T

Sodium thiosulfate (Pedmarqsi)

Breast-feeding, sodium thiosulfate [2] ---> SmPC of [2] of EMA

Sodium thiosulfate is only intended to be administered in conjunction with cisplatin chemotherapy, during which breastfeeding is contraindicated in female patients.

Cisplatin, pregnancy ---> SmPC of [sodium thiosulfate] of EMA

Patients receiving cisplatin are warned of the need to use appropriate contraception during treatment and for 6 months following cisplatin treatment, as cisplatin is embryotoxic and fetotoxic.

Cisplatin, sodium thiosulfate [2] ---> SmPC of [2] of EMA

Relevant pharmacokinetic interactions are unlikely as administration of thiosulfate is infrequent, only in conjunction with cisplatin and thiosulfate is rapidly eliminated within hours after administration.

Fertility, sodium thiosulfate [2] ---> SmPC of [2] of EMA

Sodium thiosulfate is only intended to be administered in conjunction with cisplatin chemotherapy. Cisplatin treatment is known to adversely affect fertility.

Nursing, sodium thiosulfate [2] ---> SmPC of [2] of EMA

Sodium thiosulfate is contraindicated in preterm and term newborn infants from birth to less than 1 month of age. Patients < 1 month of age have less well-developed sodium homeostasis

Pregnancy, sodium thiosulfate [2] ---> SmPC of [2] of EMA

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

Sodium thiosulfate [1], time ---> SmPC of [1] of EMA

Sodium thiosulfate should only be given at least 6 hours after the end of cisplatin infusion.

CONTRAINDICATIONS of Sodium thiosulfate (Pedmarqsi)

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

- Neonates under the age of 1 month due to the risk of hypernatremia (see section 4.4).

https://www.ema.europa.eu/en/documents/product-information/pedmarqsi-epar-product-information_en.pdf 01/07/2025

Tabelecleucel (Ebvallo)

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

Ebvallo has minor influence on the ability to drive and use machines, e.g. dizziness, fatigue (see section 4.8).

Anti CD20 antibody, tabelecleucel [2] ---> SmPC of [2] of EMA

Because in vitro characterisation data demonstrated the absence of CD20 expression on tabelecleucel, it is not expected that anti-CD20 antibody treatments will affect tabelecleucel activity.

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

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

Brentuximab vedotin, tabelecleucel [2] ---> SmPC of [2] of EMA

Certain concomitant or recently administered medicinal could potentially impact the efficacy of Ebvallo. Ebvallo should only be administered after an adequate washout period of such agents.

Chemotherapy, tabelecleucel [2] ---> SmPC of [2] of EMA

Certain concomitant or recently administered medicinal could potentially impact the efficacy of Ebvallo. Ebvallo should only be administered after an adequate washout period of such agents.

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

For patients receiving chronic corticosteroid therapy, the dose of these drugs should be reduced as much as is clinically safe and appropriate; recommended no greater than 1 mg/kg per day of prednisone or equivalent.

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

In clinical studies, patients received ciclosporin, tacrolimus, sirolimus and other immunosuppressive therapies at the lowest dose considered clinically safe and appropriate.

Extracorporeal photopheresis, tabelecleucel [2] ---> SmPC of [2] of EMA

Certain concomitant or recently administered medicinal could potentially impact the efficacy of Ebvallo. Ebvallo should only be administered after an adequate washout period of such agents.

Fertility, tabelecleucel [2] ---> SmPC of [2] of EMA

There are no data on the effect of tabelecleucel on fertility.

Immunosuppressives, tabelecleucel [2] ---> SmPC of [2] of EMA

In clinical studies, patients received ciclosporin, tacrolimus, sirolimus and other immunosuppressive therapies at the lowest dose considered clinically safe and appropriate.

Pregnancy, tabelecleucel [2] ---> SmPC of [2] of EMA

Ebvallo is not recommended during pregnancy and in women of childbearing potential not using contraception. Pregnant women should be advised on potential risks for the foetus.

Sirolimus, tabelecleucel [2] ---> SmPC of [2] of EMA

In clinical studies, patients received ciclosporin, tacrolimus, sirolimus and other immunosuppressive therapies at the lowest dose considered clinically safe and appropriate.

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

In clinical studies, patients received ciclosporin, tacrolimus, sirolimus and other immunosuppressive therapies at the lowest dose considered clinically safe and appropriate.

CONTRAINDICATIONS of Tabelecleucel (Ebvallo)

- 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/ebvallo-epar-product-information_en.pdf 24/11/2025

Tacrolimus (Modigraf)

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

Tacrolimus may cause visual and neurological disturbances. This effect may be enhanced if tacrolimus is administered in association with alcohol.

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

Administration of NSAID drugs together with tacrolimus is thought to increase the risk of nephrotoxicity due to decreased synthesis of prostacyclin in the kidney. During combination therapy it is therefore important to carefully monitor renal function.

Acetylsalicylic acid, tacrolimus [2] ---> SmPC of [2] of EMA

Products known to have nephrotoxic or neurotoxic effects: May enhance nephrotoxic or neurotoxic effects of tacrolimus. Concurrent use of tacrolimus with drugs known to have nephrotoxic effects should be avoided.

Aciclovir, tacrolimus [2] ---> SmPC of [2] of EMA

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

Adagrasib is a strong CYP3A4 inhibitor. Co-administration of medicinal products 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

Adefovir dipivoxil [1], tacrolimus ---> SmPC of [1] of EMA

Co-administration of 10 mg adefovir dipivoxil with other medicinal products that are eliminated by tubular secretion or alter tubular function may increase serum concentrations of either adefovir or the co-administered medicinal product

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

Therefore, it is recommended to administer strong P-gp inhibitors using staggered dosing, preferably 6 hours or 12 hours apart from GIOTRIF (see section 4.2).

Aluminium hydroxide, tacrolimus [2] ---> SmPC of [2] of EMA

May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation).

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

The combination may increase the risk of nephrotoxicity. Renal function must be closely monitored.

Amiloride, tacrolimus [2] ---> SmPC of [2] of EMA

As tacrolimus treatment may be associated with hyperkalaemia, or may increase pre-existing hyperkalaemia, high potassium intake, or potassium-sparing diuretics (e.g. amiloride, triamterene, or spironolactone) should be avoided (see section 4.4).

Amiloride/hydrochlorothiazide [1], tacrolimus ---> SmPC of [1] of eMC

When amiloride hydrochloride is administered concomitantly with tacrolimus the risk of hyperkalaemia may be increased.

Aminoglycoside antibiotics, tacrolimus [2] ---> SmPC of [2] of EMA

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

May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation). A rapid increase in tacrolimus level may occur. Monitor tacrolimus whole blood trough levels frequently,

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

There is a risk of increased tacrolimus blood levels when co-administered with amlodipine.

Amphotericin, tacrolimus [2] ---> SmPC of [2] of EMA

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

Frequent therapeutic concentration monitoring of immunosuppressant levels is recommended until levels have stabilised as plasma concentrations of immunosuppressant may be increased when co-administered with amprenavir

Amprenavir/ritonavir, tacrolimus ---> SmPC of [amprenavir] of EMA

Apalutamide, tacrolimus [2] ---> SmPC of [2] of EMA

May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see section 4.4]. It is recommended that concomitant use should be avoided.

Aplasia, tacrolimus [2] ---> SmPC of [2] of EMA

Cases of pure red cell aplasia (PRCA) have been reported in patients treated with tacrolimus.

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

Caution is advised during concomitant administration of aprepitant and orally administered active substances that are metabolised primarily through CYP3A4 and with a narrow therapeutic range

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

Concentrations of the immunosuppressant may be increased when co-administered with REYATAZ due to CYP3A4 inhibition.

Atazanavir/cobicistat [1], tacrolimus ---> SmPC of [1] of EMA

Concentrations of the immunosuppressant may be increased when co-administered with EVOTAZ. The mechanism of interaction is inhibition of CYP3A4 by atazanavir and cobicistat.

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

Avacopan is a weak inhibitor of CYP3A4 in vivo and may increase the plasma exposures of concomitant medicinal products that are CYP3A4 substrates with a narrow therapeutic index

Azathioprine, tacrolimus

The co-administration may increase the risk of an excessive immunsuppression

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

Azole antifungals, tacrolimus [2] ---> SmPC of [2] of EMA

May increase tacrolimus whole blood trough levels and increase the risk of serious adverse reactions (e.g., nephrotoxicity, neurotoxicity, QT prolongation) which requires close monitoring. It is recommended that concomitant use should be avoided.

Basiliximab, tacrolimus [2] ---> SmPC of [2] of EMA

A combination of immunosuppressives such as antilymphocytic antibodies (e.g. basiliximab, daclizumab) given concomitantly increases the risk of EBV-associated lymphoproliferative disorders.

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

Combination of bendamustine with tacrolimus may result in excessive immunosuppression with risk of lymphoproliferation.

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

Caution is advised in case of combination of bexarotene with CYP3A4 substrates having a narrow therapeutic margin

Bleomycin, tacrolimus

Exaggerated immunosuppression with risk of lymphoproliferation

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

The CYP3A4 inhibition by boceprevir increases the tacrolimus plasma levels. The combination requires significant dose reduction and prolongation of the dosing interval for tacrolimus

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

The co-administration may increase the bosentan plasma concentrations and decrease the levels of tacrolimus. The coadministration is not recommended

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

As detrimental effects on the newborn cannot be excluded, women should not breast-feed whilst receiving tacrolimus.

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

Coadministration of Alunbrig with CYP3A substrates with a narrow therapeutic index (e.g., alfentanil, fentanyl, quinidine, cyclosporine, sirolimus, tacrolimus) should be avoided as their effectiveness may be reduced.

Bromocriptine, tacrolimus [2] ---> SmPC of [2] of EMA

May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation). Monitor tacrolimus whole blood trough concentrations and reduce tacrolimus dose if needed.

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

As a precautionary measure, close clinical monitoring is warranted for co-administered narrow-therapeutic-index drugs which are sensitive CYP3A4 substrates

Cannabidiol, tacrolimus [2] ---> SmPC of [2] of EMA

Increases in exposure of other orally administered sensitive P-gp substrates (e.g., sirolimus, tacrolimus, digoxin) may occur on coadministration with cannabidiol.

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

Dose adjustment may be required for medicinal products that are primarily eliminated via CYP3A metabolism and have narrow therapeutic window (e.g. carbamazepine, cyclosporine, fentanyl, pimozide, simvastatin, tacrolimus).

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

It is recommended that concomitant use of strong CYP3A4 inducers (such as rifampicin, phenytoin, carbamazepine), with tacrolimus should be avoided.

Carboplatin, tacrolimus

The co-administration of carboplatin with tacrolimus may cause an excessive immunosuppression with risk of lymphoproliferation

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

Caspofungin reduced the trough concentration of tacrolimus by 26 % in healthy adult volunteers. For patients receiving both therapies, standard monitoring of tacrolimus blood concentrations and appropriate tacrolimus dosage adjustments are mandatory.

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

The combination may increase the risk of nephrotoxicity. Renal function must be closely monitored.

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

Co-administration of ceritinib with substrates primarily metabolised by CYP3A or CYP3A substrates known to have narrow therapeutic indices should be avoided

Cimetidine, tacrolimus [2] ---> SmPC of [2] of EMA

May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation).

Cisapride, tacrolimus [2] ---> SmPC of [2] of EMA

The combination may increase systemic exposure of tacrolimus

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

It is recommended that concomitant use of strong CYP3A4 inhibitors (such as ritonavir, cobicistat, ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin or josamycin) with tacrolimus should be avoided.

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

The concomitant use of medicinal products eliminated by tubular secretion should be avoided

Clotrimazole, tacrolimus [2] ---> SmPC of [2] of EMA

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

The co-administration may increase the plasma levels of immunosuppressive

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

Contraceptives, tacrolimus [2] ---> SmPC of [2] of EMA

As tacrolimus may reduce the clearance of steroid-based contraceptives leading to increased hormone exposure, particular care should be exercised when deciding upon contraceptive measures.

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

Maintenance doses of corticosteroids: May decrease tacrolimus whole blood trough levels and increase the risk of rejection. Monitor tacrolimus whole blood trough concentrations and increase tacrolimus dose if needed. Monitor graft function closely.

Cortisone, tacrolimus [2] ---> SmPC of [2] of EMA

Cotrimoxazole, tacrolimus [2] ---> SmPC of [2] of EMA

Crizotinib, tacrolimus [2] ---> SmPC of [2] of EMA

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

The combined administration of ciclosporin and tacrolimus should be avoided and care should be taken when administering tacrolimus to patients who have previously received ciclosporin (see sections 4.2 and 4.5).

CYP3A4 inductors, tacrolimus [2] ---> SmPC of [2] of EMA

Discontinuation of CYP3A4 inducers may affect the rate of metabolism of tacrolimus, thereby leading to supratherapeutic blood levels of tacrolimus, and therefore requires close monitoring and supervision of a transplant specialist.

CYP3A4 inductors, tacrolimus [2] ---> SmPC of [2] of EMA

Concomitant use with CYP3A4 inducers may decrease tacrolimus blood levels, potentially increasing the risk of transplant rejection.

CYP3A4 inhibitors, tacrolimus [2] ---> SmPC of [2] of EMA

Discontinuation of CYP3A4 inhibitors may affect the rate of metabolism of tacrolimus, thereby leading to subtherapeutic blood levels of tacrolimus, and therefore requires close monitoring and supervision of a transplant specialist.

CYP3A4 inhibitors, tacrolimus [2] ---> SmPC of [2] of EMA

Concomitant use with CYP3A4 inhibitors may increase tacrolimus blood levels, which could lead to serious adverse reactions, including nephrotoxicity, neurotoxicity and QT prolongation.

Cytostatics, tacrolimus

The co-administration may cause an excessive immunosuppression with risk of lymphoproliferation

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 [1], tacrolimus ---> SmPC of [1] 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 tacrolimus is not recommended

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.

Dacarbazine, tacrolimus

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.

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

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

Daclizumab, tacrolimus [2] ---> SmPC of [2] of EMA

A combination of immunosuppressives such as antilymphocytic antibodies (e.g. basiliximab, daclizumab) given concomitantly increases the risk of EBV-associated lymphoproliferative disorders.

Danazol, tacrolimus [2] ---> SmPC of [2] 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).

Dapsone, tacrolimus [2] ---> SmPC of [2] of EMA

Darbepoetin alfa [1], tacrolimus ---> SmPC of [1] 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.

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.

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/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/ritonavir, tacrolimus ---> SmPC of [darunavir] of EMA

Exposure to the immunosuppressant will be increased when co-administered with boosted darunavir. (CYP3A inhibition)

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).

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

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.

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

Excessive immunosuppression with risk of lymphoproliferative disease

Diarrhoe, tacrolimus [2] ---> SmPC of [2] of EMA

Since levels of tacrolimus in blood may significantly change during diarrhoea episodes, extra monitoring of tacrolimus concentrations is recommended during episodes of diarrhoea.

Diltiazem, tacrolimus [2] ---> SmPC of [2] of EMA

Direct acting antivirals, tacrolimus [2] ---> SmPC of [2] of EMA

May have impact on the pharmacokinetics of tacrolimus by changes in liver function during DAA therapy, related to clearance of HCV virus.

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/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)

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

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

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Drugs metabolised by CYP3A4, tacrolimus [2] ---> SmPC of [2] of EMA

Tacrolimus is a known CYP3A4 inhibitor; thus concomitant use of tacrolimus with medicinal products known to be metabolised by CYP3A4 may affect the metabolism of such medicinal products.

Drugs primarily metabolised by CYP3A4, tacrolimus [2] ---> SmPC of [2] of EMA

Tacrolimus is a known CYP3A4 inhibitor; thus concomitant use of tacrolimus with medicinal products known to be metabolised by CYP3A4 may affect the metabolism of such medicinal products.

Drugs with high protein binding, tacrolimus [2] ---> SmPC of [2] of EMA

Tacrolimus is extensively bound to plasma proteins. Possible interactions with other active substances known to have high affinity for plasma proteins should be considered

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.

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

Decreased exposure of the immunosuppressant may be expected (CYP3A4 induction). This immunosuppressant is not anticipated to affect exposure of efavirenz.

Elbasvir/grazoprevir [1], tacrolimus ---> SmPC of [1] of EMA

CYP3A inhibition. Frequent monitoring of tacrolimus whole blood concentrations, changes in renal function, and tacrolimus-associated adverse events upon the initiation of coadministration is recommended.

Electrolyte imbalance, tacrolimus [2] ---> SmPC of [2] of EMA

Caution should be exercised in patients on concomitant medications known to prolong the QT interval, induce electrolyte abnormalities or known to increase tacrolimus exposure

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

Loss of efficacy can occur, especially when medicinal products with low dose and narrow therapeutic index (e.g. alfentanil, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus), are co-administered with Eluxadoline.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [1], tacrolimus ---> SmPC of [1] of EMA

Concentrations of this immunosuppressant agent may be increased when administered with cobicistat. Therapeutic monitoring is recommended upon co-administration with Genvoya.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], tacrolimus ---> SmPC of [1] of EMA

The co-administration may increase the plasma levels of immunosuppressive

Emtricitabine/rilpivirine/tenofovir disoproxil [1], tacrolimus ---> SmPC of [1] of EMA

No dose adjustment is required.

Emtricitabine/tenofovir disoproxil [1], tacrolimus ---> SmPC of [1] of EMA

No dose adjustment of tacrolimus is required.

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

Caution is advised when entrectinib is administered together with sensitive CYP3A4 substrates with a narrow therapeutic range, due to the increased risk of adverse drug reactions.

Enzalutamide, tacrolimus [2] ---> SmPC of [2] of EMA

May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see section 4.4]. It is recommended that concomitant use should be avoided.

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

Tacrolimus may lead to impaired renal function and increase the risk of hyperkalaemia. The concomitant use of eplerenone and tacrolimus should be avoided.

Ergotamine, tacrolimus [2] ---> SmPC of [2] of EMA

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

Caution and monitoring for adverse effects is recommended with concomitant use of substances that have a narrow therapeutic window and that are eliminated mainly via CYP3A4-mediated metabolism

Erythromycin, tacrolimus [2] ---> SmPC of [2] of EMA

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

Concomitant administration of esomeprazole has been reported to increase the serum levels of tacrolimus. A reinforced monitoring of tacrolimus concentrations as well as renal function should be performed, and dosage of tacrolimus adjusted if needed.

Estrogens, tacrolimus [2] ---> SmPC of [2] of EMA

As tacrolimus may reduce the clearance of steroid-based contraceptives leading to increased hormone exposure, particular care should be exercised when deciding upon contraceptive measures.

Ethinyl estradiol, tacrolimus [2] ---> SmPC of [2] of EMA

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

Although this interaction has not been studied with etoricoxib, coadministration of ciclosporin or tacrolimus with any NSAID may increase the nephrotoxic effect of ciclosporin or tacrolimus.

Etravirine, tacrolimus [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inducers: May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see section 4.4]. Monitor graft function closely.

Everolimus, tacrolimus [2] ---> SmPC of [2] of EMA

Co-administration of tacrolimus with a mammalian target of rapamycin (mTOR) inhibitor (e.g., sirolimus, everolimus) may increase the risk of thrombotic microangiopathy (including haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura)

Exposure to sunlight and ultraviolet light, tacrolimus [2] ---> SmPC of [2] of EMA

As with other immunosuppressive agents, owing to the potential risk of malignant skin changes, exposure to sunlight and UV light should be limited by wearing protective clothing and using a sunscreen with a high protection factor.

Extract of Schisandra sphenanthera, tacrolimus [2] ---> SmPC of [2] of EMA

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

Felodipine may increase the plasma levels of tacrolimus

Felodipine/metoprolol [1], tacrolimus ---> SmPC of [1] of eMC

Felodipine may increase the plasma levels of tacrolimus

Felodipine/ramipril [1], tacrolimus ---> SmPC of [1] of eMC

Felodipine may increase the tacrolimus concentration. When used together, the tacrolimus serum concentration should be followed

Fertility, tacrolimus [2] ---> SmPC of [2] of EMA

A negative effect of tacrolimus on male fertility in the form of reduced sperm counts and motility was observed in rats (see section 5.3).

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

Combination of filgotinib with other potent immunosuppressants such as ciclosporin, tacrolimus, biologics or other Janus kinase (JAK) inhibitors is not recommended as a risk of additive immunosuppression cannot be excluded.

Flucloxacillin, tacrolimus [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inducers: May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see section 4.4]. Monitor graft function closely.

Fluconazole, tacrolimus [2] ---> SmPC of [2] of EMA

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

Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.

Fosamprenavir/ritonavir, tacrolimus ---> SmPC of [fosamprenavir] of EMA

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

Caution is advised during co-administration of fosaprepitant and orally administered active principles metabolised primarily through CYP3A4 and with a narrow therapeutic range

Foscarnet, tacrolimus [2] ---> SmPC of [2] of EMA

Ganciclovir, tacrolimus [2] ---> SmPC of [2] of EMA

Gastrointestinal perforation, tacrolimus [2] ---> SmPC of [2] of EMA

Gastrointestinal perforation has been reported in patients treated with tacrolimus.

Gentamicin, tacrolimus [2] ---> SmPC of [2] of EMA

Gestodene, tacrolimus [2] ---> SmPC of [2] of EMA

Glecaprevir/pibrentasvir [1], tacrolimus ---> SmPC of [1] of EMA

Increase of tacrolimus exposure is expected. Therefore, a therapeutic drug monitoring of tacrolimus is recommended and a dose adjustment of tacrolimus made accordingly

Grapefruit juice, tacrolimus [2] ---> SmPC of [2] of EMA

May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see section 4.4]. Avoid grapefruit or grapefruit juice.

Grapefruit, tacrolimus [2] ---> SmPC of [2] of EMA

Gyrase inhibitors, tacrolimus [2] ---> SmPC of [2] of EMA

Hydroxychloroquine, tacrolimus

Tacrolimus (topical) may enhance the adverse reactions of hydroxychloroquine. Hydroxychloroquine with systemic tacrolimus may enhance the effect of QTc interval prolongation

Hyperkalemia, tacrolimus [2] ---> SmPC of [2] of EMA

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

Caution should be exercised if co-administering ibrutinib with CYP3A4 substrates administered orally with narrow therapeutic range (such as dihydroergotamine, ergotamine, fentanyl, cyclosporine, sirolimus and tacrolimus).

Ibuprofen, tacrolimus [2] ---> SmPC of [2] of EMA

Idarubicin, tacrolimus

The co-administration may cause an excessive immunosuppression with risk of lymphoproliferation

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

CYP3A4 substrates known to have a narrow therapeutic index should be administered with caution in patients receiving idebenone.

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

The co-administration of idelalisib with tacrolimus may increase the serum concentrations of tacrolimus. Therapeutic monitoring is recommended.

Imatinib, tacrolimus [2] ---> SmPC of [2] of EMA

Immunosuppressives, tacrolimus [2] ---> SmPC of [2] of EMA

As with other potent immunosuppressive compounds, the risk of secondary cancer is unknown (see section 4.8).

Indinavir/ritonavir, tacrolimus ---> SmPC of [indinavir] of EMA

Indinavir and ritonavir inhibit CYP3A4 and as a result are expected to increase the plasma concentrations of tacrolimus. Careful monitoring of therapeutic and adverse effects is recommended when tacrolimus is concomitantly administered with indinavir/ritonavir

Infection, tacrolimus [2] ---> SmPC of [2] of EMA

Patients treated with immunosuppressants, including Modigraf, are at increased risk for infections including opportunistic infections

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

Caution should be exercised if co-administration of iptacopan with sensitive CYP3A4 substrates is required, especially for those with a narrow therapeutic index

Isavuconazole, tacrolimus [2] ---> SmPC of [2] of EMA

Isoniazid, tacrolimus [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inducers: May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see section 4.4]. Monitor graft function closely.

Itraconazol, tacrolimus [2] ---> SmPC of [2] of EMA

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

When used concomitantly with digoxin or other substrates of P-gp with a narrow therapeutic index, such as ciclosporin, everolimus, sirolimus or tacrolimus, caution and appropriate monitoring should be used.

