] of EMA

The combination of piperaquine with drugs that are known to prolong the QTc interval is contraindicated: additive effect on the QTc interval

Disopyramide, piperaquine/artenimol [2] ---> SmPC of [2] of EMA

The combination of piperaquine/dihydroartemisinin with drugs that are known to prolong the QTc interval is contraindicated: additive effect on the QTc interval

Disopyramide, primidone [2] ---> SmPC of [2] of eMC

Inducers of CYP3A may reduce disopyramide and increase MN-disopyramide serum levels. Since the magnitude of such potential effects is not foreseeable, such drug combinations are not recommended.

Disopyramide, procyclidine [2] ---> SmPC of [2] of eMC

Drugs with anticholinergic properties may increase the anticholinergic action

Disopyramide, promazine [2] ---> SmPC of [2] of eMC

Concomitant use of promazine with drugs known to prolong the QT interval may increase the risk of ventricular arrhythmias, including torsade de pointes. Therefore, concomitant use of these products is not recommended.

Disopyramide, propranolol [2] ---> SmPC of [2] of eMC

Class I anti-arrhythmic drugs may increase atrial-conduction time and induce negative inotropic effect when administered concomitantly with beta-blockers.

Disopyramide, ranolazine [2] ---> SmPC of [2] of EMA

There is a theoretical risk that concomitant treatment of ranolazine with other drugs known to prolong the QTc interval may give rise to a pharmacodynamic interaction and increase the possible risk of ventricular arrhythmias.

Disopyramide, ribociclib [2] ---> SmPC of [2] of EMA

Co-administration of Kisqali with medicinal products with a known potential to prolong the QT interval such as anti-arrhythmic medicinal products should be avoided

Disopyramide, rifabutin

Rifabutin has a similar structure as rifampicin. Concomitant use of rifabutin and disopyramide may decrease disopyramide effects

Disopyramide, risperidone [2] ---> SmPC of [2] of eMC

Caution is advised when prescribing risperidone with medicinal products known to prolong the QT interval

Disopyramide, ritonavir [2] ---> SmPC of [2] of EMA

Cardiac and neurologic events have been reported when ritonavir has been co-administered with disopyramide. The possibility of drug interaction cannot be excluded

Disopyramide, roxithromycin

Caution is warranted for concomitant use of roxitromycin with other QT interval prolonging medicines

Disopyramide, saquinavir [2] ---> SmPC of [2] of EMA

Saquinavir, CYP3A4 inhibitor, may increase the plasma concentrations of disopyramide.

Disopyramide, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Saquinavir, CYP3A4 inhibitor, may increase the plasma concentrations of disopyramide. Contraindicated due to the potential for life threatening cardiac arrhythmia

Disopyramide, scopolamine

Scopolamine may enhance the anticholinergic effect

Disopyramide, simeprevir [2] ---> SmPC of [2] of EMA

Simeprevir, inhibitor of intestinal CYP3A4, may increase the plasma levels of this antiarrhythmic drug.

Disopyramide, sotalol [2] ---> SmPC of [2] of eMC

Sotalol should be given with extreme caution in conjunction with other drugs known to prolong the QT-interval. Drugs that prolong the QT-interval may cause torsades de pointes. The co-administration with sotalol is contraindicated

Disopyramide, sulfonylureas

Potentiation of the blood-sugar-lowering effect and possible hypoglycaemia

Disopyramide, sulpiride [2] ---> SmPC of [2] of eMC

The combination of sulpiride with class Ia antiarrhythmic agents is not recommended

Disopyramide, talinolol

Disopyramide, telithromycin [2] ---> SmPC of [2] of EMA

Due to a potential to increase the QT interval, telithromycin should be used with care during concomitant administration with QT interval prolonging agents

Disopyramide, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Periodic monitoring of serum potassium and ECG is recommended when MicardisPlus is administered with drugs affected by serum potassium disturbances (e.g. digitalis glycosides, antiarrhythmics) and torsades de pointes inducing medicinal products

Disopyramide, tiapride

Tiapride should not be combined with drugs that prolong the QT interval. These drugs (with the exception of anti-infectious) should be discontinued, if possible, if they induce torsades de pointes

Disopyramide, toremifene [2] ---> SmPC of [2] of EMA

An additive effect on QT interval prolongation between toremifene and medicinal products that may prolong the QTc interval cannot be excluded. This might lead to an increased risk of ventricular arrhythmias. Co-administration is contraindicated

Disopyramide, triamcinolone acetonide

Concomitant use of triamcinolone with class I antiarrhythmics is not recommended

Disopyramide, xipamide

The combination increases the risk of ventricular arrhythmias, particularly torsades de pointes (favored by hypokaliemia). It is recommended a special caution

CONTRAINDICATIONS of Disopyramide

- Hypersensitivity to Disopyramide Phosphate or to any of the excipients.

- Disopyramide is contra-indicated in un-paced second or third degree atrioventricular block;

- bundle-branch block associated with first-degree atrioventricular block;

- un-paced bifascicular block;

- pre-existing long QT syndromes;

- severe sinus node dysfunction;

- severe heart failure, unless secondary to cardiac arrhythmia;

- hypersensitivity to disopyramide.

- It is also contra-indicated in concomitant administration with other anti-arrhythmics or other drugs liable to provoke ventricular arrhythmias, especially Torsade de Pointes (see section 4.5).

The sustained release formulation is contra-indicated in patients with renal or hepatic impairment.

http://www.medicines.org.uk/emc/

Dithranol

Breast-feeding, dithranol

A decision must be made to either discontinue breast-feeding or to discontinue/abstain from therapy

Coal tar, dithranol

The topical co-administration may decrease the dithranol effect

Dithranol, photosensitizing agents

The co-administration may increase the photosensitizing effect

Dithranol, polyethylenglycol

The co-administration may oxidize and inactivate dithranol

Dithranol, pregnancy

The cream may be applied, when the necessity is evident

Dithranol, salicylic acid

The topical co-administration may increase the dithranol effect

Dithranol, starch

The topical co-administration may decrease the dithranol effect

Dithranol, urea

The topical co-administration may increase the dithranol effect

Dithranol, zinc oxide

The topical co-administration may decrease the dithranol effect

Docetaxel (Docetaxel Accord)

Ability to drive, docetaxel [2] ---> SmPC of [2] of EMA

The amount of alcohol in this medicinal product and the side effects of the product may impair the ability to drive or use machines (see sections 4.4 and 4.8).

Alcohol, docetaxel [2] ---> SmPC of [2] of EMA

The amount of alcohol in this medicinal product may alter the effects of other medicinal products.

Aprepitant [1], docetaxel ---> SmPC of [1] of EMA

EMEND, when given as a regimen of 125 mg on Day 1 and 80 mg/day on Days 2 and 3, did not influence the pharmacokinetics of docetaxel administered intravenously on Day 1 or vinorelbine administered intravenously on Day 1 or Day 8.

Azole antifungals, docetaxel [2] ---> SmPC of [2] of EMA

If the concomitant use of a strong CYP3A4 cannot be avoided, a close clinical surveillance is warranted and a dose-adjustment of docetaxel may be suitable during the treatment with the strong CYP3A4 inhibitor

Breast-feeding, docetaxel [2] ---> SmPC of [2] of EMA

Consequently, because of the potential for adverse reactions in nursing infants, breast feeding must be discontinued for the duration of docetaxel therapy.

Bulevirtide [1], docetaxel ---> SmPC of [1] of EMA

In vitro an inhibition of OATP1B1/3 transporters by bulevirtide was observed, albeit only at a concentration ≥ 0.5 µM. As a precautionary measure, close clinical monitoring is warranted when OATP1B1/3 substrates are co-administered.

Carboplatin, docetaxel [2] ---> SmPC of [2] of EMA

Limited data from a single uncontrolled study were suggestive of an interaction between docetaxel and carboplatin. When combined to docetaxel, the clearance of carboplatin was about 50% higher than values previously reported for carboplatin monotherapy.

Cisplatin, docetaxel [2] ---> SmPC of [2] of EMA

Docetaxel Accord in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer, in patients who have not previously received chemotherapy for this condition.

Clarithromycin, docetaxel [2] ---> SmPC of [2] of EMA

Cyclosporine, docetaxel [2] ---> SmPC of [2] of EMA

Cyclosporine may inhibit competitively the CYP3A and there is a potential for a significant interaction

Dexamethasone, docetaxel [2] ---> SmPC of [2] of EMA

Dexamethasone did not affect protein binding of docetaxel

Digoxin, docetaxel [2] ---> SmPC of [2] of EMA

Docetaxel did not influence the binding of digitoxin

Diphenhydramine, docetaxel [2] ---> SmPC of [2] of EMA

In vitro interactions with tightly protein-bound agents such as erythromycin, diphenhydramine, propranolol, propafenone, phenytoin, salicylate, sulfamethoxazole and sodium valproate did not affect protein binding of docetaxel.

Docetaxel [1], doxorubicine ---> SmPC of [1] of EMA

The pharmacokinetics of docetaxel, doxorubicin and cyclophosphamide were not influenced by their co-administration.

Docetaxel [1], drugs primarily metabolised by CYP3A4 ---> SmPC of [1] of EMA

In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant administration of compounds which are metabolised by (and thus may inhibit the enzyme competitively) cytochrome P450-3A

Docetaxel [1], drugs with high protein binding ---> SmPC of [1] of EMA

Docetaxel [1], erythromycin ---> SmPC of [1] of EMA

Erythromycin may inhibit competitively the CYP3A and there is a potential for a significant interaction

Docetaxel [1], erythromycin ---> SmPC of [1] of EMA

Docetaxel [1], fertility ---> SmPC of [1] of EMA

Studies in animals have shown that docetaxel may alter male fertility (see section 5.3). Therefore, males being treated with docetaxel must seek advice on conservation of sperm prior to treatment.

Docetaxel [1], indinavir ---> SmPC of [1] of EMA

Docetaxel [1], itraconazol ---> SmPC of [1] of EMA

Docetaxel [1], ketoconazole ---> SmPC of [1] of EMA

In a pharmacokinetic study with 7 patients, the co-administration of docetaxel with the strong CYP3A4 inhibitor ketoconazole leads to a significant decrease in docetaxel clearance by 49%.

Docetaxel [1], men ---> SmPC of [1] of EMA

Women of childbearing potential and men receiving docetaxel should be advised to avoid becoming pregnant, and not to father a child and to inform the treating physician immediately should this occur.

Docetaxel [1], men ---> SmPC of [1] of EMA

Men must use effective method of contraception during treatment and for 4 months after cessation of treatment with docetaxel.

Docetaxel [1], moderate CYP3A4 inductors ---> SmPC of [1] of EMA

In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant administration of compounds which induce cytochrome P450-3A. Caution should be exercised since there is a potential for a significant interaction.

Docetaxel [1], nefazodone ---> SmPC of [1] of EMA

Docetaxel [1], nelfinavir ---> SmPC of [1] of EMA

Docetaxel [1], phenytoin ---> SmPC of [1] of EMA

Docetaxel [1], prednisone ---> SmPC of [1] of EMA

Docetaxel is metabolised by CYP3A4 and prednisone is known to induce CYP3A4. No statistically significant effect of prednisone on the pharmacokinetics of docetaxel was observed.

Docetaxel [1], pregnancy ---> SmPC of [1] of EMA

Docetaxel must not be used during pregnancy unless clearly indicated.

Docetaxel [1], propafenone ---> SmPC of [1] of EMA

Docetaxel [1], propranolol ---> SmPC of [1] of EMA

Docetaxel [1], ritonavir ---> SmPC of [1] of EMA

Docetaxel [1], salicylates ---> SmPC of [1] of EMA

Docetaxel [1], saquinavir ---> SmPC of [1] of EMA

Docetaxel [1], sodium valproate ---> SmPC of [1] of EMA

Docetaxel [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Docetaxel [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Docetaxel [1], sulfamethoxazol ---> SmPC of [1] of EMA

Docetaxel [1], telithromycin ---> SmPC of [1] of EMA

Docetaxel [1], voriconazole ---> SmPC of [1] of EMA

Docetaxel [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential and men receiving docetaxel should be advised to avoid becoming pregnant, and not to father a child and to inform the treating physician immediately should this occur.

Docetaxel [1], women of childbearing potential ---> SmPC of [1] of EMA

Due to the genotoxic risk of docetaxel (see section 5.3), women of childbearing potential must use effective method of contraception during treatment and for 2 months after cessation of treatment with docetaxel.

Docetaxel, enzalutamide [2] ---> SmPC of [2] of EMA

Xtandi (160 mg once daily) had no clinically relevant effect on the pharmacokinetics of intravenously administered docetaxel (75 mg/m2 by infusion every 3 weeks).

Docetaxel, epirubicin [2] ---> SmPC of [2] of eMC

One study found that docetaxel may increase the plasma concentrations of epirubicin metabolites, when administered immediately after epirubicin.

Docetaxel, fosaprepitant [2] ---> SmPC of [2] of EMA

Based on studies with oral aprepitant and docetaxel and vinorelbine, IVEMEND 150 mg is not expected to have a clinically relevant interaction with intravenously administered docetaxel and vinorelbine.

Docetaxel, imatinib [2] ---> SmPC of [2] of EMA

Imatinib inhibits CYP3A4 and may increase plasma concentration of other CYP3A4 metabolised drugs. Caution is recommended when administering imatinib with CYP3A4 substrates with a narrow therapeutic window

Docetaxel, lapatinib [2] ---> SmPC of [2] of EMA

Co-administration of lapatinib with intravenously administered docetaxel did not significantly affect the AUC or Cmax of either active substance. However, the occurrence of docetaxel-induced neutropenia was increased.

Docetaxel, midazolam

Increased serum levels of docetaxel.

Docetaxel, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

Netupitant is a moderate CYP3A4 inhibitor and can increase the exposure of chemotherapeutic agents that are substrates for CYP3A4. Therefore, patients should be monitored for increased toxicity of chemotherapeutic agents that are substrates for CYP3A4

Docetaxel, nintedanib [2] ---> SmPC of [2] of EMA

Co-administration of nintedanib with docetaxel (75 mg/m ²) did not alter the pharmacokinetics of either medicinal product to a relevant extent.

Docetaxel, orphenadrine

Increased serum levels of docetaxel.

Docetaxel, pertuzumab [2] ---> SmPC of [2] of EMA

No pharmacokinetic (PK) interactions were observed and no evidence of a drug-drug interaction has been shown between pertuzumab and docetaxel

Docetaxel, pitolisant [2] ---> SmPC of [2] of EMA

The combination of pitolisant with substrates of CYP3A4 and having a narrow therapeutic margin (e.g. immunosuppressants, docetaxel, kinase inhibitors, cisapride, pimozide, halofantrine) should be avoided

Docetaxel, ramucirumab [2] ---> SmPC of [2] of EMA

The pharmacokinetics of docetaxel or erlotinib were not affected when co-administered with ramucirumab.

Docetaxel, sorafenib [2] ---> SmPC of [2] of EMA

Caution is recommended when sorafenib is co-administered with docetaxel

Docetaxel, terfenadine

Terfenadine may inhibit competitively the CYP3A and there is a potential for a significant interaction

Docetaxel, trastuzumab [2] ---> SmPC of [2] of EMA

Data from study JP16003 suggested that concomitant administration of Herceptin had no effect on the single dose pharmacokinetics of docetaxel

Docetaxel, troleandomycin

Troleandomycin may inhibit competitively the CYP3A and there is a potential for a significant interaction

Docetaxel, vandetanib

Vandetanib, CYP3A4 inductor, may decrease the plasma levels of docetaxel. Caution should be exercised

Docetaxel, vinflunine [2] ---> SmPC of [2] of EMA

A possible interaction with paclitaxel and docetaxel (CYP3 substrates) has been suggested from an in vitro study (slight inhibition of vinflunine metabolism).

CONTRAINDICATIONS of Docetaxel (Docetaxel Accord)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Patients with baseline neutrophil count of < 1,500 cells/mm3.

- Patients with severe liver impairment (see sections 4.2 and 4.4).

- Contraindications for other medicinal products also apply, when combined with docetaxel.

https://www.ema.europa.eu/en/documents/product-information/docetaxel-accord-epar-product-information_en.pdf 31/07/2024

Other trade names: Docefrez, Docetaxel Kabi, Docetaxel Teva, Docetaxel Zentiva (previously Docetaxel Winthrop), Taxespira (previously Docetaxel Hospira UK Limited), Taxotere,

Docosanol

Breast-feeding, docosanol [2] ---> SmPC of [2] of eMC

No effects on the suckling child are anticipated since the systemic exposure of the breast-feeding woman to docosanol is negligible. Docosanol can be used during breast-feeding.

Docosanol [1], pregnancy ---> SmPC of [1] of eMC

Since systemic exposure to docosanol is negligible, docosanol can be used during pregnancy.

CONTRAINDICATIONS of Docosanol

- Hypersensitivity to the active substance "docosanol" or to any of the excipients.

http://www.medicines.org.uk/emc/

Dofetilide

Abemaciclib [1], dofetilide ---> SmPC of [1] of EMA

Abemaciclib and its major active metabolites inhibit the renal transporters OCT2, MATE1, and MATE2-K. In vivo interactions of abemaciclib with clinically relevant substrates of these transporters, such as dofetilide or creatinine, may occur

Abiraterone [1], dofetilide ---> SmPC of [1] of EMA

Amiloride, dofetilide

Caution should be taken when drugs that are actively secreted via this route are co-administered with dofetilide

Arsenic trioxide [1], dofetilide ---> SmPC of [1] of EMA

Caution is advised when arsenic trioxide is coadministered with other medicinal products known to cause QT/QTc interval prolongation

Azithromycin [1], dofetilide ---> SmPC of [1] of eMC

Azithromycin should be used with caution in patients currently receiving treatment with other active substances known to prolong QT interval

Azole antifungals, dofetilide [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the plasma concentrations of dofetilide. The co-administration is contraindicated

Bepridil, dofetilide [2] ---> SmPC of [2] of EMA

The co-administration of dofetilide with drugs known to prolong the QT interval is contraindicated

Breast-feeding, dofetilide [2] ---> SmPC of [2] of EMA

Mothers should discontinue breast-feeding

Carteolol, dofetilide

The co-administration increases the risk of heart rhythm disorders, particularly torsades de pointes

Ceritinib [1], dofetilide ---> SmPC of [1] of EMA

Chlorprothixene, dofetilide

The co-administration of chlorprothixene with medicinal products that prolong the interval QT is contraindicated

Cimetidine, dofetilide [2] ---> SmPC of [2] of EMA

The co-administration may increase the plasma levels of dofetilide. The combination is contraindicated

Cisapride, dofetilide [2] ---> SmPC of [2] of EMA

The co-administration of dofetilide with drugs known to prolong the QT interval is contraindicated

Class IA antiarrhythmic agents, dofetilide [2] ---> SmPC of [2] of EMA

The co-administration of dofetilide with drugs known to prolong the QT interval is contraindicated

Class III antiarrhythmic agents, dofetilide [2] ---> SmPC of [2] of EMA

The co-administration of dofetilide with drugs known to prolong the QT interval is contraindicated

Cotrimoxazole [1], dofetilide ---> SmPC of [1] of EMA

Drugs that inhibit the renal cation transport system (e. g. trimethoprim) are contraindicated with dofetilide

Crizotinib [1], dofetilide ---> SmPC of [1] of EMA

Concomitant use of crizotinib (prolongs QT interval) with medicinal products known to prolong QT interval or medicinal products able to induce Torsades de pointes should be carefully considered.

Degarelix [1], dofetilide ---> SmPC of [1] of EMA

The combination of degarelix with medicinal products known to prolong the QTc interval or medicinal products able to induce torsades de pointes should be carefully evaluated

Delamanid [1], dofetilide ---> SmPC of [1] of EMA

Dofetilide [1], erythromycin ---> SmPC of [1] of EMA

The co-administration of dofetilide with drugs known to prolong the QT interval is contraindicated

Dofetilide [1], ketoconazole ---> SmPC of [1] of EMA

The strong CYP3A4 inhibition may increase the plasma concentrations of dofetilide and prolong the QT interval. The co-administration is contraindicated

Dofetilide [1], macrolide antibiotics ---> SmPC of [1] of EMA

The strong CYP3A4 inhibition may increase the plasma concentrations of dofetilide. The co-administration is contraindicated

Dofetilide [1], megestrol ---> SmPC of [1] of EMA

Drugs that inhibit the renal cation transport system are contraindicated with dofetilide

Dofetilide [1], metformin ---> SmPC of [1] of EMA

Caution should be taken when drugs that are actively secreted via this route are co-administered with dofetilide

Dofetilide [1], OCT inhibitors ---> SmPC of [1] of EMA

Drugs that inhibit the renal cation transport system are contraindicated with dofetilide

Dofetilide [1], OCT2 inhibitors ---> SmPC of [1] of EMA

Drugs that inhibit the renal cation transport system are contraindicated with dofetilide

Dofetilide [1], pregnancy ---> SmPC of [1] of EMA

Should not be used in pregnant women unless clearly necessary

Dofetilide [1], prochlorperazine ---> SmPC of [1] of EMA

Drugs that inhibit the renal cation transport system are contraindicated with dofetilide

Dofetilide [1], protease inhibitors ---> SmPC of [1] of EMA

The strong CYP3A4 inhibition may increase the plasma concentrations of dofetilide. The co-administration is contraindicated

Dofetilide [1], QT interval prolonging drugs ---> SmPC of [1] of EMA

The co-administration of dofetilide with drugs known to prolong the QT interval is contraindicated

Dofetilide [1], ritonavir ---> SmPC of [1] of EMA

The strong CYP3A4 inhibition may increase the plasma concentrations of dofetilide. The co-administration is contraindicated

Dofetilide [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

The strong CYP3A4 inhibition may increase the plasma concentrations of dofetilide. The co-administration is contraindicated

Dofetilide [1], tricyclic antidepressant ---> SmPC of [1] of EMA

The co-administration of dofetilide with drugs known to prolong the QT interval is contraindicated

Dofetilide [1], trimethoprim ---> SmPC of [1] of EMA

Drugs that inhibit the renal cation transport system are contraindicated with dofetilide

Dofetilide [1], verapamil ---> SmPC of [1] of EMA

The co-administration may increase the plasma levels of dofetilide. The combination is contraindicated

Dofetilide, dolutegravir [2] ---> SmPC of [2] of EMA

Dolutegravir, OCT2 inhibitor, may increase the plasma levels of dofetilide. Dolutegravir and dofetilide co-administration is contraindicated due to potential life-threatening toxicity caused by high dofetilide concentration

Dofetilide, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

Dofetilide, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

Dofetilide, enzalutamide [2] ---> SmPC of [2] of EMA

The concomitant use of enzalutamide with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes should be carefully evaluated

Dofetilide, flupentixol

The co-administration of drugs that can prolong the QT interval should be avoided

Dofetilide, haloperidol [2] ---> SmPC of [2] of eMC

Dofetilide, hydrochlorothiazide ---> SmPC of [losartan/hydrochlorothiazide] of eMC

Periodic monitoring of serum potassium and ECG is recommended, when hydrochlorothiazide is administered with drugs which may induce torsades de pointes

Dofetilide, hydroquinidine

Concomitant use of hydroquinidine with drugs that can induce torsades de pointes is contraindicated due to increased risk of heart rhythm disorders (torsades de pointes)

Dofetilide, hypokalemia

Periodic monitoring of serum potassium is recommended, when dofetilide is administered with drugs which may cause hypokaliemia

Dofetilide, indapamide [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Dofetilide, itraconazol [2] ---> SmPC of [2] of eMC

The co-administration of itraconazole with CYP3A4 metabolised substrates that can prolong the QT-interval is contraindicated

Dofetilide, losartan/hydrochlorothiazide [2] ---> SmPC of [2] of eMC

Periodic monitoring of serum potassium and ECG is recommended when losartan/hydrochlorothiazide is administered with torsades de pointes-inducing medicinal products

Dofetilide, mequitazine

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Dofetilide, miconazole [2] ---> SmPC of [2] of eMC

Miconazole, strong CYP3A4 inhibitor, is contraindicated with medicines that are metabolised by CYP3A4 and also may prolong the QT interval

Dofetilide, moxifloxacin [2] ---> SmPC of [2] of eMC

Dofetilide, pasireotide [2] ---> SmPC of [2] of EMA

Pasireotide should be used with caution in patients who are concomitantly receiving medicinal products that prolong the QT interval

Dofetilide, piperaquine ---> SmPC of [piperaquine/artenimol] of EMA

The combination of piperaquine with drugs that are known to prolong the QTc interval is contraindicated: additive effect on the QTc interval

Dofetilide, piperaquine/artenimol [2] ---> SmPC of [2] of EMA

The combination of piperaquine/dihydroartemisinin with drugs that are known to prolong the QTc interval is contraindicated: additive effect on the QTc interval

Dofetilide, promazine

It is not recommended the combination of promazine with drugs that can prolong the QT-interval (increased risk of ventricular arrhythmias, incl. torsades de pointes)

Dofetilide, ranolazine [2] ---> SmPC of [2] of EMA

Concomitant administration of class III antiarrhythmics (other than amiodarone) with ranolazine is contraindicated

Dofetilide, roxithromycin

Caution is warranted for concomitant use of roxitromycin with other QT interval prolonging medicines

Dofetilide, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Dofetilide, sotalol [2] ---> SmPC of [2] of eMC

Dofetilide, telithromycin [2] ---> SmPC of [2] of EMA

Due to a potential to increase the QT interval, telithromycin should be used with care during concomitant administration with QT interval prolonging agents

Dofetilide, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Dofetilide, tiapride

Tiapride should not be combined with drugs that prolong the QT interval. These drugs (with the exception of anti-infectious) should be discontinued, if possible, if they induce torsades de pointes

Dofetilide, toremifene [2] ---> SmPC of [2] of EMA

Dofetilide, triamterene

Caution should be taken when drugs that are actively secreted via this route are co-administered with dofetilide

Dofetilide, tubular secretion

Caution should be taken when drugs that are actively secreted via this route are co-administered with dofetilide

Dofetilide, xipamide

The combination increases the risk of ventricular arrhythmias, particularly torsades de pointes (favored by hypokaliemia). It is recommended a special caution

Dofetilide, zuclopenthixol [2] ---> SmPC of [2] of eMC

The co-administration of zuclopenthixol with drugs that can prolong the QT interval should be avoided

CONTRAINDICATIONS of Dofetilide

Dofetilide is contraindicated in patients:

- with congenital or acquired long QT syndromes.

- with a known hypersensitivity to dofetilide or any of the excipients of the product.

- with baseline (pre-treatment) QTc greater than 440 msec (or 500 msec in patients with ventricular conduction abnormalities)

- with severe renal impairment (creatinine clearance <20 ml/min), including patients on dialysis

- with severe hepatic impairment

- with second or third degree AV block or sick sinus syndrome (unless a functioning pacemaker is in situ)

- with bradycardia (less than 50 bpm)

- with hypokalaemia

- under the age of 18

In addition, dofetilide is contraindicated in combination with the following medications:

- cimetidine

- verapamil

- ketoconazole

- QT prolonging drugs (including Class I and other Class III antiarrhythmic agents)

- drugs that inhibit the renal cation transport system (trimethoprim, megestrol and prochlorperazine)

- CYP3A4 inhibitors (e.g. azole antifungal agents, macrolide antibiotics and protease inhibitors)

EMA/H/C/000238. 313299en4.pdf.

Dolutegravir (Tivicay)

Ability to drive, dolutegravir [2] ---> SmPC of [2] of EMA

Patients should be informed that dizziness has been reported during treatment with dolutegravir.

Aluminium hydroxide, dolutegravir [2] ---> SmPC of [2] of EMA

Magnesium/ aluminium-containing antacid should be taken well separated in time from the administration of dolutegravir (minimum 2 hours after or 6 hours before).

Aluminium, dolutegravir [2] ---> SmPC of [2] of EMA

Magnesium/aluminium-containing antacid should be taken well separated in time from the administration of dolutegravir (minimum 2 hours after or 6 hours before).

Antacids, dolutegravir [2] ---> SmPC of [2] of EMA

Magnesium/aluminium-containing antacid should be taken well separated in time from the administration of dolutegravir (minimum 2 hours after or 6 hours before).

Atazanavir, dolutegravir [2] ---> SmPC of [2] of EMA

Increased dolutegravir plasma levels. No dosage adjustment necessary. (Inhibition of UGT1A1 and CYP3A enzymes)

Atazanavir/cobicistat [1], dolutegravir ---> SmPC of [1] of EMA

Co-administration with EVOTAZ is expected to increase dolutegravir plasma concentrations. The mechanism of interaction is inhibition of UGT1A1 by atazanavir. EVOTAZ and dolutegravir can be used without dose adjustments.

Atazanavir/ritonavir, dolutegravir [2] ---> SmPC of [2] of EMA

Increased dolutegravir plasma levels. No dosage adjustment necessary. (Inhibition of UGT1A1 and CYP3A enzymes)

Azole antifungals, dolutegravir [2] ---> SmPC of [2] of EMA

The inhibition of CYP3A4 may increase plasma levels of dolutegravir. No dose adjustment is necessary. Based on data from other CYP3A4 inhibitors, a marked increase is not expected.

BCRP inductors, dolutegravir [2] ---> SmPC of [2] of EMA

Medicinal products that induce those enzymes may decrease dolutegravir plasma concentration and reduce the therapeutic effect of dolutegravir

BCRP inhibitors, dolutegravir [2] ---> SmPC of [2] of EMA

Dolutegravir is eliminated mainly through metabolism by UGT1A1. Co-administration of dolutegravir and other medicinal products that inhibit these enzymes may increase dolutegravir plasma concentration

Boceprevir, dolutegravir [2] ---> SmPC of [2] of EMA

No dosage adjustment necessary.

Breast-feeding, dolutegravir [2] ---> SmPC of [2] of EMA

It is recommended that HIV infected women do not breast-feed their infants under any circumstances in order to avoid transmission of HIV.

Calcium, dolutegravir [2] ---> SmPC of [2] of EMA

Complex binding to polyvalent ions decreases dolutegravir exposition. Calcium supplements, iron supplements or multivitamins should be taken well separated in time from the administration of dolutegravir (minimum 2 hours after or 6 hours before).

Carbamazepine, dolutegravir [2] ---> SmPC of [2] of EMA

The CYP3A4 and UGT1A1 induction may decrease plasma levels of dolutegravir. Co-administration with this enzyme inducer should be avoided.

CYP2C9 substrates, dolutegravir [2] ---> SmPC of [2] of EMA

Based on in vivo and/or in vitro data, dolutegravir is not expected to affect the pharmacokinetics of medicinal products that are substrates of any major enzyme or transporter such as CYP3A4, CYP2C9 and P-gp

CYP3A4 substrates, dolutegravir [2] ---> SmPC of [2] of EMA

Daclatasvir [1], dolutegravir ---> SmPC of [1] of EMA

No dose adjustments required

Darunavir/cobicistat [1], dolutegravir ---> SmPC of [1] of EMA

Based on theoretical considerations dolutegravir is not expected to affect the pharmacokinetics of REZOLSTA. REZOLSTA and dolutegravir can be used without dose adjustments.