Ivacaftor/tezacaftor/elexacaftor [1], tacrolimus ---> SmPC of [1] of EMA

When used concomitantly with digoxin or other substrates of P-gp with a narrow therapeutic index such as ciclosporin, everolimus, sirolimus, and tacrolimus, caution and appropriate monitoring should be used.

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

Patients should be monitored for loss of substrate efficacy (substrate with a narrow therapeutic index) if use of such medicinal products cannot be avoided (see section 5.2).

Josamycin, tacrolimus

Josamycin, tacrolimus [2] ---> SmPC of [2] of EMA

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

Increased in plasma concentrations of tacrolimus have been observed. Not recommended unless necessary. Careful monitoring and dose adjustment of this drug may be required

Ketoconazole, tacrolimus [2] ---> SmPC of [2] of EMA

Ketoprofen, tacrolimus ---> SmPC of [piroxicam] of eMC

Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.

Lansoprazole, tacrolimus [2] ---> SmPC of [2] of EMA

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

Exercise caution with concomitant use of CYP3A substrates with narrow therapeutic range (e.g. alfentanil, ciclosporin, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, or tacrolimus) in patients taking VITRAKVI.

Ledipasvir/sofosbuvir [1], tacrolimus ---> SmPC of [1] of EMA

No dose adjustment of Harvoni or tacrolimus is required at initiation of co-administration. Afterwards, close monitoring and potential dose adjustment of tacrolimus may be required.

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

Co-administration of PREVYMIS may result in clinically relevant increases in the plasma concentrations of co-administered CYP3A substrates

Lidocaine, tacrolimus [2] ---> SmPC of [2] of EMA

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

Weak CYP3A4 inhibitors are expected to increase the exposure of lomitapide when taken simultaneously. Separate the dose of the medications by 12 hours OR decrease the dose of Lojuxta by half.

Lopinavir/ritonavir [1], tacrolimus ---> SmPC of [1] of EMA

Lopinavir/ritonavir, CYP3A4 inhibitors, may increase the plasma concentrations of tacrolimus. Monitoring is recommended

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

Concurrent administration of lorlatinib with CYP3A4/5 substrates with narrow therapeutic indices, should be avoided since the concentration of these medicinal products may be reduced by lorlatinib

Lornoxicam, tacrolimus

Tacrolimus increases the risk of nephrotoxicity due to reduced synthesis of prostacyclin in the kidneys. During the combination it is necessary to control the renal function

Loss of vision, tacrolimus [2] ---> SmPC of [2] of EMA

Eye disorders, sometimes progressing to loss of vision, have been reported in patients treated with tacrolimus.

Lumacaftor/ivacaftor [1], tacrolimus ---> SmPC of [1] of EMA

Concomitant use of lumacaftor/ivacaftor with this immunosuppressant is not recommended. Lumacaftor/ivacaftor will decrease the exposure of the immunosuppressant, which may reduce the efficacy of the immunosuppressant.

Lumiracoxib, tacrolimus

The co-administration may increase the risk of nephrotoxicity due to reduced synthesis of renal prostaglandins. Renal function must be closely monitored

Magnesium hydroxide, tacrolimus [2] ---> SmPC of [2] of EMA

May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation).

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

Frequently monitor tacrolimus levels, especially following initiation and after discontinuation of maribavir and adjust dose, as needed.

Meloxicam, tacrolimus

Nephrotoxicity of calcineurin inhibitor may be enhanced by meloxicam via renal prostaglandin-mediated effects.

Mephenytoin, tacrolimus [2] ---> SmPC of [2] of EMA

Meropenem/vaborbactam [1], tacrolimus ---> SmPC of [1] of EMA

When coadministering Vaborem with medicinal products that are predominantly metabolised by CYP3A4, there could be a potential risk of interaction which may result in decreased plasma levels of the co-administered medicinal product.

Metamizole, tacrolimus [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inducers: May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see section 4.4]. Monitor graft function closely.

Methylprednisolone, tacrolimus [2] ---> SmPC of [2] of EMA

High dose prednisolone or methylprednisolone administered for the treatment of acute rejection have the potential to increase or decrease tacrolimus blood levels.

Methylthioninium chloride [1], tacrolimus ---> SmPC of [1] of EMA

These interactions could have a clinical relevance with narrow therapeutic index medicinal products that are metabolised by one of these enzymes

Metoclopramide, tacrolimus [2] ---> SmPC of [2] of EMA

May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation).

Metronidazole, tacrolimus

Metronidazole increases the plasma levels and toxicity of tacrolimus

Mibefradil, tacrolimus

Possible increase of tacrolimus plasma concentrations.

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

No evidence of altered pharmacokinetics of micafungin was observed. No micafungin dose adjustments are necessary when these medicines are administered concomitantly.

Miconazole, tacrolimus [2] ---> SmPC of [2] of EMA

Midazolam, tacrolimus [2] ---> SmPC of [2] of EMA

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

If co-administration of Pyrukynd with sensitive CYP3A4 substrates is unavoidable, patients should be carefully monitored especially for those substrates with a narrow therapeutic index

Mitotane, tacrolimus [2] ---> SmPC of [2] of EMA

May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see section 4.4]. It is recommended that concomitant use should be avoided.

Moderate CYP3A4 inhibitors, tacrolimus [2] ---> SmPC of [2] of EMA

MTOR inhibitors, tacrolimus [2] ---> SmPC of [2] of EMA

Mycophenolate mofetil [1], tacrolimus ---> SmPC of [1] of EMA

There was an increase of approximately 20% in tacrolimus AUC when multiple doses of mycophenolate mofetil (1.5 g taken twice a day [BID], morning and evening) were administered to hepatic transplant patients taking tacrolimus.

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

In renal transplant patients, tacrolimus concentration did not appear to be altered by mycophenolate mofetil

Mycophenolic acid, tacrolimus [2] ---> SmPC of [2] of EMA

Drugs which interfere with mycophenolic acid's enterohepatic cycle have potential to reduce the plasma level and efficacy of mycophenolic acid.

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

Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.

Naproxen/esomeprazole [1], tacrolimus ---> SmPC of [1] of eMC

As with all NSAIDs, there is a possible risk of nephrotoxicity when naproxen is co-administered with tacrolimus. Concomitant administration of esomeprazole has been reported to increase the serum levels of tacrolimus.

Nefazodone, tacrolimus [2] ---> SmPC of [2] of EMA

Nelfinavir, tacrolimus [2] ---> SmPC of [2] of EMA

Nephrotoxic substances, tacrolimus [2] ---> SmPC of [2] of EMA

Nephrotoxicity, tacrolimus [2] ---> SmPC of [2] of EMA

Concurrent use of tacrolimus with drugs known to have nephrotoxic effects should be avoided.

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

This might be clinically relevant for patients who are treated concomitantly with therapeutic agents with a narrow therapeutic window whose absorption involves P-gp transporters in the gastrointestinal tract

Netupitant/palonosetron [1], tacrolimus ---> SmPC of [1] of EMA

Netupitant/palonosetron should be used with caution in patients receiving concomitant orally administered active substances that are metabolised primarily through CYP3A4 and with a narrow therapeutic range

Neurotoxic substances, tacrolimus [2] ---> SmPC of [2] of EMA

Certain combinations of tacrolimus with drugs known to have neurotoxic effects may increase the risks of these effects (see section 4.5).

Nicardipine, tacrolimus [2] ---> SmPC of [2] of EMA

Nifedipine, tacrolimus [2] ---> SmPC of [2] of EMA

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

Nilotinib is a moderate CYP3A4 inhibitor. Appropriate monitoring and dose adjustment may be necessary for drugs that are CYP3A4 substrates and have a narrow therapeutic index when co-administered with nilotinib.

Nilvadipine, tacrolimus [2] ---> SmPC of [2] of EMA

In vitro nilvadipine have been shown to be potential inhibitor of tacrolimus metabolism

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

Caution is recommended when niraparib is combined with principles the metabolism of which is CYP3A4-dependent and, notably, those having a narrow therapeutic range (e.g. ciclosporin, tacrolimus, alfentanil, ergotamine, pimozide, quetiapine, and halofantrine

Nirmatrelvir/ritonavir [1], tacrolimus ---> SmPC of [1] of EMA

Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent inhibits CYP3A4 and as a result is expected to increase the plasma concentrations of cyclosporine, tacrolimus or everolimus.

Nisoldipine, tacrolimus

The CYP3A4 inhibition may increase the plasma concentrations of nisoldipine

Norethindrone, tacrolimus [2] ---> SmPC of [2] of EMA

NSAID, tacrolimus [2] ---> SmPC of [2] of EMA

Tacrolimus is extensively bound to plasma proteins. Possible interactions with other active substances known to have high affinity for plasma proteins should be considered

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

Olaparib inhibits CYP3A4 in vitro and is predicted to be a mild CYP3A inhibitor in vivo. Therefore, caution should be exercised when sensitive CYP3A substrates or substrates with a narrow therapeutic margin are combined with olaparib.

Olmesartan medoxomil [1], tacrolimus ---> SmPC of [1] of eMC

Tacrolimus may provoke a hyperkalaemia

Ombitasvir/paritaprevir/ritonavir [1], tacrolimus ---> SmPC of [1] of EMA

CYP3A4 substrates may require dose adjustment and/or clinical monitoring

Ombitasvir/paritaprevir/ritonavir, tacrolimus [2] ---> SmPC of [2] of EMA

Omeprazole, tacrolimus [2] ---> SmPC of [2] of EMA

Oral anticoagulants, tacrolimus [2] ---> SmPC of [2] of EMA

Tacrolimus is extensively bound to plasma proteins. Possible interactions with other active substances known to have high affinity for plasma proteins should be considered

Oral antidiabetics, tacrolimus [2] ---> SmPC of [2] of EMA

Tacrolimus is extensively bound to plasma proteins. Possible interactions with other active substances known to have high affinity for plasma proteins should be considered

Oxaprozin, tacrolimus

The co-administration may increase the risk of nephrotoxicity due to reduced synthesis of renal prostaglandins. Renal function must be closely monitored

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

Oxcarbazepine and its pharmacologically active metabolite (the monohydroxy derivative, MHD) are weak inducers of the cytochrome P450 enzymes CYP3A4 and CYP3A5, resulting in a lower plasma levels of drug coadministered with oxcarbazepine

P-glycoprotein and CYP3A4 inhibitors, tacrolimus

The P-glycoprotein and CYP3A4 inhibition may increase the plasma concentrations of tacrolimus (small therapeutic range)

P-gp inhibitors, tacrolimus [2] ---> SmPC of [2] of EMA

Caution should be observed when co-administering tacrolimus with drugs that inhibit P-glycoprotein, as an increase in tacrolimus levels may occur. An adjustment of the tacrolimus dose may be required (see section 4.5).

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

The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced when coadministered with IBRANCE as IBRANCE may increase their exposure.

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

Co-administration of NSAIDs and tacrolimus has been suggested to increase the nephrotoxic effect of tacrolimus. Renal function should be monitored when these medicinal products are co-administered.

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

In vitro studies have shown no potential interaction of patiromer with the other active substances

Pentobarbital, tacrolimus [2] ---> SmPC of [2] of EMA

Animal data have shown that tacrolimus could potentially decrease the clearance and increase the half-life of pentobarbital.

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

The combination of these drugs increases the risk of hyperkalaemia.

Phenazone, tacrolimus [2] ---> SmPC of [2] of EMA

Animal data have shown that tacrolimus could potentially decrease the clearance and increase the half-life of phenazone.

Phenobarbital, tacrolimus [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inducers: May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see section 4.4]. Monitor graft function closely.

Phenytoin, tacrolimus [2] ---> SmPC of [2] of EMA

It is recommended that concomitant use of strong CYP3A4 inducers (such as rifampicin, phenytoin, carbamazepine), with tacrolimus should be avoided.

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

Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.

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

If co-administration with narrow therapeutic index CYP3A substrates (e.g alfentanil, midazolam, tacrolimus) cannot be avoided, close clinical monitoring should be considered.

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

Blood counts should be closely monitored when co-administered with agents which inhibit such transporters such as cyclosporine A or tacrolimus, and the anti-HIV agents ritonavir, saquinavir, or nelfinavir.

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

Clinically significant interactions resulting in hospitalisation and/or posaconazole discontinuation were reported in clinical efficacy studies

Posaconazole, tacrolimus [2] ---> SmPC of [2] of EMA

Posterior reversible encephalopathy syndrome, tacrolimus [2] ---> SmPC of [2] of EMA

Patients treated with tacrolimus have been reported to develop posterior reversible encephalopathy syndrome (PRES).

Potassium chloride, tacrolimus

The combination may lead to hyperkalemia, particularly in renal failure. Co-administration is not recommended

Potassium, tacrolimus [2] ---> SmPC of [2] of EMA

Potassium-sparing diuretics, tacrolimus [2] ---> SmPC of [2] of EMA

Prednisolone, tacrolimus [2] ---> SmPC of [2] of EMA

High dose prednisolone or methylprednisolone administered for the treatment of acute rejection have the potential to increase or decrease tacrolimus blood levels.

Pregnancy, tacrolimus [2] ---> SmPC of [2] of EMA

Tacrolimus treatment can be considered in pregnant women, when there is no safer alternative and when the perceived benefit justifies the potential risk to the foetus.

Prokinetics, tacrolimus [2] ---> SmPC of [2] of EMA

May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation).

Protease inhibitors, tacrolimus [2] ---> SmPC of [2] of EMA

QT interval prolonging drugs, tacrolimus [2] ---> SmPC of [2] of EMA

Caution should be exercised in patients on concomitant medications known to prolong the QT interval, induce electrolyte abnormalities or known to increase tacrolimus exposure

Quinidine, tacrolimus [2] ---> SmPC of [2] of EMA

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

Co-administration of VANFLYTA with other medicinal products that prolong the QT interval may further increase the incidence of QT prolongation. Caution should be used when co-administering medicinal products that prolong the QT interval with VANFLYTA

Ramipril, tacrolimus

Hyperkalaemia may occur, therefore close monitoring of serum potassium is required. Caution is recommended

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

Dose adjustment of CYP3A4 substrates with a narrow therapeutic range may be required as ranolazine may increase plasma concentrations of these drugs.

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

The need for dose adjustments is considered unlikely for tacrolimus, cyclosporine, ibrutinib, mycophenolate mofetil, and venetoclax when administered with rezafungin.

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

Caution is recommended in case of concomitant use with sensitive CYP3A4 substrates with a narrow therapeutic index (see section 4.4). The dose of a sensitive CYP3A4 substrate with a narrow therapeutic index

Rifabutin, tacrolimus [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inducers: May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see section 4.4]. Monitor graft function closely.

Rifampicin, tacrolimus [2] ---> SmPC of [2] of EMA

It is recommended that concomitant use of strong CYP3A4 inducers (such as rifampicin, phenytoin, carbamazepine), with tacrolimus should be avoided.

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

Caution is recommended when co-administering ripretinib with sensitive CYP3A4 substrates with a narrow therapeutic window (e.g. cyclosporine, tacrolimus) or that are mostly metabolised in the intestine (e.g. midazolam).

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

Dose adjustment recommendations for the CYP3A substrate (e.g., colchicine, everolimus, tacrolimus, sirolimus) should be considered.

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

Careful monitoring of therapeutic and adverse effects is recommended when these medicines are concomitantly administered with ritonavir.

Ritonavir, tacrolimus [2] ---> SmPC of [2] of EMA

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

Caution is advised when co-administering medicinal products that CYP3A substrates with a narrow therapeutic index. Dose adjustments may be considered, if clinically indicated based on observed adverse reactions.

Saquinavir, tacrolimus [2] ---> SmPC of [2] of EMA

Contraindicated in combination with Invirase/ritonavir due to the potential for life threatening cardiac arrhythmia (see sections 4.3 and 4.4).

Saquinavir/ritonavir, tacrolimus ---> SmPC of [saquinavir] of EMA

Contraindicated in combination with Invirase/ritonavir due to the potential for life threatening cardiac arrhythmia

Sevelamer carbonate [1], tacrolimus ---> SmPC of [1] of EMA

Decreased bioavailability of tacrolimus. A close monitoring of blood concentrations should be considered

Sevelamer hydrochloride [1], tacrolimus ---> SmPC of [1] of EMA

Reduced levels of ciclosporin, mycophenolate mofetil and tacrolimus have been reported in transplant patients when coadministered with sevelamer hydrochloride without any clinical consequences (i.e graft rejection).

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

Increased simeprevir concentrations may occur due to inhibition of OATP1B1 by tacrolimus. No dose adjustment is required

Sirolimus, tacrolimus [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate [1], tacrolimus ---> SmPC of [1] of EMA

Therefore, tacrolimus should be taken at least 2 hours before or after Lokelma.

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

No dose adjustment of sofosbuvir or tacrolimus is required at initiation of co-administration. Afterwards, close monitoring and potential dose adjustment of tacrolimus may be required.

Sofosbuvir/velpatasvir [1], tacrolimus ---> SmPC of [1] of EMA

No dose adjustment of Epclusa or tacrolimus is required at initiation of co-administration. Afterwards, close monitoring and potential dose adjustment of tacrolimus may be required.

Sofosbuvir/velpatasvir/voxilaprevir [1], tacrolimus ---> SmPC of [1] of EMA

No dose adjustment of Vosevi or tacrolimus is required.

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

Avoid co-administration of LUMYKRAS with CYP3A4 substrates with narrow therapeutic indices. If co-administration cannot be avoided, adjust the CYP3A4 substrate dose in accordance with the current summary of product characteristics.

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

Therefore, initiation of sparsentan as co-medication with a CYP3A4 substrate such as alfentanil, conivaptan, indinavir, cyclosporin and tacrolimus should be done with caution.

Spironolactone, tacrolimus [2] ---> SmPC of [2] of EMA

St. John's wort, tacrolimus [2] ---> SmPC of [2] of EMA

Herbal preparations containing St. John's wort (Hypericum perforatum) or other herbal preparations should be avoided when taking Modigraf due to the risk of interactions

Statins, tacrolimus [2] ---> SmPC of [2] of EMA

Available data suggests that the pharmacokinetics of statins are largely unaltered by the co-administration of tacrolimus.

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

Raised blood levels of immunosuppressant (decreased hepatic metabolism). The combination is to be avoided unless strictly necessary

Strong CYP3A4 inductors, tacrolimus [2] ---> SmPC of [2] of EMA

It is recommended that concomitant use of strong CYP3A4 inducers (such as rifampicin, phenytoin, carbamazepine), with tacrolimus should be avoided.

Strong CYP3A4 inhibitors, tacrolimus [2] ---> SmPC of [2] of EMA

Sunitinib, tacrolimus

The additive QT-prolonging may increase the risk of severe ventricular arrhythmias. The co-administration should be avoided

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

In clinical studies, patients received ciclosporin, tacrolimus, sirolimus and other immunosuppressive therapies at the lowest dose considered clinically safe and appropriate.

Tacrolimus [1], tamoxifen ---> SmPC of [1] of EMA

Tacrolimus [1], triamterene ---> SmPC of [1] of EMA

Tacrolimus [1], troleandomycin ---> SmPC of [1] of EMA

Tacrolimus [1], vaccinations ---> SmPC of [1] of EMA

Immunosuppressants may affect the response to vaccination and vaccination during treatment with tacrolimus may be less effective. The use of live attenuated vaccines should be avoided

Tacrolimus [1], vancomycin ---> SmPC of [1] of EMA

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

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

Tacrolimus, tecovirimat [2] ---> SmPC of [2] of EMA

A risk for decreases in tacrolimus plasma concentrations cannot be excluded (CYP3A4 substrate). The combination of tecovirimat and tacrolimus should be used with caution.

Tacrolimus, telaprevir [2] ---> SmPC of [2] of EMA

Increased plasma concentrations of tacrolimus and telaprevir. Possible prolongation of the QT interval. A careful monitoring is recommended

Tacrolimus, telithromycin [2] ---> SmPC of [2] of EMA

Tacrolimus, telmisartan [2] ---> SmPC of [2] of EMA

As with other medicinal products acting on the renin-angiotensin-aldosterone system, telmisartan may provoke hyperkalaemia. The risk may increase in case of treatment combination with other medicinal products that may also provoke hyperkalaemia

Tacrolimus, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

There is a risk of increased tacrolimus blood levels when co-administered with amlodipine but the pharmacokinetic mechanism of this interaction is not fully understood.

Tacrolimus, temsirolimus

Possible decrease of tacrolimus plasma concentrations.

Tacrolimus, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Given that tacrolimus can affect renal function, close monitoring is recommended when it is co-administered with tenofovir disoproxil.

Tacrolimus, thiotepa [2] ---> SmPC of [2] of EMA

Excessive immunosuppression with risk of lymphoproliferation

Tacrolimus, tiaprofenic acid [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of nephrotoxicity due to reduced synthesis of renal prostaglandins. Renal function must be closely monitored

Tacrolimus, tigecycline [2] ---> SmPC of [2] of EMA

Concomitant use of tigecycline and calcineurin inhibitors such as tacrolimus or cyclosporine may lead to an increase in serum trough concentrations of the calcineurin inhibitors.

Tacrolimus, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Concentrations of tacrolimus cannot be predicted when co-administered with tipranavir/ritonavir. More frequent concentration monitoring of these medicinal products is recommended

Tacrolimus, tobramycin [2] ---> SmPC of [2] of EMA

Increased potential toxicity of parenterally administered aminoglycosides

Tacrolimus, tocofersolan [2] ---> SmPC of [2] of EMA

Due to inhibition of P-Glycoprotein transporter, tocofersolan may also enhance intestinal absorption of other concomitant fat-soluble vitamins (A, D, E, K) or that of highly lipophilic medicinal products

Tacrolimus, tofacitinib [2] ---> SmPC of [2] of EMA

Coadministration with tacrolimus (mild CYP3A4 inhibitor) and cyclosporine (moderate CYP3A4 inhibitor) increased tofacitinib AUC

Tacrolimus, topotecan

The inhibition of P-glycoprotein may increase the bioavailability of oral topotecan

Tacrolimus, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of tacrolimus thus increasing risk of toxicity

Tacrolimus, trastuzumab

Trastuzumab may increase the risk of neutropenia and anemia

Tacrolimus, triacetyloleandomycin [2] ---> SmPC of [2] of EMA

Tacrolimus, 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.

Tacrolimus, upadacitinib [2] ---> SmPC of [2] of EMA

Combination with other potent immunosuppressants has not been evaluated in clinical studies and is not recommended as a risk of additive immunosuppression cannot be excluded.

Tacrolimus, valaciclovir [2] ---> SmPC of [2] of eMC

The co-administration of aciclovir with nephrotoxic drugs should only done with caution, particularly in patients with renal failure

Tacrolimus, valdecoxib [2] ---> SmPC of [2] of EMA

The co-administration may increase the risk of nephrotoxicity due to reduced synthesis of renal prostaglandins. Renal function must be closely monitored

Tacrolimus, vandetanib

Vandetanib, CYP3A4 inductor, may decrease the plasma levels of tacrolimus. Caution should be exercised

Tacrolimus, vinblastine

The co-administration may cause an excessive immunosuppression with risk of lymphoproliferation

Tacrolimus, vincristine

The co-administration may cause an excessive immunosuppression with risk of lymphoproliferation

Tacrolimus, vinflunine

The co-administration may cause an excessive immunosuppression with risk of lymphoproliferation

Tacrolimus, vinorelbine [2] ---> SmPC of [2] of eMC

The co-administration may cause an excessive immunosuppression with risk of lymphoproliferation

Tacrolimus, voxelotor [2] ---> SmPC of [2] of EMA

Coadministration of voxelotor with sensitive CYP3A4 substrates with a narrow therapeutic index should be avoided. If concomitant use is unavoidable, consider dose reduction of the sensitive CYP3A4 substrate(s).

Tacrolimus, xipamide

Risk of increased creatinine plasma levels without modification of circulating cyclosporine levels, even with normal water and sodium balance

Tacrolimus, zanubrutinib [2] ---> SmPC of [2] of EMA

Narrow therapeutic index medicinal products that are metabolised by CYP3A should be used with caution, as zanubrutinib may decrease the plasma exposures of these medicinal products.

CONTRAINDICATIONS of Tacrolimus (Modigraf)

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

- Hypersensitivity to other macrolides.

https://www.ema.europa.eu/en/documents/product-information/modigraf-epar-product-information_en.pdf 03/03/2025

Other trade names: Adoport, Advagraf, Envarsus, Prograf, Protopic, Tacforius, Tacrolimús Cinfa, Tacrolimús Mylan,

Tadalafil (CIALIS)

5-alpha reductase inhibitors, tadalafil [2] ---> SmPC of [2] of EMA

As a formal drug-drug interaction study evaluating the effects of tadalafil and 5-alpha reductase inhibitors (5-ARIs) has not been performed, caution should be exercised when tadalafil is coadministered with 5-ARIs.

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

Although the frequency of reports of dizziness in placebo and tadalafil arms in clinical trials was similar, patients should be aware of how they react to CIALIS, before driving or using machines.

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

Tadalafil (10 mg except for studies with angiotensin II receptor blockers and amlodipine in which a 20 mg dose was applied) had no clinically significant interaction

Acetylsalicylic acid, tadalafil [2] ---> SmPC of [2] of EMA

Tadalafil (10 mg and 20 mg) did not potentiate the increase in bleeding time caused by acetyl salicylic acid.

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

Tadalafil (10 mg except for studies with angiotensin II receptor blockers and amlodipine in which a 20 mg dose was applied) had no clinically significant interaction

Alcohol, tadalafil [2] ---> SmPC of [2] of EMA

Alcohol concentrations (mean maximum blood concentration 0.08 %) were not affected by co-administration with tadalafil (10 mg or 20 mg). In addition, no changes in tadalafil concentrations were seen 3 hours after co-administration with alcohol.

Alfa1-adrenergic receptor blockers, tadalafil [2] ---> SmPC of [2] of EMA

Caution should be exercised when using tadalafil in patients treated with any alpha-blockers

Alpha-blockers, tadalafil [2] ---> SmPC of [2] of EMA

However, caution should be exercised when using tadalafil in patients treated with any alpha-blockers, and notably in the elderly. Treatments should be initiated at minimal dosage and progressively adjusted.

Ambrisentan [1], tadalafil ---> SmPC of [1] of EMA

Co-administration of ambrisentan with a phosphodiesterase inhibitor, either sildenafil or tadalafil (both substrates of CYP3A4) in healthy volunteers did not significantly affect the pharmacokinetics of the phosphodiesterase inhibitor or ambrisentan

Antidiabetics, tadalafil [2] ---> SmPC of [2] of EMA

Specific interaction studies with antidiabetic medicinal products were not conducted.

Antihypertensives, tadalafil [2] ---> SmPC of [2] of EMA

Tadalafil (10 mg except for studies with angiotensin II receptor blockers and amlodipine in which a 20 mg dose was applied) had no clinically significant interaction

Atazanavir [1], tadalafil ---> SmPC of [1] of EMA

Tadalafil is metabolised by CYP3A4. Co-administration with Atazanavir may result in increased concentrations of the PDE5 inhibitor and an increase in PDE5-associated adverse events, including hypotension, visual changes, and priapism.

Atazanavir/cobicistat [1], tadalafil ---> SmPC of [1] of EMA

Tadalafil is metabolised by CYP3A4. Co-administration with EVOTAZ may result in increased concentrations of the PDE5 inhibitor. The mechanism of this interaction is CYP3A4 inhibition by atazanavir and cobicistat.

Betablockers, tadalafil [2] ---> SmPC of [2] of EMA

Tadalafil (10 mg except for studies with angiotensin II receptor blockers and amlodipine in which a 20 mg dose was applied) had no clinically significant interaction

Boceprevir, tadalafil

Possible decreased tadalafil metabolism

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

Available pharmacodynamic/toxicological data in animals have shown excretion of tadalafil in milk. A risk to the suckling child cannot be excluded. CIALIS should not be used during breast feeding.

Calcium antagonists, tadalafil [2] ---> SmPC of [2] of EMA

Tadalafil (10 mg except for studies with angiotensin II receptor blockers and amlodipine in which a 20 mg dose was applied) had no clinically significant interaction

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

The CYP3A4 induction may decrease the plasma concentrations of tadalafil

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

Tadalafil is principally metabolised by CYP3A4. CYP3A4 inhibitors should be co-administered with caution as they would be expected to increase plasma concentrations of tadalafil

Cobicistat [1], tadalafil ---> SmPC of [1] of EMA

Co-administration with cobicistat may result in increased tadalafil plasma concentrations, which may result in PDE-5 inhibitor-associated adverse reactions.

CYP1A2 substrates, tadalafil [2] ---> SmPC of [2] of EMA

When tadalafil 10 mg was administered with theophylline (a non-selective phosphodiesterase inhibitor) in a clinical pharmacology study, there was no pharmacokinetic interaction. The only pharmacodynamic effect was a small (3.5 bpm) increase in heart rate

CYP2C9 substrates, tadalafil [2] ---> SmPC of [2] of EMA

Tadalafil (10 mg and 20 mg) had no clinically significant effect on exposure (AUC) to S-warfarin or R-warfarin (CYP2C9 substrate), nor did tadalafil affect changes in prothrombin time induced by warfarin.

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

Tadalafil is not expected to cause clinically significant inhibition or induction of the clearance of medicinal products metabolised by CYP450 isoforms.

Darunavir, tadalafil

Possible decreased tadalafil metabolism

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/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/ritonavir, tadalafil ---> SmPC of [darunavir] of EMA

The co-administration may increase the plasma levels of tadalafil and is not recommended for the treatment of pulmonary arterial hypertension

Doxazosin, tadalafil [2] ---> SmPC of [2] of EMA

The co-administration of doxazosin (4 and 8 mg daily) and tadalafil (5 mg daily dose and 20 mg as a single dose) increases the blood pressure-lowering effect of this alpha-blocker in a significant manner.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [1], tadalafil ---> SmPC of [1] of EMA

Caution should be exercised, including consideration of dose reduction, when co-administering Genvoya with tadalafil for the treatment of pulmonary arterial hypertension.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], tadalafil ---> SmPC of [1] of EMA

Cobicistat, strong CYP3A4 inhibitor, may increase the plasma levels of tadalafil

Emtricitabine/rilpivirine/tenofovir alafenamide [1], tadalafil ---> SmPC of [1] of EMA

No dose adjustment is required.

Emtricitabine/rilpivirine/tenofovir disoproxil [1], tadalafil ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Erythromycin, tadalafil [2] ---> SmPC of [2] of EMA

Tadalafil is principally metabolised by CYP3A4. CYP3A4 inhibitors should be co-administered with caution as they would be expected to increase plasma concentrations of tadalafil

Ethinyl estradiol, tadalafil [2] ---> SmPC of [2] of EMA

Tadalafil has been demonstrated to produce an increase in the oral bioavailability of ethinylestradiol; a similar increase may be expected with oral administration of terbutaline

Etravirine [1], tadalafil ---> SmPC of [1] of EMA

Concomitant use of PDE-5 inhibitors with etravirine may require dose adjustment of the PDE-5 inhibitor to attain the desired clinical effect.

Fertility, tadalafil [2] ---> SmPC of [2] of EMA

Effects were seen in dogs that might indicate impairment of fertility. Two subsequent clinical studies suggest that this effect is unlikely in humans, although a decrease in sperm concentration was seen in some men

Finasteride, tadalafil [2] ---> SmPC of [2] of EMA

In a clinical trial that compared tadalafil 5 mg coadministered with finasteride 5 mg to placebo plus finasteride 5 mg in the relief of BPH symptoms, no new adverse reactions were identified.

Fosamprenavir/ritonavir, tadalafil ---> SmPC of [fosamprenavir] of EMA

Fosamprenavir/ritonavir, CYP3A4 inhibitors, may increase the tadalafil plasma levels and cause hypotension, visual changes and priapism. The combination is not recommended

Grapefruit juice, tadalafil [2] ---> SmPC of [2] of EMA

Tadalafil is principally metabolised by CYP3A4. CYP3A4 inhibitors should be co-administered with caution as they would be expected to increase plasma concentrations of tadalafil

Idelalisib [1], tadalafil ---> SmPC of [1] of EMA

The co-administration of idelalisib with tadalafil may increase tadalafil serum levels. For pulmonary arterial hypertension: Caution should be exercised when co-administering. For erectile dysfunction: Particular caution must be used

Indinavir [1], tadalafil ---> SmPC of [1] of EMA

Coadministration of indinavir with tadalafil is likely to result in an increase of tadalafil by competitive inhibition of metabolism.

Indinavir/ritonavir, tadalafil ---> SmPC of [indinavir] of EMA

Coadministration of indinavir with tadalafil is likely to result in an increase of sildenafil by competitive inhibition of metabolism.

Isosorbide dinitrate [1], tadalafil ---> SmPC of [1] of eMC

The hypotensive effect of nitrates is potentiated by concurrent administration of phosphodiesterase inhibitors

Isosorbide mononitrate [1], tadalafil ---> SmPC of [1] of eMC

Phosphodiesterase type-5 inhibitors have been shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitrates or nitric oxide donors is therefore contra-indicated.

Itraconazol, tadalafil [2] ---> SmPC of [2] of EMA

Tadalafil is principally metabolised by CYP3A4. CYP3A4 inhibitors should be co-administered with caution as they would be expected to increase plasma concentrations of tadalafil

Ketoconazole, tadalafil [2] ---> SmPC of [2] of EMA

Tadalafil is principally metabolised by CYP3A4. CYP3A4 inhibitors should be co-administered with caution as they would be expected to increase plasma concentrations of tadalafil

Lenacapavir [1], tadalafil ---> SmPC of [1] of EMA

Use of PDE-5 inhibitors for pulmonary arterial hypertension: Co-administration with tadalafil is not recommended. Erectile dysfunction: For use as needed: no more than 10 mg every 72 hours. For once daily use: dose not to exceed 2.5 mg

Lopinavir, tadalafil

Possible decreased tadalafil metabolism

Lopinavir/ritonavir [1], tadalafil ---> SmPC of [1] of EMA

Lopinavir/ritonavir, CYP3A4 inhibitors, increase the plasma concentrations of tadalafil. The combination is not recommended

Molsidomine, tadalafil

The co-administration is contraindicated due to the risk of pronounced potentiation of hypotensive effects that can cause syncopes and myocardial infarctation

Nefazodone, tadalafil

Possible decreased tadalafil metabolism

Nelfinavir [1], tadalafil ---> SmPC of [1] of EMA

Concomitant use of tadalafil and nelfinavir may increase plasma levels of tadalafil. Co-administration of tadalafil for the treatment of pulmonary arterial hypertension with nelfinavir is not recommended.

Nicorandil [1], tadalafil ---> SmPC of [1] of eMC

Concurrent use of nicorandil and phosphodiesterase 5 inhibitors is contraindicated, since it can lead to a serious drop in blood pressure.

Nirmatrelvir/ritonavir [1], tadalafil ---> SmPC of [1] of EMA

The concomitant use of tadalafil for the treatment of erectile dysfunction with ritonavir should be with caution at reduced doses of no more than 10 mg tadalafil every 72 hours with increased monitoring for adverse reactions.

Nitric oxide donors, tadalafil [2] ---> SmPC of [2] of EMA

In clinical studies, tadalafil was shown to augment the hypotensive effects of nitrates. Therefore, administration of tadalafil to patients who are using any form of organic nitrate is contraindicated

Nitroglycerine [1], tadalafil ---> SmPC of [1] of eMC

Phosphodiesterase type 5 inhibitors have been shown to potentiate the hypotensive effects of nitrates, and coadministration with glyceryl trinitrate is therefore contraindicated

Organic nitrates, tadalafil [2] ---> SmPC of [2] of EMA

PDE5 inhibitors, riociguat ---> SmPC of [tadalafil] of EMA

In clinical studies, riociguat has been shown to augment the hypotensive effects of PDE5 inhibitors. Concomitant use of riociguat with PDE5 inhibitors, including tadalafil, is contraindicated

Phenobarbital, tadalafil [2] ---> SmPC of [2] of EMA

The CYP3A4 induction may decrease the plasma concentrations of tadalafil

Phentolamine, tadalafil

Tadalafil may enhance the hypotensive effect of phentolamine

Phenytoin, tadalafil [2] ---> SmPC of [2] of EMA

The CYP3A4 induction may decrease the plasma concentrations of tadalafil

Pregnancy, tadalafil [2] ---> SmPC of [2] of EMA

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

Protease inhibitors, tadalafil [2] ---> SmPC of [2] of EMA

Tadalafil is principally metabolised by CYP3A4. CYP3A4 inhibitors should be co-administered with caution as they would be expected to increase plasma concentrations of tadalafil

Rifampicin, tadalafil [2] ---> SmPC of [2] of EMA

The CYP3A4 induction may decrease the plasma concentrations of tadalafil

Rilpivirine [1], tadalafil ---> SmPC of [1] of EMA

No dose adjustment is required.

Riociguat [1], tadalafil ---> SmPC of [1] of EMA

In clinical studies, riociguat has been shown to augment the hypotensive effects of PDE5 inhibitors. Concomitant use of riociguat with PDE5 inhibitors, including tadalafil, is contraindicated

Ritonavir, tadalafil [2] ---> SmPC of [2] of EMA

Caution should be exercised when prescribing tadalafil to patients using potent CYP3A4 inhibitors as increased tadalafil exposure (AUC) has been observed if the medicinal products are combined

Saquinavir, tadalafil [2] ---> SmPC of [2] of EMA

Caution should be exercised when prescribing tadalafil to patients using potent CYP3A4 inhibitors as increased tadalafil exposure (AUC) has been observed if the medicinal products are combined

Saquinavir/ritonavir, tadalafil ---> SmPC of [saquinavir] of EMA

Saquinavir may increase the plasma concentrations of tadalafil. Contraindicated due to the potential for life threatening cardiac arrhythmia

Silodosin [1], tadalafil ---> SmPC of [1] of EMA

Patients taking PDE-5 inhibitors concomitantly with silodosin should be monitored for possible adverse reactions.

Simeprevir [1], tadalafil ---> SmPC of [1] of EMA

The intestinal CYP3A4 enzyme inhibition may increase the concentrations of PDE-5 inhibitors.

Strong CYP3A4 inductors, tadalafil [2] ---> SmPC of [2] of EMA

The CYP3A4 induction may decrease the plasma concentrations of tadalafil

Strong CYP3A4 inhibitors, tadalafil [2] ---> SmPC of [2] of EMA

Caution should be exercised when prescribing tadalafil to patients using potent CYP3A4 inhibitors as increased tadalafil exposure (AUC) has been observed if the medicinal products are combined

Tadalafil [1], terbutaline ---> SmPC of [1] of EMA

Tadalafil has been demonstrated to produce an increase in the oral bioavailability of ethinylestradiol; a similar increase may be expected with oral administration of terbutaline

Tadalafil [1], theophylline ---> SmPC of [1] of EMA

Tadalafil [1], thiazides ---> SmPC of [1] of EMA

Tadalafil (10 mg except for studies with angiotensin II receptor blockers and amlodipine in which a 20 mg dose was applied) had no clinically significant interaction

Tadalafil [1], transporters ---> SmPC of [1] of EMA

The role of transporters (for example p-glycoprotein) in the disposition of tadalafil is not known. Therefore there is the potential of drug interactions mediated by inhibition of transporters.

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

Tadalafil, tecovirimat [2] ---> SmPC of [2] of EMA

A risk for decreases in PDE-5 inhibitor plasma concentrations cannot be excluded (CYP3A4 substrate). The combination of tecovirimat and PDE-5 inhibitors should be used with caution.

Tadalafil, telaprevir [2] ---> SmPC of [2] of EMA

Increased plasma levels of tadalafil. Association contraindicated in the treatment of pulmonary arterial hypertension

Tadalafil, terazosine [2] ---> SmPC of [2] of eMC

Concomitant use of phosphodiesterase-5-inhibitors and terazosin may lead to symptomatic hypotension in some patients

Tadalafil, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

It is recommended to prescribe tadalafil after at least 7 days of tipranavir/ritonavir dosing.

CONTRAINDICATIONS of Tadalafil (CIALIS)

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

In clinical studies, tadalafil was shown to augment the hypotensive effects of nitrates. This is thought to result from the combined effects of nitrates and tadalafil on the nitric oxide/cGMP pathway. Therefore, administration of CIALIS to patients who are using any form of organic nitrate is contraindicated.

CIALIS must not be used in men with cardiac disease for whom sexual activity is inadvisable. Physicians should consider the potential cardiac risk of sexual activity in patients with pre-existing cardiovascular disease.

The following groups of patients with cardiovascular disease were not included in clinical trials and the use of tadalafil is therefore contraindicated:

- patients with myocardial infarction within the last 90 days,

- patients with unstable angina or angina occurring during sexual intercourse,

- patients with New York Heart Association Class 2 or greater heart failure in the last 6 months,

- patients with uncontrolled arrhythmias, hypotension (< 90/50 mm Hg), or uncontrolled hypertension,

- patients with a stroke within the last 6 months.

CIALIS is contraindicated in patients who have loss of vision in one eye because of non-arteritic anterior ischaemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure

The co-administration of PDE5 inhibitors, including tadalafil, with guanylate cyclase stimulators, such as riociguat, is contraindicated as it may potentially lead to symptomatic hypotension (see section 4.5).

https://www.ema.europa.eu/en/documents/product-information/cialis-epar-product-information_en.pdf. 20/09/2023

Tafamidis (Vyndaqel)

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

On the basis of the pharmacodynamic and pharmacokinetic profile, tafamidis meglumine is believed to have no or negligible influence on the ability to drive or use machines.

Adefovir, tafamidis [2] ---> SmPC of [2] of EMA

Tafamidis inhibits the uptake transporters OAT1 and OAT3 (organic anion transporters) and may cause drug-drug interactions at clinically relevant concentrations with substrates of these transporters

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

In vitro tafamidis inhibits the efflux transporter CRP breast cancer resistant protein) and may cause drug-drug interactions at clinically relevant concentrations with substrates of this transporter

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

Available data in animals have shown excretion of tafamidis in milk. A risk to the newborns/infants cannot be excluded. Tafamidis meglumine should not be used during breast-feeding.

Bumetanide, tafamidis [2] ---> SmPC of [2] of EMA

Tafamidis inhibits the uptake transporters OAT1 and OAT3 (organic anion transporters) and may cause drug-drug interactions at clinically relevant concentrations with substrates of these transporters

Cidofovir, tafamidis [2] ---> SmPC of [2] of EMA

Tafamidis inhibits the uptake transporters OAT1 and OAT3 (organic anion transporters) and may cause drug-drug interactions at clinically relevant concentrations with substrates of these transporters

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

In a clinical study in healthy volunteers, 20 mg tafamidis meglumine did not induce or inhibit the cytochrome P450 enzyme CYP3A4.

Fertility, tafamidis [2] ---> SmPC of [2] of EMA

No impairment of fertility has been observed in nonclinical studies (see section 5.3).

Furosemide, tafamidis [2] ---> SmPC of [2] of EMA

Tafamidis inhibits the uptake transporters OAT1 and OAT3 (organic anion transporters) and may cause drug-drug interactions at clinically relevant concentrations with substrates of these transporters

Ganciclovir, tafamidis [2] ---> SmPC of [2] of EMA

Tafamidis inhibits the uptake transporters OAT1 and OAT3 (organic anion transporters) and may cause drug-drug interactions at clinically relevant concentrations with substrates of these transporters

Imatinib, tafamidis [2] ---> SmPC of [2] of EMA

In vitro tafamidis inhibits the efflux transporter CRP breast cancer resistant protein) and may cause drug-drug interactions at clinically relevant concentrations with substrates of this transporter

Lamivudine, tafamidis [2] ---> SmPC of [2] of EMA

Tafamidis inhibits the uptake transporters OAT1 and OAT3 (organic anion transporters) and may cause drug-drug interactions at clinically relevant concentrations with substrates of these transporters

Methotrexate, tafamidis [2] ---> SmPC of [2] of EMA

In vitro tafamidis inhibits the efflux transporter CRP breast cancer resistant protein) and may cause drug-drug interactions at clinically relevant concentrations with substrates of this transporter

NSAID, tafamidis [2] ---> SmPC of [2] of EMA

Tafamidis inhibits the uptake transporters OAT1 and OAT3 (organic anion transporters) and may cause drug-drug interactions at clinically relevant concentrations with substrates of these transporters

OAT1 substrates, tafamidis [2] ---> SmPC of [2] of EMA

Tafamidis inhibits the uptake transporters OAT1 and OAT3 (organic anion transporters) and may cause drug-drug interactions at clinically relevant concentrations with substrates of these transporters

OAT3 substrates, tafamidis [2] ---> SmPC of [2] of EMA

Tafamidis inhibits the uptake transporters OAT1 and OAT3 (organic anion transporters) and may cause drug-drug interactions at clinically relevant concentrations with substrates of these transporters

Oseltamivir, tafamidis [2] ---> SmPC of [2] of EMA

Tafamidis inhibits the uptake transporters OAT1 and OAT3 (organic anion transporters) and may cause drug-drug interactions at clinically relevant concentrations with substrates of these transporters

Pregnancy, tafamidis [2] ---> SmPC of [2] of EMA

Tafamidis meglumine is not recommended during pregnancy and in women of childbearing potential not using contraception.

Rosuvastatin, tafamidis [2] ---> SmPC of [2] of EMA

In vitro tafamidis inhibits the efflux transporter CRP breast cancer resistant protein) and may cause drug-drug interactions at clinically relevant concentrations with substrates of this transporter

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

Tafamidis inhibits the uptake transporters OAT1 and OAT3 (organic anion transporters) and may cause drug-drug interactions at clinically relevant concentrations with substrates of these transporters

Tafamidis [1], thyroxine ---> SmPC of [1] of EMA

Tafamidis may decrease serum concentrations of total thyroxine, without an accompanying change in free thyroxine (T4) or thyroid stimulating hormone (TSH). No corresponding clinical findings consistent with thyroid dysfunction have been observed.

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

Contraceptive measures should be used by women of childbearing potential during treatment with tafamidis meglumine, and for one month after stopping treatment, due to the prolonged half-life.

Tafamidis [1], zalcitabine ---> SmPC of [1] of EMA

Tafamidis inhibits the uptake transporters OAT1 and OAT3 (organic anion transporters) and may cause drug-drug interactions at clinically relevant concentrations with substrates of these transporters

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

Tafamidis inhibits the uptake transporters OAT1 and OAT3 (organic anion transporters) and may cause drug-drug interactions at clinically relevant concentrations with substrates of these transporters

CONTRAINDICATIONS of Tafamidis (Vyndaqel)

- 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/vyndaqel-epar-product-information_en.pdf 17/09/2025

Tafasitamab (Minjuvi)

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

MINJUVI has no or negligible influence on the ability to drive and use machines. However, fatigue has been reported in patients taking tafasitamab and this should be taken into account when driving or using machines.

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

Women should be advised not to breast-feed during and for at least 3 months after the last dose of tafasitamab.

Female gender, tafasitamab [2] ---> SmPC of [2] of EMA

Treatment with tafasitamab in combination with lenalidomide should not be initiated in female patients unless pregnancy has been excluded. Please also refer to the SmPC of lenalidomide.

Fertility, tafasitamab [2] ---> SmPC of [2] of EMA

No adverse effects on male and female reproductive organs were observed in a repeat-dose toxicity study in animals (see section 5.3).

Infection, tafasitamab [2] ---> SmPC of [2] of EMA

Fatal and serious infections, including opportunistic infections, occurred in patients during treatment with tafasitamab.

Myelosuppression, tafasitamab [2] ---> SmPC of [2] of EMA

Complete blood counts should be monitored throughout treatment and prior to administration of each treatment cycle.