Darunavir/ritonavir, dolutegravir [2] ---> SmPC of [2] of EMA

No dosage adjustment necessary. (Induction of UGT1A1 and CYP3A enzymes)

Dofetilide, dolutegravir [2] ---> SmPC of [2] of EMA

Dolutegravir [1], efavirenz ---> SmPC of [1] of EMA

Efavirenz, UGT1A1 and CYP3A inductor, decreased dolutegravir plasma levels. In the presence of integrase class resistance alternative combinations that do not include efavirenz should be considered

Dolutegravir [1], ethinyl estradiol ---> SmPC of [1] of EMA

Dolutegravir had no pharmacodynamic effect on Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH) and progesterone. No dose adjustment of oral contraceptives is necessary when co-administered with dolutegravir.

Dolutegravir [1], etravirine ---> SmPC of [1] of EMA

Etravirine without boosted protease inhibitors decreased plasma dolutegravir concentration. Induction of UGT1A1 and CYP3A enzymes

Dolutegravir [1], fampridine ---> SmPC of [1] of EMA

Fampridine co-administration with dolutegravir is contraindicated.

Dolutegravir [1], fertility ---> SmPC of [1] of EMA

Women of childbearing potential (WOCBP) should be counselled about the potential risk of neural tube defects with dolutegravir (see below), including consideration of effective contraceptive measures.

Dolutegravir [1], fluconazole ---> SmPC of [1] of EMA

The inhibition of CYP3A4 may increase plasma levels of dolutegravir. No dose adjustment is necessary. Based on data from other CYP3A4 inhibitors, a marked increase is not expected.

Dolutegravir [1], foods ---> SmPC of [1] of EMA

Dolutegravir is recommended to be taken with food by patients infected with HIV with integrase class resistance

Dolutegravir [1], fosamprenavir/ritonavir ---> SmPC of [1] of EMA

The induction of UGT1A1 and CYP3A may decrease dolutegravir plasma levels. No dose adjustment is necessary in the absence of integrase class resistance. In the presence of resistance, alternative combinations should be considered.

Dolutegravir [1], iron ---> SmPC of [1] of EMA

Dolutegravir [1], itraconazol ---> SmPC of [1] of EMA

The inhibition of CYP3A4 may increase plasma levels of dolutegravir. No dose adjustment is necessary. Based on data from other CYP3A4 inhibitors, a marked increase is not expected.

Dolutegravir [1], ketoconazole ---> SmPC of [1] of EMA

The inhibition of CYP3A4 may increase plasma levels of dolutegravir. No dose adjustment is necessary. Based on data from other CYP3A4 inhibitors, a marked increase is not expected.

Dolutegravir [1], lopinavir/ritonavir ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Dolutegravir [1], magnesium ---> SmPC of [1] of EMA

Magnesium/aluminium-containing antacid should be taken well separated in time from the administration of dolutegravir (minimum 2 hours after or 6 hours before).

Dolutegravir [1], magnesium hydroxide ---> SmPC of [1] of EMA

Magnesium/ aluminium-containing antacid should be taken well separated in time from the administration of dolutegravir (minimum 2 hours after or 6 hours before).

Dolutegravir [1], MATE1 substrates ---> SmPC of [1] of EMA

Dolutegravir may increase plasma concentrations of medical products in which excretion is dependent upon MATE-1.

Dolutegravir [1], metformin ---> SmPC of [1] of EMA

Dolutegravir, OCT2 inhibitor, may increase plasma levels of metformin. A dose adjustment of metformin may be necessary.

Dolutegravir [1], methadone ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Dolutegravir [1], midazolam ---> SmPC of [1] of EMA

In vivo, dolutegravir did not have an effect on midazolam, a CYP3A4 probe.

Dolutegravir [1], nelfinavir ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Dolutegravir [1], nevirapine ---> SmPC of [1] of EMA

Nevirapine, enzymatic inductor, may decrease dolutegravir plasma levels. In the presence of integrase class resistance alternative combinations that do not include nevirapine should be considered

Dolutegravir [1], norgestimate ---> SmPC of [1] of EMA

Dolutegravir [1], OAT3 substrates ---> SmPC of [1] of EMA

Dolutegravir may increase plasma concentrations of medical products in which excretion is dependent upon OAT3.

Dolutegravir [1], OCT2 substrates ---> SmPC of [1] of EMA

Dolutegravir may increase plasma concentrations of medical products in which excretion is dependent upon OCT2.

Dolutegravir [1], oral contraceptives ---> SmPC of [1] of EMA

Dolutegravir [1], oxcarbamazepine ---> SmPC of [1] of EMA

Not studied, decrease expected due to induction of UGT1A1 and CYP3A enzymes, a similar reduction in exposure as observed with carbamazepine is expected

Dolutegravir [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

Dolutegravir [1], P-gp inductors ---> SmPC of [1] of EMA

Medicinal products that induce those enzymes may decrease dolutegravir plasma concentration and reduce the therapeutic effect of dolutegravir

Dolutegravir [1], P-gp inhibitors ---> SmPC of [1] of EMA

Dolutegravir [1], pharmacokinetics ---> SmPC of [1] of EMA

Dolutegravir [1], phenobarbital ---> SmPC of [1] of EMA

Not studied, decrease expected due to induction of UGT1A1 and CYP3A enzymes, a similar reduction in exposure as observed with carbamazepine is expected

Dolutegravir [1], phenytoin ---> SmPC of [1] of EMA

Not studied, decrease expected due to induction of UGT1A1 and CYP3A enzymes, a similar reduction in exposure as observed with carbamazepine is expected

Dolutegravir [1], posaconazole ---> SmPC of [1] of EMA

The inhibition of CYP3A4 may increase plasma levels of dolutegravir. No dose adjustment is necessary. Based on data from other CYP3A4 inhibitors, a marked increase is not expected.

Dolutegravir [1], prednisone ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Dolutegravir [1], pregnancy ---> SmPC of [1] of EMA

Dolutegravir should be used during pregnancy only if the expected benefit justifies the potential risk to the foetus.

Dolutegravir [1], rifabutin ---> SmPC of [1] of EMA

The induction of UGT1A1 and CYP3A may decrease the dolutegravir plasma levels. No dosage adjustment necessary.

Dolutegravir [1], rifampicin ---> SmPC of [1] of EMA

The induction of UGT1A1 and CYP3A may decrease the dolutegravir plasma levels. In the presence of integrase class resistance this combination should be avoided

Dolutegravir [1], rilpivirine ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Dolutegravir [1], St. John's wort ---> SmPC of [1] of EMA

Not studied, decrease expected due to induction of UGT1A1 and CYP3A enzymes, a similar reduction in exposure as observed with carbamazepine is expected

Dolutegravir [1], strong UGT1A1 inductors ---> SmPC of [1] of EMA

Dolutegravir is eliminated mainly through metabolism by UGT1A1. Medicinal products that induce this enzyme may decrease dolutegravir plasma concentration and reduce the therapeutic effect of dolutegravir

Dolutegravir [1], strong UGT1A1 inhibitors ---> SmPC of [1] of EMA

Dolutegravir [1], telaprevir ---> SmPC of [1] of EMA

No dosage adjustment necessary. (Inhibition of CYP3A enzymes)

Dolutegravir [1], tenofovir ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Dolutegravir [1], tipranavir/ritonavir ---> SmPC of [1] of EMA

The induction of UGT1A1 and CYP3A enzymes may decrease the dolutegravir plasma levels. In the presence of integrase class resistance this combination should be avoided

Dolutegravir [1], UGT1A1 inductors ---> SmPC of [1] of EMA

Dolutegravir [1], UGT1A1 inhibitors ---> SmPC of [1] of EMA

Dolutegravir [1], voriconazole ---> SmPC of [1] of EMA

The inhibition of CYP3A4 may increase plasma levels of dolutegravir. No dose adjustment is necessary. Based on data from other CYP3A4 inhibitors, a marked increase is not expected.

Dolutegravir, doravirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Dolutegravir, elbasvir/grazoprevir [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Dolutegravir, encorafenib [2] ---> SmPC of [2] of EMA

Concomitant agents that are substrates of UGT1A1 (e.g. raltegravir, atorvastatin, dolutegravir) may have increased exposure and should be therefore administered with caution.

Dolutegravir, ertugliflozin/metformin [2] ---> SmPC of [2] of EMA

Inhibitors of OCT2 may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration.

Dolutegravir, fosamprenavir/ritonavir ---> SmPC of [fosamprenavir] of EMA

No dosage adjustment of fosamprenavir or dolutegravir is recommended based on observed exposure-response relationships of clinical data.

Dolutegravir, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

No dosage adjustment necessary.

Dolutegravir, maribavir [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Dolutegravir, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Co-administration of metformin with inhibitors of OCT2 may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration;

Dolutegravir, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

No dose adjustment needed for dolutegravir when administered with Viekirax with or without dasabuvir.

Dolutegravir, simeprevir [2] ---> SmPC of [2] of EMA

Not studied. No clinically relevant drug-drug interaction is expected. No dose adjustment is required.

Dolutegravir, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

No dose adjustment of Epclusa or dolutegravir is required.

Dolutegravir, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

No dose adjustment of Vosevi or dolutegravir is required.

Dolutegravir, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No dose adjustment of Vemlidy or dolutegravir is required.

CONTRAINDICATIONS of Dolutegravir (Tivicay)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Medicinal products with narrow therapeutic windows that are substrates of organic cation transporter 2 (OCT2), including but not limited to fampridine (also known as dalfampridine; see section 4.5).

https://www.ema.europa.eu/es/documents/product-information/tivicay-epar-product-information_en.pdf 14/11/2025

Other trade names: Dovato,

Dolutegravir/abacavir/lamivudine (Triumeq)

Abacavir, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

Triumeq should not be taken with any other medicinal products containing dolutegravir, abacavir, lamivudine or emtricitabine.

Ability to drive, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

Patients should be informed that dizziness has been reported during treatment with dolutegravir.

Alcohol dehydrogenase inductors, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

The co-administration of inducers (e.g. rifampicin, carbamazepine and phenytoin) or inhibitors (e.g. valproic acid) of UGT enzymes or with compounds eliminated through alcohol dehydrogenase could alter abacavir exposure.

Alcohol dehydrogenase inhibitors, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

Co-administration of abacavir and inducers or inhibitors of UGT enzymes or with compounds eliminated through alcohol dehydrogenase could alter abacavir exposure.

Alcohol, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

Increase of the AUC of abacavir by inhibition of alcohol dehydrogenase. No dosage adjustment necessary.

Aluminium hydroxide, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

Magnesium/ aluminium-containing antacid should be taken well separated in time from the administration of dolutegravir (minimum 2 hours after or 6 hours before).

Aluminium, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

Magnesium/aluminium-containing antacid should be taken well separated in time from the administration of dolutegravir (minimum 2 hours after or 6 hours before).

Antacids, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

The absorption of dolutegravir is reduced by certain anti-acid medicinal products (see Table 1).

Atazanavir, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

Increased dolutegravir plasma levels. No dosage adjustment necessary. (Inhibition of UGT1A1 and CYP3A enzymes)

Atazanavir/ritonavir, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

No dosage adjustment necessary.

Boceprevir, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

No dosage adjustment necessary.

Breast-feeding, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

There are no data available on the safety of abacavir and lamivudine when administered to babies less than three months old.

Calcium, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

Carbamazepine, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

Cimetidine, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

No dosage adjustment necessary.

Cladribine, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

In vitro lamivudine inhibits the intracellular phosphorylation of cladribine leading to a potential risk of cladribine loss of efficacy in case of combination in the clinical setting. Concomitant use is not recommended

Cotrimoxazole/abacavir, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

The organic cation transporter inhibition may increase lamivudine exposition. No dolutegravir/abacavir/lamivudine dosage adjustment necessary, unless patient has renal impairment

Cotrimoxazole/lamivudine, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

The organic cation transporter inhibition may increase lamivudine exposition. No dolutegravir/abacavir/lamivudine dosage adjustment necessary, unless patient has renal impairment

Daclatasvir [1], dolutegravir/abacavir/lamivudine ---> SmPC of [1] of EMA

No dose adjustments required

Daclatasvir, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

Daclatasvir did not change dolutegravir plasma concentration to a clinically relevant extent. Dolutegravir did not change daclatasvir plasma concentration. No dose adjustment is necessary.

Darunavir/ritonavir, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

The induction of UGT1A1 and CYP3A may decrease dolutegravir plasma levels. No dose adjustment is necessary

Dofetilide, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

Dolutegravir, dolutegravir/abacavir/lamivudine [2] ---> SmPC of [2] of EMA

Triumeq should not be taken with any other medicinal products containing dolutegravir, abacavir, lamivudine or emtricitabine.

Dolutegravir/abacavir/lamivudine [1], efavirenz ---> SmPC of [1] of EMA

The recommended dose of dolutegravir is 50 mg twice daily when coadministered with efavirenz.

Dolutegravir/abacavir/lamivudine [1], emtricitabine ---> SmPC of [1] of EMA

Triumeq is not recommended for use in combination with emtricitabine containing products, since both lamivudine (in Triumeq) and emtricitabine are cytidine analogues (i.e. risk for intracellular interactions, (see section 4.4))

Dolutegravir/abacavir/lamivudine [1], ethinyl estradiol ---> SmPC of [1] of EMA

Dolutegravir/abacavir/lamivudine [1], etravirine ---> SmPC of [1] of EMA

Induction of UGT1A1 and CYP3A enzymes. Etravirine without boosted protease inhibitors decreased plasma dolutegravir concentration.

Dolutegravir/abacavir/lamivudine [1], fertility ---> SmPC of [1] of EMA

There are no data on the effects of dolutegravir, abacavir or lamivudine on human male or female fertility. Animal studies indicate no effects of dolutegravir, abacavir or lamivudine on male or female fertility (see section 5.3).

Dolutegravir/abacavir/lamivudine [1], fosamprenavir/ritonavir ---> SmPC of [1] of EMA

Fosamprenavir/ritonavir decreases dolutegravir concentrations, but based on limited data, did not result in decreased efficacy in Phase III studies. No dose adjustment is necessary.

Dolutegravir/abacavir/lamivudine [1], glucuronidation inductors ---> SmPC of [1] of EMA

Dolutegravir/abacavir/lamivudine [1], glucuronidation inhibitors ---> SmPC of [1] of EMA

Dolutegravir/abacavir/lamivudine [1], iron ---> SmPC of [1] of EMA

Dolutegravir/abacavir/lamivudine [1], isotretinoin ---> SmPC of [1] of EMA

Possible interaction due to common metabolic pathway through alcohol dehydrogenase (abacavir-component).

Dolutegravir/abacavir/lamivudine [1], lactitol ---> SmPC of [1] of EMA

When possible, avoid chronic coadministration of Triumeq with medicinal products containing sorbitol or other osmotic acting poly-alcohols or monosaccharide alcohols (eg: xylitol, mannitol, lactitol, maltitol).

Dolutegravir/abacavir/lamivudine [1], lamivudine ---> SmPC of [1] of EMA

Triumeq should not be taken with any other medicinal products containing dolutegravir, abacavir, lamivudine or emtricitabine.

Dolutegravir/abacavir/lamivudine [1], lopinavir/ritonavir ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Dolutegravir/abacavir/lamivudine [1], magnesium ---> SmPC of [1] of EMA

Magnesium/aluminium-containing antacid should be taken well separated in time from the administration of dolutegravir (minimum 2 hours after or 6 hours before).

Dolutegravir/abacavir/lamivudine [1], magnesium hydroxide ---> SmPC of [1] of EMA

Magnesium/ aluminium-containing antacid should be taken well separated in time from the administration of dolutegravir (minimum 2 hours after or 6 hours before).

Dolutegravir/abacavir/lamivudine [1], mannitol ---> SmPC of [1] of EMA

Dolutegravir/abacavir/lamivudine [1], MATE1 inhibitors ---> SmPC of [1] of EMA

Co-administration of lamivudine with MATE1 inhibitors could increase lamivudine exposure.

Dolutegravir/abacavir/lamivudine [1], MATE1 substrates ---> SmPC of [1] of EMA

Dolutegravir may increase plasma concentrations of medicinal products in which excretion is dependent upon MATE-1

Dolutegravir/abacavir/lamivudine [1], metformin ---> SmPC of [1] of EMA

Dolutegravir, OCT2 inhibitor, may increase plasma levels of metformin. A dose adjustment of metformin may be necessary.

Dolutegravir/abacavir/lamivudine [1], methadone ---> SmPC of [1] of EMA

Methadone dosage adjustment likely not needed in majority of patients; occasionally methadone re-titration may be required.

Dolutegravir/abacavir/lamivudine [1], midazolam ---> SmPC of [1] of EMA

Dolutegravir/abacavir/lamivudine [1], mitochondrial dysfunction ---> SmPC of [1] of EMA

Nucleoside and nucleotide analogues have been demonstrated in vitro and in vivo to cause a variable degree of mitochondrial damage.

Dolutegravir/abacavir/lamivudine [1], nelfinavir ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Dolutegravir/abacavir/lamivudine [1], nevirapine ---> SmPC of [1] of EMA

Co-administration with nevirapine may decrease dolutegravir plasma concentration due to enzyme induction and has not been studied.

Dolutegravir/abacavir/lamivudine [1], norgestimate ---> SmPC of [1] of EMA

Dolutegravir/abacavir/lamivudine [1], OAT3 substrates ---> SmPC of [1] of EMA

Dolutegravir may increase plasma concentrations of medical products in which excretion is dependent upon OAT3.

Dolutegravir/abacavir/lamivudine [1], OCT inhibitors ---> SmPC of [1] of EMA

Co-administration of lamivudine with OCT inhibitors could increase lamivudine exposure.

Dolutegravir/abacavir/lamivudine [1], OCT2 substrates ---> SmPC of [1] of EMA

Dolutegravir may increase plasma concentrations of medicinal products in which excretion is dependent upon OCT2

Dolutegravir/abacavir/lamivudine [1], oral contraceptives ---> SmPC of [1] of EMA

Dolutegravir/abacavir/lamivudine [1], oxcarbamazepine ---> SmPC of [1] of EMA

The CYP3A4 and UGT1A1 induction may decrease plasma levels of dolutegravir. Co-administration with this enzyme inducer should be avoided.

Dolutegravir/abacavir/lamivudine [1], phenobarbital ---> SmPC of [1] of EMA

The CYP3A4 and UGT1A1 induction may decrease plasma levels of dolutegravir. Co-administration with this enzyme inducer should be avoided.

Dolutegravir/abacavir/lamivudine [1], phenytoin ---> SmPC of [1] of EMA

Dolutegravir/abacavir/lamivudine [1], polyvalent cations ---> SmPC of [1] of EMA

Triumeq should not be co-administered with polyvalent cation-containing antacids. Triumeq is recommended to be administered 2 hours before or 6 hours after these agents

Dolutegravir/abacavir/lamivudine [1], prednisone ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Dolutegravir/abacavir/lamivudine [1], pregnancy ---> SmPC of [1] of EMA

Triumeq may be used during the second and third trimester of pregnancy when the expected benefit justifies the potential risk to the foetus.

Dolutegravir/abacavir/lamivudine [1], ranitidine ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Dolutegravir/abacavir/lamivudine [1], retinoids ---> SmPC of [1] of EMA

Possible interaction due to common metabolic pathway through alcohol dehydrogenase (abacavir-component).

Dolutegravir/abacavir/lamivudine [1], reverse transcriptase inhibitors ---> SmPC of [1] of EMA

No dose adjustment is necessary when Triumeq is combined with nucleoside reverse transcript inhibitors.

Dolutegravir/abacavir/lamivudine [1], ribavirin/abacavir ---> SmPC of [1] of EMA

Both drugs are guanosine analogues, and there is a potential to reduce intracellular phosphorylated metabolites. Caution should be exercised when both drugs are co-administered

Dolutegravir/abacavir/lamivudine [1], rifabutin ---> SmPC of [1] of EMA

The induction of UGT1A1 and CYP3A may decrease the dolutegravir plasma levels. No dosage adjustment necessary.

Dolutegravir/abacavir/lamivudine [1], rifampicin ---> SmPC of [1] of EMA

Dolutegravir/abacavir/lamivudine [1], rilpivirine ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Dolutegravir/abacavir/lamivudine [1], riociguat ---> SmPC of [1] of EMA

Riociguat dose may need to be reduced, consult the riociguat prescribing information for dosing recommendations.

Dolutegravir/abacavir/lamivudine [1], sorbitol ---> SmPC of [1] of EMA

Dolutegravir/abacavir/lamivudine [1], St. John's wort ---> SmPC of [1] of EMA

The strong CYP3A4 and UGT1A1 induction may decrease plasma levels of dolutegravir. Co-administration with St. John's wort is discouraged.

Dolutegravir/abacavir/lamivudine [1], strong BCRP inhibitors ---> SmPC of [1] of EMA

Co-administration of dolutegravir/abacavir/lamivudine and other drugs that inhibit BCRP may increase dolutegravir plasma concentration.

Dolutegravir/abacavir/lamivudine [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Co-administration of dolutegravir/abacavir/lamivudine and other drugs that inhibit CYP3A4 may increase dolutegravir plasma concentration.

Dolutegravir/abacavir/lamivudine [1], strong P-gp inductors ---> SmPC of [1] of EMA

Co-administration of dolutegravir/abacavir/lamivudine and other drugs that induce P-gp may decrease dolutegravir plasma concentration and reduce the therapeutic effect of dolutegravir

Dolutegravir/abacavir/lamivudine [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

Co-administration of dolutegravir/abacavir/lamivudine and other drugs that inhibit P-gp may increase dolutegravir plasma concentration.

Dolutegravir/abacavir/lamivudine [1], strong UGT1A1 inductors ---> SmPC of [1] of EMA

Co-administration of dolutegravir/abacavir/lamivudine and other drugs that induce UGT1A1 may decrease dolutegravir plasma concentration and reduce the therapeutic effect of dolutegravir

Dolutegravir/abacavir/lamivudine [1], strong UGT1A1 inhibitors ---> SmPC of [1] of EMA

Co-administration of dolutegravir/abacavir/lamivudine and other drugs that inhibit UGT1A1 may increase dolutegravir plasma concentration.

Dolutegravir/abacavir/lamivudine [1], strong UGT1A3 inhibitors ---> SmPC of [1] of EMA

Co-administration of dolutegravir/abacavir/lamivudine and other drugs that inhibit UGT1A3 may increase dolutegravir plasma concentration.

Dolutegravir/abacavir/lamivudine [1], strong UGT1A9 inhibitors ---> SmPC of [1] of EMA

Co-administration of dolutegravir/abacavir/lamivudine and other drugs that inhibit UGT1A9 may increase dolutegravir plasma concentration.

Dolutegravir/abacavir/lamivudine [1], telaprevir ---> SmPC of [1] of EMA

No dosage adjustment necessary. (Inhibition of CYP3A enzymes)

Dolutegravir/abacavir/lamivudine [1], tenofovir ---> SmPC of [1] of EMA

No dose adjustment is necessary when Triumeq is combined with nucleoside reverse transcript inhibitors.

Dolutegravir/abacavir/lamivudine [1], tipranavir/ritonavir ---> SmPC of [1] of EMA

The induction of UGT1A1 and CYP3A enzymes may decrease the dolutegravir plasma levels. The co-administration of tipranavir/ritonavir with dolutegravir/abacavir/lamivudine is not recommended.

Dolutegravir/abacavir/lamivudine [1], trimethoprim ---> SmPC of [1] of EMA

Trimethoprim (an inhibitor of these drug transporters) has been shown to increase lamivudine plasma concentrations, however the resulting increase was not clinically significant (see Table 1).

Dolutegravir/abacavir/lamivudine [1], valproic acid ---> SmPC of [1] of EMA

Dolutegravir/abacavir/lamivudine [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should be counselled about the potential risk of neural tube defects with dolutegravir (a component of Triumeq, see below), including consideration of effective contraceptive measures.

Dolutegravir/abacavir/lamivudine [1], xylitol ---> SmPC of [1] of EMA

Mitochondrial dysfunction, nucleoside analogues ---> SmPC of [dolutegravir/abacavir/lamivudine] of EMA

Nucleoside and nucleotide analogues have been demonstrated to cause a variable degree of mitochondrial damage. There have been reports of mitochondrial dysfunction in HIV-negative infants exposed in utero and/or post-natally to nucleoside analogues

Mitochondrial dysfunction, nucleotide analogues ---> SmPC of [dolutegravir/abacavir/lamivudine] of EMA

CONTRAINDICATIONS of Dolutegravir/abacavir/lamivudine (Triumeq)

- Hypersensitivity to dolutegravir, abacavir or lamivudine or to any of the excipients listed in section 6.1.

- Co-administration with medicinal products with narrow therapeutic windows, that are substrates of organic cation transporter (OCT) 2, including but not limited to fampridine (also known as dalfampridine; see section 4.5).

https://www.ema.europa.eu/en/documents/product-information/triumeq-epar-product-information_en.pdf 26/01/2026

Dolutegravir/lamivudine

Ability to drive, dolutegravir/lamivudine [2] ---> SmPC of [2] of EMA

Patients should be informed that dizziness and somnolence has been reported during treatment with dolutegravir.

Aluminium hydroxide, dolutegravir/lamivudine [2] ---> SmPC of [2] of EMA

Magnesium/ aluminium-containing antacids should be taken well separated in time from the administration of Dovato (minimum 2 hours after or 6 hours before).

Aluminium, dolutegravir/lamivudine [2] ---> SmPC of [2] of EMA

Magnesium/ aluminium-containing antacids should be taken well separated in time from the administration of Dovato (minimum 2 hours after or 6 hours before).

Antacids, dolutegravir/lamivudine [2] ---> SmPC of [2] of EMA

If Dovato is administered under fasting conditions, supplements or multivitamins containing calcium, iron or magnesium are recommended to be taken 2 hours after or 6 hours before Dovato

Antacids, dolutegravir/lamivudine [2] ---> SmPC of [2] of EMA

Dovato should not be co-administered with polyvalent cation-containing antacids. Polyvalent cation-containing antacids are recommended to be taken 2 hours after or 6 hours before Dovato

Atazanavir, dolutegravir/lamivudine [2] ---> SmPC of [2] of EMA

No dose adjustment is necessary.

Atazanavir/ritonavir, dolutegravir/lamivudine [2] ---> SmPC of [2] of EMA

No dose adjustment is necessary.

Boceprevir, dolutegravir/lamivudine [2] ---> SmPC of [2] of EMA

No dose adjustment is necessary.

Breast-feeding, dolutegravir/lamivudine [2] ---> SmPC of [2] of EMA

It is recommended that HIV infected women do not breast-feed their infants under any circumstances in order to avoid transmission of HIV.

Carbamazepine, dolutegravir/lamivudine [2] ---> SmPC of [2] of EMA

As Dovato is a fixed-dose tablet, an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato for the duration of the co-administration with these metabolic inducers. Induction of UGT1A1 and CYP3A

Cimetidine, dolutegravir/lamivudine [2] ---> SmPC of [2] of EMA

No dose adjustment is necessary.

Cladribine, dolutegravir/lamivudine [2] ---> SmPC of [2] of EMA

Concomitant use of Dovato with cladribine is not recommended. In vitro lamivudine inhibits the intracellular phosphorylation of cladribine leading to a potential risk of cladribine loss of efficacy in case of combination in the clinical setting.

Cotrimoxazole, dolutegravir/lamivudine [2] ---> SmPC of [2] of EMA

No dose adjustment is necessary.

CYP3A4 inductors, dolutegravir/lamivudine [2] ---> SmPC of [2] of EMA

Medicinal products that induce this enzyme or transporter may decrease dolutegravir plasma concentration and reduce the therapeutic effect of dolutegravir.

CYP3A4 inhibitors, dolutegravir/lamivudine [2] ---> SmPC of [2] of EMA

Co-administration of Dovato and other medicinal products that inhibit UGT1A1, UGT1A3, UGT1A9, CYP3A4, and/or P-gp may, therefore, increase dolutegravir plasma concentration.

Daclatasvir, dolutegravir/lamivudine [2] ---> SmPC of [2] of EMA

No dose adjustment is necessary.

Darunavir/ritonavir [1], dolutegravir/lamivudine ---> SmPC of [1] of EMA

No dose adjustment is necessary.

Didanosine, dolutegravir/lamivudine [2] ---> SmPC of [2] of EMA

No dose adjustment is necessary when Dovato is combined with tenofovir, didanosine, stavudine or zidovudine.

Dolutegravir, dolutegravir/lamivudine [2] ---> SmPC of [2] of EMA

Dovato should not be taken with any other medicinal product containing dolutegravir or lamivudine, except where a dose adjustment of dolutegravir is indicated due to drug-drug interactions

Dolutegravir/lamivudine [1], efavirenz ---> SmPC of [1] of EMA

As Dovato is a fixed-dose tablet, an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato for the duration of the efavirenz co-administration. Induction of UGT1A1 and CYP3A enzymes

Dolutegravir/lamivudine [1], emtricitabine ---> SmPC of [1] of EMA

Dovato is not recommended for use in combination with emtricitabine containing products, since both lamivudine (in Dovato) and emtricitabine are cytidine analogues (i.e. risk for intracellular interactions)

Dolutegravir/lamivudine [1], etravirine ---> SmPC of [1] of EMA

Etravirine without boosted protease inhibitors decreased plasma dolutegravir concentration. Induction of UGT1A1 and CYP3A enzymes

Dolutegravir/lamivudine [1], fosamprenavir/ritonavir ---> SmPC of [1] of EMA

Fosamprenavir/ritonavir decreases dolutegravir concentrations, but based on limited data, did not result in decreased efficacy in Phase III studies. No dose adjustment is necessary. Induction of UGT1A1 and CYP3A enzymes

Dolutegravir/lamivudine [1], H2 antagonists ---> SmPC of [1] of EMA

No dose adjustment is necessary.

Dolutegravir/lamivudine [1], lactitol ---> SmPC of [1] of EMA

When possible, avoid chronic coadministration of Dovato with medicinal products containing sorbitol or other osmotic acting poly-alcohols or monosaccharide alcohols (eg: xylitol, mannitol, lactitol, maltitol).

Dolutegravir/lamivudine [1], lamivudine ---> SmPC of [1] of EMA

Dovato should not be taken with any other medicinal product containing dolutegravir or lamivudine, except where a dose adjustment of dolutegravir is indicated due to drug-drug interactions

Dolutegravir/lamivudine [1], ledipasvir/sofosbuvir ---> SmPC of [1] of EMA

No dose adjustment is necessary.

Dolutegravir/lamivudine [1], lopinavir/ritonavir ---> SmPC of [1] of EMA

No dose adjustment is necessary.

Dolutegravir/lamivudine [1], magnesium ---> SmPC of [1] of EMA

Magnesium/ aluminium-containing antacids should be taken well separated in time from the administration of Dovato (minimum 2 hours after or 6 hours before).

Dolutegravir/lamivudine [1], magnesium hydroxide ---> SmPC of [1] of EMA

Magnesium/ aluminium-containing antacids should be taken well separated in time from the administration of Dovato (minimum 2 hours after or 6 hours before).