Pregnancy, tafasitamab [2] ---> SmPC of [2] of EMA

Lenalidomide can cause embryo-foetal harm and is contraindicated for use in pregnancy and in women of childbearing potential unless all of the conditions of the lenalidomide pregnancy prevention programme are met.

Pregnancy, tafasitamab [2] ---> SmPC of [2] of EMA

Tafasitamab is not recommended during pregnancy and in women of childbearing potential not using contraception.

Progressive multifocal leukoencephalopathy, tafasitamab [2] ---> SmPC of [2] of EMA

Progressive multifocal leukoencephalopathy (PML) has been reported during combination therapy with tafasitamab.

Tafasitamab [1], tumor lysis syndrome ---> SmPC of [1] of EMA

Patients with high tumour burden and rapidly proliferative tumour may be at increased risk of tumour lysis syndrome.

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

The safety of immunisation with live vaccines following tafasitamab therapy has not been investigated and vaccination with live vaccines is not recommended concurrently with tafasitamab therapy.

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

Women of childbearing potential should be advised to use effective contraception during and for at least 3 months after end of treatment with tafasitamab.

CONTRAINDICATIONS of Tafasitamab (Minjuvi)

- 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/minjuvi-epar-product-information_en.pdf 17/09/2024

Tafluprost

Ability to drive, tafluprost [2] ---> SmPC of [2] of eMC

As with any ocular treatment, if transient blurred vision occurs at instillation, the patient should wait until the vision clears before driving or using machinery.

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

Tafluprost should not be used during breast-feeding.

Pregnancy, tafluprost [2] ---> SmPC of [2] of eMC

Tafluprost should not be used during pregnancy unless clearly necessary (in case no other treatment options are available).

CONTRAINDICATIONS of Tafluprost

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

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

Tagraxofusp (Elzonris)

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

Breast-feeding should be discontinued during treatment with ELZONRIS and for at least one week after the last dose.

Fertility, tagraxofusp [2] ---> SmPC of [2] of EMA

No fertility studies have been conducted with tagraxofusp (see section 5.3). There are no data on the effect of tagraxofusp on human fertility.

Pregnancy, tagraxofusp [2] ---> SmPC of [2] of EMA

ELZONRIS should not be used during pregnancy unless the clinical condition of the woman requires treatment with tagraxofusp

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

In women of childbearing potential, a negative pregnancy test should be obtained within 7 days prior to initiation of therapy. Effective contraception should be used before the first dose is administered and for at least one week after the last dose.

CONTRAINDICATIONS of Tagraxofusp (Elzonris)

- 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/elzonris-epar-product-information_en.pdf 27/10/2025

Talazoparib (Talzenna)

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

Talzenna may have a minor influence on the ability to drive and use machines. Fatigue/asthenia or dizziness may occur following administration of talazoparib.

Amiodarone, 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).

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

Population PK analysis indicates that co-administration of acid-reducing agents had no significant impact on the absorption of talazoparib.

BCRP inhibitors, talazoparib [2] ---> SmPC of [2] of EMA

Co-administration of talazoparib with BCRP inhibitors may increase talazoparib exposure.

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

A risk to breast-fed children cannot be excluded and therefore breast-feeding is not recommended during treatment with Talzenna and for at least 1 month after the final dose.

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

Other P-gp inducers (including but not limited to carbamazepine, phenytoin, and St. John's wort) may decrease talazoparib exposure.

Carvedilol, 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).

Clarithromycin, 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).

Cobicistat, 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).

Curcumin, talazoparib [2] ---> SmPC of [2] of EMA

Concomitant use of strong BCRP inhibitors (including but not limited to curcumin and cyclosporine) should be avoided.

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

Concomitant use of strong BCRP inhibitors (including but not limited to curcumin and cyclosporine) should be avoided.

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).

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).

Erythromycin, 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).

Fertility, talazoparib [2] ---> SmPC of [2] of EMA

There is no information on fertility in patients. Based on non-clinical findings in testes (partially reversible) and ovary (reversible), Talzenna may impair fertility in males of reproductive potential (see section 5.3).

Hormonal contraceptives, talazoparib [2] ---> SmPC of [2] of EMA

Since the use of hormonal contraception is not recommended in patients with breast cancer, two non-hormonal and complementary contraception methods should be used.

Indinavir, 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).

Itraconazol, 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).

Ketoconazole, 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).

Lapatinib, 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).

Lopinavir, 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).

Men, talazoparib [2] ---> SmPC of [2] of EMA

Male patients with female partners of reproductive potential or pregnant partners should be advised to use effective contraception (even after vasectomy) during treatment with Talzenna, and for at least 4 months after the final dose (see section 4.4).

Oral contraceptives, talazoparib [2] ---> SmPC of [2] of EMA

Drug-drug interaction studies between talazoparib and oral contraceptives have not been conducted.

Phenytoin, talazoparib [2] ---> SmPC of [2] of EMA

Other P-gp inducers (including but not limited to carbamazepine, phenytoin, and St. John's wort) may decrease talazoparib exposure.

Pregnancy, talazoparib [2] ---> SmPC of [2] of EMA

Talzenna may cause foetal harm when administered to a pregnant woman. Talzenna is not recommended during pregnancy or for women of childbearing potential not using contraception

Propafenone, 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).

Proton pump inhibitors, talazoparib [2] ---> SmPC of [2] of EMA

Population PK analysis indicates that co-administration of acid-reducing agents had no significant impact on the absorption of talazoparib.

Quinidine, 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).

Ranolazine, 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).

Rifampicin, talazoparib [2] ---> SmPC of [2] of EMA

No talazoparib dose adjustments are required when co-administered with rifampin.

Ritonavir, 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).

Saquinavir, 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).

St. John's wort, talazoparib [2] ---> SmPC of [2] of EMA

Other P-gp inducers (including but not limited to carbamazepine, phenytoin, and St. John's wort) may decrease talazoparib exposure.

Strong BCRP inhibitors, talazoparib [2] ---> SmPC of [2] of EMA

Concomitant use of strong BCRP inhibitors (including but not limited to curcumin and cyclosporine) should be avoided.

Strong P-gp inhibitors, 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).

Talazoparib [1], telaprevir ---> SmPC of [1] 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).

Talazoparib [1], tipranavir ---> SmPC of [1] 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).

Talazoparib [1], verapamil ---> SmPC of [1] 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).

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

Women of childbearing potential should not become pregnant while receiving Talzenna and should not be pregnant at the beginning of treatment. A pregnancy test should be performed on all women of childbearing potential prior to treatment

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

Women of childbearing potential must use highly effective forms of contraception (see section 4.4) prior to starting treatment with talazoparib, during treatment, and for 7 months after stopping treatment with talazoparib.

CONTRAINDICATIONS of Talazoparib (Talzenna)

- Hypersensitivity to the active substance 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/talzenna-epar-product-information_en.pdf. 16/01/2024

Talquetamab (Talvey)

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

Due to the potential for ICANS, patients receiving TALVEY are at risk of depressed level of consciousness (see section 4.4).

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

Because the potential for serious adverse reactions in breast-fed infants is unknown for TALVEY, patients should not breast-feed during treatment with TALVEY and for at least 3 months after the last dose.

CYP450 substrates, talquetamab [2] ---> SmPC of [2] of EMA

Monitor for toxicity or concentrations of medicinal products that are CYP (e.g., CYP2C9, CYP2C19, CYP3A4/5, CYP2D6) substrates where minimal concentration changes may lead to serious adverse reactions.

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

Talquetamab causes release of cytokines (see section 5.1) that may suppress activity of cytochrome P450 (CYP) enzymes, potentially resulting in increased exposure of CYP substrates.

Fertility, talquetamab [2] ---> SmPC of [2] of EMA

There are no data on the effect of talquetamab on fertility. Effects of talquetamab on male and female fertility have not been evaluated in animal studies.

Pregnancy, talquetamab [2] ---> SmPC of [2] of EMA

TALVEY is not recommended for women who are pregnant or for women of childbearing potential not using contraception.

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

Vaccination with live virus vaccines is not recommended for at least 4 weeks prior to the start of treatment, during treatment, and at least 4 weeks after treatment.

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

Females of reproductive potential should use effective contraception during treatment and for 3 months after the last dose of TALVEY.

CONTRAINDICATIONS of Talquetamab (Talvey)

- 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/talvey-epar-product-information_en.pdf 28/06/2024

Tamoxifen

Abemaciclib [1], tamoxifen ---> SmPC of [1] of EMA

In a clinical study in patients with breast cancer, there was no clinically-relevant pharmacokinetic drug interaction between abemaciclib and anastrozole, fulvestrant, exemestane, letrozole or tamoxifen.

Ability to drive, tamoxifen [2] ---> SmPC of [2] of eMC

Since visual disturbances and light-headedness have been observed commonly with the use of tamoxifen, caution is advised when driving or using machines.

Acenocoumarol [1], tamoxifen ---> SmPC of [1] of eMC

The co-administration may enhance the anticoagulant effect of acenocoumarol and increase the bleeding risk

Amiodarone, tamoxifen

Amiodarone may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites.

Anastrozole [1], tamoxifen ---> SmPC of [1] of eMC

Tamoxifen should not be co-administered with anastrozole, as this may diminish its pharmacological action

Antineoplastics, tamoxifen

The co-administration may increase the risk of thromboembolia

Aromatase inhibitors, tamoxifen

The use of tamoxifen in combination with an aromatase inhibitor as adjuvant therapy has not showed greater efficacy, compared with tamoxifen alone

Bexarotene [1], tamoxifen ---> SmPC of [1] of EMA

Caution is advised in case of combination of bexarotene with CYP3A4-metabolised cytotoxics

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

Tamoxifen treatment is contraindicated during breast-feeding

Bromocriptine, tamoxifen

Tamoxifen may cancel de effect of bromocriptine

Bupropion, tamoxifen [2] ---> SmPC of [2] of eMC

Concomitant medications that inhibit CYP2D6 may lead to reduced concentrations of the active metabolite endoxifen. Therefore, potent inhibitors of CYP2D6 should whenever possible be avoided during tamoxifen treatment

Capecitabine, tamoxifen

Capecitabine may increase the plasma levels of tamoxifen.

Cinacalcet, tamoxifen [2] ---> SmPC of [2] of eMC

Coumarin anticoagulants, tamoxifen [2] ---> SmPC of [2] of eMC

When coumarin-type anti-coagulants are used in combination with tamoxifen a significant increase in anticoagulant effect may occur.

Cyclophosphamide, tamoxifen

The co-administration may increase the risk of thromboembolic complications

CYP3A4 and CYP2B6 inductors, tamoxifen

The CYP3A and CYP2B6 inductions may decrease the plasma levels of tamoxifen

Cytotoxic agents, tamoxifen [2] ---> SmPC of [2] of eMC

When cytotoxic agents are used in combination with tamoxifen there is increased risk of thromboembolic events occurring

Dextromethorphan/quinidine [1], tamoxifen ---> SmPC of [1] 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.

Droperidol [1], tamoxifen ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Duloxetine, tamoxifen

Duloxetine may decrease the therapeutic effect of tamoxifen by decreasing the production of active metabolite

Estrogens, tamoxifen [2] ---> SmPC of [2] of eMC

Hormone preparations, particularly oestrogens (e.g. oral contraceptives) should not be combined with tamoxifen because a mutual decrease in effect is possible.

Fluorouracil, tamoxifen

Fluorouracil may increase the plasma levels of tamoxifen.

Fluoxetine, tamoxifen [2] ---> SmPC of [2] of eMC

Hormones, tamoxifen [2] ---> SmPC of [2] of eMC

Hormone preparations, particularly oestrogens (e.g. oral contraceptives) should not be combined with tamoxifen because a mutual decrease in effect is possible.

Letrozol [1], tamoxifen ---> SmPC of [1] of eMC

Co-administration of letrozole with tamoxifen should be avoided as it may diminish the pharmacological action of letrozole

Lomitapide [1], tamoxifen ---> SmPC of [1] of EMA

Caution should be exercised when lomitapide is used with other medicinal products known to have potential for hepatotoxicity

Miconazole, tamoxifen

Oral miconazole is contraindicated with medicinal products that are metabolised by CYP3A4 and may prolong also the QT interval

Mytomicin, tamoxifen

The long-term co-administration may cause a hemolytic uremic syndrome

Naltrexone/bupropion [1], tamoxifen ---> SmPC of [1] of EMA

Drugs which require metabolic activation by CYP2D6 in order to be effective (e.g., tamoxifen), may have reduced efficacy when administered concomitantly with inhibitors of CYP2D6 such as bupropion.

Nevirapine, tamoxifen

The CYP3A and CYP2B6 inductions may decrease the plasma levels of tamoxifen

Oral contraceptives, tamoxifen [2] ---> SmPC of [2] of eMC

Hormone preparations, particularly oestrogens (e.g. oral contraceptives) should not be combined with tamoxifen because a mutual decrease in effect is possible.

Ospemifene [1], tamoxifen ---> SmPC of [1] of EMA

The safety of using ospemifene concomitantly with oestrogens or other SERMS has not been studied and its concurrent use is not recommended.

Palbociclib [1], tamoxifen ---> SmPC of [1] of EMA

Data from a DDI study in healthy male subjects indicated that palbociclib exposures were comparable when a single dose of palbociclib was coadministered with multiple doses of tamoxifen and when palbociclib was given alone.

Paroxetine, tamoxifen [2] ---> SmPC of [2] of eMC

Phenprocoumon, tamoxifen [2] ---> SmPC of [2] of eMC

When coumarin-type anti-coagulants are used in combination with tamoxifen a significant increase in anticoagulant effect may occur.

Platelet aggregation inhibitors, tamoxifen [2] ---> SmPC of [2] of eMC

In order to avoid bleeding during a possible thrombocytopenic interval thrombocyte aggregation inhibitors should not be combined with tamoxifen.

Pregnancy, tamoxifen [2] ---> SmPC of [2] of eMC

The use of tamoxifen during pregnancy is contraindicated

Pyrimethamine, tamoxifen

Pyrimethamine may decrease the therapeutic effect of tamoxifen

Quinidine, tamoxifen [2] ---> SmPC of [2] of eMC

Rifampicin, tamoxifen [2] ---> SmPC of [2] of eMC

As tamoxifen is metabolised by cytochrome P450 3A4, care is required when co-administered with drugs known to induce this enzyme, such as rifampicin, as tamoxifen levels may be reduced.

Rolapitant [1], tamoxifen ---> SmPC of [1] of EMA

Caution should be taken when rolapitant is combined with a medicinal product metabolised by CYP2D6, notably those having a narrow therapeutic margin

Strong CYP2D6 inhibitors, tamoxifen [2] ---> SmPC of [2] of eMC

Strong CYP3A4 inductors, tamoxifen [2] ---> SmPC of [2] of eMC

As tamoxifen is metabolised by cytochrome P450 3A4, care is required when co-administered with drugs known to induce this enzyme, such as rifampicin, as tamoxifen levels may be reduced.

Tacrolimus [1], tamoxifen ---> SmPC of [1] of EMA

Possible inhibition of the tacrolimus metabolism

Tamoxifen, thiotepa [2] ---> SmPC of [2] of EMA

Thiotepa, weak inhibitor for CYP2B6, may increase plasma concentrations of substances metabolised by CYP2B6

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

Tamoxifen potentiates the effect of warfarin

CONTRAINDICATIONS of Tamoxifen

- Pregnancy and lactation

- Hypersensitivity to tamoxifen or to any of the excipients

- Concurrent anastrozole therapy

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

Tamsulosin

Ability to drive, tamsulosin [2] ---> SmPC of [2] of eMC

Patients should be aware of the fact that dizziness can occur.

Alfa1-adrenergic receptor blockers, tamsulosin [2] ---> SmPC of [2] of eMC

Concurrent administration of tamsulosin with another alfa1-adrenoreceptor antagonist may lower blood pressure.

Antihypertensives, tamsulosin

Possible enhanced hypotensive effects

Avanafil [1], tamsulosin ---> 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], tamsulosin ---> SmPC of [1] of EMA

The concomitant use of boceprevir with tamsulosin may increase plasma concentrations of tamsulosin. The combination is not recommended

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

Tamsulosin is intended for male patients only

Carteolol, tamsulosin

Increased antihypertensive effect, increased risk of orthostatic hypotension

Chlorpromazine, tamsulosin

Chlorpromazine, strong CYP2D6 inhibitor, may increase the plasma levels of tamsulosin

Cimetidine, tamsulosin [2] ---> SmPC of [2] of eMC

Concomitant cimetidine raises plasma concentrations of tamsulosin but, as the concentration of tamsulosin remains within the normal range, posology need not be altered.

CYP2D6 inhibitors, tamsulosin

The CYP2D6 inhibition may increase the plasma concentrations of tamsulosin

CYP3A4 inhibitors, tamsulosin

The CYP3A4 inhibition may increase the plasma concentrations of tamsulosin

Diclofenac, tamsulosin [2] ---> SmPC of [2] of eMC

Diclofenac may increase the elimination rate of tamsulosin

Efavirenz, tamsulosin

The CYP3A4 inhibition may increase plasma concentrations of tamsulosin

Furosemide, tamsulosin [2] ---> SmPC of [2] of eMC

Concomitant furosemide lowers plasma concentrations of tamsulosin but, as the concentration of tamsulosin remains within the normal range, posology need not be altered.

Ketoconazole, tamsulosin

The strong CYP3A4 inhibition may increase the plasma concentrations of tamsulosin

Pregnancy, tamsulosin [2] ---> SmPC of [2] of eMC

Tamsulosin is intended for male patients only

Ramipril [1], tamsulosin ---> SmPC of [1] of eMC

Potentiation of the risk of hypotension is to be anticipated. Caution is recommended

Strong CYP2D6 inhibitors, tamsulosin

The strong CYP2D6 inhibition may increase the plasma concentrations of tamsulosin

Strong CYP3A4 inhibitors, tamsulosin

The strong CYP3A4 inhibition may increase the plasma concentrations of tamsulosin

Tamsulosin [1], warfarin ---> SmPC of [1] of eMC

Warfarin may increase the elimination rate of tamsulosin

Tamsulosin, vardenafil [2] ---> SmPC of [2] of EMA

The concomitant use may lead to symptomatic hypotension in some patients. Vardenafil may be administered at any time with tamsulosin or with alfuzosin.

Tamsulosin, xipamide

Increased hypotensive effect. Risk of orthostatic hypotension

CONTRAINDICATIONS of Tamsulosin

- Hypersensitivity to tamsulosin or any of the excipients.

- Orthostatic hypotension observed earlier (history of orthostatic hypotension).

- A history of tamsulosin induced angio-oedema.

- Severe hepatic insufficiency.

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

Tapentadol

Ability to drive, tapentadol [2] ---> SmPC of [2] of eMC

Tapentadol may have major influence on the ability to drive and use machines because it may adversely affect central nervous system functions

Acetylsalicylic acid, tapentadol

The co-administration may increase the systemic exposition of tapentadol

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

The co-administration may enhance the sedative effect of tapentadol

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

The co-administration may enhance the sedative effect of tapentadol

Barbiturates, tapentadol [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of respiratory depression

Benzodiazepines, tapentadol [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of respiratory depression and enhance the sedative effect of tapentadol

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

A risk to the suckling child cannot be excluded. Tapentadol should not be used during breast feeding.

Buprenorphine, tapentadol [2] ---> SmPC of [2] of eMC

Care should be taken when combining tapentadol with mixed mu-opioid agonist/antagonists or partial mu-opioid agonists

CNS depressants, tapentadol [2] ---> SmPC of [2] of eMC

The co-administration may enhance the sedative effect of tapentadol

Enzyme inductors, tapentadol [2] ---> SmPC of [2] of eMC

For patients on tapentadol treatment, caution should be exercised if concomitant drug administration of strong enzyme inducing drugs starts or stops, since this may lead to decreased efficacy or risk for adverse effects, respectively.

Fluconazole, tapentadol [2] ---> SmPC of [2] of eMC

Concomitant administration of tapentadol with strong inhibitors of UGT2B7 may lead to increased systemic exposure of tapentadol

IMAOs, tapentadol [2] ---> SmPC of [2] of eMC

Treatment with tapentadol should be avoided in patients who are receiving MAO inhibitors or who have taken them within the last 14 days due to potential additive effects on synaptic noradrenaline concentrations

Mefenamic acid, tapentadol [2] ---> SmPC of [2] of eMC

Concomitant administration of tapentadol with strong inhibitors of UGT1A9 may lead to increased systemic exposure of tapentadol

Nalbuphine, tapentadol [2] ---> SmPC of [2] of eMC

Care should be taken when combining tapentadol with mixed mu-opioid agonist/antagonists or partial mu-opioid agonists

Naproxen, tapentadol

The co-administration may increase the systemic exposition of tapentadol

Neuroleptics, tapentadol [2] ---> SmPC of [2] of eMC

The co-administration may enhance the sedative effect of tapentadol

Opiates, tapentadol [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of respiratory depression

Opioid agonist/antagonists, tapentadol [2] ---> SmPC of [2] of eMC

Care should be taken when combining tapentadol with mixed mu-opioid agonist/antagonists or partial mu-opioid agonists

Opioid analgesics, tapentadol [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of respiratory depression

Paracetamol, tapentadol

The co-administration may increase the systemic exposition of tapentadol

Pentazocine, tapentadol [2] ---> SmPC of [2] of eMC

Care should be taken when combining tapentadol with mixed mu-opioid agonist/antagonists or partial mu-opioid agonists

Phenobarbital, tapentadol [2] ---> SmPC of [2] of eMC

Phenytoin, tapentadol [2] ---> SmPC of [2] of eMC

Pregnancy, tapentadol [2] ---> SmPC of [2] of eMC

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

Probenecide, tapentadol

The co-administration may increase the systemic exposition of tapentadol

Rifampicin, tapentadol [2] ---> SmPC of [2] of eMC

Serotonergic medicines, tapentadol [2] ---> SmPC of [2] of eMC

In isolated cases there have been reports of serotonin syndrome in a temporal connection with the therapeutic use of tapentadol in combination with serotoninergic medicinal products

Serotonin agonists, tapentadol [2] ---> SmPC of [2] of eMC

In isolated cases there have been reports of serotonin syndrome in a temporal connection with the therapeutic use of tapentadol in combination with serotoninergic medicinal products

SSRI, tapentadol [2] ---> SmPC of [2] of eMC

In isolated cases there have been reports of serotonin syndrome in a temporal connection with the therapeutic use of tapentadol in combination with serotoninergic medicinal products

St. John's wort, tapentadol [2] ---> SmPC of [2] of eMC

Strong UGT1A6 inhibitors, tapentadol [2] ---> SmPC of [2] of eMC

Concomitant administration of tapentadol with strong inhibitors of UGT1A6 may lead to increased systemic exposure of tapentadol

Strong UGT1A9 inhibitors, tapentadol [2] ---> SmPC of [2] of eMC

Concomitant administration of tapentadol with strong inhibitors of UGT1A9 may lead to increased systemic exposure of tapentadol

Strong UGT2B7 inhibitors, tapentadol [2] ---> SmPC of [2] of eMC

Concomitant administration of tapentadol with strong inhibitors of UGT2B7 may lead to increased systemic exposure of tapentadol

CONTRAINDICATIONS of Tapentadol

Tapentadol is contraindicated

- in patients with hypersensitivity to tapentadol or to any of the excipients

- in situations where active substances with mu-opioid receptor agonist activity are contraindicated, i.e. patients with significant respiratory depression (in unmonitored settings or the absence of resuscitative equipment), and patients with acute or severe bronchial asthma or hypercapnia

- in any patient who has or is suspected of having paralytic ileus

- in patients with acute intoxication with alcohol, hypnotics, centrally acting analgesics, or psychotropic active substances

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

Tasimelteon (Hetlioz)

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

Tasimelteon may cause somnolence, and therefore may have an influence on driving and using machines.

Alcohol, tasimelteon [2] ---> SmPC of [2] of EMA

On some psychomotor test measures (intoxication, drunk, alertness/drowsiness, balance platform test), there was a trend towards greater effects of tasimelteon plus ethanol versus ethanol alone, but the effects were not deemed significant.