Dolutegravir/lamivudine [1], maltitol ---> SmPC of [1] of EMA

Dolutegravir/lamivudine [1], mannitol ---> SmPC of [1] of EMA

Dolutegravir/lamivudine [1], metformin ---> SmPC of [1] of EMA

Dolutegravir increased metformin concentrations. A dose adjustment of metformin should be considered when starting and stopping coadministration of Dovato with metformin, to maintain glycaemic control

Dolutegravir/lamivudine [1], metformin ---> SmPC of [1] of EMA

Metformin is eliminated renally and, therefore, it is of importance to monitor renal function when co-treated with Dovato.

Dolutegravir/lamivudine [1], nevirapine ---> SmPC of [1] of EMA

As Dovato is a fixed-dose tablet, an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato for the duration of the nevirapine co-administration. Induction of UGT1A1 and CYP3A enzymes

Dolutegravir/lamivudine [1], oral contraceptives ---> SmPC of [1] of EMA

No dose adjustment of oral contraceptives is necessary when co-administered with Dovato.

Dolutegravir/lamivudine [1], oxcarbazepine ---> SmPC of [1] of EMA

Dolutegravir/lamivudine [1], P-gp inductors ---> SmPC of [1] of EMA

Medicinal products that induce this enzyme or transporter may decrease dolutegravir plasma concentration and reduce the therapeutic effect of dolutegravir.

Dolutegravir/lamivudine [1], P-gp inhibitors ---> SmPC of [1] of EMA

Co-administration of Dovato and other medicinal products that inhibit UGT1A1, UGT1A3, UGT1A9, CYP3A4, and/or P-gp may, therefore, increase dolutegravir plasma concentration.

Dolutegravir/lamivudine [1], phenobarbital ---> SmPC of [1] of EMA

Dolutegravir/lamivudine [1], phenytoin ---> SmPC of [1] of EMA

Dolutegravir/lamivudine [1], prednisone ---> SmPC of [1] of EMA

No dose adjustment is necessary.

Dolutegravir/lamivudine [1], pregnancy ---> SmPC of [1] of EMA

Dovato should be used during pregnancy only if the expected benefit justifies the potential risk to the foetus.

Dolutegravir/lamivudine [1], ranitidine ---> SmPC of [1] of EMA

No dose adjustment is necessary.

Dolutegravir/lamivudine [1], ribavirin ---> SmPC of [1] of EMA

No dose adjustment is necessary.

Dolutegravir/lamivudine [1], rifabutin ---> SmPC of [1] of EMA

No dose adjustment is necessary.

Dolutegravir/lamivudine [1], rifampicin ---> SmPC of [1] of EMA

As Dovato is a fixed-dose tablet, an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato for the duration of the rifampicin co-administration. Induction of UGT1A1 and CYP3A enzymes

Dolutegravir/lamivudine [1], rilpivirine ---> SmPC of [1] of EMA

No dose adjustment is required.

Dolutegravir/lamivudine [1], sofosbuvir/velpatasvir ---> SmPC of [1] of EMA

No dose adjustment is necessary.

Dolutegravir/lamivudine [1], sorbitol ---> SmPC of [1] of EMA

Dolutegravir/lamivudine [1], St. John's wort ---> SmPC of [1] of EMA

As Dovato is a fixed-dose tablet, an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato for the duration of the St. John's wort co-administration. Induction of UGT1A1 and CYP3A enzymes

Dolutegravir/lamivudine [1], stavudine ---> SmPC of [1] of EMA

No dose adjustment is necessary when Dovato is combined with tenofovir, didanosine, stavudine or zidovudine.

Dolutegravir/lamivudine [1], tenofovir ---> SmPC of [1] of EMA

No dose adjustment is necessary when Dovato is combined with tenofovir, didanosine, stavudine or zidovudine.

Dolutegravir/lamivudine [1], tipranavir/ritonavir ---> SmPC of [1] of EMA

As Dovato is a fixed-dose tablet, an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato for the duration of the tipranavir/ritonavir co-administration. Induction of UGT1A1 and CYP3A enzymes

Dolutegravir/lamivudine [1], UGT1A1 inductors ---> SmPC of [1] of EMA

Medicinal products that induce this enzyme or transporter may decrease dolutegravir plasma concentration and reduce the therapeutic effect of dolutegravir.

Dolutegravir/lamivudine [1], UGT1A1 inhibitors ---> SmPC of [1] of EMA

Co-administration of Dovato and other medicinal products that inhibit UGT1A1, UGT1A3, UGT1A9, CYP3A4, and/or P-gp may, therefore, increase dolutegravir plasma concentration.

Dolutegravir/lamivudine [1], UGT1A3 inductors ---> SmPC of [1] of EMA

Medicinal products that induce this enzyme or transporter may decrease dolutegravir plasma concentration and reduce the therapeutic effect of dolutegravir.

Dolutegravir/lamivudine [1], UGT1A3 inhibitors ---> SmPC of [1] of EMA

Co-administration of Dovato and other medicinal products that inhibit UGT1A1, UGT1A3, UGT1A9, CYP3A4, and/or P-gp may, therefore, increase dolutegravir plasma concentration.

Dolutegravir/lamivudine [1], UGT1A9 inductors ---> SmPC of [1] of EMA

Medicinal products that induce this enzyme or transporter may decrease dolutegravir plasma concentration and reduce the therapeutic effect of dolutegravir.

Dolutegravir/lamivudine [1], UGT1A9 inhibitors ---> SmPC of [1] of EMA

Co-administration of Dovato and other medicinal products that inhibit UGT1A1, UGT1A3, UGT1A9, CYP3A4, and/or P-gp may, therefore, increase dolutegravir plasma concentration.

Dolutegravir/lamivudine [1], xylitol ---> SmPC of [1] of EMA

Dolutegravir/lamivudine [1], zidovudine ---> SmPC of [1] of EMA

No dose adjustment is necessary when Dovato is combined with tenofovir, didanosine, stavudine or zidovudine.

Lamivudine, OCT inhibitors [2] ---> SmPC of [2] of EMA

Lamivudine is cleared renally. Active renal secretion of lamivudine in the urine is mediated through organic cation transporters (OCTs); co-administration of lamivudine with OCT inhibitors may increase lamivudine exposure.

CONTRAINDICATIONS of Dolutegravir/lamivudine

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/dovato-epar-product-information_en.pdf. 04/09/2019

Dolutegravir/rilpivirine (Juluca)

Ability to drive, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

Patients should be informed that fatigue, dizziness and somnolence have been reported during treatment with the components of Juluca.

Aluminium hydroxide, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

The combination of Juluca and antacids should be used with particular caution. Antacids should be taken well separated in time from the administration of Juluca (minimum 6 hours before or 4 hours after).

Antacids, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

Juluca should not be co-administered at the same time as antacids. These medicinal products are recommended to be administered 6 hours before or 4 hours after Juluca

Antiretrovirals, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

Juluca is intended for use as a complete regimen for the treatment of HIV-1 infection and should not be administered with other antiretroviral medicinal products for the treatment of HIV.

Artemether/lumefantrine, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

Decreased exposure of rilpivirine is expected (induction of CYP3A enzymes). The combination of Juluca and artemether/lumefantrine should be used with caution.

Atorvastatin, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Atovaquone/proguanil, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

BCRP inductors, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

Medicinal products that induce those enzymes may decrease dolutegravir plasma concentration and reduce the therapeutic effect of dolutegravir

BCRP inhibitors, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

Boceprevir, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Breast-feeding, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

There is insufficient information on the effects of dolutegravir in newborns/infants. It is recommended that women living with HIV do not breast-feed their infants in order to avoid transmission of HIV.

Calcium carbonate, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

Calcium supplements, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

Calcium supplements should be co-administered at the same time as Juluca, with a meal. If calcium supplements cannot be taken at the same time as Juluca, these supplements are recommended to be administered 6 hours before or 4 hours after taking Juluca

Carbamazepine, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

Metabolic inducers may significantly decrease dolutegravir/rilpivirine plasma concentrations, resulting in loss of therapeutic effect. Co-administration of Juluca with these metabolic inducers is contraindicated

Cimetidine, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

Only H2-receptor antagonists that can be dosed once daily should be used. H2-receptor antagonists should be taken well separated in time from the administration of Juluca (minimum 4 hours after or 12 hours before)

Clarithromycin, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

Increased exposure of rilpivirine is expected (inhibition of CYP3A enzymes). Where possible, alternatives such as azithromycin should be considered.

Dabigatran etexilate, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

A risk for increases in dabigatran plasma concentrations cannot be excluded. The combination of Juluca and dabigatran etexilate should be used with caution.

Daclatasvir, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Dexamethasone, dolutegravir/rilpivirine ---> SmPC of [rilpivirine] of EMA

The CYP3A4 induction by dexamethasone may decrease the plasma concentrations and the therapeutic effect of rilpivirine. Contra-indicated (except as a single dose)

Digoxin, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Dofetilide, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

Dolutegravir, dolutegravir/rilpivirine [2] ---> SmPC of [2] of EMA

Juluca should not be taken with any other medicinal product containing dolutegravir or rilpivirine, except in case of co-administration with rifabutin

Dolutegravir/rilpivirine [1], entecavir ---> SmPC of [1] of EMA

No dose adjustment is required.

Dolutegravir/rilpivirine [1], erythromycin ---> SmPC of [1] of EMA

Increased exposure of rilpivirine is expected (inhibition of CYP3A enzymes). Where possible, alternatives such as azithromycin should be considered.

Dolutegravir/rilpivirine [1], esomeprazole ---> SmPC of [1] of EMA

Co-administration may significantly decrease rilpivirine plasma concentration. This may result in loss of therapeutic effect of Juluca. Co-administration of Juluca with proton pump inhibitors is contraindicated

Dolutegravir/rilpivirine [1], famotidine ---> SmPC of [1] of EMA

Dolutegravir/rilpivirine [1], fampridine ---> SmPC of [1] of EMA

Co-administration of dolutegravir has the potential to cause seizures due to increased fampridine plasma concentration via inhibition of OCT2 transporter. Fampridine co-administration with dolutegravir/rilpivirine is contraindicated (see section 4.3).

Dolutegravir/rilpivirine [1], fertility ---> SmPC of [1] of EMA

There are no data on the effects of dolutegravir or rilpivirine on human male or female fertility. Animal studies indicate no clinically relevant effects on male or female fertility (see section 5.3).

Dolutegravir/rilpivirine [1], fluconazole ---> SmPC of [1] of EMA

May cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes). No dose adjustment is required.

Dolutegravir/rilpivirine [1], gastric pH increasing medication ---> SmPC of [1] of EMA

Co-administration of Juluca with medicinal products that increase gastric pH may result in decreased plasma concentrations of rilpivirine which could potentially reduce the therapeutic effect of Juluca.

Dolutegravir/rilpivirine [1], H2 antagonists ---> SmPC of [1] of EMA

Juluca should not be co-administered at the same time as H2-receptor antagonists. These medicinal products are recommended to be administered 12 hours before or 4 hours after Juluca.

Dolutegravir/rilpivirine [1], iron supplements ---> SmPC of [1] of EMA

Iron supplements should be co-administered at the same time as Juluca, with a meal. If iron supplements cannot be taken at the same time as Juluca, these supplements are recommended to be administered 6 hours before or 4 hours after taking Juluca

Dolutegravir/rilpivirine [1], isavuconazole ---> SmPC of [1] of EMA

May cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes). No dose adjustment is required.

Dolutegravir/rilpivirine [1], itraconazol ---> SmPC of [1] of EMA

May cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes). No dose adjustment is required.

Dolutegravir/rilpivirine [1], ketoconazole ---> SmPC of [1] of EMA

Induction of CYP3A due to high rilpivirine dose in the study. No dose adjustment is required.

Dolutegravir/rilpivirine [1], lamivudine ---> SmPC of [1] of EMA

No dose adjustment is required.

Dolutegravir/rilpivirine [1], lansoprazole ---> SmPC of [1] of EMA

Dolutegravir/rilpivirine [1], ledipasvir/sofosbuvir ---> SmPC of [1] of EMA

No dose adjustment is required.

Dolutegravir/rilpivirine [1], macrolide antibiotics ---> SmPC of [1] of EMA

Increased exposure of rilpivirine is expected (inhibition of CYP3A enzymes). Where possible, alternatives such as azithromycin should be considered.

Dolutegravir/rilpivirine [1], magnesium hydroxide ---> SmPC of [1] of EMA

Dolutegravir/rilpivirine [1], MATE1 substrates ---> SmPC of [1] of EMA

Dolutegravir may increase plasma concentrations of medical products in which excretion is dependent upon MATE-1.

Dolutegravir/rilpivirine [1], meal ---> SmPC of [1] of EMA

Juluca must be taken with a meal

Dolutegravir/rilpivirine [1], metformin ---> SmPC of [1] of EMA

Dolutegravir increased metformin concentrations. A dose adjustment of metformin should be considered when starting and stopping co-administration of Juluca with metformin, to maintain glycaemic control

Dolutegravir/rilpivirine [1], methadone ---> SmPC of [1] of EMA

No dose adjustments are required when initiating co-administration of methadone with Juluca. However, clinical monitoring is recommended as methadone maintenance therapy may need to be adjusted in some patients.

Dolutegravir/rilpivirine [1], multivitamin supplements ---> SmPC of [1] of EMA

Multivitamins should be co-administered at the same time as Juluca, with a meal. If cannot be taken at the same time as Juluca, these supplements are recommended to be administered 6 hours before or 4 hours after taking Juluca

Dolutegravir/rilpivirine [1], nizatidine ---> SmPC of [1] of EMA

Dolutegravir/rilpivirine [1], OAT3 substrates ---> SmPC of [1] of EMA

Dolutegravir may increase plasma concentrations of medical products in which excretion is dependent upon OAT3.

Dolutegravir/rilpivirine [1], OCT2 substrates ---> SmPC of [1] of EMA

Dolutegravir may increase plasma concentrations of medical products in which excretion is dependent upon OCT2.

Dolutegravir/rilpivirine [1], omeprazole ---> SmPC of [1] of EMA

Dolutegravir/rilpivirine [1], oral contraceptives ---> SmPC of [1] of EMA

No dose adjustment of oral contraceptives is required when co-administered with Juluca.

Dolutegravir/rilpivirine [1], oxcarbazepine ---> SmPC of [1] of EMA

Dolutegravir/rilpivirine [1], P-gp inductors ---> SmPC of [1] of EMA

Medicinal products that induce those enzymes may decrease dolutegravir plasma concentration and reduce the therapeutic effect of dolutegravir

Dolutegravir/rilpivirine [1], P-gp inhibitors ---> SmPC of [1] of EMA

Dolutegravir/rilpivirine [1], pantoprazole ---> SmPC of [1] of EMA

Dolutegravir/rilpivirine [1], paracetamol ---> SmPC of [1] of EMA

No dose adjustment is required.

Dolutegravir/rilpivirine [1], phenobarbital ---> SmPC of [1] of EMA

Dolutegravir/rilpivirine [1], phenytoin ---> SmPC of [1] of EMA

Dolutegravir/rilpivirine [1], posaconazole ---> SmPC of [1] of EMA

May cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes). No dose adjustment is required.

Dolutegravir/rilpivirine [1], prednisone ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Dolutegravir/rilpivirine [1], pregnancy ---> SmPC of [1] of EMA

Lower exposures of dolutegravir or rilpivirine were observed when taken once daily, in combination with a background regimen, during pregnancy. Therefore, use of Juluca during pregnancy is not recommended

Dolutegravir/rilpivirine [1], proton pump inhibitors ---> SmPC of [1] of EMA

Dolutegravir/rilpivirine [1], rabeprazole ---> SmPC of [1] of EMA

Dolutegravir/rilpivirine [1], ranitidine ---> SmPC of [1] of EMA

Dolutegravir/rilpivirine [1], ribavirin ---> SmPC of [1] of EMA

No dose adjustment is required.

Dolutegravir/rilpivirine [1], rifampicin ---> SmPC of [1] of EMA

Co-administration may cause significant decreases in rilpivirine plasma concentrations. This may result in loss of therapeutic effect of Juluca. Co-administration of Juluca with rifampicin is contraindicated

Dolutegravir/rilpivirine [1], rifapentine ---> SmPC of [1] of EMA

Co-administration may cause significant decreases in rilpivirine plasma concentrations. This may result in loss of therapeutic effect of Juluca (induction of CYP3A enzymes). Co-administration of Juluca with rifapentine is contraindicated

Dolutegravir/rilpivirine [1], rilpivirine ---> SmPC of [1] of EMA

Juluca should not be taken with any other medicinal product containing dolutegravir or rilpivirine, except in case of co-administration with rifabutin

Dolutegravir/rilpivirine [1], sildenafil ---> SmPC of [1] of EMA

No dose adjustment is required.

Dolutegravir/rilpivirine [1], simeprevir ---> SmPC of [1] of EMA

No dose adjustment is required.

Dolutegravir/rilpivirine [1], sofosbuvir ---> SmPC of [1] of EMA

No dose adjustment is required.

Dolutegravir/rilpivirine [1], sofosbuvir/velpatasvir ---> SmPC of [1] of EMA

No dose adjustment is required.

Dolutegravir/rilpivirine [1], St. John's wort ---> SmPC of [1] of EMA

Dolutegravir/rilpivirine [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Co-administration of Juluca with medicinal products that induce CYP3A may result in decreased plasma concentrations of rilpivirine, which could reduce the therapeutic effect of Juluca

Dolutegravir/rilpivirine [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Rilpivirine is primarily metabolised by cytochrome P450 (CYP)3A. Co-administration of rilpivirine and medicinal products that inhibit CYP3A has been observed to increase the plasma concentrations of rilpivirine

Dolutegravir/rilpivirine [1], strong UGT1A1 inductors ---> SmPC of [1] of EMA

Dolutegravir/rilpivirine [1], strong UGT1A1 inhibitors ---> SmPC of [1] of EMA

Dolutegravir/rilpivirine [1], tadalafil ---> SmPC of [1] of EMA

No dose adjustment is required.

Dolutegravir/rilpivirine [1], tenofovir alafenamide ---> SmPC of [1] of EMA

No dose adjustment is required.

Dolutegravir/rilpivirine [1], tenofovir disoproxil ---> SmPC of [1] of EMA

No dose adjustment is required.

Dolutegravir/rilpivirine [1], torsades de pointes inducing drugs ---> SmPC of [1] of EMA

Juluca should be used with caution when co-administered with medicinal products with a known risk of Torsade de Pointes

Dolutegravir/rilpivirine [1], vardenafil ---> SmPC of [1] of EMA

No dose adjustment is required.

Dolutegravir/rilpivirine [1], voriconazole ---> SmPC of [1] of EMA

May cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes). No dose adjustment is required.

Dolutegravir/rilpivirine [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should be counselled about the potential risk of neural tube defects with dolutegravir (a component of Juluca, see below), including consideration of effective contraceptive measures.

Dolutegravir/rilpivirine, torsades de pointes inducing drugs ---> SmPC of [rilpivirine] of EMA

Rilpivirine should be used with caution when co-administered with a medicinal product with a known risk of Torsade de Pointes.

CONTRAINDICATIONS of Dolutegravir/rilpivirine (Juluca)

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

- Co-administration with the following medicinal products:

- fampridine (also known as dalfampridine);

- carbamazepine, oxcarbazepine, phenobarbital, phenytoin;

- rifampicin, rifapentine;

- proton pump inhibitors, such as omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole;

- systemic dexamethasone, except as a single dose treatment;

- St John's wort (Hypericum perforatum).

https://www.ema.europa.eu/en/documents/product-information/juluca-epar-product-information_en.pdf 14/11/2025

Domperidone

Acetylsalicylic acid, domperidone [2] ---> SmPC of [2] of eMC

Domperidone increased rate of absorption of aspirin

Amifampridine [1], domperidone ---> SmPC of [1] of EMA

Bosutinib [1], domperidone ---> SmPC of [1] of EMA

Breast-feeding, domperidone [2] ---> SmPC of [2] of eMC

Breast-feeding is not recommended for mothers who are taking domperidone.

Bromocriptine [1], domperidone ---> SmPC of [1] of eMC

Dopamine antagonists may reduce the prolactin-lowering and antiparkinsonian effects of bromocriptine.

Ceritinib [1], domperidone ---> SmPC of [1] of EMA

Delamanid [1], domperidone ---> SmPC of [1] of EMA

Diamorphine [1], domperidone ---> SmPC of [1] of eMC

There may be antagonism of the gastrointestinal effects

Domperidone [1], electrolyte imbalance ---> SmPC of [1] of eMC

Use of domperidone and drugs which prolong QTc requires that caution be exercised in patients who have existing prolongation of cardiac conduction intervals, with significant electrolyte disturbances or underlying cardiac diseases

Domperidone [1], erythromycin ---> SmPC of [1] of eMC

Co-administration of domperidone with potent CYP3A4 inhibitors that prolong the QTc interval should be avoided

Domperidone [1], potent CYP3A4 inhibitors that prolong the QT interval ---> SmPC of [1] of eMC

Co-administration of domperidone with potent CYP3A4 inhibitors that prolong the QTc interval should be avoided

Domperidone [1], pregnancy ---> SmPC of [1] of eMC

Domperidone should only be used during pregnancy when justified by the anticipated therapeutic benefit.

Domperidone [1], QT interval prolonging drugs ---> SmPC of [1] of eMC

Domperidone [1], strong CYP3A4 inhibitors ---> SmPC of [1] of eMC

In vitro data suggest that the concomitant use of drugs that significantly inhibit CYP3A4 may result in increased plasma levels of domperidone.

Domperidone, droperidol [2] ---> SmPC of [2] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Domperidone, ketoconazole [2] ---> SmPC of [2] of EMA

Not recommended due to an increased risk in QT prolongation.

Domperidone, lisuride

Domperidone inhibits only the peripheral, but doesn't the central effects of lisuride and has no influence on Parkinson symptomatic

Domperidone, meptazinol [2] ---> SmPC of [2] of eMC

Concomitant use of meptazinol with domperidone may result in antagonism of gastrointestinal side-effects.

Domperidone, paracetamol [2] ---> SmPC of [2] of eMC

The absorption of paracetamol is increased by domperidone.

Domperidone, pethidine

Pethidine has an antagonistic effect on metoclopramide and domperidone

Domperidone, piperaquine ---> SmPC of [piperaquine/artenimol] of EMA

The combination of piperaquine with drugs that are known to prolong the QTc interval is contraindicated: additive effect on the QTc interval

Domperidone, piperaquine/artenimol [2] ---> SmPC of [2] of EMA

The combination of piperaquine/dihydroartemisinin with drugs that are known to prolong the QTc interval is contraindicated: additive effect on the QTc interval

Domperidone, protirelin

Enhancement of TSH-increase

Domperidone, ropinirole

Domperidone antagonises the dopaminergic actions of ropinirole peripherally

Domperidone, rotigotine [2] ---> SmPC of [2] of EMA

Co-administration of domperidone with rotigotine had no effect on the pharmacokinetics of rotigotine.

Domperidone, telaprevir [2] ---> SmPC of [2] of EMA

Telaprevir, CYP3A4 inhibitor, may increase the plasma levels of domperidone. The concomitant use should be avoided

Domperidone, triptorelin [2] ---> SmPC of [2] of eMC

Drugs which raise prolactin levels should not be prescribed concomitantly as they reduce the level of GnRH receptors in the pituitary.

CONTRAINDICATIONS of Domperidone

- Known hypersensitivity to domperidone or any of the excipients.

- Prolactin-releasing pituitary tumour (prolactinoma.)

- Hepatic and/or renal impairment

Domperidone should not be used when stimulation of gastric motility could be harmful: gastro-intestinal haemorrhage, mechanical obstruction or perforation.

http://www.medicines.org.uk/emc/

Donepezil

Ability to drive, donepezil [2] ---> SmPC of [2] of eMC

Donepezil can induce fatigue, dizziness and muscle cramps

Alcohol, donepezil [2] ---> SmPC of [2] of eMC

The enzymatic induction may decrease the plasma levels of donepezil

Anticholinergics, donepezil

Donepezil hydrochloride has the potential to interfere with medications having anticholinergic activity.

Anticholinergics, donepezil [2] ---> SmPC of [2] of eMC

Donepezil hydrochloride has the potential to interfere with medications having anticholinergic activity.

Atracurium [1], donepezil ---> SmPC of [1] of eMC

Treatment with anticholinesterases, commonly used in the treatment of Alzheimer's disease e.g. donepezil, may shorten the duration and diminish the magnitude of neuromuscular blockade with atracurium.

Breast-feeding, donepezil [2] ---> SmPC of [2] of eMC

Women on donepezil should not breast feed.

Carbamazepine, donepezil [2] ---> SmPC of [2] of eMC

The enzymatic induction may decrease the plasma levels of donepezil

Carteolol, donepezil

Risk of excessive bradycardia (addition of bradycardic effects)

Cisatracurium [1], donepezil ---> SmPC of [1] of eMC

Treatment with donepezil may shorten the duration and diminish the magnitude of neuromuscular blockade with cisatracurium.

Donepezil [1], enzyme inductors ---> SmPC of [1] of eMC

The enzymatic induction may decrease the plasma levels of donepezil

Donepezil [1], erythromycin ---> SmPC of [1] of eMC

The strong CYP3A4-inhibition may increase the plasma levels of donepezil

Donepezil [1], fluoxetine ---> SmPC of [1] of eMC

The strong CYP2D6 inhibition may increase the plasma concentrations of donepezil.

Donepezil [1], itraconazol ---> SmPC of [1] of eMC

The strong CYP3A4-inhibition may increase the plasma levels of donepezil

Donepezil [1], ketoconazole ---> SmPC of [1] of eMC

The strong CYP3A4-inhibition may increase the plasma levels of donepezil

Donepezil [1], muscle relaxants ---> SmPC of [1] of eMC

There is the potential for synergistic activity of donepezil with concomitant treatment involving medications such as other neuro-muscular blocking agents

Donepezil [1], parasympathomimetics ---> SmPC of [1] of eMC

There is the potential for synergistic activity of donepezil with concomitant treatment involving medications such as cholinergic agonists

Donepezil [1], phenytoin ---> SmPC of [1] of eMC

The enzymatic induction may decrease the plasma levels of donepezil

Donepezil [1], pregnancy ---> SmPC of [1] of eMC

Donepezil should not be used during pregnancy unless clearly necessary.

Donepezil [1], quinidine ---> SmPC of [1] of eMC

The strong CYP2D6 inhibition may increase the plasma concentrations of donepezil.

Donepezil [1], rifampicin ---> SmPC of [1] of eMC

The enzymatic induction may decrease the plasma levels of donepezil

Donepezil [1], strong CYP2D6 inhibitors ---> SmPC of [1] of eMC

The strong CYP2D6 inhibition may increase the plasma concentrations of donepezil.

Donepezil [1], strong CYP3A4 inhibitors ---> SmPC of [1] of eMC

The strong CYP3A4-inhibition may increase the plasma levels of donepezil

Donepezil [1], succinylcholine ---> SmPC of [1] of eMC

There is the potential for synergistic activity of donepezil with concomitant treatment involving medications such as succinylcholine

Donepezil [1], suxamethonium ---> SmPC of [1] of eMC

There is the potential for synergistic activity of donepezil with concomitant treatment involving medications such as succinylcholine

Donepezil, galantamine [2] ---> SmPC of [2] of eMC

Because of its mechanism of action, galantamine should not be given concomitantly with other cholinomimetics

Donepezil, hydroquinidine

Risk excessive bradycardia due to the bradycardic effects of both active ingredients may be additive

Donepezil, sotalol

Bradycardia-inducing medicinal products enhance the risk of torsades de pointes

CONTRAINDICATIONS of Donepezil

- Hypersensitivity to donepezil hydrochloride, piperidine derivatives, or to any of the excipients

http://www.medicines.org.uk/emc/

Dopamine

Alfa-adrenergic receptor blockers, dopamine [2] ---> SmPC of [2] of eMC

The peripheral vasoconstriction caused by high doses of dopamine is antagonised by alfa-adrenergic blocking agents.

Alkalinizing agents, dopamine

The addition of alkalizing agents may inactivate dopamine

Amantadine, dopamine

Amantadine enhances the effect of dopamine

Benzylpenicillin, dopamine

Incompatible with benzylpenicillin in solution

Betablockers, dopamine [2] ---> SmPC of [2] of eMC

The cardiac effects of dopamine are antagonised by beta-adrenergic blocking agents

Breast-feeding, dopamine [2] ---> SmPC of [2] of eMC

It is not known if dopamine is excreted in breast milk, nor is the effect on the infant known.

Bromperidol, dopamine

The peripheral vasodilatation (e. g. renal arteries) or in high doses vasoconstriction may be antagonized by bromperidol

Butyrophenones, dopamine [2] ---> SmPC of [2] of eMC

Dopamine induced renal and mesenteric vasodilation is antagonised by haloperidol or other butyrophenones

Catecholamine-O-methyltransferase inhibitors, dopamine

The COMT-inhibition may increase the plasma levels of dopamine

Chlorprothixene, dopamine

The peripheral vasodilatation (e. g. renal arteries) or in high doses vasoconstriction may be antagonized by chlorprothixene

Cyclopropane, dopamine [2] ---> SmPC of [2] of eMC

The myocardium is sensitised by the effect of dopamine, cyclopropane or halogenated hydrocarbon anaesthetics, and these should be avoided. This interaction applies both to pressor activity and cardiac beta adrenergic stimulation.

Diuretics, dopamine [2] ---> SmPC of [2] of eMC

Dopamine may increase the effect of diuretic agents.

Dopamine [1], ergot derivatives ---> SmPC of [1] of eMC

The ergot alkaloids should be avoided because of the possibility of excessive vasoconstriction.

Dopamine [1], guanethidine ---> SmPC of [1] of eMC

Guanethidine may potentiate the pressor response to dopamine.

Dopamine [1], halogenated anaesthetics ---> SmPC of [1] of eMC

Dopamine [1], haloperidol ---> SmPC of [1] of eMC

Dopamine induced renal and mesenteric vasodilation is antagonised by haloperidol or other butyrophenones

Dopamine [1], IMAOs ---> SmPC of [1] of eMC

MAO inhibitors potentiate the effect of dopamine and its duration of action. Patients who have been treated with MAO inhibitors prior to administration of dopamine will therefore require a substantially reduced dosage.

Dopamine [1], metoprolol ---> SmPC of [1] of eMC

The cardiac effects of dopamine are antagonised by beta-adrenergic blocking agents

Dopamine [1], phenothiazines ---> SmPC of [1] of eMC

Dopamine induced renal and mesenteric vasodilation is antagonised by phenothiazines

Dopamine [1], phenytoin ---> SmPC of [1] of eMC

Administration of IV phenytoin to patients receiving dopamine has resulted in hypotension and bradycardia

Dopamine [1], pregnancy ---> SmPC of [1] of eMC

The drug should be used in pregnant women only when the expected benefits outweigh the potential risk to the foetus.

Dopamine [1], propranolol ---> SmPC of [1] of eMC

The cardiac effects of dopamine are antagonised by beta-adrenergic blocking agents

Dopamine [1], tricyclic antidepressant ---> SmPC of [1] of eMC

Tricyclic antidepressants may potentiate the pressor response to dopamine.

Dopamine, doubutamine

The combination of dobutamine and dopamine increases the blood pressure and decreases or doesn't change the ventricular filling pressure

Dopamine, entacapone [2] ---> SmPC of [2] of EMA

Because of its mechanism of action, entacapone may interfere with the metabolism of medicinal products containing a catechol group and potentiate their action

Dopamine, furosemide

Dopamine may increase the effect of diuretic agents.

Dopamine, hydroxycobalamin

Physical incompatibility (particle formation). These medicinal products must not be administered simultaneously through the same intravenous line as hydroxocobalamine

Dopamine, linezolid [2] ---> SmPC of [2] of eMC

The co-administration is contraindicated, unless there are facilities available for close observation and monitoring of blood pressure

Dopamine, metoclopramide

Metoclopramide may decrease the desired effect of dopamine

Dopamine, phenelzine [2] ---> SmPC of [2] of eMC

Phenelzine may potentiate the action of dopamine

Dopamine, propofol

It has been reported an interaction between dopamine and propofol, because a reduction of propofol concentration has been observed in patients treated with dopamine

Dopamine, prothipendyl

Prothipendyl, dopamine D1 and D2 antagonist, may antagonize with the dopamine receptor agonist

Dopamine, protirelin

Reduction of TSH-increase

Dopamine, ramipril [2] ---> SmPC of [2] of eMC

The antihypertensive effect may be reduced: Blood pressure monitoring is recommended.

Dopamine, somatorelin [2] ---> SmPC of [2] of eMC

Concomitant use of somatorelin and substances influencing the release of growth hormone should be avoided.

Dopamine, terazosine [2] ---> SmPC of [2] of eMC

Terazosin may reduce blood pressure and vasculare reactions to dopamine

Dopamine, tolazoline

Concomitant use of dopamine and tolazoline (alfa-adrenergic blocker) may cause severe hypotension

Dopamine, vasoconstrictors

The co-administration of dopamine and vasoconstrictor drugs may cause an excessive vasoconstriction.

Dopamine, venlafaxine

The combination of venlafaxine with the alfa- and beta-adrenergic agonist administered intravenously can cause paroxysmal hypertension with possible heart rhythm disorders

CONTRAINDICATIONS of Dopamine

Dopamine should not be used in patients with

- Hypersensitivity to dopamine or any of the excipients.

- Phaeochromocytoma or hyperthyroidism

- Dopamine should not be used in the presence of uncorrected atrial or ventricular tachyarrhythmias or ventricular fibrillation.

- Cyclopropane and halogenated hydrocarbon anaesthetics should be avoided.

http://www.medicines.org.uk/emc/

Doravirine (Pifeltro)

Abacavir, doravirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Ability to drive, doravirine [2] ---> SmPC of [2] of EMA

Patients should be informed that fatigue, dizziness, and somnolence have been reported during treatment with doravirine (see section 4.8). This should be considered when assessing a patient's ability to drive or operate machinery.

Aluminium hydroxide, doravirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Antacids, doravirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Atorvastatin, doravirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Boosted protease-inhibitors, doravirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Bosentan, doravirine [2] ---> SmPC of [2] of EMA

If co-administration with other moderate CYP3A inducers cannot be avoided, the doravirine dose should be increased to 100 mg twice daily (the doses should be taken approximately 12 hours apart)

Breast-feeding, doravirine [2] ---> SmPC of [2] of EMA

Available pharmacodynamic/toxicological data in animals have shown excretion of doravirine in milk (see section 5.3). It is recommended that women living with HIV do not breast-feed their infants in order to avoid transmission of HIV.

Buprenorphine/naloxone, doravirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Canagliflozin, doravirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Carbamazepine, doravirine [2] ---> SmPC of [2] of EMA

Doravirine should not be co-administered with medicinal products that are strong CYP3A enzyme inducers as significant decreases in doravirine plasma concentrations are expected to occur, which may decrease the effectiveness of doravirine

Cobicistat, doravirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Cobicistat-boosted elvitegravir, doravirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Cobicistat-boosted protease inhibitors, doravirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

CYP enzymes, doravirine [2] ---> SmPC of [2] of EMA

Doravirine at a dose of 100 mg once daily is not likely to have a clinically relevant effect on the plasma levels of medicinal products that are dependent on transport proteins for absorption and/or elimination or that are metabolised by CYP enzymes.

CYP3A4 inhibitors, doravirine [2] ---> SmPC of [2] of EMA

Co-administration of doravirine and medicinal products that are inhibitors of CYP3A may result in increased plasma concentrations of doravirine. However, no dose adjustment is needed when doravirine is co-administered with CYP3A inhibitors.

Dabrafenib, doravirine [2] ---> SmPC of [2] of EMA

If co-administration with other moderate CYP3A inducers cannot be avoided, the doravirine dose should be increased to 100 mg twice daily (the doses should be taken approximately 12 hours apart)

Daclatasvir, doravirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Dasabuvir, doravirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Diltiazem, doravirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Dolutegravir, doravirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Doravirine [1], drugs primarily metabolised by CYP3A4 with narrow therapeutic index ---> SmPC of [1] of EMA

Caution should be used when co-administering doravirine with medicinal products that are sensitive CYP3A substrates that also have a narrow therapeutic window (e.g., tacrolimus and sirolimus)

Doravirine [1], elbasvir/grazoprevir ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], emtricitabine ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], enfuvirtide ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], enzalutamide ---> SmPC of [1] of EMA

Doravirine [1], ethinyl estradiol/levonorgestrel ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], ethinylestradiol/norgestimate ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], fertility ---> SmPC of [1] of EMA

No human data on the effect of doravirine on fertility are available. Animal studies do not indicate harmful effects of doravirine on fertility at exposure levels higher than the exposure in humans at the recommended clinical dose (see section 5.3).

Doravirine [1], fluconazole ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], glecaprevir/pibrentasvir ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], itraconazol ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], ketoconazole ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], ledipasvir/sofosbuvir ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], lesinurad ---> SmPC of [1] of EMA

If co-administration with other moderate CYP3A inducers cannot be avoided, the doravirine dose should be increased to 100 mg twice daily (the doses should be taken approximately 12 hours apart)

Doravirine [1], liraglutide ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], lisinopril ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], lumacaftor ---> SmPC of [1] of EMA

Doravirine [1], magnesium hydroxide ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], maraviroc ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], metformin ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], methadone ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], midazolam ---> SmPC of [1] of EMA

Co-administration of doravirine and the sensitive CYP3A substrate midazolam resulted in a 18 % decrease in midazolam exposure, suggesting that doravirine may be a weak CYP3A inducer.

Doravirine [1], mitotane ---> SmPC of [1] of EMA

Doravirine [1], modafinil ---> SmPC of [1] of EMA

If co-administration with other moderate CYP3A inducers cannot be avoided, the doravirine dose should be increased to 100 mg twice daily (the doses should be taken approximately 12 hours apart)

Doravirine [1], moderate CYP3A4 inductors ---> SmPC of [1] of EMA

Co-administration of doravirine with other moderate CYP3A inducers has not been evaluated, but decreased doravirine concentrations are expected.

Doravirine [1], nafcillin ---> SmPC of [1] of EMA

If co-administration with other moderate CYP3A inducers cannot be avoided, the doravirine dose should be increased to 100 mg twice daily (the doses should be taken approximately 12 hours apart)

Doravirine [1], ombitasvir/paritaprevir/ritonavir ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], omeprazole ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], oxcarbazepine ---> SmPC of [1] of EMA

Doravirine [1], pantoprazole ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], phenobarbital ---> SmPC of [1] of EMA

Doravirine [1], phenytoin ---> SmPC of [1] of EMA

Doravirine [1], posaconazole ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], pregnancy ---> SmPC of [1] of EMA

As a precautionary measure, it is preferable to avoid the use of doravirine during pregnancy.

Doravirine [1], proton pump inhibitors ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], raltegravir ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], ribavirin ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], rifabutin ---> SmPC of [1] of EMA

When doravirine is co-administered with rifabutin, the doravirine dose should be increased to 100 mg twice daily (the doses should be taken approximately 12 hours apart)

Doravirine [1], rifampicin ---> SmPC of [1] of EMA

Doravirine [1], rifapentine ---> SmPC of [1] of EMA

Doravirine [1], ritonavir ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], ritonavir-boosted elvitegravir ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], ritonavir-boosted protease inhibitors ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], rosuvastatin ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], simvastatine ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], sirolimus ---> SmPC of [1] of EMA

Caution should be used when co-administering doravirine with medicinal products that are sensitive CYP3A substrates that also have a narrow therapeutic window (e.g., tacrolimus and sirolimus)

Doravirine [1], sitagliptin ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], sofosbuvir ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], sofosbuvir/velpatasvir ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], St. John's wort ---> SmPC of [1] of EMA

Doravirine [1], statins ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Co-administration with medicinal products that are strong cytochrome P450 (CYP)3A enzyme inducers is contraindicated as significant decreases in doravirine plasma concentrations are expected to occur, which may decrease the effectiveness of Pifeltro

Doravirine [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Doravirine [1], tacrolimus ---> SmPC of [1] of EMA

Caution should be used when co-administering doravirine with medicinal products that are sensitive CYP3A substrates that also have a narrow therapeutic window (e.g., tacrolimus and sirolimus)

Doravirine [1], telotristat ethyl ---> SmPC of [1] of EMA

If co-administration with other moderate CYP3A inducers cannot be avoided, the doravirine dose should be increased to 100 mg twice daily (the doses should be taken approximately 12 hours apart)

Doravirine [1], tenofovir alafenamide ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], tenofovir disoproxil ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], thioridazine ---> SmPC of [1] of EMA

If co-administration with other moderate CYP3A inducers cannot be avoided, the doravirine dose should be increased to 100 mg twice daily (the doses should be taken approximately 12 hours apart)

Doravirine [1], verapamil ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], voriconazole ---> SmPC of [1] of EMA

No dose adjustment is required.

CONTRAINDICATIONS of Doravirine (Pifeltro)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Co-administration with medicinal products that are strong cytochrome P450 (CYP)3A enzyme inducers is contraindicated as significant decreases in doravirine plasma concentrations are expected to occur, which may decrease the effectiveness of Pifeltro (see sections 4.4 and 4.5). These medicinal products include, but are not limited, to the following:

- carbamazepine, oxcarbazepine, phenobarbital, phenytoin

- rifampicin, rifapentine

- St. John's wort (Hypericum perforatum)

- mitotane

- enzalutamide

- lumacaftor

https://www.ema.europa.eu/en/documents/product-information/pifeltro-epar-product-information_en.pdf 11/12/2025

Doravirine/lamivudine/tenofovir disoproxil (Delstrigo)

Ability to drive, doravirine/lamivudine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Patients should be informed that fatigue, dizziness, and somnolence have been reported during treatment with Delstrigo. This should be considered when assessing a patient's ability to drive or operate machinery.

Aciclovir, doravirine/lamivudine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Due to the tenofovir disoproxil component of doravirine/lamivudine/tenofovir disoproxil, use of the product should be avoided with concurrent or recent use of nephrotoxic medicinal products.

Aluminium hydroxide, doravirine/lamivudine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Aminoglycoside antibiotics, doravirine/lamivudine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Due to the tenofovir disoproxil component of doravirine/lamivudine/tenofovir disoproxil, use of the product should be avoided with concurrent or recent use of nephrotoxic medicinal products.

Antacids, doravirine/lamivudine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Antiretrovirals, doravirine/lamivudine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Delstrigo is a complete regimen for the treatment of HIV-1 infection; therefore, Delstrigo should not be administered with other antiretroviral medicinal products.

Atorvastatin, doravirine/lamivudine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Bosentan, doravirine/lamivudine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

If co-administration with other moderate CYP3A inducers cannot be avoided, the doravirine dose should be increased to 100 mg twice daily (the doses should be taken approximately 12 hours apart)

Breast-feeding, doravirine/lamivudine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Because of the potential for HIV-1 transmission and the potential for serious adverse reactions in breast-feeding infants, mothers should be instructed not to breastfeed if they are receiving Delstrigo.

Buprenorphine/naloxone, doravirine/lamivudine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Canagliflozin, doravirine/lamivudine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Carbamazepine, doravirine/lamivudine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Cidofovir, doravirine/lamivudine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Due to the tenofovir disoproxil component of doravirine/lamivudine/tenofovir disoproxil, use of the product should be avoided with concurrent or recent use of nephrotoxic medicinal products.

Dabrafenib, doravirine/lamivudine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Daclatasvir, doravirine/lamivudine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, doravirine/lamivudine/tenofovir disoproxil ---> SmPC of [ombitas

No dose adjustment is required.

Dasabuvir, doravirine/lamivudine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Diltiazem, doravirine/lamivudine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Doravirine, doravirine/lamivudine/tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Doravirine/lamivudine/tenofovir disoproxil should not be administered with doravirine unless needed for dose adjustment (e.g., with rifabutin)

Doravirine/lamivudine/tenofovir disoproxil [1], CYP3A4 inhibitors ---> SmPC of [1] of EMA

Co-administration of doravirine/lamivudine/tenofovir disoproxil and medicinal products that are inhibitors of CYP3A may result in increased plasma concentrations of doravirine. However, no dose adjustment is needed

Doravirine/lamivudine/tenofovir disoproxil [1], drugs primarily metabolised by CYP3A4 with narrow therapeutic index

Caution should be used when co-administering doravirine with medicinal products that are sensitive CYP3A substrates that also have a narrow therapeutic window (e.g., tacrolimus and sirolimus)

Doravirine/lamivudine/tenofovir disoproxil [1], elbasvir/grazoprevir ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], enzalutamide ---> SmPC of [1] of EMA

Doravirine/lamivudine/tenofovir disoproxil [1], ethinyl estradiol/levonorgestrel ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], ethinylestradiol/norgestimate ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], fertility ---> SmPC of [1] of EMA

Animal studies do not indicate harmful effects of doravirine, lamivudine, or tenofovir disoproxil on fertility at exposure levels higher than the exposure in humans at the recommended clinical dose (see section 5.3).

Doravirine/lamivudine/tenofovir disoproxil [1], fluconazole ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], ganciclovir ---> SmPC of [1] of EMA

Due to the tenofovir disoproxil component of doravirine/lamivudine/tenofovir disoproxil, use of the product should be avoided with concurrent or recent use of nephrotoxic medicinal products.

Doravirine/lamivudine/tenofovir disoproxil [1], gentamicin ---> SmPC of [1] of EMA

Due to the tenofovir disoproxil component of doravirine/lamivudine/tenofovir disoproxil, use of the product should be avoided with concurrent or recent use of nephrotoxic medicinal products.

Doravirine/lamivudine/tenofovir disoproxil [1], glecaprevir/pibrentasvir ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], itraconazol ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], ketoconazole ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], lactitol ---> SmPC of [1] of EMA

When possible, avoid chronic co-administration of doravirine/lamivudine/tenofovir disoproxil with medicinal products containing sorbitol or other osmotic acting polyalcohols (eg: xylitol, mannitol, lactitol, maltitol).

Doravirine/lamivudine/tenofovir disoproxil [1], ledipasvir/sofosbuvir ---> SmPC of [1] of EMA

Patients receiving doravirine/lamivudine/tenofovir disoproxil concomitantly with ledipasvir/sofosbuvir should be monitored for adverse reactions associated with tenofovir disoproxil.

Doravirine/lamivudine/tenofovir disoproxil [1], lesinurad ---> SmPC of [1] of EMA

Doravirine/lamivudine/tenofovir disoproxil [1], liraglutide ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], lisinopril ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], lumacaftor ---> SmPC of [1] of EMA

Doravirine/lamivudine/tenofovir disoproxil [1], magnesium hydroxide ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], mannitol ---> SmPC of [1] of EMA

Doravirine/lamivudine/tenofovir disoproxil [1], metformin ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], methadone ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], midazolam ---> SmPC of [1] of EMA

Co-administration of doravirine and the sensitive CYP3A substrate midazolam resulted in a 18 % decrease in midazolam exposure, suggesting that doravirine may be a weak CYP3A inducer.

Doravirine/lamivudine/tenofovir disoproxil [1], mitotane ---> SmPC of [1] of EMA

Doravirine/lamivudine/tenofovir disoproxil [1], modafinil ---> SmPC of [1] of EMA

If co-administration with other moderate CYP3A inducers cannot be avoided, the doravirine dose should be increased to 100 mg twice daily (the doses should be taken approximately 12 hours apart)

Doravirine/lamivudine/tenofovir disoproxil [1], moderate CYP3A4 inductors ---> SmPC of [1] of EMA

Co-administration of doravirine/lamivudine/tenofovir disoproxil with other moderate CYP3A inducers has not been evaluated, but decreased doravirine concentrations are expected.

Doravirine/lamivudine/tenofovir disoproxil [1], nafcillin ---> SmPC of [1] of EMA

If co-administration with other moderate CYP3A inducers cannot be avoided, the doravirine dose should be increased to 100 mg twice daily (the doses should be taken approximately 12 hours apart)

Doravirine/lamivudine/tenofovir disoproxil [1], nephrotoxic substances ---> SmPC of [1] of EMA

Due to the tenofovir disoproxil component of doravirine/lamivudine/tenofovir disoproxil, use of the product should be avoided with concurrent or recent use of nephrotoxic medicinal products.

Doravirine/lamivudine/tenofovir disoproxil [1], ombitasvir/paritaprevir/ritonavir ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], omeprazole ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], oxcarbazepine ---> SmPC of [1] of EMA

Doravirine/lamivudine/tenofovir disoproxil [1], pantoprazole ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], phenobarbital ---> SmPC of [1] of EMA

Doravirine/lamivudine/tenofovir disoproxil [1], phenytoin ---> SmPC of [1] of EMA

Doravirine/lamivudine/tenofovir disoproxil [1], posaconazole ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], pregnancy ---> SmPC of [1] of EMA

As a precautionary measure, it is preferable to avoid the use of Delstrigo during pregnancy.

Doravirine/lamivudine/tenofovir disoproxil [1], proton pump inhibitors ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], ribavirin ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], rifabutin ---> SmPC of [1] of EMA

When Delstrigo is co-administered with rifabutin, a 100 mg dose of doravirine should be given daily, approximately 12 hours after doravirine/lamivudine/tenofovir disoproxil dose

Doravirine/lamivudine/tenofovir disoproxil [1], rifampicin ---> SmPC of [1] of EMA

Doravirine/lamivudine/tenofovir disoproxil [1], rifapentine ---> SmPC of [1] of EMA

Doravirine/lamivudine/tenofovir disoproxil [1], rosuvastatin ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], simvastatine ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], sirolimus ---> SmPC of [1] of EMA

Caution should be used when co-administering doravirine with medicinal products that are sensitive CYP3A substrates that also have a narrow therapeutic window (e.g., tacrolimus and sirolimus)

Doravirine/lamivudine/tenofovir disoproxil [1], sitagliptin ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], sofosbuvir ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], sofosbuvir/velpatasvir ---> SmPC of [1] of EMA

Patients receiving doravirine/lamivudine/tenofovir disoproxil concomitantly with sofosbuvir/velpatasvir should be monitored for adverse reactions associated with tenofovir disoproxil.

Doravirine/lamivudine/tenofovir disoproxil [1], sorbitol ---> SmPC of [1] of EMA

Doravirine/lamivudine/tenofovir disoproxil [1], St. John's wort ---> SmPC of [1] of EMA

Doravirine/lamivudine/tenofovir disoproxil [1], statins ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Doravirine/lamivudine/tenofovir disoproxil should not be co-administered with medicines that are strong CYP3A enzyme inducers as significant decreases in doravirine plasma levels are expected to occur, which may decrease the effectiveness

Doravirine/lamivudine/tenofovir disoproxil [1], tacrolimus ---> SmPC of [1] of EMA

Caution should be used when co-administering doravirine with medicinal products that are sensitive CYP3A substrates that also have a narrow therapeutic window (e.g., tacrolimus and sirolimus)

Doravirine/lamivudine/tenofovir disoproxil [1], telotristat ethyl ---> SmPC of [1] of EMA

If co-administration with other moderate CYP3A inducers cannot be avoided, the doravirine dose should be increased to 100 mg twice daily (the doses should be taken approximately 12 hours apart)

Doravirine/lamivudine/tenofovir disoproxil [1], tenofovir disoproxil ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], thioridazine ---> SmPC of [1] of EMA

If co-administration with other moderate CYP3A inducers cannot be avoided, the doravirine dose should be increased to 100 mg twice daily (the doses should be taken approximately 12 hours apart)

Doravirine/lamivudine/tenofovir disoproxil [1], valaciclovir ---> SmPC of [1] of EMA

Due to the tenofovir disoproxil component of doravirine/lamivudine/tenofovir disoproxil, use of the product should be avoided with concurrent or recent use of nephrotoxic medicinal products.

Doravirine/lamivudine/tenofovir disoproxil [1], valganciclovir ---> SmPC of [1] of EMA

Due to the tenofovir disoproxil component of doravirine/lamivudine/tenofovir disoproxil, use of the product should be avoided with concurrent or recent use of nephrotoxic medicinal products.

Doravirine/lamivudine/tenofovir disoproxil [1], verapamil ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], voriconazole ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], xylitol ---> SmPC of [1] of EMA

Doravirine/lamivudine/tenofovir disoproxil, lactitol [2] ---> SmPC of [2] of EMA

CONTRAINDICATIONS of Doravirine/lamivudine/tenofovir disoproxil (Delstrigo)

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

- Co-administration with medicinal products that are strong cytochrome P450 (CYP)3A enzyme inducers is contraindicated as significant decreases in doravirine plasma concentrations are expected to occur, which may decrease the effectiveness of Delstrigo (see sections 4.4 and 4.5). These medicinal products include, but are not limited to the following:

- carbamazepine, oxcarbazepine, phenobarbital, phenytoin

- rifampicin, rifapentine

- St. John's wort (Hypericum perforatum)

- mitotane

- enzalutamide

- lumacaftor

https://www.ema.europa.eu/en/documents/product-information/delstrigo-epar-product-information_en.pdf 03/12/2025

Doripenem (Doribax)

Ability to drive, doripenem [2] ---> SmPC of [2] of EMA

Based on reported adverse drug reactions, it is not anticipated that Doribax will affect the ability to drive and use machines.

Breast-feeding, doripenem [2] ---> SmPC of [2] of EMA

A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy

Cytochrome P450, doripenem [2] ---> SmPC of [2] of EMA

Based on in vitro studies it is not expected that doripenem will inhibit or induce the activities of CYP450. Therefore, no CYP450-related drug interactions are to be expected (see section 5.2).

Doripenem [1], fertility ---> SmPC of [1] of EMA

Intravenous injection of doripenem had no adverse effects on general fertility of treated male and female rats or on postnatal development and reproductive performance of the offspring at doses as high as 1 g/kg/day

Doripenem [1], pregnancy ---> SmPC of [1] of EMA

Doripenem should not be used during pregnancy unless clearly necessary.

Doripenem [1], probenecide ---> SmPC of [1] of EMA

Probenecid competes with doripenem for renal tubular secretion and reduces the renal clearance of doripenem. Therefore, co-administration of probenecid with Doribax is not recommended.

Doripenem [1], sodium valproate ---> SmPC of [1] of EMA

It has been shown that co-administration of doripenem and valproic acid significantly reduces serum valproic acid levels below the therapeutic range.

Doripenem [1], tubular secretion ---> SmPC of [1] of EMA

An interaction of doripenem with other medicinal products eliminated by renal tubular secretion cannot be excluded.

Doripenem [1], valproic acid ---> SmPC of [1] of EMA

It has been shown that co-administration of doripenem and valproic acid significantly reduces serum valproic acid levels below the therapeutic range.

CONTRAINDICATIONS of Doripenem (Doribax)

- Hypersensitivity to the active substance

- Hypersensitivity to any other carbapenem antibacterial agent

- Severe hypersensitivity (e.g. anaphylactic reaction, severe skin reaction) to any other type of beta-lactam antibacterial agent (e.g. penicillins or cephalosporins).

https://www.ema.europa.eu/en/documents/product-information/doribax-epar-product-information_en.pdf 17/10/2014 (Withdrawn )

Dornase alfa

Breast-feeding, dornase alfa [2] ---> SmPC of [2] of eMC

Caution should be exercised when dornase alfa is administered to a breast-feeding woman

Dornase alfa [1], pregnancy ---> SmPC of [1] of eMC

Caution should be exercised when prescribing dornase alfa to pregnant women.

CONTRAINDICATIONS of Dornase alfa

- Hypersensitivity to the active substance or to any of the excipients.

http://www.medicines.org.uk/emc/

Dorzolamide

Breast-feeding, dorzolamide [2] ---> SmPC of [2] of eMC

Should not be used during breast-feeding

Carbonic anhydrase inhibitors, dorzolamide

Because of possible additive effects, concomitant use with other carbonic anhydrase oral inhibitors is not advisable.

Dorzolamide [1], pregnancy ---> SmPC of [1] of eMC

Should not be used during pregnancy. In rabbits, dorzolamide produced teratogenic effect at maternotoxic doses

CONTRAINDICATIONS of Dorzolamide

- Dorzolamide is contraindicated in patients who are hypersensitive to the active substance or to any of the excipients.

- Dorzolamide has not been studied in patients with severe renal impairment (CrCl < 30 ml/min) or with hyperchloraemic acidosis. Because dorzolamide and its metabolites are excreted predominantly by the kidney, dorzolamide is therefore contra-indicated in such patients.

http://www.medicines.org.uk/emc/

Dorzolamide/timolol

Ability to drive, dorzolamide/timolol [2] ---> SmPC of [2] of eMC

Possible side effects such as blurred vision may affect some patients' ability to drive and/or operate machinery.

Adrenaline, dorzolamide/timolol [2] ---> SmPC of [2] of eMC

Beta-blocking ophthalmological preparations may block systemic beta-agonist effects e.g. of adrenaline. The anaesthesiologist should be informed when the patient is receiving timolol.

Amiodarone, dorzolamide/timolol [2] ---> SmPC of [2] of eMC

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic betablockers solution is administered concomitantly with antiarrhythmics

Antiarrhythmics, dorzolamide/timolol [2] ---> SmPC of [2] of eMC

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic betablockers solution is administered concomitantly with antiarrhythmics

Antidiabetics, dorzolamide/timolol [2] ---> SmPC of [2] of eMC

Beta-blockers may increase the hypoglycaemic effect of antidiabetic agents and mask the signs and symptoms of acute hypoglycaemia

Beta-adrenergic receptor blockers, dorzolamide/timolol [2] ---> SmPC of [2] of eMC

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic betablockers solution is administered concomitantly with beta-adrenergic blocking agents

Betablockers, dorzolamide/timolol [2] ---> SmPC of [2] of eMC

The effect on intra-ocular pressure or the known effects of systemic beta-blockade may be potentiated when timolol is given to the patients already receiving a systemic beta-blocking agent.

Breast-feeding, dorzolamide/timolol [2] ---> SmPC of [2] of eMC

If treatment is required, then lactation is not recommended.

Calcium antagonists, dorzolamide/timolol [2] ---> SmPC of [2] of eMC

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic betablockers solution is administered concomitantly with oral calcium channel blockers

Carbonic anhydrase inhibitors, dorzolamide

Because of possible additive effects, concomitant use with other carbonic anhydrase oral inhibitors is not advisable.

Carbonic anhydrase inhibitors, dorzolamide/timolol [2] ---> SmPC of [2] of eMC

The use of dorzolamide and oral carbonic anhydrase inhibitors is not recommended.

Catecholamine depleting drugs, dorzolamide/timolol [2] ---> SmPC of [2] of eMC

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic betablockers solution is administered concomitantly with catecholamine-depleting medicines

CYP2D6 inhibitors, dorzolamide/timolol [2] ---> SmPC of [2] of eMC

Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors and timolol.

Digital glycosides, dorzolamide/timolol [2] ---> SmPC of [2] of eMC

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic betablockers solution is administered concomitantly with digitalis glycosides

Dorzolamide/timolol [1], fluoxetine ---> SmPC of [1] of eMC

Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors and timolol.

Dorzolamide/timolol [1], guanethidine ---> SmPC of [1] of eMC

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic betablockers solution is administered concomitantly with guanethidine

Dorzolamide/timolol [1], IMAOs ---> SmPC of [1] of eMC

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic betablockers solution is administered concomitantly with monoamine oxidase (MAO) inhibitors

Dorzolamide/timolol [1], narcotics ---> SmPC of [1] of eMC

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic betablockers solution is administered concomitantly with narcotics

Dorzolamide/timolol [1], parasympathomimetics ---> SmPC of [1] of eMC

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic betablockers solution is administered concomitantly with parasympathomimetics

Dorzolamide/timolol [1], paroxetine ---> SmPC of [1] of eMC

Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors and timolol.

Dorzolamide/timolol [1], pregnancy ---> SmPC of [1] of eMC

It should not be used during pregnancy.

Dorzolamide/timolol [1], quinidine ---> SmPC of [1] of eMC

Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors and timolol.

Dorzolamide/timolol [1], strong CYP2D6 inhibitors ---> SmPC of [1] of eMC

Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors and timolol.

CONTRAINDICATIONS of Dorzolamide/timolol

This medicinal product is contraindicated in patients with:

- reactive airway disease, including bronchial asthma or a history of bronchial asthma, or severe chronic obstructive pulmonary disease

- sinus bradycardia, sick sinus syndrome, sino-atrial block, second- or third-degree atrioventricular block not controlled with pacemaker, overt cardiac failure, cardiogenic shock

- severe renal impairment (CrCl < 30 ml/min) or hyperchloraemic acidosis

- hypersensitivity to one or both active substances or to any of the excipients.

The above are based on the components and are not unique to the combination.

http://www.medicines.org.uk/emc/

Dostarlimab (Jemperli)

Breast-feeding, dostarlimab [2] ---> SmPC of [2] of EMA

JEMPERLI should not be used during breast-feeding and breast-feeding should be avoided for at least 4 months after the last dose of dostarlimab.

Dostarlimab [1], fertility ---> SmPC of [1] of EMA

Women of childbearing potential must use effective contraception during treatment with dostarlimab and until 4 months after the last dose of dostarlimab.

Dostarlimab [1], fertility ---> SmPC of [1] of EMA

Fertility studies have not been conducted with dostarlimab (see section 5.3).

Dostarlimab [1], pregnancy ---> SmPC of [1] of EMA

JEMPERLI is not recommended during pregnancy and in women of childbearing potential not using effective contraception.

Dostarlimab [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential must use effective contraception during treatment with dostarlimab and until 4 months after the last dose of dostarlimab.

CONTRAINDICATIONS of Dostarlimab (Jemperli)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/jemperli-epar-product-information_en.pdf 01/08/2024

Doubutamine

ACE inhibitors, doubutamine

Simultaneous administration of dobutamine and ACE inhibitors (e.g. captopril) may increase the cardiac output, accompanied by increased myocardial oxygen consumption.