Betablockers, tasimelteon [2] ---> SmPC of [2] of EMA

The efficacy of tasimelteon may be reduced in patients with concomitant administration of beta adrenergic receptor antagonists.

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

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

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

Caution should be used when administering tasimelteon in combination with strong CYP1A2 inhibitors because of a potentially large increase in tasimelteon exposure and greater risk of adverse reactions

Enoxacin, tasimelteon [2] ---> SmPC of [2] of EMA

Fertility, tasimelteon [2] ---> SmPC of [2] of EMA

Reproductive and developmental toxicity studies showed that oestrous cycles were prolonged in rats treated with high doses of tasimelteon, with no effect on mating performance or male fertility, and only a marginal effect on female fertility.

Fluvoxamine, tasimelteon [2] ---> SmPC of [2] of EMA

Foods, tasimelteon [2] ---> SmPC of [2] of EMA

Tasimelteon should be taken without food; if patients eat a high-fat meal, it is recommended to wait at least 2 hours before taking tasimelteon (see section 5.2).

Ketoconazole, tasimelteon [2] ---> SmPC of [2] of EMA

Tasimelteon exposure was increased by approximately 50% when co-administered with ketoconazole 400 mg (after 5 days of ketoconazole 400 mg per day). The clinical relevance of this single factor is unclear

Nicotine, tasimelteon [2] ---> SmPC of [2] of EMA

Tasimelteon exposure decreased by approximately 40% in smokers compared to non-smokers (see section 5.2). The patient should be instructed to cease or reduce smoking while taking tasimelteon.

Pregnancy, tasimelteon [2] ---> SmPC of [2] of EMA

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

Rifampicin, tasimelteon [2] ---> SmPC of [2] of EMA

Use of tasimelteon should be avoided in combination with rifampin or other CYP3A4 inducers because of a potentially large decrease in tasimelteon exposure with reduced efficacy

Strong CYP1A2 inhibitors, tasimelteon [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inductors, tasimelteon [2] ---> SmPC of [2] of EMA

Use of tasimelteon should be avoided in combination with rifampin or other CYP3A4 inducers because of a potentially large decrease in tasimelteon exposure with reduced efficacy

Strong CYP3A4 inhibitors, tasimelteon [2] ---> SmPC of [2] of EMA

CONTRAINDICATIONS of Tasimelteon (Hetlioz)

- 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/hetlioz-epar-product-information_en.pdf 11/10/2022

Tasonermin

Anthracyclines, tasonermin [2] ---> SmPC of [2] of EMA

Combinations of tasonermin with cardiotoxic substances (e.g. anthracyclines) should be avoided because it is possible that tasonermin could enhance cardiotoxicity

Antihypertensives, tasonermin [2] ---> SmPC of [2] of EMA

Concurrent administration of agents likely to cause significant hypotension is not recommended

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

Because of the unknown risk to the infant, breast-feeding is contraindicated within 7 days of ILP

Medicines with cardiotoxic effects, tasonermin [2] ---> SmPC of [2] of EMA

Combinations of tasonermin with cardiotoxic substances (e.g. anthracyclines) should be avoided because it is possible that tasonermin could enhance cardiotoxicity

Pregnancy, tasonermin [2] ---> SmPC of [2] of EMA

Beromun is contraindicated in pregnancy

CONTRAINDICATIONS of Tasonermin

Contraindications to Beromun isolated limb perfusion (ILP), subdivided by components of the procedure, are:

Contraindications to Beromun:

- Hypersensitivity to the active substance or to any of the excipients

- Significant cardiovascular disease, e.g. congestive heart failure (NYHA Class II, III or IV), severe angina pectoris, cardiac arrhythmias, myocardial infarction within a 3 months period prior to treatment, venous thrombosis, occlusive peripheral arterial disease, recent pulmonary embolism.

- Severe pulmonary dysfunction.

- A recent history of, or active peptic ulcer.

- Severe ascites.

- Significant haematological dysfunction, e.g. leucocytes < 2.5 x 109 /l, haemoglobin < 9 g/dl, platelets < 60 x 109 /l, haemorrhagic diathesis or active bleeding disorder.

- Significant renal dysfunction, e.g. nephrotic syndrome, serum creatinine >150 µmol/l, or creatinine clearance of < 50 ml/min.

- Significant hepatic dysfunction, e.g.>2 x upper limits of normal levels of aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase; or bilirubin levels >1.25 x upper limits of normal.

- Hypercalcaemia >12 mg/dl (2.99 mmol/l).

- Patients with contraindications to the use of vasopressor substances.

- Patients with contraindications to the use of anticoagulants.

- Simultaneous treatment with cardiotoxic substances (e.g. anthracyclines)

- Pregnancy and lactation (see section 4.6).

Contraindications to melphalan:

- Please refer to the Summary of Product Characteristics for melphalan.

Contraindications to the ILP procedure:

- Severe ascites.

- Severe lymphoedema of the limb.

- Patients with contraindications to the use of vasopressor agents.

- Patients with contraindications to the use of anticoagulants.

- Patients with contraindications to radioactive tracer monitoring.

- Patients with contraindications to limb hyperthermia.

- Patients in whom the blood supply to the extremity distal to the tumour is suspected to be highly dependent on tumour associated blood vessels. This can be

clarified by an arteriogram.

- Pregnancy and lactation.

http://www.ema.europa.eu/

Tazarotene

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

Tazarotene should not be used during breast-feeding.

Methotrexate, tazarotene

The additional administration of methotrexate with hepatotoxic and hematotoxic products increases the probability of hepatotoxic and hematotoxic effects of methotrexate

Pregnancy, tazarotene [2] ---> SmPC of [2] of eMC

Tazarotene is contraindicated in women who are or may become pregnant

CONTRAINDICATIONS of Tazarotene

- Hypersensitivity to any ingredient of the medication(s)

- Pregnancy or in women planning a pregnancy

- Breast-feeding mothers

- Since there is, as yet, no clinical experience, Zorac should not be used in the treatment of psoriasis pustulosa and psoriasis exfoliativa, and the gel should not be applied to intertriginous areas, to the face or to hair-covered scalp.

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

Tebentafusp (Kimmtrak)

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

There is insufficient information on the excretion of tebentafusp/metabolites in human milk. A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with tebentafusp.

Contraceptives, tebentafusp [2] ---> SmPC of [2] of EMA

Women of childbearing potential should use effective contraception during treatment with tebentafusp and for at least 1 week after last dose of tebentafusp.

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

These patients should be monitored for toxicity (e.g., warfarin) or drug concentrations (e.g., cyclosporine). The dose of the concomitant medicines should be adjusted as needed.

CYP450 substrates with narrow therapeutic index, tebentafusp [2] ---> SmPC of [2] of EMA

The highest drug-drug interaction risk is during the first 24 hours of the first three doses of tebentafusp in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

CYP450, tebentafusp [2] ---> SmPC of [2] of EMA

Initiation of tebentafusp treatment causes transient release of cytokines that may suppress CYP450 enzymes.

Fertility, tebentafusp [2] ---> SmPC of [2] of EMA

No fertility studies have been conducted with tebentafusp (see section 5.3). The effect of tebentafusp on male and female fertility is unknown.

Pregnancy, tebentafusp [2] ---> SmPC of [2] of EMA

Tebentafusp is not recommended during pregnancy and in women of childbearing potential not using contraception. The pregnancy status in females of reproductive potential should be verified prior to initiating tebentafusp treatment.

QT interval prolonging drugs, tebentafusp [2] ---> SmPC of [2] of EMA

Tebentafusp treatment should be administered with caution in patients with history of or predisposition to QT interval prolongation and in patients who are taking medicinal products that are known to prolong QT interval.

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

These patients should be monitored for toxicity (e.g., warfarin) or drug concentrations (e.g., cyclosporine). The dose of the concomitant medicines should be adjusted as needed.

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

Women of childbearing potential should use effective contraception during treatment with tebentafusp and for at least 1 week after last dose of tebentafusp.

CONTRAINDICATIONS of Tebentafusp (Kimmtrak)

- 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/kimmtrak-epar-product-information_en.pdf 09/12/2025

Teclistamab (Tecvayli)

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

TECVAYLI has major influence on the ability to drive and use machines. Due to the potential for ICANS, patients receiving TECVAYLI are at risk of depressed level of consciousness (see section 4.8).

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

Because of the potential for serious adverse reactions in breast-fed infants from TECVAYLI, patients should be advised not to breast-feed during treatment with TECVAYLI and for at least five months after the last dose.

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

During this time period, toxicity or medicinal product concentrations (e.g., cyclosporine) should be monitored in patients who are receiving concomitant CYP450 substrates with a narrow therapeutic index.

CYP450 substrates with narrow therapeutic index, teclistamab [2] ---> SmPC of [2] of EMA

Fertility, teclistamab [2] ---> SmPC of [2] of EMA

There are no data on the effect of teclistamab on fertility. Effects of teclistamab on male and female fertility have not been evaluated in animal studies.

Hypogammaglobulinemia, teclistamab [2] ---> SmPC of [2] of EMA

TECVAYLI is associated with hypogammaglobulinaemia, therefore, assessment of immunoglobulin levels in newborns of mothers treated with TECVAYLI should be considered.

Men, teclistamab [2] ---> SmPC of [2] of EMA

In clinical studies, male patients with a female partner of child-bearing potential used effective contraception during treatment and for three months after the last dose of teclistamab.

Pregnancy, teclistamab [2] ---> SmPC of [2] of EMA

Therefore, teclistamab, a humanised IgG4-based antibody, has the potential to be transmitted from the mother to the developing foetus. TECVAYLI is not recommended for women who are pregnant.

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

Women of child-bearing potential should use effective contraception during treatment and for five months after the final dose of TECVAYLI.

CONTRAINDICATIONS of Teclistamab (Tecvayli)

- 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/tecvayli-epar-product-information_en.pdf 08/10/2025

Tecovirimat (Tecovirimat SIGA)

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

Patients should be informed about the possible occurrence of dizziness and should be cautioned about driving or operating machines until they know how tecovirimat will affect them.

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

A risk for decreases in atorvastatin plasma concentrations cannot be excluded (CYP3A4 substrate). The combination of tecovirimat and atorvastatin should be used with caution.

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

A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with tecovirimat.

Bupropion, tecovirimat [2] ---> SmPC of [2] of EMA

No dose adjustment is required. The effectiveness of bupropion should be monitored.

CYP2B6 substrates with narrow therapeutic index, tecovirimat [2] ---> SmPC of [2] of EMA

Tecovirimat and its M4 metabolite are inducers of cytochrome P450 (CYP)3A and CYP2B6. Monitoring is advised during co-administration of tecovirimat with CYP3A4 and CYP2B6 substrates that have narrow therapeutic windows.

CYP2C19 substrates with narrow therapeutic index, tecovirimat [2] ---> SmPC of [2] of EMA

Tecovirimat is a weak inhibitor of CYP2C8 and CYP2C19. Monitoring is advised during co-administration of tecovirimat with CYP2C8 and CYP2C19 substrates that have narrow therapeutic windows.

CYP2C8 substrates with narrow therapeutic index, tecovirimat [2] ---> SmPC of [2] of EMA

Tecovirimat is a weak inhibitor of CYP2C8 and CYP2C19. Monitoring is advised during co-administration of tecovirimat with CYP2C8 and CYP2C19 substrates that have narrow therapeutic windows.

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.

Drugs primarily metabolised by CYP2B6, tecovirimat [2] ---> SmPC of [2] of EMA

Co-administration with tecovirimat may lead to reduced plasma exposures of sensitive substrates of CYP3A4 or CYP2B6, potentially leading to reduced effects.

Drugs primarily metabolised by CYP2C19, tecovirimat [2] ---> SmPC of [2] of EMA

Co-administration with tecovirimat may lead to increased plasma exposures of sensitive substrates of CYP2C8 or CYP2C19, potentially leading to increased adverse effects.

Drugs primarily metabolised by CYP2C8, tecovirimat [2] ---> SmPC of [2] of EMA

Co-administration with tecovirimat may lead to increased plasma exposures of sensitive substrates of CYP2C8 or CYP2C19, potentially leading to increased adverse effects.

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, tecovirimat [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP3A4, tecovirimat [2] ---> SmPC of [2] of EMA

Co-administration with tecovirimat may lead to reduced plasma exposures of sensitive substrates of CYP3A4 or CYP2B6, potentially leading to reduced effects.

Fertility, tecovirimat [2] ---> SmPC of [2] of EMA

Tecovirimat caused decreased fertility due to testicular toxicity in male mice (see section 5.3).

Flurbiprofen, tecovirimat [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Foods, tecovirimat [2] ---> SmPC of [2] of EMA

Tecovirimat hard capsules should be taken within 30 minutes after a meal of moderate or high fat (see section 5.2).

Lansoprazole, tecovirimat [2] ---> SmPC of [2] of EMA

Tecovirimat is a weak inhibitor of CYP2C19 and caused an increase in plasma concentrations of omeprazole. The combination of tecovirimat and proton pump inhibitors should be used with caution.

Maraviroc, tecovirimat [2] ---> SmPC of [2] of EMA

A risk for decreases in maraviroc plasma concentrations cannot be excluded (CYP3A4 substrate). The combination of tecovirimat and maraviroc should be used with caution.

Methadone, tecovirimat [2] ---> SmPC of [2] of EMA

A risk for decreases in methadone plasma concentrations cannot be excluded (CYP2B6 substrate). The combination of tecovirimat and methadone should be used with caution.

Midazolam, tecovirimat [2] ---> SmPC of [2] of EMA

Tecovirimat is a weak inducer of CYP3A4 and caused a decrease in plasma concentrations of midazolam. The effectiveness of midazolam should be monitored and the dose adjusted as necessary.

Omeprazole, tecovirimat [2] ---> SmPC of [2] of EMA

Tecovirimat is a weak inhibitor of CYP2C19 and caused an increase in plasma concentrations of omeprazole. The combination of tecovirimat and proton pump inhibitors should be used with caution.

PDE5 inhibitors, tecovirimat [2] ---> SmPC of [2] of EMA

A risk for decreases in PDE-5 inhibitor plasma concentrations cannot be excluded (CYP3A4 substrate). The combination of tecovirimat and PDE-5 inhibitors should be used with caution.

Pregnancy, tecovirimat [2] ---> SmPC of [2] of EMA

Tecovirimat is not recommended during pregnancy.

Proton pump inhibitors, tecovirimat [2] ---> SmPC of [2] of EMA

Tecovirimat is a weak inhibitor of CYP2C19 and caused an increase in plasma concentrations of omeprazole. The combination of tecovirimat and proton pump inhibitors should be used with caution.

Rabeprazole, tecovirimat [2] ---> SmPC of [2] of EMA

Tecovirimat is a weak inhibitor of CYP2C19 and caused an increase in plasma concentrations of omeprazole. The combination of tecovirimat and proton pump inhibitors should be used with caution.

Repaglinide, tecovirimat [2] ---> SmPC of [2] of EMA

Co-administration of repaglinide and tecovirimat may cause mild to moderate hypoglycemia. Blood glucose and hypoglycemic symptoms should be monitored in patients when tecovirimat is co-administered with repaglinide.

Rilpivirine, tecovirimat [2] ---> SmPC of [2] of EMA

A risk for decreases in rilpivirine plasma concentrations cannot be excluded (CYP3A4 substrate). The combination of tecovirimat and rilpivirine should be used with caution.

Sildenafil, tecovirimat [2] ---> SmPC of [2] of EMA

A risk for decreases in PDE-5 inhibitor plasma concentrations cannot be excluded (CYP3A4 substrate). The combination of tecovirimat and PDE-5 inhibitors should be used with caution.

Strong glucuronidation inductors, tecovirimat [2] ---> SmPC of [2] of EMA

Tecovirimat is a substrate of UGT1A1, 1A3 and 1A4. Co-administration of tecovirimat with strong inhibitors or inducers of these UGTs is not expected to have a clinically important effect on tecovirimat exposures.

Strong glucuronidation inhibitors, tecovirimat [2] ---> SmPC of [2] of EMA

Tacrolimus, tecovirimat [2] ---> SmPC of [2] of EMA

A risk for decreases in tacrolimus plasma concentrations cannot be excluded (CYP3A4 substrate). The combination of tecovirimat and tacrolimus should be used with caution.

Tadalafil, tecovirimat [2] ---> SmPC of [2] of EMA

A risk for decreases in PDE-5 inhibitor plasma concentrations cannot be excluded (CYP3A4 substrate). The combination of tecovirimat and PDE-5 inhibitors should be used with caution.

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

A risk for increase in voriconazole plasma concentrations cannot be excluded (CYP2C19 substrate). The combination of tecovirimat and voriconazole should be used with caution.

Tecovirimat, vardenafil [2] ---> SmPC of [2] of EMA

A risk for decreases in PDE-5 inhibitor plasma concentrations cannot be excluded (CYP3A4 substrate). The combination of tecovirimat and PDE-5 inhibitors should be used with caution.

CONTRAINDICATIONS of Tecovirimat (Tecovirimat SIGA)

- 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/tecovirimat-siga-epar-product-information_en.pdf 10/11/2025

Tedisamil

Breast-feeding, tedisamil

A decision must be made to either discontinue breast-feeding or to discontinue/abstain from therapy

Carvedilol, tedisamil

Tedisamil, strong CYP2D6 inhibitor, may increase the plasma concentrations of carvedilol

Desipramine, tedisamil

Tedisamil, strong CYP2D6 inhibitor, may increase the plasma concentrations of desipramine

Drugs primarily metabolised by CYP2D6, tedisamil

Tedisamil, strong CYP2D6 inhibitor, may increase the plasma concentrations of the medicinal products metabolised by CYP2D6

Flecainide, tedisamil

Tedisamil, strong CYP2D6 inhibitor, may increase the plasma concentrations of flecainide

Fluoxetine, tedisamil

Tedisamil, strong CYP2D6 inhibitor, may increase the plasma concentrations of fluoxetine

Imipramine, tedisamil

Tedisamil, strong CYP2D6 inhibitor, may increase the plasma concentrations of imipramine

Pregnancy, tedisamil

Caution should be exercised when prescribing to pregnant women

Propafenone, tedisamil

Tedisamil, strong CYP2D6 inhibitor, may increase the plasma concentrations of propafenone

Tedizolid (Sivextro)

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

Sivextro may have a minor influence on the ability to drive and use machines as it may cause dizziness, fatigue or, uncommonly, somnolence (see section 4.8).

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

Orally administered Sivextro can result in inhibition of BCRP at the intestinal level. If possible, an interruption of the co-administered BCRP substrate medicinal product should be considered during the six days of treatment with oral Sivextro.

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

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from therapy

CYP3A4 substrates, tedizolid [2] ---> SmPC of [2] of EMA

The effect is not clinically meaningful, and no dose adjustment for co-administered CYP3A4 substrates is necessary during Sivextro treatment.

Fertility, tedizolid [2] ---> SmPC of [2] of EMA

The effects of tedizolid phosphate on fertility in humans have not been studied. Animal studies with tedizolid phosphate do not indicate harmful effects with respect to fertility (see section 5.3).

IMAOs, tedizolid [2] ---> SmPC of [2] of EMA

Tedizolid is a reversible inhibitor of monoamine oxidase (MAO) in vitro; however, no interaction is anticipated when comparing the IC50 for MAO-A inhibition and the anticipated plasma exposures in man.

Imatinib, tedizolid [2] ---> SmPC of [2] of EMA

Lapatinib, tedizolid [2] ---> SmPC of [2] of EMA

Methotrexate, tedizolid [2] ---> SmPC of [2] of EMA

Midazolam, tedizolid [2] ---> SmPC of [2] of EMA

The effect is not clinically meaningful, and no dose adjustment for co-administered CYP3A4 substrates is necessary during Sivextro treatment.

Pitavastatin, tedizolid [2] ---> SmPC of [2] of EMA

Pregnancy, tedizolid [2] ---> SmPC of [2] of EMA

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

Pseudoephedrine, tedizolid [2] ---> SmPC of [2] of EMA

No meaningful changes in blood pressure or heart rate with pseudoephedrine were observed in the healthy volunteers, and no clinically relevant increase in tyramine sensitivity was observed.

Rosuvastatin, tedizolid [2] ---> SmPC of [2] of EMA

Serotonergic medicines, tedizolid [2] ---> SmPC of [2] of EMA

The potential for serotonergic interactions has not been studied in either patients or healthy volunteers (see section 5.2).

Sulfasalazine, tedizolid [2] ---> SmPC of [2] of EMA

Tedizolid [1], topotecan ---> SmPC of [1] of EMA

Tedizolid [1], tyramine ---> SmPC of [1] of EMA

No meaningful changes in blood pressure or heart rate with pseudoephedrine were observed in the healthy volunteers, and no clinically relevant increase in tyramine sensitivity was observed.

CONTRAINDICATIONS of Tedizolid (Sivextro)

- 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/sivextro-epar-product-information_en.pdf 20/03/2025

Teduglutide (Revestive)

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

Cases of syncope have been reported in clinical studies. Such events might impact the ability to drive and use machines

Absorption, teduglutide [2] ---> SmPC of [2] of EMA

Based upon the pharmacodynamic effect of teduglutide, there is a potential for increased absorption of concomitant medicinal products

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

As a precautionary measure, it is preferable to avoid the use of Revestive during breast-feeding

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

An in vitro study indicates that teduglutide does not inhibit cytochrome P450 drug metabolising enzymes.

Drugs with a narrow therapeutic window, teduglutide [2] ---> SmPC of [2] of EMA

The oral co-administration of medicinal products with a narrow therapeutic index with teduglutide should be monitored closely due to potential increased absorption

Fertility, teduglutide [2] ---> SmPC of [2] of EMA

There are no data on the effects of teduglutide on human fertility. Animal data do not indicate any impairment of fertility.

Pregnancy, teduglutide [2] ---> SmPC of [2] of EMA

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

CONTRAINDICATIONS of Teduglutide (Revestive)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1, or trace residues of tetracycline.

- Active or suspected malignancy

- Patients with a history of malignancies in the gastrointestinal tract including the hepatobiliary system within and pancreas the last 5 years

https://www.ema.europa.eu/en/documents/product-information/revestive-epar-product-information_en.pdf 23/05/2025

Tegafur

Ability to drive, tegafur

Vertigo, nauseas and disorientation may occur

Acenocoumarol, tegafur

Patients receiving coumarin anticoagulants (e.g. warfarin or acenocoumarol) should be closely monitored for their prothrombin time INR

Breast-feeding, tegafur

Tegafur is contraindicated during breastfeeding

Brivudine, tegafur

Co-administration of brivudine with chemotherapeutic drugs (particularly 5-FU, including its topic preparations and prodrugs) and other 5-fluoropyrimidines is contraindicated

Clotrimazole, tegafur

The co-administration of a CYP2A6 inhibitor and tegafur should be avoided as effectiveness of tegafur can be decreased

Coumarin anticoagulants, tegafur

Patients receiving coumarin anticoagulants (e.g. warfarin or acenocoumarol) should be closely monitored for their prothrombin time INR

CYP2A6 inhibitors, tegafur

The co-administration of a CYP2A6 inhibitor and tegafur should be avoided as effectiveness of tegafur can be decreased

Dihydropyrimidine dehydrogenase inhibitors, tegafur

The inhibition of dihydropyrimidine dehydrogenase increases the plasma levels of fluorouracil. Contraindicated. A period of at least 4 weeks should elapse between them.

Enzyme inductors, tegafur

The enzymatic inductor increases the release of 5-fluorouracil of tegafur

Folinates, tegafur

Caution is advised as folinic acid is known to enhance the activity of 5-FU.