Alfa-adrenergic receptor blockers, doubutamine [2] ---> SmPC of [2] of eMC

Potential for hypotension and tachycardia to occur with concomitant administration of sympathomimetics and alpha-blockers such as phenoxybenzamine

Antihypertensives, doubutamine [2] ---> SmPC of [2] of eMC

Special care is advisable in patients receiving antihypertensive therapy in whom dobutamine may increase blood pressure.

Betablockers, doubutamine [2] ---> SmPC of [2] of eMC

The inotropic effects of dobutamine on the heart are reversed by concomitant administration of beta-blockers. Dobutamine may be ineffective or may have a slight vasoconstricting effect in patients who have recently received beta-blockers.

Bisoprolol [1], doubutamine ---> SmPC of [1] of eMC

Combination of beta-sympathomimetic agents with bisoprolol may reduce the effect of both agents.

Breast-feeding, doubutamine [2] ---> SmPC of [2] of eMC

If a mother requires dobutamine treatment, breast feeding should be discontinued for the duration of treatment.

Calcium chloride, doubutamine [2] ---> SmPC of [2] of eMC

Calcium chloride infusion may reduce the cardiotonic effects of dobutamine.

Captopril, doubutamine

Simultaneous administration of dobutamine and ACE inhibitors (e.g. captopril) may increase the cardiac output, accompanied by increased myocardial oxygen consumption.

Cardiac glycosides [1], doubutamine ---> SmPC of [1] of eMC

An increased risk of arrhythmias may occur if sympathomimetic agents are given to patients receiving cardiac glycosides.

Catecholamine-O-methyltransferase inhibitors, doubutamine

The COMT-inhibition may increase the plasma levels of dobutamine

Cimetidine, doubutamine [2] ---> SmPC of [2] of eMC

It is possible that cimetidine may inhibit the uptake and/or the metabolism of dobutamine by the liver with a subsequent increase in the degree and duration of its action.

Cyclopropane, doubutamine

The inhaled anaesthetic may increase the risk of ventricular arrhythmias due to increased myocardial sensitivity

Dipyridamole, doubutamine

In an echocardiography, the administration of dipyridamole may cause a potential dangerous hypotension

Dopamine, doubutamine

The combination of dobutamine and dopamine increases the blood pressure and decreases or doesn't change the ventricular filling pressure

Doubutamine [1], doxapram ---> SmPC of [1] of eMC

An increased risk of hypertension with concomitant use of the sympathomimetic agents and doxapram

Doubutamine [1], ergometrine ---> SmPC of [1] of eMC

Potential for ergotism to occur with concomitant administration of sympathomimetics and ergometrine

Doubutamine [1], ergotamine ---> SmPC of [1] of eMC

Potential for ergotism to occur with concomitant administration of sympathomimetics and ergotamine

Doubutamine [1], halogenated anaesthetics ---> SmPC of [1] of eMC

Although it is less likely than adrenaline to produce ventricular arrhythmias, dobutamine should be used with extreme caution during anaesthesia halothane and other halogenated anaesthetics.

Doubutamine [1], methysergide ---> SmPC of [1] of eMC

Potential for ergotism to occur with concomitant administration of sympathomimetics and methysergide

Doubutamine [1], oxytocin ---> SmPC of [1] of eMC

There is a possibility of oxytocin enhancing the pressor effects of sympathomimetics with or without hypertension.

Doubutamine [1], pregnancy ---> SmPC of [1] of eMC

There are no adequate studies in human pregnancy and therefore dobutamine should not be used without very careful consideration of the balance of risk.

Doubutamine [1], quinidine ---> SmPC of [1] of eMC

An increased risk of arrhythmias may occur if sympathomimetic agents are given to patients receiving quinidine.

Doubutamine, entacapone [2] ---> SmPC of [2] of EMA

Because of its mechanism of action, entacapone may interfere with the metabolism of medicinal products containing a catechol group and potentiate their action

Doubutamine, hydroxycobalamin

Physical incompatibility (particle formation). These medicinal products must not be administered simultaneously through the same intravenous line as hydroxocobalamine

Doubutamine, IMAOs [2] ---> SmPC of [2] of eMC

Many sympathomimetics interact with MAOIs (possibility of hypertensive crisis), and should not be given to patients receiving such treatment or within 14 days of its termination.

Doubutamine, insulin

Dobutamine may increase the insulin demand in diabetic patients

Doubutamine, linezolid [2] ---> SmPC of [2] of eMC

The co-administration is contraindicated, unless there are facilities available for close observation and monitoring of blood pressure

Doubutamine, milrinone

Milrinone enhances the positive inotropic effect

Doubutamine, nitroglycerine

Concomitant use of dobutamine and vasodilatators may cause more pronounced increase in cardiac output and decrease in pulmonary arterial pressure than when either medicinal product was given alone

Doubutamine, nitroprussiate

Concomitant use of dobutamine and vasodilatators may cause more pronounced increase in cardiac output and decrease in pulmonary arterial pressure than when either medicinal product was given alone

Doubutamine, noradrenaline

The co-administration may increase the blood pressure

Doubutamine, norepinephrine

The co-administration may increase the blood pressure

Doubutamine, organic nitrates

Concomitant use of dobutamine and vasodilatators may cause more pronounced increase in cardiac output and decrease in pulmonary arterial pressure than when either medicinal product was given alone

Doubutamine, ramipril [2] ---> SmPC of [2] of eMC

The antihypertensive effect may be reduced: Blood pressure monitoring is recommended.

Doubutamine, tolcapone [2] ---> SmPC of [2] of EMA

Tolcapone, COMT inhibitor, may increase the plasma concentrations of drugs metabolised by COMT

Doubutamine, tricyclic antidepressant [2] ---> SmPC of [2] of eMC

Hypertension and an increased risk of arrhythmias may occur if sympathomimetic agents are given to patients receiving tricyclic antidepressants.

Doubutamine, vasoconstrictors

The co-administration may increase the blood pressure

Doubutamine, vasodilators

Concomitant use of dobutamine and vasodilatators may cause more pronounced increase in cardiac output and decrease in pulmonary arterial pressure than when either medicinal product was given alone

CONTRAINDICATIONS of Doubutamine

- Previous hypersensitivity to dobutamine, sodium metabisulphite or other ingredients.

- Sulphites may cause hypersensitivity reactions including anaphylactic symptoms and life-threatening or serious asthmatic attacks in those affected. Hypersensitivity is observed more frequently in asthmatic or atopic patients.

- Avoid the use of sympathomimetic agents in patients with phaeochromocytoma.

http://www.medicines.org.uk/emc/

Doxazosin

Ability to drive, doxazosin [2] ---> SmPC of [2] of eMC

The ability to engage in activities such as operating machinery or operating a motor vehicle may be impaired, especially when initiating therapy.

Adrenaline, doxazosin

Doxazosin may reduce blood pressure and vascular reactions to adrenaline

Alfa-adrenergic receptor blockers, doxazosin [2] ---> SmPC of [2] of eMC

Doxazosin potentiates the blood pressure lowering activity of other alpha-blockers

Antihypertensives, doxazosin [2] ---> SmPC of [2] of eMC

Doxazosin potentiates the blood pressure lowering activity of other antihypertensives.

Avanafil [1], doxazosin ---> SmPC of [1] of EMA

The concomitant use of alpha-blockers and avanafil may lead to symptomatic hypotension in some patients due to additive vasodilatory effects

Boceprevir [1], doxazosin ---> SmPC of [1] of EMA

The concomitant use of boceprevir with doxazosin may increase plasma concentrations of doxazosin. The combination is not recommended

Breast-feeding, doxazosin [2] ---> SmPC of [2] of eMC

Doxazosin is contraindicated during lactation

Carteolol, doxazosin

Increased antihypertensive effect, increased risk of orthostatic hypotension

Doxazosin [1], PDE5 inhibitors ---> SmPC of [1] of eMC

Concomitant administration of doxazosin with a PDE-5 inhibitor may lead to symptomatic hypotension in some patients

Doxazosin [1], pregnancy ---> SmPC of [1] of eMC

Doxazosin should be used during pregnancy only if the potential benefit outweighs the risk.

Doxazosin [1], vardenafil ---> SmPC of [1] of eMC

Concomitant administration of doxazosin with a PDE-5 inhibitor may lead to symptomatic hypotension in some patients

Doxazosin, ephedrine

Doxazosin may reduce blood pressure and vascular reactions to ephedrine

Doxazosin, epinephrine

Doxazosin may reduce blood pressure and vascular reactions to epinephrine

Doxazosin, metaraminol

Doxazosin may reduce blood pressure and vascular reactions to metaraminol

Doxazosin, methoxamine

Doxazosin may reduce blood pressure and vascular reactions to methoxamine

Doxazosin, NSAID

The co-administration may weaken the hypotensive effect

Doxazosin, organic nitrates

The co-administration may enhance the hypotensive effect

Doxazosin, ramipril [2] ---> SmPC of [2] of eMC

Potentiation of the risk of hypotension is to be anticipated. Caution is recommended

Doxazosin, sildenafil [2] ---> SmPC of [2] of EMA

Concomitant administration of sildenafil to patients taking alpha-blocker therapy may lead to symptomatic hypotension in a few susceptible individuals.

Doxazosin, sympathomimetics

The co-administration may weaken the hypotensive effect

Doxazosin, tadalafil [2] ---> SmPC of [2] of EMA

The co-administration increases the blood pressure-lowering effect. The combination is not recommended

Doxazosin, vasodilators

The co-administration may enhance the hypotensive effect

Doxazosin, xipamide

Increased hypotensive effect. Risk of orthostatic hypotension

CONTRAINDICATIONS of Doxazosin

Doxazosin is contraindicated in

- Patients with a known hypersensitivity to quinazolines (e.g. prazosin, terazosin, doxazosin), or any of the excipients

- Patients with a history of orthostatic hypotension

- Patients with benign prostatic hyperplasia and concomitant congestion of the upper urinary tract, chronic urinary tract infections or bladder stones

- Patients with a history of gastrointestinal obstruction, oesophageal obstruction, or any degree of decreased lumen diameter of the gastrointestinal tract (For patients taking the sustained release tablets only)

- During lactation (For the hypertension indication only)

- Patients with hypotension (For the benign prostatic hyperplasia indication only)

Doxazosin is contraindicated as monotherapy in patients with either overflow bladder or anuria or without progressive renal insufficiency.

http://www.medicines.org.uk/emc/

Liposome-encapsulated doxorubicin-citrate complex (Myocet liposomal)

Ability to drive, liposome-encapsulated doxorubicin-citrate complex [2] ---> SmPC of [2] of EMA

Myocet liposomal has been reported to cause dizziness. Patients who suffer from this should avoid driving and operating machinery.

Antineoplastics, liposome-encapsulated doxorubicin-citrate complex [2] ---> SmPC of [2] of EMA

Doxorubicin may potentiate the toxicity of other antineoplastic agents.

Breast-feeding, liposome-encapsulated doxorubicin-citrate complex [2] ---> SmPC of [2] of EMA

Women receiving Myocet liposomal should not breastfeed.

Calcium antagonists, liposome-encapsulated doxorubicin-citrate complex [2] ---> SmPC of [2] of EMA

Concomitant treatment of doxorubicine with other substances reported to be cardiotoxic or with cardiologically active substances (e.g. calcium antagonists) may increase the risk for cardiotoxicity.

Cardioactive drugs, liposome-encapsulated doxorubicin-citrate complex [2] ---> SmPC of [2] of EMA

Concomitant treatment of doxorubicine with other substances reported to be cardiotoxic or with cardiologically active substances (e.g. calcium antagonists) may increase the risk for cardiotoxicity.

Cyclosporine, liposome-encapsulated doxorubicin-citrate complex [2] ---> SmPC of [2] of EMA

Plasma levels of doxorubicin and its metabolite, doxorubicinol, may be increased when doxorubicin is administered with cyclosporine, verapamil, paclitaxel or other agents that inhibit P-glycoprotein (P-Gp).

Liposomal substances, liposome-encapsulated doxorubicin-citrate complex [2] ---> SmPC of [2] of EMA

Concomitant therapy with other liposomal or lipid-complexed substances or intravenous fat emulsions could change the pharmacokinetic profile of Myocet liposomal.

Liposome-encapsulated doxorubicin-citrate complex [1], medicines with cardiotoxic effects ---> SmPC of [1] of EMA

Concomitant treatment of doxorubicine with other substances reported to be cardiotoxic or with cardiologically active substances (e.g. calcium antagonists) may increase the risk for cardiotoxicity.

Liposome-encapsulated doxorubicin-citrate complex [1], paclitaxel ---> SmPC of [1] of EMA

Liposome-encapsulated doxorubicin-citrate complex [1], pregnancy ---> SmPC of [1] of EMA

Due to the known cytotoxic, mutagenic and embryotoxic properties of doxorubicin, Myocet liposomal should not be used during pregnancy unless clearly necessary.

Liposome-encapsulated doxorubicin-citrate complex [1], streptozocin ---> SmPC of [1] of EMA

Interactions with doxorubicin have also been reported for streptozocin, phenobarbital, phenytoin and warfarin.

Liposome-encapsulated doxorubicin-citrate complex [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

Liposome-encapsulated doxorubicin-citrate complex [1], verapamil ---> SmPC of [1] of EMA

Liposome-encapsulated doxorubicin-citrate complex [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should use an effective contraceptive during treatment with Myocet liposomal and for 6.5 months following discontinuation of therapy.

Liposome-encapsulated doxorubicin-citrate complex [1], women of childbearing potential ---> SmPC of [1] of EMA

Women desiring to have children following completion of therapy should be recommended to obtain genetic counselling and advice on fertility preservation before treatment.

CONTRAINDICATIONS of Liposome-encapsulated doxorubicin-citrate complex (Myocet liposomal)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/myocet-liposomal-previously-myocet-epar-product-information_en.pdf 06/06/2024

Other trade names: Caelyx, Farmiblastina, Myocet liposomal (previously Myocet)

Doxorubicine

Abacavir/lamivudine/zidovudine [1], doxorubicine ---> SmPC of [1] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine

Ability to drive, doxorubicine [2] ---> SmPC of [2] of eMC

Due to the frequent occurrence of nausea and vomiting, driving cars and operation of machinery should be discouraged.

Allopurinol [1], doxorubicine ---> SmPC of [1] of eMC

Enhanced bone marrow suppression by cyclophosphamide and other cytotoxic agents has been reported among patients with neoplastic disease (other than leukaemia), in the presence of allopurinol.

Allopurinol/lesinurad [1], doxorubicine ---> SmPC of [1] of EMA

With administration of allopurinol and cytostatics (e.g. cyclophosphamide, doxorubicin, bleomycin, procarbazine, alkylating agents), blood dyscrasias occur more frequently than when these active substances are administered alone.

Amidopyrine, doxorubicine [2] ---> SmPC of [2] of eMC

(Pre-)treatment with drugs affecting the function of the bone might lead to severe hematopoetic disturbances. The dosage of doxorubicin has to be changed if necessary.

Amphotericin, doxorubicine [2] ---> SmPC of [2] of eMC

Marked nephrotoxicity of Amphotericin B can occur during doxorubicin therapy.

Anthracyclines, doxorubicine [2] ---> SmPC of [2] of eMC

Doxorubicin cardiotoxicity is enhanced by previous or concurrent use of other anthracyclines. When doxorubicin is used together, cardiac function must be followed carefully.

Anthracyclines, trastuzumab ---> SmPC of [doxorubicine] of eMC

The use of trastuzumab in combination with anthracyclines is associated with a high cardiotoxic risk. Careful monitoring of the cardiac function is imperative.

Antiepileptics, doxorubicine [2] ---> SmPC of [2] of eMC

The absorption of anticonvulsants (e.g. carbamazepine, phenytoin, valproate) is decreased when administered in combination with doxorubicin.

Antigout preparations, doxorubicine [2] ---> SmPC of [2] of eMC

Doxorubicin therapy may lead to increased serum uric acid; therefore dose adjustment of uric acid lowering agents may be necessary.

Antineoplastics, doxorubicine [2] ---> SmPC of [2] of eMC

Doxorubicin may potentiate the toxicity of other anticancer therapies.

Antineoplastics, pegylated liposomal doxorubicin [2] ---> SmPC of [2] of EMA

Doxorubicin hydrochloride preparations may potentiate the toxicity of other anti-cancer therapies.

Antiretrovirals, doxorubicine [2] ---> SmPC of [2] of eMC

(Pre-)treatment with drugs affecting the function of the bone might lead to severe hematopoetic disturbances. The dosage of doxorubicin has to be changed if necessary.

Barbiturates, doxorubicine [2] ---> SmPC of [2] of eMC

Concomitant administration of doxorubicin with inducers of CYP450 might decrease plasma concentrations of doxorubicin and reduce efficacy.

Breast-feeding, doxorubicine [2] ---> SmPC of [2] of eMC

Doxorubicin has been reported to be excreted in human breast milk. A risk to the suckling child cannot be excluded. Breastfeeding should be discontinued during treatment with doxorubicin

Calcium antagonists, doxorubicine [2] ---> SmPC of [2] of eMC

Doxorubicin cardiotoxicity is enhanced by previous or concurrent use of other potentially cardiotoxic drugs. When doxorubicin is used together, cardiac function must be followed carefully.

Carbamazepine, doxorubicine [2] ---> SmPC of [2] of eMC

Concomitant administration of doxorubicin with inducers of CYP450 might decrease plasma concentrations of doxorubicin and reduce efficacy and decrease the absorption of carbamazepine

Carmustine, doxorubicine

The co-administration of carmustine with other myelosuppressive agents may increase the myelotoxicity (thrombopenia and leucopenia)

Chloramphenicol, doxorubicine [2] ---> SmPC of [2] of eMC

(Pre-)treatment with drugs affecting the function of the bone might lead to severe hematopoetic disturbances. The dosage of doxorubicin has to be changed if necessary.

Cimetidine, doxorubicine [2] ---> SmPC of [2] of eMC

Cimetidine has been shown to reduce the plasma clearance and increase the AUC of doxorubicin.

Cisplatin, doxorubicine [2] ---> SmPC of [2] of eMC

The toxic effects of a doxorubicin therapy may be increased in a combination with other cytostatics

Clozapine, doxorubicine [2] ---> SmPC of [2] of eMC

Clozapine may increase the risk and severity of the hematologic toxicity of doxorubicin.

Cyclophosphamide, doxorubicine [2] ---> SmPC of [2] of eMC

The toxic effects of a doxorubicin therapy may be increased in a combination with other cytostatics. Doxorubicin may cause exacerbations of hemorrhagic cystitis caused by previous cyclophosphamide therapy.

Cyclophosphamide, pegylated liposomal doxorubicin [2] ---> SmPC of [2] of EMA

In patients with AIDS, exacerbation of cyclophosphamide-induced haemorrhagic cystitis have been reported

Cyclosporine, doxorubicine [2] ---> SmPC of [2] of eMC

Ciclosporin, an inhibitor of CYP3A4 and Pgp, increased the AUC of doxorubicin and doxorubicinol by 55% and 350%, respectively. A 40% dose reduction of doxorubicin is proposed for this combination.

CYP2D6 inhibitors, doxorubicine

The CYP2D6 inhibition may increase plasma concentrations of doxorubicin, which has a narrow therapeutic index

Cytarabine, doxorubicine [2] ---> SmPC of [2] of eMC

The toxic effects of a doxorubicin therapy may be increased in a combination with other cytostatics. Necroses of the large intestine with massive haemorrhage and severe infections in connection with combination therapies with cytarabine.

Cytostatics, doxorubicine [2] ---> SmPC of [2] of eMC

The toxic effects of a doxorubicin therapy may be increased in a combination with other cytostatics

Cytotoxic agents, pegylated liposomal doxorubicin [2] ---> SmPC of [2] of EMA

Caution must be exercised when giving doxorubicin with any other cytotoxic agents, especially myelotoxic agents, at the same time.

Digoxin, doxorubicine [2] ---> SmPC of [2] of eMC

Doxorubicin may reduce oral bioavailability of digoxin.

Doxorubicine [1], enzyme inductors ---> SmPC of [1] of eMC

Concomitant administration of doxorubicin with inducers of CYP450 might decrease plasma concentrations of doxorubicin and reduce efficacy.

Doxorubicine [1], enzyme inhibitors ---> SmPC of [1] of eMC

Concomitant administration of inhibitors of CYP450 and/or Pgp might lead to increased plasma concentrations of doxorubicin and thereby increased toxicity.

Doxorubicine [1], fluorouracil ---> SmPC of [1] of eMC

Doxorubicin cardiotoxicity is enhanced by previous or concurrent use of other potentially cardiotoxic drugs. When doxorubicin is used together, cardiac function must be followed carefully.

Doxorubicine [1], heparin ---> SmPC of [1] of eMC

Doxorubicin binds to heparin. Precipitations and loss of action of both substances are therefore possible.

Doxorubicine [1], hepatotoxic chemotherapeutic agents ---> SmPC of [1] of eMC

The concomitant administration of known hepatotoxic chemotherapeutic agents (e.g. mercaptopurine, methotrexate, streptozocin) could potentially increase the toxicity of doxorubicin as a result of reduced hepatic clearance of the drug.

Doxorubicine [1], hepatotoxic drugs ---> SmPC of [1] of eMC

Doxorubicin hepatotoxicity may be enhanced by other hepatotoxic treatment modalities (e.g. 6-mercaptopurine)

Doxorubicine [1], medicines with cardiotoxic effects ---> SmPC of [1] of eMC

Doxorubicin cardiotoxicity is enhanced by previous or concurrent use of other potentially cardiotoxic drugs. When doxorubicin is used together, cardiac function must be followed carefully.

Doxorubicine [1], mercaptopurine ---> SmPC of [1] of eMC

Doxorubicine [1], methotrexate ---> SmPC of [1] of eMC

Doxorubicine [1], myelosuppressive agents ---> SmPC of [1] of eMC

(Pre-)treatment with drugs affecting the function of the bone might lead to severe hematopoetic disturbances. The dosage of doxorubicin has to be changed if necessary.

Doxorubicine [1], P-gp inhibitors ---> SmPC of [1] of eMC

Concomitant administration of inhibitors of CYP450 and/or Pgp might lead to increased plasma concentrations of doxorubicin and thereby increased toxicity.

Doxorubicine [1], paclitaxel ---> SmPC of [1] of eMC

Paclitaxel administered shortly before doxorubicin may decrease clearance and increase plasma concentrations of doxorubicin. Some data indicate that this interaction is less pronounced when doxorubicin is administered before paclitaxel.

Doxorubicine [1], phenobarbital ---> SmPC of [1] of eMC

Concomitant administration of doxorubicin with inducers of CYP450 might decrease plasma concentrations of doxorubicin and reduce efficacy.

Doxorubicine [1], phenytoin ---> SmPC of [1] of eMC

(Pre-)treatment with drugs affecting the function of the bone might lead to severe hematopoetic disturbances. The dosage of doxorubicin has to be changed if necessary.

Doxorubicine [1], pregnancy ---> SmPC of [1] of eMC

Doxorubicin should not be given during pregnancy. In general cytostatics should only be administered during pregnancy on strict indication, and the benefit to the mother weighed against possible hazards to the foetus.

Doxorubicine [1], radiotherapy ---> SmPC of [1] of eMC

Any preceding, concomitant or subsequent radiation therapy may increase the cardiotoxicity or hepatotoxicity of doxorubicin. This applies also to concomitant therapies with cardiotoxic or hepatotoxic drugs.

Doxorubicine [1], rifampicin ---> SmPC of [1] of eMC

Concomitant administration of doxorubicin with inducers of CYP450 might decrease plasma concentrations of doxorubicin and reduce efficacy.

Doxorubicine [1], ritonavir ---> SmPC of [1] of eMC

Elevated serum doxorubicin concentrations were reported after the concomitant administration of doxorubicin and ritonavir.

Doxorubicine [1], sodium valproate ---> SmPC of [1] of eMC

The absorption of anticonvulsants (e.g. carbamazepine, phenytoin, valproate) is decreased when administered in combination with doxorubicin.

Doxorubicine [1], streptozocin ---> SmPC of [1] of eMC

Doxorubicine [1], strong P-gp inhibitors ---> SmPC of [1] of eMC

Concomitant administration of inhibitors of CYP450 and/or Pgp might lead to increased plasma concentrations of doxorubicin and thereby increased toxicity.

Doxorubicine [1], sulphonamides ---> SmPC of [1] of eMC

(Pre-)treatment with drugs affecting the function of the bone might lead to severe hematopoetic disturbances. The dosage of doxorubicin has to be changed if necessary.

Doxorubicine [1], trastuzumab ---> SmPC of [1] of EMA

Trastuzumab may elevate the overall exposure of one doxorubicin metabolite, (7-deoxy-13 dihydro-doxorubicinone, D7D). The bioactivity of D7D and the clinical impact of the elevation of this metabolite was unclear

Doxorubicine [1], vaccinations ---> SmPC of [1] of eMC

During treatment with doxorubicin, patients should not be actively vaccinated and also avoid contact with recently polio vaccinated persons.

Doxorubicine, gallopamil

The concomitant use of doxorubicin and oral phenylalkylamine may increase the bioavailibility and the maximal plasma levels of doxorubicin

Doxorubicine, ganciclovir [2] ---> SmPC of [2] of eMC

Toxicity may be enhanced when valganciclovir is co-administered with, or is given immediately before or after, other drugs that inhibit replication of rapidly dividing cell populations

Doxorubicine, interferon alfa-2b [2] ---> SmPC of [2] of EMA

Administration of interferon alfa-2b in combination with other chemotherapeutic agents (e.g., Ara-C, cyclophosphamide, doxorubicin, teniposide) may lead to increased risk of toxicity (severity and duration)

Doxorubicine, isavuconazole [2] ---> SmPC of [2] of EMA

No CRESEMBA dose adjustment necessary. Daunorubicin, doxorubicin, imatinib, irinotecan, lapatinib, mitoxantrone or topotecan: careful monitoring for any occurrence of drug toxicity, and dose reduction if required.

Doxorubicine, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Doxorubicine, leflunomide [2] ---> SmPC of [2] of EMA

For substrates of BCRP, concomitant administration with leflunomide should be undertaken with caution. Patients should be closely monitored for signs and symptoms of excessive exposure to the medicinal products

Doxorubicine, mifamurtide [2] ---> SmPC of [2] of EMA

It is recommended to separate the administration times of mifamurtide and lipophilic medicinal products if used in the same chemotherapy regimen

Doxorubicine, mytomicin

The long-term co-administration may cause a hemolytic uremic syndrome and enhance the cardiotoxicity of doxorubicin

Doxorubicine, nadroparin

The co-administration may weaken the nadroparin effect

Doxorubicine, P-gp inductors

The induction of P-glycoprotein may decrease the plasma levels of doxorubicin

Doxorubicine, phenylalkylamines

The concomitant use of doxorubicin and oral phenylalkylamine may increase the bioavailibility and the maximal plasma levels of doxorubicin

Doxorubicine, quinidine

The inhibition of P-glycoprotein may increase the plasma levels of doxorubicin and its metabolite, doxorubicinol. Contra-indicated

Doxorubicine, rolapitant [2] ---> SmPC of [2] of EMA

Rolapitant is an inhibitor of Breast-Cancer-Resistance Protein (BCRP). Increased plasma concentrations of BCRP substrates may result in potential adverse reactions.

Doxorubicine, sorafenib [2] ---> SmPC of [2] of EMA

Concomitant treatment with sorafenib resulted in a small increase in the AUC of doxorubicin

Doxorubicine, stavudine [2] ---> SmPC of [2] of EMA

In vitro studies indicate that the activation of stavudine is inhibited by doxorubicin and ribavirin therefore, coadministration of stavudine with either doxorubicin or ribavirin should be undertaken with caution.

Doxorubicine, strong P-gp inductors

The strong induction of P-glycoprotein may decrease the plasma levels of doxorubicin

Doxorubicine, teriflunomide [2] ---> SmPC of [2] of EMA

Teriflunomide, BCRP inhibitor, may increase the AUC of BCRP substrate. The co-administration should be undertaken with caution

Doxorubicine, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of doxorubicine thus increasing risk of toxicity

Doxorubicine, valganciclovir [2] ---> SmPC of [2] of eMC

Toxicity may be enhanced when valganciclovir is co-administered with, or is given immediately before or after, other drugs that inhibit replication of rapidly dividing cell populations

Doxorubicine, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

Verapamil may increase the plasma concentrations of doxorubicine thus increasing risk of toxicity

Doxorubicine, vincristine

Concomitant use of vincristine and other myelosuppressive drugs (e. g. doxorubicine, particularly in combination with prednisone) may enhance the suppressive effects on bone marrow

Doxorubicine, vinflunine [2] ---> SmPC of [2] of EMA

The co-administration may increase the risk of hematological toxicity

Doxorubicine, warfarin

Interactions with doxorubicin have been reported for warfarin

Doxorubicine, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

CONTRAINDICATIONS of Doxorubicine

- Hypersensitivity to the active substance or to any of the excipients.

- Hypersensitivity to other anthracyclines or to anthracendiones.

Contraindications for intravenous administration:

- persistent myelosuppression or severe stomatitis which appeared during previous cytotoxic treatment and/or radiation

- general infection

- severe impaired liver function

- severe arrhythmia, impaired cardiac function, previous cardiac infarct, acute inflammatory heart disease

- previous treatment with anthracyclines with maximum cumulative doses

- increased haemorrhagic tendency.

Contraindications of intravesical administration:

- invasive tumours that have penetrated the bladder (beyond T1)

- urinary tract infections

- inflammation of the bladder

- problems with catheterization e.g. urethral stenosis

- haematuria.

- breast-feeding.

http://www.medicines.org.uk/emc/

Pegylated liposomal doxorubicin (Caelyx)

Antineoplastics, pegylated liposomal doxorubicin [2] ---> SmPC of [2] of EMA

Doxorubicin hydrochloride preparations may potentiate the toxicity of other anti-cancer therapies.

Breast-feeding, pegylated liposomal doxorubicin [2] ---> SmPC of [2] of EMA

Health experts recommend that HIV infected women do not breast-feed their infants under any circumstances in order to avoid transmission of HIV.

Cyclophosphamide, pegylated liposomal doxorubicin [2] ---> SmPC of [2] of EMA

In patients with AIDS, exacerbation of cyclophosphamide-induced haemorrhagic cystitis have been reported

Cytotoxic agents, pegylated liposomal doxorubicin [2] ---> SmPC of [2] of EMA

Caution must be exercised when giving doxorubicin with any other cytotoxic agents, especially myelotoxic agents, at the same time.

Medicines with myelotoxic effects, pegylated liposomal doxorubicin [2] ---> SmPC of [2] of EMA

Caution must be exercised when giving doxorubicin with any other cytotoxic agents, especially myelotoxic agents, at the same time.

Pegylated liposomal doxorubicin [1], pregnancy ---> SmPC of [1] of EMA

Doxorubicin hydrochloride is suspected to cause serious birth defects when administered during pregnancy. Therefore, it should not be used during pregnancy unless clearly necessary.

CONTRAINDICATIONS of Pegylated liposomal doxorubicin (Caelyx)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- It must not be used to treat AIDS-KS that may be treated effectively with local therapy or systemic alfa-interferon.

http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000089/WC500020180.pdf.