Folinic acid, tegafur

Caution is advised as folinic acid may increase the cytotoxicity of 5-FU

Foods, tegafur

Tegafur should be taken at least 1 hour before or 1 hour after a meal

Grapefruit juice, tegafur

Grapefruit juice inhibits the CYP2A6 and can decrease the tegafur activation to 5-FU. Grapefruit juice should not be taken

Ketoconazole, tegafur

The co-administration of a CYP2A6 inhibitor and tegafur should be avoided as effectiveness of tegafur can be decreased

Methoxypsoralen, tegafur

The co-administration of a CYP2A6 inhibitor and tegafur should be avoided as effectiveness of tegafur can be decreased

Miconazole, tegafur

The co-administration of a CYP2A6 inhibitor and tegafur should be avoided as effectiveness of tegafur can be decreased

Nucleoside analogues, tegafur

The inhibition of dihydropyrimidine dehydrogenase increases the plasma levels of tegafur. Contraindicated. A period of at least 4 weeks should elapse between them.

Phenobarbital, tegafur

The enzymatic inductor increases the release of 5-fluorouracil of tegafur

Phenytoin, tegafur

Fluoropyrimidines may increase phenytoin plasma concentration when administered concomitantly with phenytoin causing phenytoin toxicity.

Pregnancy, tegafur

Tegafur is contraindicated during pregnancy

Radiotherapy, tegafur

Previous or concomitant radiotherapy may aggravate the adverse reactions

Rifampicin, tegafur

The enzymatic inductor increases the release of 5-fluorouracil of tegafur

Sorivudine, tegafur

The inhibition of dihydropyrimidine dehydrogenase increases the plasma levels of fluorouracil. Contraindicated. A period of at least 4 weeks should elapse between them.

Strong CYP2A6 inhibitors, tegafur

The co-administration of a CYP2A6 inhibitor and tegafur should be avoided as effectiveness of tegafur can be decreased

Tegafur, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Co-administration of other fluoropyrimidines can lead to additive toxicities, and is contraindicated. A minimum washout period of 7 days is recommended between administration of tegafur/gimeracil/oteracil and other fluoropyrimidines.

Tegafur, vaccinations

Vaccinations with attenuated live vaccines should be avoided

Tegafur, vaccinations with live organism vaccines

It may be expected that in patients receiving immunosuppressive treatment an adequate response may not be achieved. Concomitant use of fluoropyrimidines and live viral vaccines may increase the risk of infection

Tegafur, warfarin

Patients receiving coumarin anticoagulants (e.g. warfarin or acenocoumarol) should be closely monitored for their prothrombin time INR

Tegafur/gimeracil/oteracil (Teysuno)

Ability to drive, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Teysuno has moderate influence on the ability to drive and use machines as fatigue, dizziness, blurred vision, and nausea are common adverse reactions of Teysuno in combination with cisplatin.

Allopurinol, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Allopurinol may decrease anti-tumour activity due to suppression of phosphorylation of 5-FU. Concomitant use should be avoided

Breast-feeding, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Teysuno is contraindicated in breast-feeding. A risk to newborns/infants cannot be excluded. Breast-feeding must be discontinued while receiving treatment with Teysuno.

Brivudine, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Sorivudine or its chemically related analogues such as brivudine irreversibly inhibit DPD, resulting in a significant increase in 5-FU exposure. This may lead to increased clinically significant fluoropyrimidine-related toxicities with potentially fatal

Calcium folinate, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Metabolites of folinate/folinic acid form a ternary structure with thymidylate synthase and fluorodeoxyuridine monophosphate (FdUMP), potentially increasing the cytotoxicity of 5-FU. Caution is advised as folinic acid enhances the activity of 5-FU.

Capecitabine, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Cimetidine, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Co-administration may decrease clearance and, thus increase plasma levels of 5-FU. Caution is advised as co-administration may increase the toxicity of tegafur/gimeracil/oteracil.

Clozapine, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Due to possible additive pharmacodynamic effects (myelotoxicity), caution is advised as co-administration may increase the risk and severity of haematologic toxicity of tegafur/gimeracil/oteracil.

Coumarin anticoagulant, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

The activity of a coumarin-derivative anticoagulant was enhanced by Teysuno. Caution is advised as co-administration of Teysuno and coumarin anticoagulation therapy may increase the risk of bleeding (see section 4.4).

Coumarin anticoagulants, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

The activity of a coumarin-derivative anticoagulant was enhanced by Teysuno. Caution is advised as co-administration may increase the risk of bleeding

CYP2A6 inhibitors, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

As CYP2A6 is the major enzyme responsible for the conversion of tegafur to 5-FU, co-administration of a known CYP2A6 inhibitor and Teysuno should be avoided as effectiveness of Teysuno could be decreased (see section 5.2).

Fertility, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

No data are available on the effect of Teysuno in combination with cisplatin on human fertility. Nonclinical studies demonstrated that Teysuno did not appear to affect male or female fertility in the rat

Flucytosine, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Fluoropyrimidines, phenytoin ---> SmPC of [tegafur/gimeracil/oteracil] of EMA

Fluoropyrimidines may increase phenytoin plasma concentration when administered concomitantly with phenytoin causing phenytoin toxicity.

Fluoropyrimidines, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Fluorouracil, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Folinates, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Folinic acid, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Foods, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

The capsules should be taken by mouth with water at least 1 hour before or 1 hour after a meal

Irreversible dihydropyrimidine dehydrogenase inhibitors, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Men, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Contraceptive measures must be taken by male patients during and up to 3 months after stopping treatment with Teysuno.

Methotrexate, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Polyglutamated methotrexate inhibits thymidylate synthase and dihydrofolate reductase, potentially increasing cytotoxicity of 5-FU. Caution is advised as co-administration may increase the toxicity of tegafur/gimeracil/oteracil.

Metronidazole, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Nitroimidazole may reduce clearance of 5-FU and thus increase plasma levels of 5-FU. Caution is advised as co-administration may increase the toxicity of tegafur/gimeracil/oteracil.

Misonidazole, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Nitroimidazole may reduce clearance of 5-FU and thus increase plasma levels of 5-FU. Caution is advised as co-administration may increase the toxicity of tegafur/gimeracil/oteracil.

Nitroimidazoles, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Nitroimidazole may reduce clearance of 5-FU and thus increase plasma levels of 5-FU. Caution is advised as co-administration may increase the toxicity of tegafur/gimeracil/oteracil.

Phenytoin, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Fluoropyrimidines may increase phenytoin plasma concentration when administered concomitantly with phenytoin causing phenytoin toxicity.

Pregnancy, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Teysuno is contraindicated in pregnancy. If the patient becomes pregnant while receiving Teysuno, treatment should be discontinued and the potential risk to the foetus must be explained.

Sorivudine, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Tegafur, tegafur/gimeracil/oteracil [2] ---> SmPC of [2] of EMA

Tegafur/gimeracil/oteracil [1], women ---> SmPC of [1] of EMA

Contraceptive measures must be taken by female patients during and up to 6 months after stopping treatment with Teysuno.

Tegafur/gimeracil/oteracil [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with this medicinal product.

CONTRAINDICATIONS of Tegafur/gimeracil/oteracil (Teysuno)

- Hypersensitivity to any of the active substances (tegafur, gimeracil, and oteracil) or to any of the excipients listed in section 6.1.

- History of severe and unexpected reactions to fluoropyrimidine therapy.

- Known complete dihydropyrimidine dehydrogenase (DPD) deficiency.

- Pregnancy and breastfeeding.

- Severe bone marrow suppression (severe leukopaenia, neutropaenia, or thrombocytopaenia)

- End stage renal disease patients requiring dialysis.

- Co-administration of other fluoropyrimidines with Teysuno

- Recent or concomitant treatment with brivudine (see section 4.4 and 4.5 for drug-drug interaction).

- Contraindications for cisplatin; oxaliplatin, irinotecan and bevacizumab refer to the corresponding SmPCs.

https://www.ema.europa.eu/en/documents/product-information/teysuno-epar-product-information_en.pdf. 18/01/2024

Tegomil (Riulvy)

Alcohol, tegomil [2] ---> SmPC of [2] of EMA

Consumption of large quantities of strong alcoholic drinks (more than 30% alcohol by volume) should be avoided within an hour of taking dimethyl fumarate, as alcohol may lead to increased frequency of gastrointestinal adverse reactions.

Aminoglycosides, tegomil [2] ---> SmPC of [2] of EMA

Concurrent therapy with nephrotoxic medicin products (such as aminoglycosides, diuretics, non-steroidal anti-inflammatory drugs or lithium) may increase the potential of renal adverse reactions (e.g. proteinuria) in patients taking tegomil fumarate

Attenuated vaccines, tegomil [2] ---> SmPC of [2] of EMA

Live vaccines might carry an increased risk of clinical infection and should not be given to patients treated with tegomil fumarate unless, in exceptional cases, this potential risk is considered to be outweighed by the risk of not vaccinating.

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

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

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

Although not studied with tegomil fumarate, in vitro CYP induction studies did not demonstrate an interaction between dimethyl fumarate and oral contraceptives.

Diuretics, tegomil [2] ---> SmPC of [2] of EMA

Fanconi's syndrome, tegomil [2] ---> SmPC of [2] of EMA

Early diagnosis of Fanconi syndrome and discontinuation of tegomil fumarate treatment are important to prevent the onset of renal impairment and osteomalacia, as the syndrome is usually reversible.

Fertility, tegomil [2] ---> SmPC of [2] of EMA

There are no data on the effects of tegomil fumarate on human fertility. Data from preclinical studies with another substance dimethyl fumarate do not suggest an increased risk of reduced fertility

Hepatic function, tegomil [2] ---> SmPC of [2] of EMA

Assessment of serum aminotransferases (e.g. alanine aminotransferase (ALT), aspartate aminotransferase (AST)) and total bilirubin levels are recommended prior to treatment initiation and during treatment as clinically indicated.

Infection, tegomil [2] ---> SmPC of [2] of EMA

Patients should be instructed to discontinue tegomil fumarate and seek immediate medical care if they experience signs or symptoms of anaphylaxis. Treatment should not be restarted (see section 4.8).

Lithium, tegomil [2] ---> SmPC of [2] of EMA

Lymphopenia, tegomil [2] ---> SmPC of [2] of EMA

Tegomil fumarate should not be initiated in patients with severe lymphopenia (lymphocyte counts < 0.5 x 109/L). After starting therapy, complete blood counts, including lymphocytes, must be performed every 3 months.

Nephrotoxic substances, tegomil [2] ---> SmPC of [2] of EMA

NSAID, tegomil [2] ---> SmPC of [2] of EMA

Oral contraceptives, tegomil [2] ---> SmPC of [2] 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.

Pregnancy, tegomil [2] ---> SmPC of [2] of EMA

As a precautionary measure, it is preferable to avoid the use of tegomil fumarate during pregnancy. Tegomil fumarate should be used during pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the foetus.

Renal function, tegomil [2] ---> SmPC of [2] of EMA

Assessment of renal function (e.g. creatinine, blood urea nitrogen and urinalysis) is recommended prior to treatment initiation, after 3 and 6 months, every 6 to 12 months thereafter and as clinically indicated.

Tegomil [1], vaccinations ---> SmPC of [1] of EMA

Concomitant administration of non-live vaccines according to national vaccination schedules may be considered during tegomil fumarate therapy.

CONTRAINDICATIONS of Tegomil (Riulvy)

- 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/riulvy-epar-product-information_en.pdf 25/09/2025

Tegafur/uracil

Ability to drive, tegafur/uracil

Confusedness may occur

Breast-feeding, tegafur/uracil

Due to the potential of severe adverse fetal reactions, the use of tegafur/uracil is contraindicated during breastfeeding

Dihydropyrimidine dehydrogenase inhibitors, tegafur/uracil

The inhibition of dihydropyrimidine dehydrogenase increases the plasma levels of fluorouracil. Contraindicated. A period of at least 4 weeks should elapse between them.

Pregnancy, tegafur/uracil

Uracil/tegafur may cause severe fetal problems if is administered during pregnancy and is contraindicated during pregnancy

Teicoplanin

Ability to drive, teicoplanin [2] ---> SmPC of [2] of eMC

Teicoplanin can cause dizziness and headache.

Aminoglycoside antibiotics, teicoplanin [2] ---> SmPC of [2] of eMC

Teicoplanin should be used with care in conjunction with or sequentially with other medicinal products with known nephrotoxic or ototoxic potential.

Amphotericin, teicoplanin [2] ---> SmPC of [2] of eMC

Teicoplanin should be used with care in conjunction with or sequentially with other medicinal products with known nephrotoxic or ototoxic potential.

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

A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from therapy

Chlorprothixene, teicoplanin

Chlorprothixene may enhance the respiratory depression caused by the polypeptide antibiotic

Cisplatin, teicoplanin [2] ---> SmPC of [2] of eMC

Teicoplanin should be used with care in conjunction with or sequentially with other medicinal products with known nephrotoxic or ototoxic potential.

Colistin, teicoplanin [2] ---> SmPC of [2] of eMC

Teicoplanin should be used with care in conjunction with or sequentially with other medicinal products with known nephrotoxic or ototoxic potential.

Cyclosporine, teicoplanin [2] ---> SmPC of [2] of eMC

Teicoplanin should be used with care in conjunction with or sequentially with other medicinal products with known nephrotoxic or ototoxic potential.

Ethacrynic acid, teicoplanin [2] ---> SmPC of [2] of eMC

Teicoplanin should be used with care in conjunction with or sequentially with other medicinal products with known nephrotoxic or ototoxic potential.

Furosemide, teicoplanin [2] ---> SmPC of [2] of eMC

Teicoplanin should be used with care in conjunction with or sequentially with other medicinal products with known nephrotoxic or ototoxic potential.

Nephrotoxic substances, teicoplanin [2] ---> SmPC of [2] of eMC

Teicoplanin should be used with care in conjunction with or sequentially with other medicinal products with known nephrotoxic or ototoxic potential.

Ototoxic agents, teicoplanin [2] ---> SmPC of [2] of eMC

Teicoplanin should be used with care in conjunction with or sequentially with other medicinal products with known nephrotoxic or ototoxic potential.

Pregnancy, teicoplanin [2] ---> SmPC of [2] of eMC

Teicoplanin should not be used during pregnancy unless clearly necessary. A potential risk of inner ear and renal damage to the foetus cannot be excluded

CONTRAINDICATIONS of Teicoplanin

Hypersensitivity to teicoplanin or to any of the excipients

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

Telaprevir (Incivo)

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

An effect of telaprevir on UDP-glucuronyltransferases cannot be ruled out and may affect the plasma concentrations of abacavir.

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

Syncope and retinopathy have been reported in some patients taking INCIVO and should be considered when assessing a patient's ability to drive or operate machines.

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

If the strong CYP3A/P-gp inhibitors (e.g., ketoconazole, conivaptan, clarithromycin, indinavir, itraconazole, ritonavir, telaprevir, posaconazole, voriconazole) will be used short-term, treatment with Calquence should be interrupted

Alfentanyl, telaprevir [2] ---> SmPC of [2] of EMA

The co-administration increases the alfentanil plasma levels. Careful monitoring of therapeutic and adverse effects is recommended

Alfuzosin, telaprevir [2] ---> SmPC of [2] of EMA

Concomitant administration of telaprevir is contraindicated 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.

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

The CYP3A4 inhibition may increase the plasma levels of alprazolam.

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

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

Telaprevir, CYP3A4 inhibitor, may increase the plasma levels of amlodipine. Caution and clinical monitoring are recommended

Astemizole, telaprevir [2] ---> SmPC of [2] of EMA

Atazanavir/cobicistat [1], telaprevir ---> SmPC of [1] of EMA

No dose adjustment is required for telaprevir if co-administered with EVOTAZ. Clinical and laboratory monitoring for hyperbilirubinaemia is recommended.

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

Increased/decreased plasma concentrations of atazanavir/telaprevir. Hyperbilirubinaemia is frequent with this combination. Clinical and laboratory monitoring for hyperbilirubinaemia is recommended

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

The inhibition of CYP3A and OATPs by telaprevir may increase atorvastatin concentration. Co-administration of atorvastatin and telaprevir is contraindicated

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

Strong CYP3A4 enzyme inhibitors should be used with caution in patients who are being treated with avacopan.

Bepridil, telaprevir [2] ---> SmPC of [2] of EMA

Bosentan, telaprevir [2] ---> SmPC of [2] of EMA

Concomitant administration of INCIVO and drugs transported by these transporters such as fluvastatin, pravastatin, rosuvastatin, pitavastatin, bosentan and repaglinide should be undertaken with caution (see table 2).

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

The concomitant use of bosutinib with potent 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, telaprevir [2] ---> SmPC of [2] of EMA

Because of the potential for adverse reactions in breastfed infants, due to the combined treatment of INCIVO with peginterferon alfa and ribavirin, breast-feeding must be discontinued prior to initiation of therapy. See also the Summary of Product Charac

Budesonide, telaprevir [2] ---> SmPC of [2] of EMA

Telaprevir, CYP3A4 inhibitor, may increase the plasma levels of budesonide. Co-administration is not recommended

Buprenorphine, telaprevir [2] ---> SmPC of [2] of EMA

No adjustment of the buprenorphine dose is required when co-administered with telaprevir.

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

Patients should be closely monitored for adverse reactions during co-administration of Tabrecta with strong CYP3A inhibitors

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

Co-administration with inducers may lead to lower exposure of telaprevir with risk of lower efficacy. Potent CYP3A inducers, such as carbamazepine, phenytoin and phenobarbital, are contraindicated (see section 4.3).

Cariprazine [1], telaprevir ---> 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

Cisapride, telaprevir [2] ---> SmPC of [2] of EMA

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

The CYP3A4 inhibition increases the plasma levels of both principle actives. QT interval prolongation and Torsade de Pointes have been reported. Caution is recommended

Class IA antiarrhythmic agents, telaprevir [2] ---> SmPC of [2] of EMA

INCIVO must not be administered concurrently with Class Ia or III antiarrhythmics, except for intravenous lidocaine.

Class III antiarrhythmic agents, telaprevir [2] ---> SmPC of [2] of EMA

INCIVO must not be administered concurrently with Class Ia or III antiarrhythmics, except for intravenous lidocaine.

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

No dose adjustment is required when cobicistat is co-administered with telaprevir.

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

Avoid concurrent use of strong CYP3A inhibitors during treatment with cobimetinib. If concomitant use of a strong CYP3A inhibitor is unavoidable, patients should be carefully monitored for safety.

Colchicine, telaprevir [2] ---> SmPC of [2] of EMA

Telaprevir, CYP3A4 inhibitor, may increase the plasma levels of colchicine. Patients with renal or hepatic impairment should not be given colchicine with telaprevir, due to the risk of colchicine toxicity.

Corticosteroids, telaprevir

The CYP3A4 induction/inhibition may decrease/increase the plasma levels of telaprevir/ corticosteroid. The concomitant use is not recommended

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

Increased plasma concentrations of cyclosporine and telaprevir. A careful monitoring is recommended

CYP3A4 inductors, telaprevir [2] ---> SmPC of [2] of EMA

Mild and moderate CYP3A inducers should be avoided, particularly in patients who are prior non-responders (partial or null responders for peginterferon alfa/ribavirin), unless specific dose recommendations are given

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

Increased plasma concentrations of dabigatran (effect on P-gp transport in the gut). Caution is recommended

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

Darunavir/cobicistat, telaprevir ---> 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

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], telaprevir ---> SmPC of [1] 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.

Darunavir/ritonavir, telaprevir [2] ---> SmPC of [2] of EMA

It is not recommended to co-administer darunavir/ritonavir and telaprevir

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.

Digoxin, telaprevir [2] ---> SmPC of [2] of EMA

The lowest dose of digoxin should be initially prescribed. The serum digoxin concentrations should be monitored and used for titration of digoxin dose to obtain the desired clinical

Dihydroergotamine, telaprevir [2] ---> SmPC of [2] of EMA

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.

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

No dosage adjustment necessary. (Inhibition of CYP3A enzymes)

Dolutegravir/abacavir/lamivudine [1], telaprevir ---> SmPC of [1] of EMA

No dosage adjustment necessary. (Inhibition of CYP3A enzymes)

Domperidone, telaprevir [2] ---> SmPC of [2] of EMA

Telaprevir, CYP3A4 inhibitor, may increase the plasma levels of domperidone. The concomitant use should be avoided

Drugs primarily metabolised by CYP3A4, telaprevir [2] ---> SmPC of [2] of EMA

Administration of INCIVO may increase systemic exposure to medicinal products that are substrates of CYP3A or P-gp, which could increase or prolong their therapeutic effect and adverse reactions.

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

If efavirenz and telaprevir are coadministered, telaprevir 1,125 mg every 8 hours should be used.

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

Concomitant administration of ORSERDU with strong CYP3A4 inhibitors should be avoided which may increase the risk of adverse reactions

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

Increased eliglustat exposition would be expected for strong inhibitors of CYP3A. Caution should be used with strong CYP3A inhibitors in intermediate and extensive metabolisers.

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

Co-administration of a single dose of eltrombopag 200 mg with telaprevir 750 mg Q8h did not alter plasma telaprevir exposure. Dose adjustment is not required when eltrombopag is co-administered with telaprevir

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [1], telaprevir ---> SmPC of [1] of EMA

Co-administration with telaprevir has the potential to adversely affect the intracellular activation and clinical antiviral efficacy of tenofovir alafenamide, therefore co-administration of Genvoya and telaprevir is not recommended.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], telaprevir ---> SmPC of [1] of EMA

No dose adjustment is required when Stribild is co-administered with telaprevir.

Emtricitabine/rilpivirine/tenofovir alafenamide [1], telaprevir ---> SmPC of [1] of EMA

Co-administration is not recommended. Boceprevir or telaprevir have the potential to adversely affect the intracellular activation and clinical antiviral efficacy of tenofovir alafenamide based on in vitro data.

Emtricitabine/rilpivirine/tenofovir disoproxil [1], telaprevir ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Emtricitabine/tenofovir alafenamide [1], telaprevir ---> SmPC of [1] of EMA

Co-administration with boceprevir or telaprevir has the potential to adversely affect the intracellular activation and clinical antiviral efficacy of tenofovir alafenamide, therefore co-administration is not recommended.

Enfortumab vedotin [1], telaprevir ---> SmPC of [1] of EMA

Patients receiving concomitant strong CYP3A4 inhibitors should be monitored more closely for signs of toxicities.

Ergonovine, telaprevir [2] ---> SmPC of [2] of EMA

Ergot derivatives, telaprevir [2] ---> SmPC of [2] of EMA

Ergotamine, telaprevir [2] ---> SmPC of [2] of EMA

Erythromycin, telaprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 inhibition increases the plasma levels of both principle actives. QT interval prolongation and Torsade de Pointes have been reported. Caution is recommended

Escitalopram, telaprevir [2] ---> SmPC of [2] of EMA

Based on the results of drug-drug interaction clinical studies (e.g., escitalopram, zolpidem, ethinylestradiol), induction of metabolic enzymes by telaprevir cannot be excluded.

Esomeprazole, telaprevir [2] ---> SmPC of [2] of EMA

Proton pump inhibitors can be used without dose modification.

Estradiol/norethisterone, telaprevir

Telaprevir, although known as strong inhibitor, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

Estrogens, telaprevir

Patients using oestrogens as hormone replacement therapy should be clinically monitored for signs of oestrogen deficiency.

Ethinyl estradiol, telaprevir [2] ---> SmPC of [2] of EMA

Based on the results of drug-drug interaction clinical studies (e.g., escitalopram, zolpidem, ethinylestradiol), induction of metabolic enzymes by telaprevir cannot be excluded.

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

Decreased plasma levels of telaprevir. If co-administered, no dose adjustment is required.

Felodipine, 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.

Fentanyl, telaprevir [2] ---> SmPC of [2] of EMA

The co-administration increases the fentanyl plasma levels. Careful monitoring of therapeutic and adverse effects is recommended

Fertility, telaprevir [2] ---> SmPC of [2] of EMA

INCIVO had no effects on fertility or fecundity when evaluated in rats.

Flecainide, telaprevir [2] ---> SmPC of [2] of EMA

INCIVO should be used with caution with Class Ic antiarrhythmics propafenone and flecainide, including appropriate clinical and ECG monitoring (see section 4.4).