Doxorubicin pegylated liposomal (Zolsketil pegylated liposomal)

Ability to drive, doxorubicin pegylated liposomal [2] ---> SmPC of [2] of EMA However, in clinical studies to date, dizziness and somnolence were associated infrequently (< 5%) with the administration of doxorubicin pegylated liposomal. Patients who suffer from these effects must avoid driving and operating machinery.

Antineoplastics, pegylated liposomal doxorubicin [2] ---> SmPC of [2] of EMA Doxorubicin hydrochloride preparations may potentiate the toxicity of other anti-cancer therapies.

Breast-feeding, doxorubicin pegylated liposomal [2] ---> SmPC of [2] of EMA Because many medicinal products, incl. anthracyclines, are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants, therefore mothers must discontinue nursing prior to beginning treatment.

Breast-feeding, pegylated liposomal doxorubicin [2] ---> SmPC of [2] of EMA Health experts recommend that HIV infected women do not breast-feed their infants under any circumstances in order to avoid transmission of HIV.

Cyclophosphamide, pegylated liposomal doxorubicin [2] ---> SmPC of [2] of EMA In patients with AIDS, exacerbation of cyclophosphamide-induced haemorrhagic cystitis have been reported

Cytotoxic agents, pegylated liposomal doxorubicin [2] ---> SmPC of [2] of EMA Caution must be exercised when giving doxorubicin with any other cytotoxic agents, especially myelotoxic agents, at the same time.

Doxorubicin pegylated liposomal [1], fertility ---> SmPC of [1] of EMA The effect of doxorubicin hydrochloride on human fertility has not been evaluated (see section 5.3).

Doxorubicin pegylated liposomal [1], men ---> SmPC of [1] of EMA Men are recommended to use effective contraceptive measures and to not father a child while receiving doxorubicin pegylated liposomal and for 6 months following completion of treatment.

Doxorubicin pegylated liposomal [1], women of childbearing potential ---> SmPC of [1] of EMA Due to the genotoxic potential of doxorubicin hydrochloride, women of child-bearing potential should use effective contraceptive measures while being treated with doxorubicin pegylated liposomal and for 8 months following completion of treatment.

Doxorubicin pegylated liposomal, vinflunine [2] ---> SmPC of [2] of EMA A pharmacokinetic interaction between vinflunine and pegylated/liposomal doxorubicin was observed, resulting in a 15% to 30% apparent increase in vinflunine exposure and a 2 to 3-fold apparent decrease of doxorubicin AUC

Medicines with myelotoxic effects, pegylated liposomal doxorubicin [2] ---> SmPC of [2] of EMA Caution must be exercised when giving doxorubicin with any other cytotoxic agents, especially myelotoxic agents, at the same time.

Pegylated liposomal doxorubicin [1], pregnancy ---> SmPC of [1] of EMA Doxorubicin hydrochloride is suspected to cause serious birth defects when administered during pregnancy. Therefore, it should not be used during pregnancy unless clearly necessary.

CONTRAINDICATIONS of Doxorubicin pegylated liposomal (Zolsketil pegylated liposomal)

- Hypersensitivity to the active substance, peanut or soya, or to any of the excipients listed in section 6.1.

- Doxorubicin pegylated liposomal must not be used to treat AIDS-KS that may be treated effectively with local therapy or systemic alfa-interferon.

https://www.ema.europa.eu/en/documents/product-information/zolsketil-pegylated-liposomal-epar-product-information_en.pdf 13/03/2025

Doxycycline

Activated charcoal, doxycycline

Decreased absorption of doxycycline. It is recommended to administer the two substances at least 2 to 3 hours apart.

Alcohol, doxycycline [2] ---> SmPC of [2] of eMC

Alcohol may decrease the half-life of doxycycline.

Almasilate, doxycycline

Absorption reduction of the active principle co-administered with almasilate due to formation of non-soluble complexes. It is recommended to administer the two substances at least 2 to 3 hours apart.

Aluminium, tetracyclines

Decreased absorption of tetracycline. It is recommended to administer the two substances at least 3 hours apart.

Antacids, doxycycline [2] ---> SmPC of [2] of eMC

Absorption of doxycycline may be impaired by concurrently administered with drugs containing aluminium, calcium, magnesium or other these cations; oral zinc, iron salts or bismuth preparations. Dosages should be maximally separated.

Antacids, tetracyclines

Decreased absorption of tetracycline. It is recommended to administer the two substances at least 3 hours apart.

Anticoagulants, tetracyclines

Tetracycline may decrease the plasma prothrombin time and increase the anticoagulant activity. A reduction of anti-coagulant doses may be required

Bactericides, doxycycline

The co-administration of bactericide with bacteriostatic antibiotics should be avoided due to possible antagonist effects

Barbiturates, doxycycline

The enzymatic inductor may decrease the plasma levels of doxycycline

Beta-lactam antibiotics, doxycycline

The co-administration of a bactericide antibiotic with a bacteriostatic should be avoided due to possible antagonist effects

Bismuth, doxycycline [2] ---> SmPC of [2] of eMC

Bismuth, tetracyclines

Decreased absorption of tetracycline. It is recommended to administer the two substances at least 3 hours apart.

Breast-feeding, doxycycline [2] ---> SmPC of [2] of eMC

Tetracyclines are excreted into milk and are therefore contra-indicated in nursing mothers.

Breast-feeding, tetracyclines ---> SmPC of [doxycycline] of eMC

Tetracyclines are excreted into milk and are therefore contra-indicated in nursing mothers.

Calcium acetate [1], doxycycline ---> SmPC of [1] of eMC

Decreased absorption of tetracycline. It is recommended to administer the two substances at least 1-2 hours apart.

Calcium aspartate, tetracyclines ---> SmPC of [doxycycline] of eMC

Oral calcium administration may reduce the absorption of oral tetracyclines. An interval of 3 hours should be observed if the two are to be given.

Calcium citrate, tetracyclines ---> SmPC of [doxycycline] of eMC

Oral calcium administration may reduce the absorption of oral tetracyclines. An interval of 3 hours should be observed if the two are to be given.

Calcium, doxycycline [2] ---> SmPC of [2] of eMC

Carbamazepine [1], doxycycline ---> SmPC of [1] of eMC

Carbamazepine may lower the plasma level of doxycycline

Cephalosporins, doxycycline

The co-administration of bactericide with bacteriostatic antibiotics should be avoided due to possible antagonist effects

Chelating agents, doxycycline [2] ---> SmPC of [2] of eMC

Cholestyramine [1], doxycycline ---> SmPC of [1] of eMC

Cholestyramine may delay or reduce the absorption of tetracycline. Patients should take other drugs at least 1 hour before or 4-6 hours after colestyramine to minimize possible interference with their absorption.

Collagenase clostridium histolyticum [1], doxycycline ---> SmPC of [1] of EMA

Use of Xiapex in patients who have received tetracycline antibiotics (e.g., doxycycline) within 14 days prior to receiving an injection of Xiapex is not recommended.

Coumarin anticoagulants, doxycycline

Doxycycline depresses plasma prothrombin activity thereby potentiating the effect of anticoagulant of the dicoumarol type

Cyclosporine, doxycycline [2] ---> SmPC of [2] of eMC

Doxycycline may increase the plasma concentration of ciclosporin. Co-administration should only be undertaken with appropriate monitoring.

Dabrafenib [1], doxycycline ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Dairy products, doxycycline [2] ---> SmPC of [2] of eMC

Diphenylhydantoin, doxycycline

The enzymatic inductor may decrease the plasma levels of doxycycline

Divalent cations, doxycycline [2] ---> SmPC of [2] of eMC

Doxycycline [1], enzyme inductors ---> SmPC of [1] of eMC

Drugs that induce hepatic enzymes may accelerate the decomposition of doxycycline

Doxycycline [1], iron ---> SmPC of [1] of eMC

Doxycycline [1], magnesium ---> SmPC of [1] of eMC

Doxycycline [1], magnesium hydroxide ---> SmPC of [1] of eMC

Doxycycline [1], methoxyflurane ---> SmPC of [1] of eMC

The concurrent use of tetracyclines and methoxyflurane has been reported to result in fatal renal toxicity.

Doxycycline [1], milk ---> SmPC of [1] of eMC

Doxycycline [1], penicillins ---> SmPC of [1] of eMC

Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving doxycycline in conjunction with penicillin.

Doxycycline [1], phenytoin ---> SmPC of [1] of eMC

Phenytoin may increase the metabolism of doxycycline (reduced half-life). An increase in the daily dosage of doxycycline should be considered.

Doxycycline [1], pregnancy ---> SmPC of [1] of eMC

Doxycycline is contra-indicated in pregnancy. It appears that the risks associated with the use of tetracyclines during pregnancy are predominantly due to effects on teeth and skeletal development.

Doxycycline [1], primidone ---> SmPC of [1] of eMC

Primidone may increase the metabolism of doxycycline (reduced half-life). An increase in the daily dosage of doxycycline should be considered.

Doxycycline [1], rifampicin ---> SmPC of [1] of eMC

Drugs that induce hepatic enzymes such as rifampicin may accelerate the decomposition of doxycycline

Doxycycline [1], sucralfate ---> SmPC of [1] of eMC

Doxycycline [1], sun ---> SmPC of [1] of eMC

Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines, including doxycycline.

Doxycycline [1], trivalent cations ---> SmPC of [1] of eMC

Doxycycline [1], warfarin ---> SmPC of [1] of eMC

There have been reports of prolonged prothrombin time in patients taking warfarin and doxycycline.

Doxycycline, ferric citrate coordination complex [2] ---> SmPC of [2] of EMA

Any medicinal product that has the potential to interact with Fexeric, should be taken at least 2 hours before or after Fexeric.

Doxycycline, fosphenytoin [2] ---> SmPC of [2] of eMC

Blood levels and/or effects of doxycycline may be altered by phenytoin

Doxycycline, gastric pH increasing medication

Medicinal products which increase gastric pH may reduce the absorption of doxycycline, and should be taken at least 2 hours after doxycycline

Doxycycline, lanthanum carbonate [2] ---> SmPC of [2] of eMC

Interactions with tetracycline and doxycycline are theoretically possible and if these compounds are to be co-administered, it is recommended that they are not to be taken within 2 hours of dosing with lanthanum carbonate

Doxycycline, phenobarbital [2] ---> SmPC of [2] of eMC

Phenobarbital increases the rate of metabolism reducing serum concentrations of doxycycline

Doxycycline, strontium ranelate [2] ---> SmPC of [2] of EMA

As divalent cations can form complexes with oral tetracycline at the gastro-intestinal level and thereby reduce their absorption, simultaneous administration is not recommended.

Doxycycline, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

When administering any medicinal product that is already known to interact with iron (like alendronate and doxycycline), the medicinal product should be administered at least 1 hour before or 2 hours after Velphoro.

Doxycycline, sulfonylureas

Potentiation of the blood-sugar-lowering effect and possible hypoglycaemia

Iron, tetracyclines

Decreased absorption of tetracycline. It is recommended to administer the two substances at least 3 hours apart.

Kaolin, tetracyclines ---> SmPC of [doxycycline] of eMC

Kaolin possibly reduces the absorption tetracyclines

Magaldrate, tetracyclines

Considerable decrease in the absorption of tetracycline. During the treatment with a tetracycline is not recommended la administration of magaldrate

Magnesium, tetracyclines

Decreased absorption of tetracycline. It is recommended to administer the two substances at least 3 hours apart.

Methoxyflurane, tetracyclines ---> SmPC of [doxycycline] of eMC

The concurrent use of tetracyclines and methoxyflurane has been reported to result in fatal renal toxicity.

Polycarbophil calcium, tetracyclines

Decreased absorption of tetracycline. It is recommended to administer the two substances at least 3 hours apart.

CONTRAINDICATIONS of Doxycycline

- Hypersensitivity to doxycycline, any of the tetracyclines or any of the ingredients

- The use of drugs of the tetracycline class during tooth development (pregnancy, infancy and childhood to the age of 12 years) may cause permanent discolouration of the teeth (yellow-grey-brown). This adverse reaction is more common during long-term use of the drugs but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. Doxycycline is contra-indicated in these groups of patients.

- Children under 12 years of age: Contraindicated in children under the age of 12 years. As with other tetracyclines, doxycycline forms a stable calcium complex in any bone-forming tissue. A decrease in the fibula growth rate has been observed in prematures given oral tetracyclines in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued.

- Pregnancy: Doxycycline is contra-indicated in pregnancy. It appears that the risks associated with the use of tetracyclines during pregnancy are predominantly due to effects on teeth and skeletal development.

- Nursing mothers: Tetracyclines are excreted into milk and are therefore contra-indicated in nursing mothers.

http://www.medicines.org.uk/emc/

Doxylamine

Ability to drive, doxylamine

Decreased ability to react may occur

Adrenaline, doxylamine

Hypotension (adrenaline reversal)

Alcohol, doxylamine

Alcohol intake should be avoided during treatment with doxylamine because alcohol may potentiate the doxylamine action in an unpredictable fashion.

Alpha-methyldopa, doxylamine

Enhanced sedation

Aminoglycoside antibiotics, doxylamine

Antihistaminics may mask the ototoxic effects of other drugs

Anaesthetics, doxylamine

Antihistaminic agents have additive effects with other CNS depressants

Analgesics, doxylamine

Antihistaminic agents have additive effects with other CNS depressants

Antiarrhythmics, doxylamine

Concomitant use of doxylamine with drugs that prolong the QT interval should be avoided

Anticholinergics, doxylamine

The combination of doxylamine with other anticholinergic medicinal products may enhance the anticholinergic effects

Antidepressants, doxylamine

Antihistaminic agents have additive effects with other CNS depressants

Antiepileptics, doxylamine

Antihistaminic agents have additive effects with other CNS depressants

Antihistamines, carboplatin

Antihistaminics may mask the ototoxic effects of other drugs

Antihistamines, chloroquine

Antihistaminics may mask the ototoxic effects of other drugs

Antihistamines, erythromycin

Antihistaminics may mask the ototoxic effects of other drugs

Antihistamines, ototoxic agents

Antihistaminics may mask the ototoxic effects of other drugs

Antiparkinsonian agents, doxylamine

The combination of doxylamine with other anticholinergic medicinal products may enhance the anticholinergic effects

Anxiolytics, doxylamine

Antihistaminic agents have additive effects with other CNS depressants

Atropine, doxylamine

The combination of doxylamine with other anticholinergic medicinal products may enhance the anticholinergic effects

Azole antifungals, doxylamine

Concomitant use of doxylamine with inhibitors of cytochrome P450 should be avoided

Barbiturates, doxylamine

Antihistaminic agents have additive effects with other CNS depressants

Biperiden, doxylamine

The combination of doxylamine with other anticholinergic medicinal products may enhance the anticholinergic effects

Breast-feeding, doxylamine

Doxylamine is contraindicated during breastfeeding

CNS depressants, doxylamine

Antihistaminic agents have additive effects with other CNS depressants

Centrally-acting antihypertensives, doxylamine

Enhanced sedation

Clonidine, doxylamine

Enhanced sedation

Disturbances of electrolyte balance, doxylamine

Concomitant use of doxylamine with drugs that cause electrolyte imbalance should be avoided

Doxylamine, drugs inducing hypokaliemia

Concomitant use of doxylamine with drugs that cause electrolyte imbalance should be avoided

Doxylamine, enzyme inhibitors

Concomitant use of doxylamine with inhibitors of cytochrome P450 should be avoided

Doxylamine, epinephrine

Hypotension (adrenaline reversal)

Doxylamine, ethosuximide

Concomitant use of doxylamine and ethosuximide should be avoided

Doxylamine, guanabenz

Enhanced sedation

Doxylamine, hypnotics

Antihistaminic agents have additive effects with other CNS depressants

Doxylamine, hypomagnesemia

Concomitant use of doxylamine with drugs that cause electrolyte imbalance should be avoided

Doxylamine, macrolide antibiotics

Concomitant use of doxylamine with inhibitors of cytochrome P450 should be avoided

Doxylamine, monoamine oxidase inhibitors

The combination of doxylamine with other anticholinergic medicinal products may enhance the anticholinergic effects

Doxylamine, neuroleptics

Antihistaminic agents have additive effects with other CNS depressants

Doxylamine, ototoxic agents

Antihistaminics may mask the ototoxic effects of other drugs

Doxylamine, phenytoin

Decreased effect of phenytoin

Doxylamine, pregnancy

Doxylamine is contraindicated during pregnancy

Doxylamine, sedatives

Antihistaminic agents have additive effects with other CNS depressants

Doxylamine, tranquilizers

Antihistaminic agents have additive effects with other CNS depressants

Doxylamine, tricyclic antidepressants

The combination of doxylamine with other anticholinergic medicinal products may enhance the anticholinergic effects

QT interval prolonging drugs, doxylamine

Concomitant use of doxylamine with drugs that prolong the QT interval should be avoided

Dronedarone (Multaq)

Ability to drive, dronedarone [2] ---> SmPC of [2] of EMA

MULTAQ has no or negligible influence on the ability to drive and use machines. However, ability to drive and use machines may be affected by adverse reactions such as fatigue.

AIIRA, dronedarone [2] ---> SmPC of [2] of EMA

No interaction was observed between dronedarone and losartan and an interaction between dronedarone and other AIIRAs is not expected.

Antidepressants metabolised by CYP2D6, dronedarone [2] ---> SmPC of [2] of EMA

Since dronedarone is a weak inhibitor of CYP 2D6 in humans, it is predicted to have limited interaction on antidepressant medicinal products metabolised by CYP 2D6.

Apixaban, dronedarone [2] ---> SmPC of [2] of EMA

Dronedarone may increase the exposure of apixaban (a CYP3A4 and P-gp substrate). However, no dose adjustment for apixaban is required when co-administered with agents that are not strong inhibitors of both CYP3A4 and P-gp, such as dronedarone.

Arrhytmogenic agents, dronedarone [2] ---> SmPC of [2] of EMA

Proarrhythmic effects may occur in particular situations such as concomitant use with medicinal products favouring arrhythmia and/or electrolytic disorders

Atazanavir/cobicistat [1], dronedarone ---> SmPC of [1] of EMA

Co-administration of medicinal products that are substrates of CYP3A and have narrow therapeutic indexes and for which elevated plasma concentrations are associated with serious and/or life-threatening events are contraindicated with EVOTAZ.

Atazanavir/ritonavir, dronedarone

The co-administration of atazanavir/ritonavir (strong CYP3A4 inhibitors) may increase the plasma concentrations of the antiarrhythmic. Caution is warranted

Atorvastatin, dronedarone [2] ---> SmPC of [2] of EMA

Dronedarone can increase exposure of statins that are substrates of CYP 3A4 and/or P-gp substrates or transported by OATP. Concomitant use of statins should be undertaken with caution.

Bepridil, dronedarone [2] ---> SmPC of [2] of EMA

Medicinal products inducing torsades de pointes are contraindicated because of the potential risk of proarrhythmias

Betablockers metabolised by CYP2D6, dronedarone [2] ---> SmPC of [2] of EMA

Dronedarone, CYP2D6 inhibitor, may increase the exposition of beta blocker metabolized by CYP2D6. In clinical studies, bradycardia was more frequently observed when dronedarone was given in combination with beta-blockers.

Bictegravir/emtricitabine/tenofovir alafenamide [1], dronedarone ---> SmPC of [1] of EMA

Therefore, caution is recommended when bictegravir is combined with medicinal products known to inhibit P-gp and/or BCRP (e.g. macrolides, ciclosporin, verapamil, dronedarone, glecaprevir/pibrentasvir)

Bosutinib [1], dronedarone ---> SmPC of [1] of EMA

Breast-feeding, dronedarone [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from MULTAQ therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Breast-feeding, dronedarone [2] ---> SmPC of [2] of EMA

Women should be advised not to breastfeed during treatment with MULTAQ and for 7 days (about 5 half-lives) after the final dose.

Calcium antagonists, dronedarone [2] ---> SmPC of [2] of EMA

The CYP3A4 inhibition may increase the exposition of calcium antagonist. In patients already on calcium antagonists at time of dronedarone initiation, an ECG should be performed and the calcium antagonist dose should be adjusted if needed

Carbamazepine, dronedarone [2] ---> SmPC of [2] of EMA

Rifampicin decreased dronedarone exposure. Therefore, co-administration of rifampicin and other potent CYP3A4 inducers is not recommended as they decrease dronedarone exposure.

Cerivastatin, dronedarone [2] ---> SmPC of [2] of EMA

Dronedarone can increase exposure of statins that are substrates of CYP 3A4 and/or P-gp substrates or transported by OATP. Concomitant use of statins should be undertaken with caution.

Cisapride, dronedarone [2] ---> SmPC of [2] of EMA

Medicinal products inducing torsades de pointes are contraindicated because of the potential risk of proarrhythmias

Clarithromycin, dronedarone [2] ---> SmPC of [2] of EMA

Concomitant use of dronedarone with strong CYP3A4 inhibitors increases dronedarone exposure. The combination of dronedarone with strong CYP3A4 inhibitors is contraindicated

Class I antiarrhythmic agents, dronedarone [2] ---> SmPC of [2] of EMA

Medicinal products inducing torsades de pointes are contraindicated because of the potential risk of proarrhythmias

Class IA antiarrhythmic agents, dronedarone [2] ---> SmPC of [2] of EMA

Medicinal products inducing torsades de pointes are contraindicated because of the potential risk of proarrhythmias

Class IB antiarrhythmic agents, dronedarone [2] ---> SmPC of [2] of EMA

Medicinal products inducing torsades de pointes are contraindicated because of the potential risk of proarrhythmias

Class IC antiarrhythmic agents, dronedarone [2] ---> SmPC of [2] of EMA

Medicinal products inducing torsades de pointes are contraindicated because of the potential risk of proarrhythmias

Class III antiarrhythmic agents, dronedarone [2] ---> SmPC of [2] of EMA

Medicinal products inducing torsades de pointes are contraindicated because of the potential risk of proarrhythmias

Clopidogrel, dronedarone [2] ---> SmPC of [2] of EMA

Dronedarone does not affect the pharmacokinetics of clopidogrel and its active metabolite.

Cyclosporine, dronedarone [2] ---> SmPC of [2] of EMA

Dronedarone could increase the cyclosporine plasma levels. Monitoring of the plasma concentrations and appropriate dose adjustment is recommended in case of combination

CYP3A4 inductors, dronedarone

The CYP3A4 induction may decrease the plasma levels of dronedarone

Dabigatran etexilate [1], dronedarone ---> SmPC of [1] of EMA

Dabigatran, dronedarone [2] ---> SmPC of [2] of EMA

When dabigatran etexilate 150 mg once daily was co-administered with dronedarone 400 mg twice daily, the dabigatran AUC0-24, and Cmax were increased by 100% and 70%, respectively. Their co-administration is contraindicated

Darunavir [1], dronedarone ---> SmPC of [1] of EMA

Co-administration of boosted PREZISTA and amiodarone, bepridil, dronedarone, ivabradine, quinidine, or ranolazine is contraindicated (see section 4.3).

Darunavir/cobicistat [1], dronedarone ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], dronedarone ---> SmPC of [1] of EMA

Co-administration is contraindicated due to the potential for serious and/or life-threatening adverse reactions

Darunavir/ritonavir, dronedarone ---> SmPC of [darunavir] of EMA

Co-administration of darunavir boosted with ritonavir, with active substances that are highly dependent on CYP3A for clearance and for which elevated plasma levels are associated with serious and/or life-threatening events is contraindicated

Digoxin, dronedarone [2] ---> SmPC of [2] of EMA

The P-glycoprotein inhibition by dronedarone increases the plasma concentrations of digoxin. Clinical, ECG and biological monitoring is recommended and digoxin dosage should be halved

Diltiazem, dronedarone [2] ---> SmPC of [2] of EMA

Calcium antagonists with depressant effects on sinus and atrio-ventricular node such as verapamil and diltiazem should be used with caution when associated with dronedarone.

Dronedarone [1], edoxaban ---> SmPC of [1] of EMA

In in vivo studies edoxaban (a CYP3A4 and P-gp substrate) exposure was increased when administered with dronedarone. The edoxaban dose should be reduced according to the edoxaban label recommendations.

Dronedarone [1], electrolyte imbalance ---> SmPC of [1] of EMA

Proarrhythmic effects may occur in particular situations such as concomitant use with medicinal products favouring arrhythmia and/or electrolytic disorders

Dronedarone [1], erythromycin ---> SmPC of [1] of EMA

Erythromycin may induce torsades de pointes and, as such, is contraindicated. Repeated doses of erythromycin resulted in an increase in steady state dronedarone exposure

Dronedarone [1], ethinyl estradiol ---> SmPC of [1] of EMA

No decreases in ethinylestradiol and levonorgestrel were observed in healthy subjects receiving dronedarone concomitantly with oral contraceptives.

Dronedarone [1], fertility ---> SmPC of [1] of EMA

Dronedarone was not shown to alter fertility in animal studies.

Dronedarone [1], foods ---> SmPC of [1] of EMA

It is recommended to swallow the tablet whole with a drink of water during a meal. The tablet cannot be divided into equal doses.

Dronedarone [1], grapefruit juice ---> SmPC of [1] of EMA

Repeated doses of 300 ml of grapefruit juice three times daily resulted in a 3-fold increase in dronedarone exposure. Therefore, patients should be warned to avoid grapefruit juice beverages while taking dronedarone

Dronedarone [1], hypokalemia ---> SmPC of [1] of EMA

Since antiarrhythmic medicinal products may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before initiation and during dronedarone therapy.

Dronedarone [1], hypomagnesemia ---> SmPC of [1] of EMA

Dronedarone [1], IMAOs ---> SmPC of [1] of EMA

MAO inhibitors might decrease the clearance of the active metabolite of dronedarone and should therefore be used with caution.

Dronedarone [1], itraconazol ---> SmPC of [1] of EMA

Concomitant use of dronedarone with strong CYP3A4 inhibitors increases dronedarone exposure. The combination of dronedarone with strong CYP3A4 inhibitors is contraindicated

Dronedarone [1], ketoconazole ---> SmPC of [1] of EMA

Concomitant use of dronedarone with strong CYP3A4 inhibitors increases dronedarone exposure. The combination of dronedarone with strong CYP3A4 inhibitors is contraindicated

Dronedarone [1], levonorgestrel ---> SmPC of [1] of EMA

No decreases in ethinylestradiol and levonorgestrel were observed in healthy subjects receiving dronedarone concomitantly with oral contraceptives.

Dronedarone [1], losartan ---> SmPC of [1] of EMA

No interaction was observed between dronedarone and losartan and an interaction between dronedarone and other AIIRAs is not expected.

Dronedarone [1], lovastatine ---> SmPC of [1] of EMA

Dronedarone can increase exposure of statins that are substrates of CYP 3A4 and/or P-gp substrates or transported by OATP. Concomitant use of statins should be undertaken with caution.

Dronedarone [1], metformin ---> SmPC of [1] of EMA

No interaction was observed between dronedarone and metformin, an OCT1 and OCT2 substrate.

Dronedarone [1], metoprolol ---> SmPC of [1] of EMA

Dronedarone increased metoprolol exposure. In clinical studies, bradycardia was more frequently observed when dronedarone was given in combination with beta-blockers.

Dronedarone [1], moderate CYP3A4 inhibitors ---> SmPC of [1] of EMA

Moderate inhibitors of CYP3A4 are likely to increase dronedarone exposure.

Dronedarone [1], nefazodone ---> SmPC of [1] of EMA

Concomitant use of dronedarone with strong CYP3A4 inhibitors increases dronedarone exposure. The combination of dronedarone with strong CYP3A4 inhibitors is contraindicated

Dronedarone [1], omeprazole ---> SmPC of [1] of EMA

Dronedarone does not affect the pharmacokinetics of omeprazole, a CYP 2C19 substrate.

Dronedarone [1], oral contraceptives ---> SmPC of [1] of EMA

No decreases in ethinylestradiol and levonorgestrel were observed in healthy subjects receiving dronedarone (800 mg twice daily) concomitantly with oral contraceptives.

Dronedarone [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

Dronedarone, strong P-glycoprotein inhibitor, may increase the exposition of the medicinal products which are P-glycoprotein substrates

Dronedarone [1], pantoprazole ---> SmPC of [1] of EMA

Pantoprazole (40 mg once daily), a medicinal product which increases gastric pH without any effect on cytochrome P450, did not interact significantly on dronedarone pharmacokinetics.

Dronedarone [1], phenobarbital ---> SmPC of [1] of EMA

Rifampicin decreased dronedarone exposure. Therefore, co-administration of rifampicin and other potent CYP3A4 inducers is not recommended as they decrease dronedarone exposure.

Dronedarone [1], phenothiazines ---> SmPC of [1] of EMA

Medicinal products inducing torsades de pointes are contraindicated because of the potential risk of proarrhythmias

Dronedarone [1], phenytoin ---> SmPC of [1] of EMA

Rifampicin decreased dronedarone exposure. Therefore, co-administration of rifampicin and other potent CYP3A4 inducers is not recommended as they decrease dronedarone exposure.

Dronedarone [1], posaconazole ---> SmPC of [1] of EMA

Concomitant use of dronedarone with strong CYP3A4 inhibitors increases dronedarone exposure. The combination of dronedarone with strong CYP3A4 inhibitors is contraindicated

Dronedarone [1], pravastatine ---> SmPC of [1] of EMA

Dronedarone can increase exposure of statins that are substrates of CYP 3A4 and/or P-gp substrates or transported by OATP. Concomitant use of statins should be undertaken with caution.

Dronedarone [1], pregnancy ---> SmPC of [1] of EMA

MULTAQ is not recommended during pregnancy and in women of childbearing potential not using contraception.

Dronedarone [1], propranolol ---> SmPC of [1] of EMA

Dronedarone increased propranolol exposure. In clinical studies, bradycardia was more frequently observed when dronedarone was given in combination with beta-blockers.

Dronedarone [1], rifampicin ---> SmPC of [1] of EMA

Rifampicin decreased dronedarone exposure. Therefore, co-administration of rifampicin and other potent CYP3A4 inducers is not recommended as they decrease dronedarone exposure.

Dronedarone [1], ritonavir ---> SmPC of [1] of EMA

Concomitant use of dronedarone with strong CYP3A4 inhibitors increases dronedarone exposure. The combination of dronedarone with strong CYP3A4 inhibitors is contraindicated

Dronedarone [1], rivaroxaban ---> SmPC of [1] of EMA

Dronedarone is likely to increase the exposure of rivaroxaban (a CYP3A4 and P-gp substrate) and consequently concomitant use may increase the risk of bleedings. Concomitant use of rivaroxaban and dronedarone is not recommended.

Dronedarone [1], simvastatine ---> SmPC of [1] of EMA

Dronedarone can increase exposure of statins that are substrates of CYP 3A4 and/or P-gp substrates or transported by OATP. Concomitant use of statins should be undertaken with caution.