Fluticasone, telaprevir [2] ---> SmPC of [2] of EMA

Telaprevir, CYP3A4 inhibitor, may increase the plasma levels of fluticasone. Co-administration is not recommended

Fluvastatin, telaprevir [2] ---> SmPC of [2] of EMA

Foods, telaprevir [2] ---> SmPC of [2] of EMA

Telaprevir should be taken with food.

Fosamprenavir/ritonavir, telaprevir ---> SmPC of [fosamprenavir] of EMA

Co-administration of fosamprenavir with ritonavir and the HCV protease inhibitor telaprevir may lead to subtherapeutic levels of both, fosamprenavir and telaprevir. Thus, co-administration is not recommended

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

Concomitant use of fostamatinib with strong CYP3A4 inhibitors increases exposure to R406 (the major active metabolite), which may increase the risk of adverse reactions.

Ganciclovir, telaprevir ---> SmPC of [valganciclovir] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

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

Caution should be used when administering concomitantly with strong CYP3A4 inhibitors as an increase in glasdegib plasma concentration may occur.

Guanfacin [1], telaprevir ---> SmPC of [1] 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.

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

The co-administration of idelalisib with telaprevir may increase the serum concentrations of telaprevir. Clinical monitoring is recommended.

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

Substances that inhibit the cytochrome P450 isoenzyme CYP3A4 activity could decrease metabolism and increase imatinib concentrations. Caution should be taken when administering imatinib with inhibitors of the CYP3A4 family.

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

Therefore, co-administration of ONIVYDE pegylated liposomal with other inhibitors of CYP3A4 may increase systemic exposure of ONIVYDE pegylated liposomal.

Itraconazol, telaprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 inhibition increases the plasma levels of itraconazol and telaprevir.

Ketoconazole, telaprevir [2] ---> SmPC of [2] of EMA

Caution is recommended when prescribing telaprevir concurrently with medicinal products known to induce QT prolongation and which are CYP3A substrates

Lidocaine, telaprevir [2] ---> SmPC of [2] of EMA

Caution is warranted and clinical monitoring is recommended when intravenous lidocaine is administered for the treatment of acute ventricular arrhythmia.

Lopinavir/ritonavir, telaprevir [2] ---> SmPC of [2] of EMA

Decreased plasma concentrations of telaprevir. Co-administration is not recommended

Lovastatine, telaprevir [2] ---> SmPC of [2] of EMA

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

Lurasidone and its active metabolite ID-14283 are primarily metabolised by CYP3A4. Lurasidone is contraindicated with strong CYP3A4 inhibitors

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

Telaprevir concentrations are not likely to be affected by maraviroc co-administration

MATE1 substrates, telaprevir [2] ---> SmPC of [2] of EMA

Based on in vitro studies, telaprevir may potentially increase plasma concentrations of medicinal products in which excretion is dependent upon multidrug and toxin extrusion (MATE)-1 and MATE2-K

Metabolized by CYP3A4 and prolong QT, telaprevir [2] ---> SmPC of [2] of EMA

Caution is recommended when prescribing telaprevir concurrently with medicinal products known to induce QT prolongation and which are CYP3A substrates

Metformin, telaprevir [2] ---> SmPC of [2] of EMA

Based on in vitro studies, telaprevir may potentially increase plasma concentrations of medicinal products in which excretion is dependent upon multidrug and toxin extrusion (MATE)-1 and MATE2-K

Methadone, telaprevir [2] ---> SmPC of [2] of EMA

Displacement of methadone from plasma proteins. QT interval prolongation and Torsade de Pointes have been reported

Methylergonovine, telaprevir [2] ---> SmPC of [2] of EMA

Midazolam, telaprevir [2] ---> SmPC of [2] of EMA

Association contraindicated with oral midazolam. Its elevated levels are associated with prolonged or increased sedation or respiratory depression

Moderate CYP3A4 inductors, telaprevir [2] ---> SmPC of [2] of EMA

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

Caution should be exercised when co-administering telaprevir with nevirapine. If co-administered with nevirapine, an adjustment in the telaprevir dose should be considered.

Nicardipine, 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.

Nifedipine, 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.

Nisoldipine, 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.

OATP substrates, telaprevir [2] ---> SmPC of [2] of EMA

Telaprevir inhibits organic anion transporter polypeptides (OATPs) OATP1B1 and OATP1B1. Concomitant administration of telaprevir and drugs transported by these transporters should be undertaken with caution

OATP1B1 substrates, telaprevir [2] ---> SmPC of [2] of EMA

OATP2B1 substrates, telaprevir [2] ---> SmPC of [2] of EMA

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

Known strong or moderate CYP3A inhibitors are not recommended with olaparib

Oral contraceptives, telaprevir [2] ---> SmPC of [2] of EMA

Additional methods of non-hormonal contraception should be used when hormonal contraceptives are co-administered with telaprevir.

P-glycoprotein substrates, telaprevir [2] ---> SmPC of [2] of EMA

Administration of INCIVO may increase systemic exposure to medicinal products that are substrates of CYP3A or P-gp, which could increase or prolong their therapeutic effect and adverse reactions.

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

Strong inhibitors of CYP3A4 may lead to increased toxicity. Concomitant use of strong CYP3A inhibitors during treatment with palbociclib should be avoided.

Phenobarbital, telaprevir [2] ---> SmPC of [2] of EMA

Phenytoin, telaprevir [2] ---> SmPC of [2] of EMA

Pimozide, telaprevir [2] ---> SmPC of [2] of EMA

Pitavastatin, telaprevir [2] ---> SmPC of [2] of EMA

Polatuzumab vedotin [1], telaprevir ---> SmPC of [1] of EMA

Patients receiving concomitant strong CYP3A4 inhibitors should be monitored more closely for signs of toxicities.

Posaconazole, telaprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 inhibition increases the plasma levels of posaconazole and telaprevir. QT interval prolongation and Torsade de Pointes have been reported.

Pravastatine, telaprevir [2] ---> SmPC of [2] of EMA

Pregnancy, telaprevir [2] ---> SmPC of [2] of EMA

It is not recommended during pregnancy and in women of childbearing potential not using contraception.

Propafenone, telaprevir [2] ---> SmPC of [2] of EMA

INCIVO should be used with caution with Class Ic antiarrhythmics propafenone and flecainide, including appropriate clinical and ECG monitoring (see section 4.4).

Proton pump inhibitors, telaprevir [2] ---> SmPC of [2] of EMA

Proton pump inhibitors can be used without dose modification.

QT interval prolonging drugs, telaprevir [2] ---> SmPC of [2] of EMA

Use telaprevir with caution in patients with a requirement for medicinal products known to prolong the QT interval but the metabolism of which is not mainly CYP3A4 dependent (e.g. methadone)

Quetiapine, telaprevir [2] ---> SmPC of [2] of EMA

Quinidine, telaprevir [2] ---> SmPC of [2] of EMA

Raltegravir, telaprevir [2] ---> SmPC of [2] of EMA

Increased plasma levels of raltegravir. If co-administered, no dose adjustment is required.

Repaglinide, telaprevir [2] ---> SmPC of [2] of EMA

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

Concomitant use of strong CYP3A4 inhibitors should be avoided and an alternative concomitant medicinal product with less potential to inhibit CYP3A4 inhibition should be considered.

Rifabutin, telaprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 induction/inhibition may decrease/increase the plasma levels of telaprevir/rifabutin. Telaprevir may be less effective due to decreased concentrations. The concomitant use of rifabutin and telaprevir is not recommended.

Rifampicin, telaprevir [2] ---> SmPC of [2] of EMA

Rifampicin reduces the telaprevir plasma AUC by approximately 92%. Therefore, INCIVO must not be co-administered with rifampicin.

Rilpivirine, telaprevir [2] ---> SmPC of [2] of EMA

Decreased plasma levels of telaprevir. If co-administered, no dose adjustment is required.

Rosuvastatin, telaprevir [2] ---> SmPC of [2] of EMA

Roxithromycin, telaprevir

Caution is warranted for concomitant use of roxitromycin with other QT interval prolonging medicines

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

When administering ruxolitinib with strong CYP3A4 inhibitors the unit dose of ruxolitinib should be reduced by approximately 50%, to be administered twice daily.

Salmeterol, telaprevir [2] ---> SmPC of [2] of EMA

Telaprevir, CYP3A4 inhibitor, may increase the plasma levels of salmeterol. Possible prolongation of the QT interval. Co-administration is not recommended

Sildenafil, telaprevir [2] ---> SmPC of [2] of EMA

Increased plasma levels of sildenafil. Association contraindicated in the treatment of pulmonary arterial hypertension and not recommended in the treatment of erectile dysfunction

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

The HCV protease inhibitor is anticipated to be cross-resistant, and co-administration with simeprevir is not recommended

Simvastatine, telaprevir [2] ---> SmPC of [2] of EMA

Simvastatin is contraindicated due to the predicted marked increase in exposure caused by multiple mechanisms.

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

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

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

No drug-drug interaction data exists regarding the co-administration of Sovaldi with boceprevir or telaprevir.

St. John's wort, telaprevir [2] ---> SmPC of [2] of EMA

Plasma concentrations of telaprevir can be reduced by concomitant use of the herbal preparation St John's wort (Hypericum perforatum). Therefore, herbal preparations containing St John's wort must not be combined with INCIVO.

Strong CYP3A4 inductors, telaprevir [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inhibitors, telaprevir [2] ---> SmPC of [2] of EMA

Co-administration of telaprevir and medicinal products that inhibit CYP3A may increase telaprevir plasma concentrations.

Strong P-gp inductors, telaprevir [2] ---> SmPC of [2] of EMA

Co-administration of telaprevir and medicinal products that induce P-gp may decrease telaprevir plasma concentrations.

Strong P-gp inhibitors, telaprevir [2] ---> SmPC of [2] of EMA

Co-administration of telaprevir and medicinal products that inhibit P-gp may increase telaprevir plasma concentrations.

Tacrolimus, telaprevir [2] ---> SmPC of [2] of EMA

Increased plasma concentrations of tacrolimus and telaprevir. Possible prolongation of the QT interval. A careful monitoring is recommended

Tadalafil, telaprevir [2] ---> SmPC of [2] of EMA

Increased plasma levels of tadalafil. Association contraindicated in the treatment of pulmonary arterial hypertension

Talazoparib [1], telaprevir ---> SmPC of [1] 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).

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

Increased plasma concentrations of tenofovir. Increased clinical and laboratory monitoring are warranted

Telaprevir [1], tenofovir disoproxil ---> SmPC of [1] of EMA

Increased plasma concentrations of tenofovir. Increased clinical and laboratory monitoring are warranted

Telaprevir [1], terfenadine ---> SmPC of [1] of EMA

Telaprevir [1], trazodone ---> SmPC of [1] of EMA

Telaprevir, CYP3A4 inhibitor, may increase the plasma levels of trazodone. Caution is recommended

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

Association contraindicated with oral triazolam. Its elevated levels are associated with prolonged or increased sedation or respiratory depression

Telaprevir [1], troleandomycin ---> SmPC of [1] of EMA

The CYP3A4 inhibition increases the plasma levels of both principle actives. Caution and clinical monitoring are recommended

Telaprevir [1], vardenafil ---> SmPC of [1] of EMA

Increased plasma levels of vardenafil. Association not recommended in the treatment of erectile dysfunction

Telaprevir [1], verapamil ---> SmPC of [1] 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.

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

CYP3A4 inhibition increases the levels of voriconazole (or decreases) and telaprevir. QT interval prolongation and Torsade de Pointes have been reported. Do not co-administer

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

Increased/decreased plasma concentrations of warfarin. It is recommended that the international normalized ratio

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

Due to the combined treatment with peginterferon alfa and ribavirin, female patients of childbearing potential and their male partners as well as male patients and their female partners must use 2 effective contraceptive methods during INCIVO treatment.

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

Female patients of childbearing potential should use 2 effective non-hormonal methods of contraception. Two months after completion of treatment, hormonal contraceptives are again appropriate as one of the two required effective methods of birth control.

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

An effect of telaprevir on UDP-glucuronyltransferases cannot be ruled out and may affect the plasma concentrations of zidovudine.

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

Based on the results of drug-drug interaction clinical studies (e.g., escitalopram, zolpidem, ethinylestradiol), induction of metabolic enzymes by telaprevir cannot be excluded.

Telaprevir, 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

Telaprevir, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

When Tipranavir/ritonavir is co-administered with telaprevir, a decrease or an increase of telaprevir exposure could be expected. Coadministration of telaprevir with tipranavir/ritonavir is not recommended.

Telaprevir, valganciclovir [2] ---> SmPC of [2] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Telaprevir, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole with vorapaxar significantly increased the vorapaxar exposition. Concomitant use of vorapaxar with strong inhibitors of CYP3A should be avoided.

Telaprevir, zanubrutinib [2] ---> SmPC of [2] of EMA

If a strong CYP3A inhibitor must be used (e.g., posaconazole, voriconazole, ketoconazole, itraconazole, clarithromycin, indinavir, lopinavir, ritonavir, telaprevir), reduce the BRUKINSA dose to 80 mg (one capsule) for the duration of the inhibitor use.

CONTRAINDICATIONS of Telaprevir (Incivo)

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

- Concomitant administration 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. These active substances include alfuzosin, amiodarone, bepridil, quinidine, astemizole, terfenadine, cisapride, pimozide, ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine), lovastatin, simvastatin, atorvastatin, sildenafil or tadalafil (only when used for treatment of pulmonary arterial hypertension), quetiapine and orally administered midazolam or triazolam

- Concomitant administration with Class Ia or III antiarrhythmics, except for intravenous lidocaine

- Concomitant administration of INCIVO with active substances that strongly induce CYP3A e.g. rifampicin, St John's wort (Hypericum perforatum), carbamazepine, phenytoin and phenobarbital and thus may lead to lower exposure and loss of efficacy of telaprevir.

- Refer to the Summary of Product Characteristics for peginterferon alfa and ribavirin for a list of their contraindications since INCIVO must be used in combination with peginterferon alfa and ribavirin.

https://www.ema.europa.eu/en/documents/product-information/incivo-epar-product-information_en.pdf 06/10/2016

Telavancin (Vibativ)

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

Dizziness, somnolence, confusion and blurred vision may occur and these may have an influence on the ability to drive and use machines

Aztreonam, telavancin [2] ---> SmPC of [2] of EMA

The pharmacokinetics of telavancin was not significantly altered by simultaneous administration of aztreonam or piperacillin-tazobactam. Also, the pharmacokinetics of aztreonam or piperacillin tazobactam was not altered by telavancin.

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

A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with telavancin should be made taking into account the benefit of breastfeeding to the child and the benefit of telavancin therapy to the woman.

Fertility, telavancin [2] ---> SmPC of [2] of EMA

Telavancin has been shown to affect sperm quantity and quality of male rats (see section 5.3) although no effect on fertility, mating, or early embryogenesis has been reported. The potential risk for humans is unknown.

Haemorrhage, telavancin [2] ---> SmPC of [2] of EMA

No evidence of increased bleeding risk has been observed in clinical trials with telavancin. Telavancin has no effect on platelet aggregation. Furthermore, no evidence of hypercoagulability has been seen

Midazolam, telavancin [2] ---> SmPC of [2] of EMA

It was demonstrated in a clinical study with intravenous midazolam that multiple doses of telavancin had no effect on the pharmacokinetics of midazolam, which is a sensitive substrate for CYP3A4.

Nephrotoxic substances, telavancin [2] ---> SmPC of [2] of EMA

Caution should be used when prescribing VIBATIV to patients receiving concomitant nephrotoxic medicines, those with preexisting renal disease or with co-morbidity known to predispose to kidney dysfunction

Ototoxic agents, telavancin [2] ---> SmPC of [2] of EMA

Patients receiving telavancin in conjunction with or sequentially with other medication with known ototoxic potential should be carefully monitored

P450, telavancin [2] ---> SmPC of [2] of EMA

Since telavancin is primarily excreted unchanged by renal clearance and multiple CYP enzymes are able to metabolise telavancin, no relevant interactions are expected with inhibitors or inducers of the CYP450 system.

Pharmacokinetics, telavancin [2] ---> SmPC of [2] of EMA

Based on their pharmacokinetic properties, no interaction is expected with other beta-lactams, clindamycin, metronidazole, or fluoroquinolones.

Piperacillin/tazobactam, telavancin [2] ---> SmPC of [2] of EMA

Pregnancy, telavancin [2] ---> SmPC of [2] of EMA

The use of VIBATIV is contraindicated during pregnancy.

QT interval prolonging drugs, telavancin [2] ---> SmPC of [2] of EMA

Caution is warranted when using telavancin to treat patients taking medicinal products known to prolong the QT interval.

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

The pregnancy status of women of childbearing potential has to be established prior to dosing with telavancin. Women of childbearing potential have to use effective contraception during treatment.

CONTRAINDICATIONS of Telavancin (Vibativ)

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

- Patients with severe renal impairment, i.e. creatinine clearance (CrCl) <30 ml/min, including patients undergoing haemodialysis

- Acute renal failure

- Pregnancy

https://www.ema.europa.eu/en/documents/product-information/vibativ-epar-product-information_en.pdf 16/05/2018 (Withdrawn)

Telbivudine (Sebivo)

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

Sebivo has minor influence on the ability to drive and use machines.

Aminoglycoside antibiotics, telbivudine [2] ---> SmPC of [2] of EMA

Since telbivudine is eliminated primarily by renal excretion, co-administration with substances that affect renal function may affect plasma concentrations of telbivudine and/or the co-administered substance. The combination should be used with caution.

Amphotericin, telbivudine [2] ---> SmPC of [2] of EMA

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

Telbivudine is excreted in the milk of rats. It is not known whether telbivudine is excreted in human milk. Women should not breastfeed if they are taking Sebivo.

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

Telbivudine is not a substrate, inhibitor or inducer of the cytochrome P450 (CYP450) enzyme system. Therefore, the potential for CYP450-mediated drug interactions involving Sebivo is low.

Fertility, telbivudine [2] ---> SmPC of [2] of EMA

In reproductive toxicology studies in adult animals, fertility was slightly reduced when both male and female rats received telbivudine.

Interferon alfa, telbivudine [2] ---> SmPC of [2] of EMA

The combination of telbivudine with any interferon alfa containing product is contraindicated (see section 4.3).

Lamivudine, telbivudine [2] ---> SmPC of [2] of EMA

Telbivudine is not recommended to be used with lamivudine because in a phase II study, the treatment response observed with combination therapy of telbivudine and lamivudine was lower than with telbivudine alone.

Loop diuretics, telbivudine [2] ---> SmPC of [2] of EMA

Nevirapine [1], telbivudine ---> SmPC of [1] of EMA

Telbivudine and nevirapine can be co-administered without dose adjustments

Peginterferon alfa-2a, telbivudine [2] ---> SmPC of [2] of EMA

The co-administration may increase the risk of peripheral neuropathy. The combination of telbivudine with any interferon alfa-containing product is contraindicated

Peginterferon alfa-2b, telbivudine [2] ---> SmPC of [2] of EMA

This combination is associated with an increased risk of developing peripheral neuropathy. The combination of PegIntron with telbivudine is contraindicated

Pegylated interferon alfa-2a, telbivudine [2] ---> SmPC of [2] of EMA

This combination is associated with an increased risk of developing peripheral neuropathy. The mechanism behind these events is not known (see section 4.4).

Pegylated interferon alfa-2a, telbivudine [2] ---> SmPC of [2] of EMA

No definitive conclusion could be drawn regarding the effects of telbivudine on the pharmacokinetics of pegylated interferon due to high interindividual variability of pegylated interferon alfa-2a concentrations.

Pharmacokinetics, telbivudine [2] ---> SmPC of [2] of EMA

In addition, telbivudine does not alter the pharmacokinetics of lamivudine, adefovir dipivoxil, tenofovir disoproxil fumarate or ciclosporin.

Pharmacokinetics, telbivudine [2] ---> SmPC of [2] of EMA

The steady-state pharmacokinetics of telbivudine were unaltered following multiple dose administration in combination with lamivudine, adefovir dipivoxil, tenofovir disoproxil fumarate, ciclosporin or pegylated interferon alfa-2a.

Platinum compounds, telbivudine [2] ---> SmPC of [2] of EMA

Pregnancy, telbivudine [2] ---> SmPC of [2] of EMA

The exposure to telbivudine in the second and/or third trimester of pregnancy has been shown to reduce the risk of HBV transmission from mother to infant if telbivudine is given in addition to Hepatitis B immune globulin and Hepatitis B vaccine.

Pregnancy, telbivudine [2] ---> SmPC of [2] of EMA

Sebivo should be used during pregnancy only if the benefit to the mother outweighs the potential risk to the foetus

Ropeginterferon alfa-2b [1], telbivudine ---> SmPC of [1] of EMA

Co-administration of pegylated interferon alfa-2a with telbivudine in patients with hepatitis B increased the risk of developing peripheral neuropathy. A combination therapy with telbivudine and ropeginterferon alfa-2b is contraindicated

Substances that affect renal function, telbivudine [2] ---> SmPC of [2] of EMA

Telbivudine [1], vancomycin ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Telbivudine (Sebivo)

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

- Combination of telbivudine with pegylated or standard interferon alfa

https://www.ema.europa.eu/en/documents/product-information/sebivo-epar-product-information_en.pdf 14/01/2021 (Withdrawn)

Telithromycin (Ketek)

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

Ketek may cause adverse reactions such as visual disturbances, confusion or hallucination which may reduce the capacity for the completion of certain tasks.

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

Appropriate monitoring is recommended for patients taking concomitant strong CYP3A inhibitors

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

The moderate inhibition of P-glycoprotein may increase aliskiren gastrointestinal absorption and decrease its biliary excretion. Caution is recommended

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

Aliskiren and ketoconazole co-administration enhances aliskiren gastrointestinal absorption and decreases biliary excretion. Caution should be exercised when aliskiren is administered with ketoconazole, verapamil or other moderate P-gp inhibitors

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

The moderate inhibition of P-glycoprotein may increase aliskiren gastrointestinal absorption and decrease its biliary excretion. Caution is recommended

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

The moderate inhibition of P-glycoprotein may increase aliskiren gastrointestinal absorption and decrease its biliary excretion. Caution is recommended

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

The CYP3A4 inhibition by telithromycin may increase the plasma levels of alprazolam.

Amiodarone, 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

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

The strong CYP3A4 inhibition may increase the plasma concentrations of amlodipine and may result in hypotension, bradycardia or loss of consciousness

Amlodipine/valsartan [1], telithromycin ---> 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.

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

Concomitant administration of aprepitant with active substances that inhibit CYP3A4 activity should be approached cautiously, as the combination is expected to result several-fold in increased plasma concentrations of aprepitant

Astemizole, 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

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

Concomitant administration with simvastatin, atorvastatin, or lovastatin is contraindicated. Treatment with these agents should be interrupted during telithromycin treatment

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

Avanafil is predominantly metabolised by CYP3A4. The strong CYP3A4 inhibitors may increase the exposition of avanafil. Co-administration of avanafil with potent CYP3A4 inhibitors is contraindicated

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

Co-administration of axitinib with strong CYP3A4/5 inhibitors may increase axitinib plasma concentrations. Selection of concomitant medicinal products with no or minimal CYP3A4/5 inhibition potential is recommended.

Azithromycin, telithromycin

The concomitant use with azithromycin may increase the risk of cardiac arrhythmia.

Azole antifungals, telithromycin [2] ---> SmPC of [2] of EMA

Due to a potential to increase the QT interval, telithromycin (contraindicated in patients with severe renal or hepatic insufficiency) should be used with care in patients concomitantly treated with potent CYP 3A4 inhibitors

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

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

Ketek should not be used by breastfeeding women.

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

The concomitant use of strong CYP3A inhibitors with Alunbrig should be avoided

Budesonide, telithromycin ---> SmPC of [budesonide/formoterol] of

Potent inhibitors of CYP3A4 are likely to markedly increase plasma levels of budesonide and concomitant use should be avoided.