Dronedarone [1], sirolimus ---> SmPC of [1] of EMA

Dronedarone could increase the sirolimus plasma levels. Monitoring of the plasma concentrations and appropriate dose adjustment is recommended in case of combination

Dronedarone [1], St. John's wort ---> SmPC of [1] of EMA

Rifampicin decreased dronedarone exposure. Therefore, co-administration of rifampicin and other potent CYP3A4 inducers is not recommended as they decrease dronedarone exposure.

Dronedarone [1], statins ---> SmPC of [1] of EMA

Dronedarone can increase exposure of statins that are substrates of CYP 3A4 and/or P-gp substrates or transported by OATP. Concomitant use of statins should be undertaken with caution.

Dronedarone [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Rifampicin decreased dronedarone exposure. Therefore, co-administration of rifampicin and other potent CYP3A4 inducers is not recommended as they decrease dronedarone exposure.

Dronedarone [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Concomitant use of dronedarone with strong CYP3A4 inhibitors increases dronedarone exposure. The combination of dronedarone with strong CYP3A4 inhibitors is contraindicated

Dronedarone [1], tacrolimus ---> SmPC of [1] of EMA

Dronedarone could increase the tacrolimus plasma levels. Monitoring of the plasma concentrations and appropriate dose adjustment is recommended in case of combination

Dronedarone [1], terfenadine ---> SmPC of [1] of EMA

Medicinal products inducing torsades de pointes are contraindicated because of the potential risk of proarrhythmias

Dronedarone [1], theophylline ---> SmPC of [1] of EMA

Dronedarone 400 mg twice daily does not increase the steady state theophylline exposure.

Dronedarone [1], torsades de pointes inducing drugs ---> SmPC of [1] of EMA

Medicinal products inducing torsades de pointes are contraindicated because of the potential risk of proarrhythmias

Dronedarone [1], tricyclic antidepressant ---> SmPC of [1] of EMA

Medicinal products inducing torsades de pointes are contraindicated because of the potential risk of proarrhythmias

Dronedarone [1], verapamil ---> SmPC of [1] of EMA

Calcium antagonists with depressant effects on sinus and atrio-ventricular node such as verapamil and diltiazem should be used with caution when associated with dronedarone.

Dronedarone [1], vitamin K antagonists ---> SmPC of [1] of EMA

Clinically significant INR elevations (≥5) usually within 1 week after starting dronedarone were reported in patients taking oral anticoagulants.

Dronedarone [1], warfarin ---> SmPC of [1] of EMA

Clinically significant INR elevations (≥5) usually within 1 week after starting dronedarone were reported in patients taking oral anticoagulants.

Dronedarone [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should use effective methods of contraception during treatment with MULTAQ and for 7 days after the final dose.

Dronedarone [1], women of childbearing potential ---> SmPC of [1] of EMA

Prior to initiating MULTAQ, the prescriber should confirm that women of childbearing potential are not pregnant.

Dronedarone, duvelisib [2] ---> SmPC of [2] of EMA

Dose reduction of duvelisib is not necessary when co-administered with moderate CYP3A4 inhibitors

Dronedarone, edoxaban [2] ---> SmPC of [2] of EMA

Edoxaban is a substrate for the efflux transporter P-gp. In pharmacokinetic (PK) studies, concomitant administration of edoxaban with the P-gp inhibitor resulted in increased plasma concentrations of edoxaban.

Dronedarone, elacestrant [2] ---> SmPC of [2] of EMA

Concomitant administration of ORSERDU with moderate CYP3A4 inhibitors should be avoided which may increase the risk of adverse reactions

Dronedarone, eliglustat [2] ---> SmPC of [2] of EMA

It is predicted that concomitant use of moderate CYP2D6 inhibitors would increase eliglustat exposure approximately up to 4-fold. Caution should be used with moderate CYP2D6 inhibitors in intermediate and extensive metabolisers

Dronedarone, everolimus [2] ---> SmPC of [2] of EMA

Increase in everolimus concentration is expected. Use caution when co-administration of moderate CYP3A4 inhibitors or PgP inhibitors cannot be avoided.

Dronedarone, fidaxomicin [2] ---> SmPC of [2] of EMA

Fidaxomicin is a substrate of P-gp. Co-administration of potent inhibitors of P-gp increases fidaxomicin exposure. Co-administration of potent inhibitors of P-gp is not recommended.

Dronedarone, glecaprevir/pibrentasvir [2] ---> SmPC of [2] of EMA

Co-administration of Maviret with medicinal products that inhibit P-gp and BCRP may slow elimination of glecaprevir and pibrentasvir and thereby increase plasma exposure of the antivirals.

Dronedarone, ibrutinib [2] ---> SmPC of [2] of EMA

Concomitant use of IMBRUVICA and medicinal products that strongly or moderately inhibit CYP3A4 can increase ibrutinib exposure and strong CYP3A4 inhibitors should be avoided.

Dronedarone, ketoconazole [2] ---> SmPC of [2] of EMA

Concomitant therapy of ketoconazole with substances that may have their plasma concentrations increased and have QT prolonging potential is contraindicated

Dronedarone, lomitapide [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase lomitapide AUC. The combination of lomitapide with strong CYP3A4 inhibitors is contra-indicated

Dronedarone, lopinavir/ritonavir [2] ---> SmPC of [2] of EMA

Increased plasma concentrations of amiodarone and dronedarone. Thereby, increasing the risk of arrhythmias or other serious adverse reactions

Dronedarone, mequitazine

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Dronedarone, mexiletine [2] ---> SmPC of [2] of EMA

The concomitant use of mexiletine and antiarrhythmic medicines inducing torsades de pointes is contraindicated

Dronedarone, miconazole

Oral miconazole is contraindicated with medicinal products that are metabolised by CYP3A4 and may prolong also the QT interval

Dronedarone, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir coadministration is likely to result in increased plasma concentrations of amiodarone, bepridil, dronedarone, encainide, flecainide, propafenone and quinidine and is therefore contraindicated

Dronedarone, OATP substrates

Dronedarone, OATP inhibitor, may increase the exposition to the OATP substrate

Dronedarone, pasireotide [2] ---> SmPC of [2] of EMA

Pasireotide should be used with caution in patients who are concomitantly receiving medicinal products that prolong the QT interval

Dronedarone, pralsetinib [2] ---> SmPC of [2] of EMA

Co-administration of pralsetinib with P-gp and/or strong or moderate CYP3A4 inhibitors may increase pralsetinib plasma concentrations, which may increase the risk of adverse reactions of pralsetinib. The coadministration should be avoided

Dronedarone, relugolix [2] ---> SmPC of [2] of EMA

Concomitant use of Orgovyx with erythromycin, azithromycin and other oral P-gp inhibitors is not recommended

Dronedarone, rivaroxaban [2] ---> SmPC of [2] of EMA

Given the limited clinical data available with dronedarone, co-administration with rivaroxaban should be avoided.

Dronedarone, sotalol [2] ---> SmPC of [2] of eMC

Dronedarone, talazoparib [2] ---> SmPC of [2] of EMA

Concomitant use of strong P-gp inhibitors should be avoided. If co-administration with a strong P-gp inhibitor is unavoidable, the Talzenna dose should be reduced (see section 4.2).

Dronedarone, telithromycin [2] ---> SmPC of [2] of EMA

Concomitant administration of telithromycin with medicinal products that prolong the QT interval and are CYP3A4 substrates is contraindicated

Dronedarone, zanubrutinib [2] ---> SmPC of [2] of EMA

If a moderate CYP3A inhibitor must be used, reduce the BRUKINSA dose to 160 mg (two capsules) for the duration of the inhibitor use.

CONTRAINDICATIONS of Dronedarone (Multaq)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Second- or third-degree Atrio-Ventricular block, complete bundle branch block, distal block, sinus node dysfunction, atrial conduction defects, or sick sinus syndrome (except when used in conjunction with a functioning pacemaker).

- Bradycardia <50 beats per minute (bpm)

- Permanent AF with an AF duration ≥ 6 months (or duration unknown) and attempts to restore sinus rhythm no longer considered by the physician

- Patients in unstable hemodynamic conditions,

- History of, or current heart failure or left ventricular systolic dysfunction

- Patients with liver and lung toxicity related to the previous use of amiodarone

- Co-administration with potent cytochrome P 450 (CYP) 3A4 inhibitors, such as ketoconazole, itraconazole, voriconazole, posaconazole, telithromycin, clarithromycin, nefazodone and ritonavir

- Medicinal products inducing torsades de pointes such as phenothiazines, cisapride, bepridil, tricyclic antidepressants, terfenadine and certain oral macrolides (such as erythromycin), Class I and III antiarrhythmics

- QTc Bazett interval ≥ 500 milliseconds

- Severe hepatic impairment

- Severe renal impairment (CrCl <30 ml/min)

- Co-administration with dabigatran

https://www.ema.europa.eu/en/documents/product-information/multaq-epar-product-information_en.pdf 05/09/2024

Droperidol

Ability to drive, droperidol [2] ---> SmPC of [2] of eMC

Patients should not drive or operate a machine for 24 hours after droperidol administration.

Alcohol, droperidol [2] ---> SmPC of [2] of eMC

Consumption of alcoholic beverages and medicines should be avoided.

Amantadine, droperidol

The dopamine antagonist should be avoided with amantadine

Amiodarone, droperidol [2] ---> SmPC of [2] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Amisulpride, droperidol [2] ---> SmPC of [2] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Amitriptyline, droperidol [2] ---> SmPC of [2] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Antihypertensives, droperidol [2] ---> SmPC of [2] of eMC

Droperidol may potentiate the action of antihypertensive agents, so that orthostatic hypotension may ensue.

Antimalarial agents, droperidol [2] ---> SmPC of [2] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Astemizole, droperidol [2] ---> SmPC of [2] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Azithromycin, droperidol [2] ---> SmPC of [2] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Barbiturates, droperidol [2] ---> SmPC of [2] of eMC

Droperidol may potentiate the action of sedatives

Benzodiazepines, droperidol [2] ---> SmPC of [2] of eMC

Droperidol may potentiate the action of sedatives

Breast-feeding, droperidol [2] ---> SmPC of [2] of eMC

Butyrophenones are known to be excreted in breast milk; treatment with droperidol should be limited to a single administration. Repeat administration is not recommended.

Bromocriptine, droperidol [2] ---> SmPC of [2] of eMC

Since droperidol blocks dopamine receptors, it may inhibit the action of dopamine agonists, such as bromocriptine, lisuride, and of L-dopa.

Carteolol, droperidol

The co-administration increases the risk of heart rhythm disorders, particularly torsades de pointes

Ceritinib [1], droperidol ---> SmPC of [1] of EMA

Chloroquine, droperidol [2] ---> SmPC of [2] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Chlorpromazine, droperidol [2] ---> SmPC of [2] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Cimetidine, droperidol [2] ---> SmPC of [2] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzymes CYP1A2 and CYP3A4 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Ciprofloxacin, droperidol [2] ---> SmPC of [2] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzyme CYP1A2 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Cisapride, droperidol

The co-administration of cisapride with drugs that may prolong the QT interval and/or induce torsades de pointes is contraindicated

Clarithromycin, droperidol [2] ---> SmPC of [2] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Class IA antiarrhythmic agents, droperidol [2] ---> SmPC of [2] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Class III antiarrhythmic agents, droperidol [2] ---> SmPC of [2] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

CYP1A2 and CYP3A4 inhibitors, droperidol [2] ---> SmPC of [2] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzymes CYP1A2 and CYP3A4 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Delamanid [1], droperidol ---> SmPC of [1] of EMA

Diltiazem, droperidol [2] ---> SmPC of [2] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzyme CYP3A4 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Disopyramide, droperidol [2] ---> SmPC of [2] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Diuretics, droperidol [2] ---> SmPC of [2] of eMC

To prevent QT prolongation, caution is necessary when patients are taking medicinal products likely to induce electrolyte imbalance

Domperidone, droperidol [2] ---> SmPC of [2] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Dopamine agonists, droperidol [2] ---> SmPC of [2] of eMC

Since droperidol blocks dopamine receptors, it may inhibit the action of dopamine agonists, such as bromocriptine, lisuride, and of L-dopa.

Droperidol [1], electrolyte imbalance ---> SmPC of [1] of eMC

To prevent QT prolongation, caution is necessary when patients are taking medicinal products likely to induce electrolyte imbalance

Droperidol [1], erythromycin ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], fluconazole ---> SmPC of [1] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzyme CYP3A4 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Droperidol [1], fluoxetine ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], fluvoxamine ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], glucocorticoids ---> SmPC of [1] of eMC

To prevent QT prolongation, caution is necessary when patients are taking medicinal products likely to induce electrolyte imbalance

Droperidol [1], halofantrine ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], haloperidol ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], hypokalemia ---> SmPC of [1] of eMC

To prevent QT prolongation, caution is necessary when patients are taking medicinal products likely to induce electrolyte imbalance

Droperidol [1], hypomagnesemia ---> SmPC of [1] of eMC

To prevent QT prolongation, caution is necessary when patients are taking medicinal products likely to induce electrolyte imbalance

Droperidol [1], indinavir ---> SmPC of [1] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzyme CYP3A4 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Droperidol [1], itraconazol ---> SmPC of [1] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzyme CYP3A4 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Droperidol [1], ketoconazole ---> SmPC of [1] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzyme CYP3A4 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Droperidol [1], laxatives ---> SmPC of [1] of eMC

To prevent QT prolongation, caution is necessary when patients are taking medicinal products likely to induce electrolyte imbalance

Droperidol [1], levodopa ---> SmPC of [1] of eMC

Since droperidol blocks dopamine receptors, it may inhibit the action of dopamine agonists, such as bromocriptine, lisuride, and of L-dopa.

Droperidol [1], lisuride ---> SmPC of [1] of eMC

Since droperidol blocks dopamine receptors, it may inhibit the action of dopamine agonists, such as bromocriptine, lisuride, and of L-dopa.

Droperidol [1], macrolide antibiotics ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], maprotiline ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], medicines that induce extrapyramidal symptoms ---> SmPC of [1] of eMC

Concomitant use of droperidol with medicinal products that induce extrapyramidal symptoms may lead to an increased incidence of these symptoms and should therefore be avoided.

Droperidol [1], melperone ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], methadone ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], metoclopramide ---> SmPC of [1] of eMC

Concomitant use of droperidol with medicinal products that induce extrapyramidal symptoms may lead to an increased incidence of these symptoms and should therefore be avoided.

Droperidol [1], mibefradil ---> SmPC of [1] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzymes CYP1A2 and CYP3A4 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Droperidol [1], morphine ---> SmPC of [1] of eMC

Droperidol may potentiate the action of sedatives

Droperidol [1], nefazodone ---> SmPC of [1] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzyme CYP3A4 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Droperidol [1], nelfinavir ---> SmPC of [1] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzyme CYP3A4 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Droperidol [1], neuroleptics ---> SmPC of [1] of eMC

Concomitant use of droperidol with medicinal products that induce extrapyramidal symptoms may lead to an increased incidence of these symptoms and should therefore be avoided.

Droperidol [1], non-potassium-sparing diuretics ---> SmPC of [1] of eMC

To prevent QT prolongation, caution is necessary when patients are taking medicinal products likely to induce electrolyte imbalance

Droperidol [1], opiates ---> SmPC of [1] of eMC

Like other sedatives, droperidol may potentiate respiratory depression caused by opioids.

Droperidol [1], pentamidine ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], phenothiazines ---> SmPC of [1] of eMC

There is an increased risk of arrhythmias when neuroleptics are used with drugs that prolong the QT interval

Droperidol [1], pregnancy ---> SmPC of [1] of eMC

As a precautionary measure, it is preferable not to administer droperidol during pregnancy. In late pregnancy, if its administration is necessary, monitoring of the newborn's neurological functions is recommended.

Droperidol [1], procainamide ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], QT interval prolonging drugs ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], quinidine ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], quinine ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], quinolones ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], ritonavir ---> SmPC of [1] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzyme CYP3A4 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Droperidol [1], saquinavir ---> SmPC of [1] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzyme CYP3A4 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Droperidol [1], sedatives ---> SmPC of [1] of eMC

Droperidol may potentiate the action of sedatives

Droperidol [1], sertindole ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], sertraline ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], sparfloxacin ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], strong CYP1A2 inhibitors ---> SmPC of [1] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzyme CYP1A2 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Droperidol [1], strong CYP3A4 inhibitors ---> SmPC of [1] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzyme CYP3A4 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Droperidol [1], sulpiride ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], tacrolimus ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], tamoxifen ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], terfenadine ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], thioridazine ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol [1], ticlopidine ---> SmPC of [1] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzyme CYP1A2 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Droperidol [1], verapamil ---> SmPC of [1] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzyme CYP3A4 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Droperidol [1], vincamine ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol, hydroquinidine

Concomitant use is not recommended due to increased risk of heart rhythm disorders (torsades de pointes)

Droperidol, ibutilide

Possible increase of proarrhythmic risk if ibutilide is used with drugs that prolong the QT interval. Contraindicated within 4 hours after completing infusion

Droperidol, indapamide [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Droperidol, losartan/hydrochlorothiazide [2] ---> SmPC of [2] of eMC

Periodic monitoring of serum potassium and ECG is recommended when losartan/hydrochlorothiazide is administered with torsades de pointes-inducing medicinal products

Droperidol, pimozide [2] ---> SmPC of [2] of eMC

Concomitant use of pimozide with drugs known to prolong the QT interval is contra-indicated

Droperidol, piperaquine ---> SmPC of [piperaquine/artenimol] of EMA

The combination of piperaquine with drugs that are known to prolong the QTc interval is contraindicated: additive effect on the QTc interval

Droperidol, piperaquine/artenimol [2] ---> SmPC of [2] of EMA

The combination of piperaquine/dihydroartemisinin with drugs that are known to prolong the QTc interval is contraindicated: additive effect on the QTc interval

Droperidol, rivastigmine [2] ---> SmPC of [2] of EMA

Since bradycardia constitutes a risk factor in the occurrence of torsades de pointes, the combination of rivastigmine with torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Droperidol, sotalol [2] ---> SmPC of [2] of eMC

Droperidol, SSRI [2] ---> SmPC of [2] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Droperidol, tiapride [2] ---> SmPC of [2] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol, tricyclic antidepressant [2] ---> SmPC of [2] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Droperidol, xipamide

The combination increases the risk of ventricular arrhythmias, particularly torsades de pointes (favored by hypokaliemia). It is recommended a special caution

CONTRAINDICATIONS of Droperidol

Droperidol is contraindicated in patients with:

- Hypersensitivity to droperidol or to any of the excipients;

- Hypersensitivity to butyrophenones;

- Known or suspected prolonged QT interval (QTc of > 450 msec in females and > 440 msec in males). This includes patients with congenitally long QT interval, patients who have a family history of congenital QT prolongation and those treated with medicinal products known to prolong the QT interval

- Hypokalaemia or hypomagnesaemia;

- Bradycardia (< 55 heartbeats per minute);

- Known concomitant treatment leading to bradycardia

- Phaeochromocytoma;

- Comatose states;

- Parkinson's Disease;

- Severe depression.

http://www.medicines.org.uk/emc/

Drospirenone/estetrol (Drovelis)

ACE inhibitors, drospirenone/estetrol [2] ---> SmPC of [2] of EMA

In patients without renal impairment, the concomitant use of drospirenone and angiotensin converting enzyme (ACE)-inhibitors or non-steroidal anti-inflammatory drugs (NSAIDs) did not show a significant effect on serum potassium.

Aldosterone antagonists, drospirenone/estetrol [2] ---> SmPC of [2] of EMA

Concomitant use of Drovelis with aldosterone antagonists or potassium-sparing diuretics has not been studied. In this case, serum potassium should be tested during the first treatment cycle.

Barbiturates, drospirenone/estetrol [2] ---> SmPC of [2] of EMA

Medicinal products increasing the clearance of CHCs

Bosentan, drospirenone/estetrol [2] ---> SmPC of [2] of EMA

Medicinal products increasing the clearance of CHCs

Breast-feeding, drospirenone/estetrol [2] ---> SmPC of [2] of EMA

The use of CHCs should not be recommended until the breast-feeding mother has completely weaned her child and an alternative method of contraception should be proposed to women wishing to breastfeed.

Carbamazepine, drospirenone/estetrol [2] ---> SmPC of [2] of EMA

Medicinal products increasing the clearance of CHCs

Cyclosporine, drospirenone/estetrol [2] ---> SmPC of [2] of EMA

Oral contraceptives may affect the metabolism of certain other active substances. Accordingly, plasma and tissue concentrations may either increase (e.g., ciclosporin) or decrease (e.g., lamotrigine).

Cyclosporine, oral contraceptives ---> SmPC of [drospirenone/estetrol] of EMA

Dasabuvir with ombitasvir/paritaprevir/ritonavir, drospirenone/estetrol [2] ---> SmPC of [2] of EMA

Drospirenone/estetrol [1], efavirenz ---> SmPC of [1] of EMA

Medicinal products increasing the clearance of CHCs

Drospirenone/estetrol [1], enzyme inductors ---> SmPC of [1] of EMA

Women on treatment with enzyme-inducing medicinal products should temporarily use a barrier method or another method of contraception in addition to the CHC and for 28 days after its discontinuation.

Drospirenone/estetrol [1], enzyme inhibitors ---> SmPC of [1] of EMA

Medicinal products decreasing the clearance of CHCs (enzyme inhibitors)

Drospirenone/estetrol [1], felbamate ---> SmPC of [1] of EMA

Medicinal products increasing the clearance of CHCs

Drospirenone/estetrol [1], fertility ---> SmPC of [1] of EMA

Drovelis is indicated for oral contraception. For information on return to fertility, see section 5.1.

Drospirenone/estetrol [1], griseofulvin ---> SmPC of [1] of EMA

Medicinal products increasing the clearance of CHCs

Drospirenone/estetrol [1], ketoconazole ---> SmPC of [1] of EMA

The co-administration of the strong CYP3A4 inhibitor ketoconazole for 10 days increased the area under the curve during a 24-hour period (AUC(0-24 h)) of drospirenone (and ethinylestradiol) 2.7-fold (and 1.4-fold, respectively).

Drospirenone/estetrol [1], lamotrigine ---> SmPC of [1] of EMA

Drospirenone/estetrol [1], marker substrate ---> SmPC of [1] of EMA

Based on in vitro inhibition studies and in vivo interaction studies in female volunteers using marker substrate, an interaction of drospirenone at doses of 3 mg with the metabolism of other active substances is unlikely.

Drospirenone/estetrol [1], metabolism ---> SmPC of [1] of EMA

Based on in vitro inhibition studies, an interaction of estetrol contained in Drovelis with the metabolism of other active substances is unlikely.

Drospirenone/estetrol [1], nevirapine ---> SmPC of [1] of EMA

Medicinal products increasing the clearance of CHCs

Drospirenone/estetrol [1], NRTI ---> SmPC of [1] of EMA

When co-administered with CHCs, many combinations of HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors, including combinations with HCV inhibitors can increase or decrease plasma concentrations of oestrogens and progestogens.

Drospirenone/estetrol [1], NSAID ---> SmPC of [1] of EMA

Drospirenone/estetrol [1], ombitasvir/paritaprevir/ritonavir ---> SmPC of [1] of EMA

Caution is warranted for co-administration with the combination therapeutic regimen ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin and also the regimen with glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir

Drospirenone/estetrol [1], oxcarbazepine ---> SmPC of [1] of EMA

Medicinal products increasing the clearance of CHCs

Drospirenone/estetrol [1], phenytoin ---> SmPC of [1] of EMA

Medicinal products increasing the clearance of CHCs

Drospirenone/estetrol [1], potassium-sparing diuretics ---> SmPC of [1] of EMA

Concomitant use of Drovelis with aldosterone antagonists or potassium-sparing diuretics has not been studied. In this case, serum potassium should be tested during the first treatment cycle.

Drospirenone/estetrol [1], pregnancy ---> SmPC of [1] of EMA

Drovelis is not indicated during pregnancy. If pregnancy occurs while taking Drovelis, further intake must be stopped.

Drospirenone/estetrol [1], primidone ---> SmPC of [1] of EMA

Medicinal products increasing the clearance of CHCs

Drospirenone/estetrol [1], protease inhibitors ---> SmPC of [1] of EMA

Drospirenone/estetrol [1], rifampicin ---> SmPC of [1] of EMA

Medicinal products increasing the clearance of CHCs

Drospirenone/estetrol [1], ritonavir ---> SmPC of [1] of EMA

Medicinal products increasing the clearance of CHCs

Drospirenone/estetrol [1], St. John's wort ---> SmPC of [1] of EMA

Medicinal products increasing the clearance of CHCs

Drospirenone/estetrol [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Concomitant administration of strong CYP3A4 inhibitors can increase plasma concentrations of oestrogens or progestogens or both.

Drospirenone/estetrol [1], topiramate ---> SmPC of [1] of EMA

Medicinal products increasing the clearance of CHCs

Drospirenone/estetrol [1], valproic acid ---> SmPC of [1] of EMA

No clinically relevant interaction was observed with estetrol and the strong UGT inhibitor valproic acid.

Lamotrigine, oral contraceptives ---> SmPC of [drospirenone/estetrol] of EMA

CONTRAINDICATIONS of Drospirenone/estetrol (Drovelis)

As no epidemiological data are yet available for estetrol-containing CHCs, the contraindications for ethinylestradiol-containing CHCs are considered applicable to the use of Drovelis. CHCs should not be used in the following conditions. Should any of the conditions appear for the first time during Drovelis use, the medicinal product should be stopped immediately.

-Presence or risk of venous thromboembolism (VTE)

-VTE -current VTE (on anticoagulants) or history of VTE (e.g., deep venous thrombosis [DVT] or pulmonary embolism [PE]).

-Known hereditary or acquired predisposition for venous thromboembolism, such as activated protein C (APC)-resistance (including factor V Leiden), antithrombin-III-deficiency, protein C deficiency, protein S deficiency.

-Major surgery with prolonged immobilisation (see section 4.4).

-A high risk of venous thromboembolism due to the presence of multiple risk factors (see section 4.4).

-Presence or risk of arterial thromboembolism (ATE)

-ATE -current ATE, history of ATE (e.g., myocardial infarction [MI]) or prodromal condition (e.g., angina pectoris).

-Cerebrovascular disease - current stroke, history of stroke or prodromal condition (e.g., transient ischaemic attack [TIA]).

-Known hereditary or acquired predisposition for arterial thromboembolism, such as hyperhomocysteinaemia and antiphospholipid-antibodies (anticardiolipin-antibodies, lupus anticoagulant).

-History of migraine with focal neurological symptoms.

-A high risk of arterial thromboembolism due to multiple risk factors (see section 4.4) or to the presence of one serious risk factor such as:

-diabetes mellitus with vascular symptoms;

-severe hypertension;

-severe dyslipoproteinaemia.

-Presence or history of severe hepatic disease as long as liver function values have not returned to normal.

-Severe renal insufficiency or acute renal failure.

-Presence or history of liver tumours (benign or malignant).

-Known or suspected sex steroid-influenced malignancies (e.g., of the genital organs or the breasts).

-Undiagnosed vaginal bleeding.

-Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/drovelis-epar-product-information_en.pdf 19/06/2024

Other trade names: Lydisilka,

Drotrecogin alfa (Xigris)

Abciximab, drotrecogin alfa [2] ---> SmPC of [2] of EMA

Caution should be employed when using drotrecogin alfa with other drugs that affect haemostasis

Breast-feeding, drotrecogin alfa [2] ---> SmPC of [2] of EMA

The patient should not breast feed whilst treated

Clopidogrel, drotrecogin alfa [2] ---> SmPC of [2] of EMA

Caution should be employed when using drotrecogin alfa with other drugs that affect haemostasis

Drotrecogin alfa [1], eptifibatide ---> SmPC of [1] of EMA

Caution should be employed when using drotrecogin alfa with other drugs that affect haemostasis

Drotrecogin alfa [1], GP IIb/IIIa inhibitors ---> SmPC of [1] of EMA

Caution should be employed when using drotrecogin alfa with other drugs that affect haemostasis

Drotrecogin alfa [1], heparin ---> SmPC of [1] of EMA

The concurrent heparin therapy ≥ 15 International Units/kg/hr is contraindicated

Drotrecogin alfa [1], hirudin ---> SmPC of [1] of EMA

Caution should be employed when using drotrecogin alfa with other drugs that affect haemostasis

Drotrecogin alfa [1], iloprost ---> SmPC of [1] of EMA

Caution should be employed when using drotrecogin alfa with other drugs that affect haemostasis

Drotrecogin alfa [1], NSAID ---> SmPC of [1] of EMA

Caution should be employed when using drotrecogin alfa with other drugs that affect haemostasis

Drotrecogin alfa [1], oral anticoagulants ---> SmPC of [1] of EMA

Caution should be employed when using drotrecogin alfa with other drugs that affect haemostasis

Drotrecogin alfa [1], platelet aggregation inhibitors ---> SmPC of [1] of EMA

Caution should be employed when using drotrecogin alfa with other drugs that affect haemostasis

Drotrecogin alfa [1], pregnancy ---> SmPC of [1] of EMA

Should not be used during pregnancy unless clearly necessary

Drotrecogin alfa [1], prostacyclin analogues ---> SmPC of [1] of EMA

Caution should be employed when using drotrecogin alfa with other drugs that affect haemostasis

Drotrecogin alfa [1], protein C ---> SmPC of [1] of EMA

Caution should be employed when using drotrecogin alfa with other drugs that affect haemostasis

Drotrecogin alfa [1], thrombolytics ---> SmPC of [1] of EMA

Caution should be employed when using drotrecogin alfa with other drugs that affect haemostasis

Drotrecogin alfa [1], ticlopidine ---> SmPC of [1] of EMA

Caution should be employed when using drotrecogin alfa with other drugs that affect haemostasis

Drotrecogin alfa [1], tirofiban ---> SmPC of [1] of EMA

Caution should be employed when using drotrecogin alfa with other drugs that affect haemostasis

CONTRAINDICATIONS of Drotrecogin alfa (Xigris)

Hypersensitivity to the active substance, to any of the excipients or to bovine thrombin (a trace residue from the manufacturing process).

Drotrecogin alfa (activated) is contraindicated in children below the age of 18 years

Because drotrecogin alfa (activated) may increase the risk of bleeding, Xigris is contraindicated in the following situations:

- Active internal bleeding

- Patients with intracranial pathology; neoplasm or evidence of cerebral herniation

- Concurrent heparin therapy ≥ 15 International Units/kg/hr

- Known bleeding diathesis except for acute coagulopathy related to sepsis

- Chronic severe hepatic disease

- Platelet count < 30,000 x 106/l, even if the platelet count is increased after transfusions

- Patients at increased risk for bleeding (for example):

a) any major surgery, defined as surgery that requires general or spinal anesthesia, performed within the 12-hour period immediately preceding drug infusion, or any postoperative patient who demonstrates evidence of active bleeding, or any patient with planned or anticipated surgery during the drug infusion period.

b) history of severe head trauma that required hospitalization, intracranial or intraspinal surgery, or haemorrhagic stroke within the previous 3 months, or any history of intracerebral arteriovenous malformation, cerebral aneurysm, or central nervous system mass lesion; patients with an epidural catheter or who are anticipated to receive an epidural catheter during drug infusion

c) history of congenital bleeding diatheses

d) gastrointestinal bleeding within the last 6 weeks that has required medical intervention unless definitive surgery has been performed

e) trauma patients at increased risk of bleeding

https://www.ema.europa.eu/en/documents/product-information/xigris-epar-product-information_en.pdf 21/02/2012 (withdrawn)

Dulaglutide (Trulicity)

Ability to drive, dulaglutide [2] ---> SmPC of [2] of EMA

When it is used in combination with a sulphonylurea or insulin, patients should be advised to take precautions to avoid hypoglycaemia while driving and using machines (see section 4.4).

Atorvastatin, dulaglutide [2] ---> SmPC of [2] of EMA

No dose adjustment of atorvastatin is necessary when administered with dulaglutide.

Breast-feeding, dulaglutide [2] ---> SmPC of [2] of EMA

Dulaglutide should not be used during breast-feeding.

Digoxin, dulaglutide [2] ---> SmPC of [2] of EMA

No dose adjustment of digoxin is necessary when administered with dulaglutide.

Dulaglutide [1], fertility ---> SmPC of [1] of EMA

The effect of dulaglutide on fertility in humans is unknown. In the rat, there was no direct effect on mating or fertility following treatment with dulaglutide (see section 5.3).

Dulaglutide [1], lisinopril ---> SmPC of [1] of EMA

No dose adjustment of lisinopril is necessary when administered with dulaglutide.

Dulaglutide [1], medicinal products ---> SmPC of [1] of EMA

Dulaglutide delays gastric emptying and has the potential to impact the rate of absorption of concomitantly administered oral medicinal products.

Dulaglutide [1], metformin ---> SmPC of [1] of EMA

No dose adjustment for metformin IR is recommended when given with dulaglutide.

Dulaglutide [1], metoprolol ---> SmPC of [1] of EMA

No dose adjustment of metoprolol is necessary when administered with dulaglutide.

Dulaglutide [1], oral contraceptives ---> SmPC of [1] of EMA

No dose adjustment of oral contraceptives is necessary when administered with dulaglutide.

Dulaglutide [1], paracetamol ---> SmPC of [1] of EMA

No dose adjustment of paracetamol is necessary when administered with dulaglutide.

Dulaglutide [1], pregnancy ---> SmPC of [1] of EMA

The use of dulaglutide is not recommended during pregnancy.

Dulaglutide [1], sitagliptin ---> SmPC of [1] of EMA

Dulaglutide coadministration with sitagliptin increased dulaglutide exposure and Cmax by approximately 38 %and 27 %. The increased exposure may enhance the effects of dulaglutide on blood glucose levels.

Dulaglutide [1], warfarin ---> SmPC of [1] of EMA

No dose adjustment of warfarin is necessary when administered with dulaglutide.

CONTRAINDICATIONS of Dulaglutide (Trulicity)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/trulicity-epar-product-information_en.pdf 30/01/2026

Duloxetine (Yentreve)

Ability to drive, duloxetine [2] ---> SmPC of [2] of EMA

Patients should be instructed that if they experience sedation or dizziness they should avoid potentially hazardous tasks such as driving or operating machinery.

Abrocitinib [1], duloxetine ---> SmPC of [1] of EMA

The exposures of medicinal products metabolised by CYP2B6 (e.g. bupropion, efavirenz) and CYP1A2 (e.g. alosetron, duloxetine, ramelteon, tizanidine) may be decreased

Alcohol, duloxetine [2] ---> SmPC of [2] of EMA

Caution is advised when duloxetine is taken in combination with other centrally acting medicinal products or substances, including alcohol and sedative medicinal products

Amitriptyline, duloxetine [2] ---> SmPC of [2] of EMA

In rare cases, serotonin syndrome has been reported in patients using SSRIs/SNRIs concomitantly with serotonergic agents. Caution is advisable if duloxetine is used concomitantly with serotonergic agents

Antacids, duloxetine [2] ---> SmPC of [2] of EMA

Co-administration of YENTREVE with aluminium- and magnesium-containing antacids or with famotidine had no significant effect on the rate or extent of duloxetine absorption after administration of a 40 mg oral dose.

Antidepressants with serotonergic effect, duloxetine [2] ---> SmPC of [2] of EMA

Benzodiazepines, duloxetine [2] ---> SmPC of [2] of EMA

Caution is advised when duloxetine is taken in combination with other centrally acting medicinal products or substances, including alcohol and sedative medicinal products

Binimetinib [1], duloxetine ---> SmPC of [1] of EMA

Binimetinib is a potential inducer of CYP1A2, and caution should be taken when it is used with sensitive substrates (such as duloxetine or theophylline).

Breast-feeding, duloxetine [2] ---> SmPC of [2] of EMA

As the safety of duloxetine in infants is not known, the use of YENTREVE while breast-feeding is not recommended.

Ciprofloxacin, duloxetine [2] ---> SmPC of [2] of EMA

YENTREVE should not be used in combination with CYP1A2 inhibitors, like fluvoxamine, ciprofloxacin or enoxacin since the combination results in elevated plasma concentrations of duloxetine

Clomipramine, duloxetine [2] ---> SmPC of [2] of EMA

CYP1A2 inductors, duloxetine [2] ---> SmPC of [2] of EMA

Population pharmacokinetic studies analyses have shown that smokers have almost 50% lower plasma concentrations of duloxetine compared with non-smokers.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, duloxetine

Viekirax administered with or without dasabuvir did not affect the exposures of the CYP2D6/CYP1A2 substrate, duloxetine.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, duloxetine ---> SmPC of [dasabuvir] of EMA

Dasabuvir administered with ombitasvir/paritaprevir/ritonavir did not affect the exposures of the CYP2D6 /CYP1A2 substrate duloxetine.

Desipramine, duloxetine [2] ---> SmPC of [2] of EMA

Duloxetine is a moderate inhibitor of CYP2D6. Caution is advised if duloxetine is co-administered with medicinal products that are predominantly metabolised by CYP2D6

Drugs metabolised by CYP1A2, duloxetine [2] ---> SmPC of [2] of EMA

The pharmacokinetics of theophylline, a CYP1A2 substrate, were not significantly affected by co-administration with duloxetine (60 mg twice daily).

Drugs primarily metabolised by CYP2D6 with narrow therapeutic index, duloxetine [2] ---> SmPC of [2] of EMA

Duloxetine is a moderate inhibitor of CYP2D6. Caution is advised if duloxetine is co-administered with medicinal products that are predominantly metabolised by CYP2D6, particularly if they have a narrow therapeutic index

Drugs primarily metabolised by CYP2D6, duloxetine [2] ---> SmPC of [2] of EMA

Duloxetine is a moderate inhibitor of CYP2D6. Caution is advised if duloxetine is co-administered with medicinal products that are predominantly metabolised by CYP2D6

Duloxetine [1], enoxacin ---> SmPC of [1] of EMA

YENTREVE should not be used in combination with CYP1A2 inhibitors, like fluvoxamine, ciprofloxacin or enoxacin since the combination results in elevated plasma concentrations of duloxetine

Duloxetine [1], famotidine ---> SmPC of [1] of EMA

Co-administration of YENTREVE with aluminium-and magnesium containing antacids or with famotidine had no significant effect on the rate or extent of duloxetine absorption after administration of a 40 mg oral dose.

Duloxetine [1], fertility ---> SmPC of [1] of EMA

In animal studies, duloxetine had no effect on male fertility, and effects in females were only evident at doses that caused maternal toxicity.

Duloxetine [1], flecainide ---> SmPC of [1] of EMA

Duloxetine [1], fluvoxamine ---> SmPC of [1] of EMA

YENTREVE should not be used in combination with CYP1A2 inhibitors, like fluvoxamine, ciprofloxacin or enoxacin since the combination results in elevated plasma concentrations of duloxetine

Duloxetine [1], imipramine ---> SmPC of [1] of EMA

Duloxetine is a moderate inhibitor of CYP2D6. Caution is advised if duloxetine is co-administered with medicinal products that are predominantly metabolised by CYP2D6

Duloxetine [1], linezolid ---> SmPC of [1] of EMA

The antibiotic linezolid is a reversible non-selective MAOI and should not be given to patients treated with YENTREVE (see section 4.4).

Duloxetine [1], metoprolol ---> SmPC of [1] of EMA

Duloxetine [1], moclobemide ---> SmPC of [1] of EMA

The concomitant use of YENTREVE with selective, reversible MAOIs, like moclobemide, is not recommended

Duloxetine [1], neuroleptics ---> SmPC of [1] of EMA

Caution is advised when duloxetine is taken in combination with other centrally acting medicinal products or substances, including alcohol and sedative medicinal products

Duloxetine [1], nortriptyline ---> SmPC of [1] of EMA

Duloxetine is a moderate inhibitor of CYP2D6. Caution is advised if duloxetine is co-administered with medicinal products that are predominantly metabolised by CYP2D6

Duloxetine [1], oral anticoagulants ---> SmPC of [1] of EMA

Caution should be exercised when duloxetine is combined with oral anticoagulants or antiplatelet agents due to a potential increased risk of bleeding attributable to a pharmacodynamic interaction.

Duloxetine [1], oral contraceptives ---> SmPC of [1] of EMA

Results of in vitro studies demonstrate that duloxetine does not induce the catalytic activity of CYP3A. Specific in vivo drug interaction studies have not been performed.

Duloxetine [1], pethidine ---> SmPC of [1] of EMA

Duloxetine [1], phenobarbital ---> SmPC of [1] of EMA

Caution is advised when duloxetine is taken in combination with other centrally acting medicinal products or substances, including alcohol and sedative medicinal products

Duloxetine [1], platelet aggregation inhibitors ---> SmPC of [1] of EMA

Caution should be exercised when duloxetine is combined with oral anticoagulants or antiplatelet agents due to a potential increased risk of bleeding attributable to a pharmacodynamic interaction.

Duloxetine [1], pregnancy ---> SmPC of [1] of EMA

YENTREVE should be used in pregnancy only if the potential benefit justifies the potential risk to the foetus. Women should be advised to notify their physician if they become pregnant, or intend to become pregnant, during therapy.

Duloxetine [1], propafenone ---> SmPC of [1] of EMA

Duloxetine [1], risperidone ---> SmPC of [1] of EMA

Duloxetine is a moderate inhibitor of CYP2D6. Caution is advised if duloxetine is co-administered with medicinal products that are predominantly metabolised by CYP2D6

Duloxetine [1], sedating antihistamines ---> SmPC of [1] of EMA

Caution is advised when duloxetine is taken in combination with other centrally acting medicinal products or substances, including alcohol and sedative medicinal products

Duloxetine [1], sedatives ---> SmPC of [1] of EMA

Caution is advised when duloxetine is taken in combination with other centrally acting medicinal products or substances, including alcohol and sedative medicinal products

Duloxetine [1], serotonergic medicines ---> SmPC of [1] of EMA

Duloxetine [1], smokers ---> SmPC of [1] of EMA

Population pharmacokinetic studies analyses have shown that smokers have almost 50% lower plasma concentrations of duloxetine compared with non-smokers.

Duloxetine [1], St. John's wort ---> SmPC of [1] of EMA

Duloxetine [1], steroids ---> SmPC of [1] of EMA

Results of in vitro studies demonstrate that duloxetine does not induce the catalytic activity of CYP3A. Specific in vivo drug interaction studies have not been performed.

Duloxetine [1], strong CYP1A2 inhibitors ---> SmPC of [1] of EMA

Because CYP1A2 is involved in duloxetine metabolism, concomitant use of YENTREVE with potent inhibitors of CYP1A2 is likely to result in higher concentrations of duloxetine.

Duloxetine [1], theophylline ---> SmPC of [1] of EMA

The pharmacokinetics of theophylline, a CYP1A2 substrate, were not significantly affected by co-administration with duloxetine (60 mg twice daily).

Duloxetine [1], tramadol ---> SmPC of [1] of EMA

Duloxetine [1], trazodone ---> SmPC of [1] of EMA

Duloxetine [1], tricyclic antidepressant ---> SmPC of [1] of EMA

Duloxetine [1], triptans ---> SmPC of [1] of EMA

Duloxetine [1], tryptophan ---> SmPC of [1] of EMA

Duloxetine [1], warfarin ---> SmPC of [1] of EMA

Increases in INR values have been reported when duloxetine was co-administered to patients treated with warfarin.

Duloxetine, eliglustat [2] ---> SmPC of [2] of EMA

Duloxetine, irreversible non-selective MAO-inhibitors ---> SmPC of [duloxetine] of EMA

Due to the risk of serotonin syndrome, duloxetine should not be used in combination with non-selective irreversible monoamine oxidase inhibitors (MAOIs), or within at least 14 days of discontinuing treatment with an MAOI.

Duloxetine, leflunomide [2] ---> SmPC of [2] of EMA

Medicinal products metabolised by CYP1A2 (such as duloxetine, alosetron, theophylline and tizanidine) should be used with caution during treatment, as it could lead to the reduction of the efficacy of these products.

Duloxetine, mequitazine

Mequitazine should not be used with CYP2D6 inhibitor drugs. The increased plasma levels of mequitazine may increase the risk of QT interval prolongation

Duloxetine, morphinomimetics [2] ---> SmPC of [2] of EMA

Caution is advised when duloxetine is taken in combination with other centrally acting medicinal products or substances, including alcohol and sedative medicinal products

Duloxetine, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

Viekirax administered with or without dasabuvir did not affect the exposures of the CYP2D6/CYP1A2 substrate, duloxetine.

Duloxetine, pitolisant [2] ---> SmPC of [2] of EMA

Given the 2-fold increase of pitolisant exposure, its coadministration with CYP2D6 inhibitors should be done with caution. A dosage adjustment during the combination could eventually be considered.

Duloxetine, reversible selective MAO-A inhibitors ---> SmPC of [duloxetine] of EMA

Risk of serotonin syndrome. The concomitant use of Duloxetine with selective, reversible MAOIs is not recommended

Duloxetine, reversible selective MAO-B inhibitors ---> SmPC of [duloxetine] of EMA

Risk of serotonin syndrome. The concomitant use of Duloxetine with selective, reversible MAOIs is not recommended

Duloxetine, SNRIs ---> SmPC of [duloxetine] of EMA

Duloxetine, SSNRI ---> SmPC of [duloxetine] of EMA

Duloxetine, SSRI ---> SmPC of [duloxetine] of EMA

Duloxetine, tamoxifen

Duloxetine may decrease the therapeutic effect of tamoxifen by decreasing the production of active metabolite

Duloxetine, teriflunomide [2] ---> SmPC of [2] of EMA

Medicinal products metabolised by CYP1A2 should be used with caution during treatment with teriflunomide, as it could lead to the reduction of the efficacy of these products.

Duloxetine, tetrabenazine [2] ---> SmPC of [2] of eMC

Inhibitors of CYP2D6 may result in increased plasma concentrations of the active metabolite dihydrotetrabenazine, why they should only be combined with caution. A reduction of the tetrabenazine dose may be necessary.

Duloxetine, tranylcypromine

Tranylcypromine should not be used concomitantly with drugs with marked serotonin-reuptake inhibition. Risk of serotonin syndrome with symptoms like hypertension, irritability, hyperthermia with possible fatal outcome

Duloxetine, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib may increase the plasma exposure of substances predominantly metabolised by CYP1A2 and dose adjustments may be considered, if clinically indicated.

Serotonergic medicines, SNRIs ---> SmPC of [duloxetine] of EMA

In rare cases, serotonin syndrome has been reported in patients using SSRIs/SNRIs concomitantly with serotonergic agents. Caution is advisable

Serotonergic medicines, SSNRI ---> SmPC of [duloxetine] of EMA

In rare cases, serotonin syndrome has been reported in patients using SSRIs/SNRIs concomitantly with serotonergic agents. Caution is advisable

Serotonergic medicines, SSRI ---> SmPC of [duloxetine] of EMA

In rare cases, serotonin syndrome has been reported in patients using SSRIs/SNRIs concomitantly with serotonergic agents. Caution is advisable

CONTRAINDICATIONS of Duloxetine (Yentreve)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Liver disease resulting in hepatic impairment

- YENTREVE should not be used in combination with nonselective, irreversible monoamine oxidase inhibitors - MAOIs

- YENTREVE should not be used in combination with CYP1A2 inhibitors, like fluvoxamine, ciprofloxacin or enoxacin since the combination results in elevated plasma concentrations of duloxetine

- Severe renal impairment (creatinine clearance < 30 ml/min)

- The initiation of treatment with duloxetine is contraindicated in patients with uncontrolled hypertension that could expose patients to a potential risk of hypertensive crisis

https://www.ema.europa.eu/en/documents/product-information/yentreve-epar-product-information_en.pdf 09/07/2024

Other trade names: Ariclaim, Cymbalta, Duloxetine Lilly, Duloxetine Mylan, Duloxetine Zentiva, Nodetrip (previously Xeristar),

Dupilumab (Dupixent)

Breast-feeding, dupilumab [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue Dupixent therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

CYP450, dupilumab [2] ---> SmPC of [2] of EMA

The data gathered from this study did not indicate clinically relevant effects of dupilumab on CYP1A2, CYP3A, CYP2C19, CYP2D6, or CYP2C9 activity.

Dupilumab [1], fertility ---> SmPC of [1] of EMA

Animal studies showed no impairment of fertility (see section 5.3).

Dupilumab [1], pharmacokinetics ---> SmPC of [1] of EMA

Based on the population analysis, commonly co-administered medicinal products had no effect on dupilumab pharmacokinetics on patients with moderate to severe asthma.

Dupilumab [1], pregnancy ---> SmPC of [1] of EMA

Dupixent should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.

Dupilumab [1], vaccinations ---> SmPC of [1] of EMA

Patients receiving dupilumab may receive concurrent inactivated or non-live vaccinations. For information on live vaccines see section 4.4.

CONTRAINDICATIONS of Dupilumab (Dupixent)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/dupixent-epar-product-information_en.pdf 02/12/2024

Durvalumab (Imfinzi)

Breast-feeding, durvalumab [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast feeding or to discontinue or abstain from durvalumab therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Chemotherapy, durvalumab [2] ---> SmPC of [2] of EMA

Additionally, based on population PK analysis, concomitant chemotherapy treatment did not meaningfully impact the PK of durvalumab

Corticosteroids, durvalumab [2] ---> SmPC of [2] of EMA

The use of systemic corticosteroids or immunosuppressants before starting durvalumab, except physiological dose of systemic corticosteroids, is not recommended because of their potential interference with the pharmacodynamic activity of durvalumab. However, systemic corticosteroids or other immunosuppressants can be used after starting durvalumab to treat immune-related adverse reactions (see section 4.4).

Durvalumab [1], fertility ---> SmPC of [1] of EMA

There are no data on the potential effects of durvalumab on fertility in humans or animals.

Durvalumab [1], pharmacokinetics ---> SmPC of [1] of EMA

PK drug-drug interaction between durvalumab and chemotherapy was assessed in the CASPIAN study and showed concomitant treatment with durvalumab did not impact the PK of etoposide, carboplatin or cisplatin.

Durvalumab [1], pharmacological interactions ---> SmPC of [1] of EMA

It showed no clinically meaningful PK interactions between tremelimumab, durvalumab, nabpaclitaxel, gemcitabine, pemetrexed, carboplatin or cisplatin in the concomitant treatment.

Durvalumab [1], pregnancy ---> SmPC of [1] of EMA

Durvalumab may cause foetal harm when administered to a pregnant woman and is not recommended during pregnancy and in women of childbearing potential not using effective contraception during treatment and for at least 3 months after the last dose.

Durvalumab [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should use effective contraception during treatment with durvalumab and for at least 3 months after the last dose of durvalumab.

CONTRAINDICATIONS of Durvalumab (Imfinzi)

- Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/imfinzi-epar-product-information_en.pdf 05/04/2024

Dutasteride

Breast-feeding, dutasteride [2] ---> SmPC of [2] of eMC

Dutasteride is contraindicated for use by women.

Cholestyramine, dutasteride [2] ---> SmPC of [2] of eMC

Administration of 12 g colestyramine one hour after a 5 mg single dose of dutasteride did not affect the pharmacokinetics of dutasteride.

Diltiazem, dutasteride [2] ---> SmPC of [2] of eMC

Dutasteride [1], indinavir ---> SmPC of [1] of eMC

Long-term combination of dutasteride with drugs that are potent inhibitors of the enzyme CYP3A4 may increase serum concentrations of dutasteride.

Dutasteride [1], itraconazol ---> SmPC of [1] of eMC

Long-term combination of dutasteride with drugs that are potent inhibitors of the enzyme CYP3A4 may increase serum concentrations of dutasteride.

Dutasteride [1], ketoconazole ---> SmPC of [1] of eMC

Long-term combination of dutasteride with drugs that are potent inhibitors of the enzyme CYP3A4 may increase serum concentrations of dutasteride.

Dutasteride [1], nefazodone ---> SmPC of [1] of eMC

Long-term combination of dutasteride with drugs that are potent inhibitors of the enzyme CYP3A4 may increase serum concentrations of dutasteride.

Dutasteride [1], pregnancy ---> SmPC of [1] of eMC

If administered to a woman carrying a male foetus, inhibit the development of the external genitalia of the foetus. Dutasteride is contraindicated for use by women.

Dutasteride [1], ritonavir ---> SmPC of [1] of eMC

Long-term combination of dutasteride with drugs that are potent inhibitors of the enzyme CYP3A4 may increase serum concentrations of dutasteride.

Dutasteride [1], strong CYP3A4 inhibitors ---> SmPC of [1] of eMC

Long-term combination of dutasteride with drugs that are potent inhibitors of the enzyme CYP3A4 may increase serum concentrations of dutasteride.

Dutasteride [1], verapamil ---> SmPC of [1] of eMC

CONTRAINDICATIONS of Dutasteride

Dutasteride is contraindicated in:

- women and children and adolescents

- patients with hypersensitivity to dutasteride, other 5-alpha reductase inhibitors soya, peanut or any of the other excipients.

- patients with severe hepatic impairment.

http://www.medicines.org.uk/emc/

Duvelisib (Copiktra)

Alfentanyl, duvelisib [2] ---> SmPC of [2] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Apalutamide, duvelisib [2] ---> SmPC of [2] of EMA

Co-administration of duvelisib with strong CYP3A4 inducers (e.g., apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's wort) should be avoided.

Aprepitant, duvelisib [2] ---> SmPC of [2] of EMA

Dose reduction of duvelisib is not necessary when co-administered with moderate CYP3A4 inhibitors

Avanafil, duvelisib [2] ---> SmPC of [2] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Bosentan, duvelisib [2] ---> SmPC of [2] of EMA

Co-administration of duvelisib with moderate CYP3A inducers decreases AUC of duvelisib to less than 1.5-fold and dose reduction is not recommended. The patient should be closely monitored for potential lack of efficacy.

Breast-feeding, duvelisib [2] ---> SmPC of [2] of EMA

Breast-feeding should be discontinued during treatment with Copiktra and for at least 1 month after the last dose.

Budesonide, duvelisib [2] ---> SmPC of [2] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Buspirone, duvelisib [2] ---> SmPC of [2] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Carbamazepine, duvelisib [2] ---> SmPC of [2] of EMA

Co-administration of duvelisib with strong CYP3A4 inducers (e.g., apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's wort) should be avoided.

Ciprofloxacin, duvelisib [2] ---> SmPC of [2] of EMA

Dose reduction of duvelisib is not necessary when co-administered with moderate CYP3A4 inhibitors

Clarithromycin, duvelisib [2] ---> SmPC of [2] of EMA

Duvelisib dose should be reduced to 15 mg twice daily when co-administered with a strong CYP3A4 inhibitor

Cobicistat, duvelisib [2] ---> SmPC of [2] of EMA

Duvelisib dose should be reduced to 15 mg twice daily when co-administered with a strong CYP3A4 inhibitor

Conivaptan, duvelisib [2] ---> SmPC of [2] of EMA

Dose reduction of duvelisib is not necessary when co-administered with moderate CYP3A4 inhibitors

Contraceptives, duvelisib [2] ---> SmPC of [2] of EMA

It is unknown whether duvelisib reduces the effectiveness of hormonal contraceptives. Therefore, women using hormonal contraceptives should be advised to add a barrier method as a second form of contraception

Crizotinib, duvelisib [2] ---> SmPC of [2] of EMA

Dose reduction of duvelisib is not necessary when co-administered with moderate CYP3A4 inhibitors

Cyclosporine, duvelisib [2] ---> SmPC of [2] of EMA

Dose reduction of duvelisib is not necessary when co-administered with moderate CYP3A4 inhibitors

Darifenacin, duvelisib [2] ---> SmPC of [2] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Darunavir, duvelisib [2] ---> SmPC of [2] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Dasatinib, duvelisib [2] ---> SmPC of [2] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Diltiazem, duvelisib [2] ---> SmPC of [2] of EMA

Dose reduction of duvelisib is not necessary when co-administered with moderate CYP3A4 inhibitors

Dronedarone, duvelisib [2] ---> SmPC of [2] of EMA

Dose reduction of duvelisib is not necessary when co-administered with moderate CYP3A4 inhibitors

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, duvelisib [2] ---> SmPC of [2] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Drugs primarily metabolised by CYP3A4, duvelisib [2] ---> SmPC of [2] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], ebastine ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], efavirenz ---> SmPC of [1] of EMA

Duvelisib [1], eletriptan ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], enzalutamide ---> SmPC of [1] of EMA

Co-administration of duvelisib with strong CYP3A4 inducers (e.g., apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's wort) should be avoided.

Duvelisib [1], eplerenone ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], erythromycin ---> SmPC of [1] of EMA

Dose reduction of duvelisib is not necessary when co-administered with moderate CYP3A4 inhibitors

Duvelisib [1], etravirine ---> SmPC of [1] of EMA

Duvelisib [1], everolimus ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], felodipine ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], fertility ---> SmPC of [1] of EMA

No human data on the effect of duvelisib on fertility are available. In rats, but not in monkeys, effects on testes were observed.

Duvelisib [1], fluconazole ---> SmPC of [1] of EMA

Dose reduction of duvelisib is not necessary when co-administered with moderate CYP3A4 inhibitors

Duvelisib [1], fluvoxamine ---> SmPC of [1] of EMA

Dose reduction of duvelisib is not necessary when co-administered with moderate CYP3A4 inhibitors

Duvelisib [1], grapefruit juice ---> SmPC of [1] of EMA

Duvelisib dose should be reduced to 15 mg twice daily when co-administered with a strong CYP3A4 inhibitor

Duvelisib [1], ibrutinib ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], imatinib ---> SmPC of [1] of EMA

Dose reduction of duvelisib is not necessary when co-administered with moderate CYP3A4 inhibitors

Duvelisib [1], indinavir ---> SmPC of [1] of EMA

Duvelisib dose should be reduced to 15 mg twice daily when co-administered with a strong CYP3A4 inhibitor

Duvelisib [1], itraconazol ---> SmPC of [1] of EMA

Duvelisib dose should be reduced to 15 mg twice daily when co-administered with a strong CYP3A4 inhibitor

Duvelisib [1], ketoconazole ---> SmPC of [1] of EMA

Duvelisib dose should be reduced to 15 mg twice daily when co-administered with a strong CYP3A4 inhibitor

Duvelisib [1], lomitapide ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], lovastatine ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], lurasidone ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], maraviroc ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], midazolam ---> SmPC of [1] of EMA

Co-administration of midazolam with duvelisib should be avoided.

Duvelisib [1], mitotane ---> SmPC of [1] of EMA

Co-administration of duvelisib with strong CYP3A4 inducers (e.g., apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's wort) should be avoided.

Duvelisib [1], moderate CYP3A4 inductors ---> SmPC of [1] of EMA

Duvelisib [1], moderate CYP3A4 inhibitors ---> SmPC of [1] of EMA

Dose reduction of duvelisib is not necessary when co-administered with moderate CYP3A4 inhibitors

Duvelisib [1], naloxegol ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], nefazodone ---> SmPC of [1] of EMA

Duvelisib dose should be reduced to 15 mg twice daily when co-administered with a strong CYP3A4 inhibitor

Duvelisib [1], nelfinavir ---> SmPC of [1] of EMA

Duvelisib dose should be reduced to 15 mg twice daily when co-administered with a strong CYP3A4 inhibitor

Duvelisib [1], nisoldipine ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], phenobarbital ---> SmPC of [1] of EMA

Duvelisib [1], phenytoin ---> SmPC of [1] of EMA

Co-administration of duvelisib with strong CYP3A4 inducers (e.g., apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's wort) should be avoided.

Duvelisib [1], posaconazole ---> SmPC of [1] of EMA

Duvelisib dose should be reduced to 15 mg twice daily when co-administered with a strong CYP3A4 inhibitor

Duvelisib [1], pregnancy ---> SmPC of [1] of EMA

As a precautionary measure, it is preferable to avoid the use of Copiktra during pregnancy.

Duvelisib [1], primidone ---> SmPC of [1] of EMA

Duvelisib [1], proton pump inhibitors ---> SmPC of [1] of EMA

Population Pharmacokinetic (POPPK) analysis has shown that proton pump inhibitors (PPI) do not affect the exposure of COPIKTRA. PPI may be co-administered with duvelisib

Duvelisib [1], quetiapine ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], rifampicin ---> SmPC of [1] of EMA

Co-administration of duvelisib with strong CYP3A4 inducers (e.g., apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's wort) should be avoided.

Duvelisib [1], ritonavir ---> SmPC of [1] of EMA

Duvelisib dose should be reduced to 15 mg twice daily when co-administered with a strong CYP3A4 inhibitor

Duvelisib [1], saquinavir ---> SmPC of [1] of EMA

Duvelisib dose should be reduced to 15 mg twice daily when co-administered with a strong CYP3A4 inhibitor

Duvelisib [1], sildenafil ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], simvastatine ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], sirolimus ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of duvelisib with strong CYP3A4 inducers (e.g., apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's wort) should be avoided.

Duvelisib [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Co-administration of duvelisib with strong CYP3A4 inducers (e.g., apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's wort) should be avoided.

Duvelisib [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Duvelisib dose should be reduced to 15 mg twice daily when co-administered with a strong CYP3A4 inhibitor

Duvelisib [1], tacrolimus ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], telithromycin ---> SmPC of [1] of EMA

Duvelisib dose should be reduced to 15 mg twice daily when co-administered with a strong CYP3A4 inhibitor

Duvelisib [1], ticagrelor ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], tipranavir ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], tofisopam ---> SmPC of [1] of EMA

Dose reduction of duvelisib is not necessary when co-administered with moderate CYP3A4 inhibitors

Duvelisib [1], tolvaptan ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], triazolam ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], vardenafil ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Duvelisib [1], verapamil ---> SmPC of [1] of EMA

Dose reduction of duvelisib is not necessary when co-administered with moderate CYP3A4 inhibitors

Duvelisib [1], voriconazole ---> SmPC of [1] of EMA

Duvelisib dose should be reduced to 15 mg twice daily when co-administered with a strong CYP3A4 inhibitor

CONTRAINDICATIONS of Duvelisib (Copiktra)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/copiktra-epar-product-information_en.pdf 03/04/2025

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