Budesonide/formoterol [1], telithromycin ---> SmPC of [1] of EMA

Potent inhibitors of CYP3A4 are likely to markedly increase plasma levels of budesonide and concomitant use should be avoided.

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

Repeated administration of ketoconazole, a strong CYP3A inhibitor, decreased cabazitaxel clearance. Therefore concomitant administration of strong CYP3A inhibitors should be avoided as an increase of plasma concentrations of cabazitaxel may occur

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

Concomitant administration of CYP3A4 inducers is likely to result in subtherapeutic levels of telithromycin and loss of effect. Telithromycin should not be used during and 2 weeks after treatment with CYP3A4 inducers.

Cariprazine [1], telithromycin ---> 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

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

If it is not possible to avoid concomitant use with strong CYP3A inhibitors, reduce the ceritinib dose by approximately one third, rounded to the nearest multiple of the 150 mg dosage strength.

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

Cinacalcet is metabolised in part by the enzyme CYP3A4. Co-administration of a strong inhibitor of CYP3A4 may increase cinacalcet levels. Dose adjustment of cinacalcet may be required

Cisapride, 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

Citalopram, 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

Class IA antiarrhythmic agents, 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

Class III antiarrhythmic agents, 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

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

Avoid concurrent use of strong CYP3A inhibitors during treatment with cobimetinib. If concomitant use of a strong CYP3A inhibitor is unavoidable, patients should be carefully monitored for safety.

Colchicine, telithromycin [2] ---> SmPC of [2] of EMA

Exposure to colchicine, a CYP3A4 and P-glycoprotein substrate, may be expected to increase if telithromycin and colchicine are co-administered. Concomitant administration is contraindicated in patients with renal and/or hepatic impairment

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

Coadministration of crizotinib with strong CYP3A inhibitors may increase crizotinib plasma concentrations. Therefore, the concomitant use of strong CYP3A inhibitors should be avoided.

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

Due to its CYP3A4 inhibitory potential, telithromycin can increase blood concentrations of the CYP3A4 substrate ciclosporin.

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

Dabrafenib [1], telithromycin ---> 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.

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.

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

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

When co-administered with moderate CYP3A4 inhibitors the recommended starting dose of darifenacin should be 7.5 mg daily.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, telithromycin ---> SmPC of [ombitasvir/paritaprevir/ritonavir] o

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

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

In vitro studies indicate that dasatinib is a CYP3A4 substrate. Concomitant use of dasatinib and medicinal products which potently inhibit CYP3A4 may increase exposure to dasatinib. Systemic administration of a potent CYP3A4 inhibitor is not recommended.

Dextromethorphan/quinidine [1], telithromycin ---> SmPC of [1] 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.

Diazepam, telithromycin

The CYP3A4 inhibition may increase the plasma levels of diazepam. Oral coadministration should be avoided

Digoxin, telithromycin [2] ---> SmPC of [2] of EMA

Dihydroergotamine, telithromycin [2] ---> SmPC of [2] of EMA

By extrapolation from erythromycin A and josamycin, concomitant medication of telithromycin and alkaloid derivatives could lead to severe vasoconstriction (ergotism) with possibly necrosis of the extremities. The combination is contraindicated

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

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

In case of combination of docetaxel with CYP3A4 inhibitors, the occurrence of docetaxel adverse reactions may increase, as a result of reduced metabolism

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

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

Drugs metabolised by CYP3A4, telithromycin [2] ---> SmPC of [2] of EMA

It is difficult to predict the degree of hepatic and/or intestinal CYP3A4 inhibition. Telithromycin should not be used with medicinal products that are CYP3A4 substrates

Drugs primarily metabolised by CYP3A4, telithromycin [2] ---> SmPC of [2] of EMA

It is difficult to predict the degree of hepatic and/or intestinal CYP3A4 inhibition. Telithromycin should not be used with medicinal products that are CYP3A4 substrates

Efavirenz, telithromycin

The co-administration may decrease the plasma levels of telithromycin

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

Increased eliglustat exposition would be expected for strong inhibitors of CYP3A. Caution should be used with strong CYP3A inhibitors in intermediate and extensive metabolisers.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [1], telithromycin ---> SmPC of [1] of EMA

Concentrations of telithromycin and/or cobicistat may be altered with co-administration of Genvoya. Clinical monitoring is recommended upon co-administration of Genvoya.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], telithromycin ---> SmPC of [1] of EMA

Concentrations of telithromycin and/or cobicistat may be altered with co-administration

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

Concomitant administration of encorafenib with strong CYP3A4 inhibitors should be avoided (due to increased encorafenib exposure and potential increase in toxicity, see section 5.2).

Eplerenone [1], telithromycin ---> SmPC of [1] of eMC

Strong CYP3A4 inhibitors may increase the AUC of eplerenone. The concomitant use of eplerenone with strong CYP3A4 inhibitors is contra-indicated

Ergot derivatives, erythromycin ---> SmPC of [telithromycin] of

Ergot derivatives, josamycin ---> SmPC of [telithromycin] of

Ergot derivatives, telithromycin [2] ---> SmPC of [2] of EMA

Ergotamine, telithromycin [2] ---> SmPC of [2] of EMA

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

Large increase in everolimus concentration is expected. Concomitant treatment of everolimus and potent CYP3A4 inhibitors is not recommended.

Ezetimibe/atorvastatin [1], telithromycin ---> SmPC of [1] 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.

Ezetimibe/simvastatine [1], telithromycin ---> SmPC of [1] of eMC

Potent inhibitors of cytochrome P450 3A4 with simvastatine increase the risk of myopathy and rhabdomyolysis. The co-administration of simvastatine with potent inhibitors of CYP3A4 is contraindicated

Felodipine, telithromycin [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition by telithromycin may increase the plasma concentrations of felodipine and may result in hypotension, bradycardia or loss of consciousness, and should therefore be avoided.

Felodipine/metoprolol, telithromycin

It has been shown that inhibitors of cytochrome P450-3A4 system increase the plasma concentrations of felodipine. The concomitant use with strong CYP3A4 inhibitors should be avoided

Felodipine/ramipril [1], telithromycin ---> SmPC of [1] of eMC

The strong CYP3A4 inhibition may increase the plasma levels of felodipine. The co-administration of felodipine with strong CYP3A4 inhibitors should be avoided

Fenofibrate/simvastatin [1], telithromycin ---> SmPC of [1] of EMA

Potent inhibitors of cytochrome P450 3A4 increase the risk of myopathy and rhabdomyolysis by increasing the concentration of HMG-CoA reductase inhibitory activity in plasma during simvastatin therapy. Concomitant use is contraindicated

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

The maximum dose of fesoterodine should be restricted to 4 mg when used concomitantly with potent CYP3A4 inhibitors

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

Co-administration of fingolimod with CYP3A4 inhibitors may increase the fingolimod exposure. Caution should be exercised with substances that may inhibit CYP3A4

Fluconazole, 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

Flunitrazepam, telithromycin

Substances that inhibit hepatic enzymes may enhance the effect of benzodiazepines. Interactions with strong CYP3A4 inhibitors cannot be excluded

Flurazepam, telithromycin

The CYP3A4 inhibition may increase the plasma levels of flurazepam. Oral coadministration should be avoided

Fluvastatin, telithromycin [2] ---> SmPC of [2] of EMA

The exposure of pravastatin, rosuvastatin and, to a lesser extent fluvastatin, may be increased due to possible involvement of transporters proteins. Patients should be carefully monitored for signs and symptoms of myopathy and rhabdomyolysis

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

Concomitant administration of fosaprepitant with active substances that inhibit CYP3A4 activity should be approached cautiously as the combination is expected to result in increased plasma concentrations of aprepitant

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

Concomitant administration with potent inhibitors of CYP3A4 activity may increase gefitinib plasma concentrations. The increase may be clinically relevant since adverse reactions are related to dose and exposure.

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

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

Potent CYP 3A4 inhibitors can inhibit the metabolism of hydrocortisone, and thus increase blood levels.

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

Ibrutinib is primarily metabolised by cytochrome P450 enzyme 3A4. Concomitant use of ibrutinib and medicinal products that strongly inhibit CYP3A4 can increase ibrutinib exposure and should be avoided.

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

The co-administration of idelalisib with telithromycin may increase the serum concentrations of telithromycin. Clinical monitoring is recommended for telithromycin.

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

Itraconazol, telithromycin [2] ---> SmPC of [2] of EMA

Itraconazol, CYP3A4 inhibitor, may increase the telithromycin plasma levels. No dosage adjustment necessary (contraindicated with severe renal/or hepatic dysfunction)

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

The concomitant use of ivabradine and potent CYP3A4 inhibitors increases plasma concentrations of ivabradine (may be associated with the risk of excessive bradycardia). The concomitant use of ivabradine with these medicinal products is contraindicated

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

Ivacaftor is a sensitive CYP3A substrate. A reduction of the Kalydeco dose to 150 mg twice a week is recommended for co-administration with strong CYP3A inhibitors

Ixabepilone, telithromycin

The strong CYP3A4 inhibition may increase the plasma concentrations of ixabepilone. The coadministration should be avoided

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

Concomitant therapy of ketoconazole with telithromycin in patients with severe renal impairment is contraindicated due to an increased risk of hepatotoxicity and QT interval prolongation

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

Lapatinib is predominantly metabolised by CYP3A. The strong CYP3A4 inhibition increases the exposition to lapatinib. Co-administration of lapatinib with strong inhibitors of CYP3A4 should be avoided.

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

The strong CYP3A4 inhibition may increase lomitapide AUC. The combination of lomitapide with strong CYP3A4 inhibitors is contra-indicated

Lovastatine, telithromycin [2] ---> SmPC of [2] of EMA

Concomitant administration with simvastatin, atorvastatin, or lovastatin is contraindicated. Treatment with these agents should be interrupted during telithromycin treatment

Lumacaftor/ivacaftor [1], telithromycin ---> SmPC of [1] of EMA

The dose of lumacaftor/ivacaftor should be reduced to one tablet daily for the first week of treatment when initiating lumacaftor/ivacaftor in patients currently taking clarithromycin. Lumacaftor/ivacaftor may decrease the exposures of telithromycin

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

Lurasidone and its active metabolite ID-14283 are primarily metabolised by CYP3A4. Lurasidone is contraindicated with strong CYP3A4 inhibitors

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

Caution should be exercised when macitentan (by CYP3A4 metabolized) is administered concomitantly with strong CYP3A4 inhibitors

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

The strong CYP3A4 inhibition by telithromycin may increase the plasma concentrations of maraviroc. Dose adjustment of maraviroc is recommended

Metabolized by CYP3A4 and prolong QT, 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

Methadone, 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

Metoprolol, telithromycin [2] ---> SmPC of [2] of EMA

When metoprolol (a CYP2D6 substrate) was coadministered with telithromycin, metoprolol Cmax and AUC were increased by approximately 38%, however, there was no effect on the elimination half-life of metoprolol.

Miconazole, telithromycin

Oral miconazole is contraindicated with medicinal products that are metabolised by CYP3A4 and may prolong also the QT interval

Midazolam, telithromycin [2] ---> SmPC of [2] of EMA

The CYP3A4 inhibition by telithromycin may increase the plasma levels of midazolam. Oral administration of midazolam concomitantly with telithromycin should be avoided.

Moxifloxacin, 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

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

Concomitant use of naloxegol with CYP3A4 inhibitors increases naloxegol exposition. Concomitant use of naloxegol with strong CYP3A4 inhibitors is contraindicated

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

Concomitant use of strong CYP3A4/Pgp inhibitors should be avoided.

Nifedipine, telithromycin [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition by telithromycin may increase the plasma concentrations of nifedipine and may result in hypotension, bradycardia or loss of consciousness, and should therefore be avoided.

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

Significant prolongation of the QT interval may occur when nilotinib is inappropriately taken with strong CYP3A4 inhibitors. Prolongation of the QT interval may expose patients to the risk of fatal outcome.

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

Known strong or moderate CYP3A inhibitors are not recommended with olaparib

Ombitasvir/paritaprevir/ritonavir [1], telithromycin ---> SmPC of [1] of EMA

Oral anticoagulants, telithromycin [2] ---> SmPC of [2] of EMA

Increased anticoagulant activity has been reported in patients simultaneously treated with anticoagulants and antibiotics, including telithromycin.

Oral contraceptives, telithromycin [2] ---> SmPC of [2] of EMA

There is no pharmacodynamic or clinically relevant pharmacokinetic interaction with low-dose triphasic oral contraceptives in healthy subjects.

P-glycoprotein substrates, telithromycin [2] ---> SmPC of [2] of EMA

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

Strong inhibitors of CYP3A4 may lead to increased toxicity. Concomitant use of strong CYP3A inhibitors during treatment with palbociclib should be avoided.

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

In patients who take concomitant medicinal products which are strong CYP3A and/or Pgp inhibitors, the dose of panobinostat should be reduced

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

Concomitant treatment with strong inhibitors of CYP3A4 should be avoided due to risk of increased exposure to pazopanib

Pentamidine, 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

Phenobarbital, telithromycin [2] ---> SmPC of [2] of EMA

Phenothiazines, 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

Phenytoin, telithromycin [2] ---> SmPC of [2] of EMA

Pimozide, 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

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

Caution should be exercised and a reduction of the starting dose should be considered with concurrent use of ponatinib with strong CYP3A inhibitors (modest increases in ponatinib systemic exposure are possible)

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

CYP3A inhibitors are not anticipated to have a significant effect on the pharmacokinetics of the prasugrel active metabolite.

Pravastatine, telithromycin [2] ---> SmPC of [2] of EMA

Pregnancy, telithromycin [2] ---> SmPC of [2] of EMA

Ketek should not be used during pregnancy unless clearly necessary.

Procainamide, 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

Protease inhibitors, telithromycin [2] ---> SmPC of [2] of EMA

QT interval prolonging drugs, 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

Quinidine, 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

Quinolones, 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

Ranitidine, telithromycin [2] ---> SmPC of [2] of EMA

Ranitidine (taken 1 hour before Ketek) and antacid containing aluminium and magnesium hydroxide has no clinically relevant influence on telithromycin pharmacokinetics.

Ranolazine, telithromycin [2] ---> SmPC of [2] of EMA

Ranolazine is a substrate of cytochrome CYP3A4. Inhibitors of CYP3A4 increase plasma concentrations of ranolazine. Combining ranolazine with potent CYP3A4 inhibitors is contraindicated

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

It is recommended to avoid concomitant use of strong inhibitors of CYP3A4 activity, as their influence on the steady-state exposure of regorafenib and its metabolites has not been studied.

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

Concomitant use of strong CYP3A4 inhibitors should be avoided and an alternative concomitant medicinal product with less potential to inhibit CYP3A4 inhibition should be considered.

Rifampicin, telithromycin [2] ---> SmPC of [2] of EMA

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

The strong CYP3A4 inhibition may increase the exposition of rimonabant. Caution is advised during concomitant use of rimonabant and potent CYP3A4 inhibitors

Ritonavir, telithromycin [2] ---> SmPC of [2] of EMA

The effect of ritonavir on telithromycin has not been studied and could lead to larger increase in telithromycin exposure. The combination should be used with caution.

Rosuvastatin, telithromycin [2] ---> SmPC of [2] of EMA

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

The strong CYP3A4 inhibition may increase ruxolitinib exposition. When co-administering with strong CYP3A4 inhibitors the unit dose of ruxolitinib should be reduced

Salmeterol [1], telithromycin ---> SmPC of [1] of eMC

The co-administration with strong CYP3A4 inhibitors with salmeterol may significant increase the plasma salmeterol exposure, what may cause a QTc interval prolongation. The co-administration should be avoided

Saquinavir, 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

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

Co-administration of simeprevir with moderate or strong inhibitors of CYP3A4 may significantly increase the plasma exposure of simeprevir. Co-administration of simeprevir with these inhibitors is not recommended.

Simvastatine, telithromycin [2] ---> SmPC of [2] of EMA

Concomitant administration with simvastatin, atorvastatin, or lovastatin is contraindicated. Treatment with these agents should be interrupted during telithromycin treatment

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

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

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

Sonidegib undergoes metabolism primarily by CYP3A4, and concomitant administration of strong inhibitors of CYP3A4 can increase sonidegib concentrations significantly. The sonidegib dose should be reduced to 200 mg every other day

Sotalol, telithromycin [2] ---> SmPC of [2] of EMA

Telithromycin has been shown to decrease the Cmax by 34 % and AUC of sotalol by 20 % due to decreased absorption.

St. John's wort, telithromycin [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inductors, telithromycin [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inhibitors, telithromycin [2] ---> SmPC of [2] of EMA

Tacrolimus, telithromycin [2] ---> SmPC of [2] of EMA

Due to its CYP3A4 inhibitory potential, telithromycin can increase blood concentrations of the CYP3A4 substrate tacrolimus.

Telaprevir, 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

Telithromycin [1], terfenadine ---> SmPC of [1] of EMA

Concomitant administration of telithromycin with medicinal products that prolong the QT interval and are CYP3A4 substrates is contraindicated

Telithromycin [1], theophylline ---> SmPC of [1] of EMA

The co-administration of both medicinal products should be separated by one hour in order to avoid possible digestive side effects such as nausea and vomiting.

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

The CYP3A4 inhibition by telithromycin may increase the plasma levels of triazolam.

Telithromycin [1], tricyclic antidepressant ---> SmPC of [1] 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

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

The strong CYP3A4 inhibition by telithromycin may increase the plasma concentrations of verapamil and may result in hypotension, bradycardia or loss of consciousness, and should therefore be avoided.

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

Although telithromycin has no clinically relevant pharmacokinetic or pharmacodynamic interaction with warfarin after single dose administration, more frequent monitoring of prothrombin time/INR values should be considered during concomitant treatment.

Telithromycin, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

When co-administered with strong CYP3A inhibitors, the dose should be adjusted to one Symkevi tablet twice a week, taken approximately 3 to 4 days apart.

Telithromycin, thiotepa [2] ---> SmPC of [2] of EMA

Thiotepa appears to be metabolised via CYP2B6 and CYP3A4. Co-administration with inhibitors of CYP2B6 or CYP3A4 may increase the plasma concentrations of thiotepa and potentially decrease the concentrations of the active metabolite TEPA.

Telithromycin, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil concentrations may be increased by telithromycin

Telithromycin, trastuzumab emtansine [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inhibitors with trastuzumab emtansine should be avoided due to the potential for an increase in DM1 exposure and toxicity.

Telithromycin, umeclidinium/vilanterol [2] ---> SmPC of [2] of EMA

Concomitant administration of strong CYP3A4 inhibitors may inhibit the metabolism of, and increase the systemic exposure to, vilanterol. Care is advised

Telithromycin, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib should be used with caution in combination with potent inhibitors of CYP3A4, glucuronidation and/or transport proteins

Telithromycin, venlafaxine [2] ---> SmPC of [2] of eMC

Concomitant use of CYP3A4 inhibitors and venlafaxine may increase levels of venlafaxine and O-desmethylvenlafaxine. Therefore, caution is advised if a patient's therapy includes a CYP3A4 inhibitor and venlafaxine concomitantly.

Telithromycin, vilanterol ---> SmPC of [umeclidinium/vilanterol] of

Concomitant administration of strong CYP3A4 inhibitors may inhibit the metabolism of, and increase the systemic exposure to, vilanterol. Care is advised

Telithromycin, vinorelbine [2] ---> SmPC of [2] of eMC

CYP3A4 is the main enzyme involved in the metabolism of vinorelbine, and the combination with a drug that inhibits this iso-enzyme can affect the concentration of vinorelbine

Telithromycin, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole with vorapaxar significantly increased the vorapaxar exposition. Concomitant use of vorapaxar with strong inhibitors of CYP3A should be avoided.

Telithromycin, vortioxetine [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the AUC of vortioxetine. No dosage adjustment necessary. It is caution recommended with CYP2D6 poor metabolisers

Telithromycin, zaleplon

The CYP3A4 inhibition may increase the plasma levels of zaleplon. Oral coadministration should be avoided

Telithromycin, zolpidem

The CYP3A4 inhibition may increase the plasma levels of zolpidem. Oral coadministration should be avoided

Telithromycin, zopiclone [2] ---> SmPC of [2] of eMC

Since zopiclone is metabolised by the cytochrome P450 (CYP) 3A4, plasma levels of zopiclone may be increased when co-administered with CYP3A4 inhibitors

CONTRAINDICATIONS of Telithromycin (Ketek)

- Hypersensitivity to the active substance, to any of the macrolide antibacterial agents, or to any of the excipients

- Myasthenia gravis

- Previous history of hepatitis and/or jaundice associated with the use of telithromycin.

- Co-administration with medicinal products that prolong the QT interval and are CYP3A4 substrates, such as cisapride, pimozide, astemizole, terfenadine, dronedarone, saquinavir

- Concomitant administration with ergot alkaloid derivatives (such as ergotamine and dihydroergotamine)

- Concomitant administration with simvastatin, atorvastatin, and lovastatin. Treatment with these agents should be interrupted during Ketek treatment

- History of congenital or a family history of long QT syndrome (if not excluded by ECG) and in patients with known acquired QT interval prolongation.

In patients with severely impaired renal and/or hepatic function, concomitant administration of Ketek and strong CYP3A4 inhibitors, such as protease inhibitors or azole antifungals (e.g. ketoconazole, fluconazole), is contraindicated.

- Concomitant administration of Ketek and colchicine in patients with renal and/or hepatic impairment

https://www.ema.europa.eu/en/documents/product-information/ketek-epar-product-information_en.pdf 19/06/2019

Telmisartan (Telmisartan Actavis)

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

When driving vehicles or operating machinery it should be taken into account that dizziness or drowsiness may occasionally occur when taking antihypertensive therapy such as Telmisartan Actavis.

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

The dual blockade of the RAA-system through the combined use of ACE-inhibitors, AIIRA or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure)

Acetylsalicylic acid, telmisartan [2] ---> SmPC of [2] of EMA

NSAIDs (i.e. acetylsalicylic acid at anti-inflammatory dosage regimens, COX-2 inhibitors and non-selective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists.

AIIRA, lithium ---> SmPC of [telmisartan] of EMA

Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin converting enzyme inhibitors, and with angiotensin II receptor antagonists, including telmisartan.

AIIRA, NSAID ---> SmPC of [telmisartan] of EMA

The combination of AIIRAs and AIIRAs (selective COX-2 inhibitors, ASA (> 3 g/day) and non-selective NSAIDs) may decrease the antihypertensive effect, increase the renal failure risk and cause hypercaliemia

Alcohol, telmisartan [2] ---> SmPC of [2] of EMA

An orthostatic hypotension may be aggravated by alcohol.

Aliskiren, telmisartan [2] ---> SmPC of [2] of EMA

Amifostine, antihypertensives ---> SmPC of [telmisartan] of EMA

Based on its pharmacological properties it can be expected that amifostine may potentiate the hypotensive effects of all antihypertensives

Amifostine, telmisartan [2] ---> SmPC of [2] of EMA

Based on its pharmacological properties it can be expected that amifostine may potentiate the hypotensive effects of all antihypertensives including telmisartan

Amiloride, telmisartan [2] ---> SmPC of [2] of EMA

Antidepressants, telmisartan [2] ---> SmPC of [2] of EMA

An orthostatic hypotension may be aggravated

Antihypertensives, telmisartan [2] ---> SmPC of [2] of EMA

The blood pressure lowering effect of telmisartan can be increased by concomitant use of other antihypertensive medicinal products.

Baclofen, telmisartan [2] ---> SmPC of [2] of EMA

Based on its pharmacological properties it can be expected that baclofen may potentiate the hypotensive effects of all antihypertensives including telmisartan

Barbiturates, telmisartan [2] ---> SmPC of [2] of EMA

An orthostatic hypotension may be aggravated

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

The lactation is not recommended. Alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.

Bulevirtide [1], telmisartan ---> 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.

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

Reduction of the antihypertensive effect

Corticosteroids, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Corticosteroids (systemic route) decrease the antihypertensive effect.

Coxibs, telmisartan [2] ---> SmPC of [2] of EMA

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

Diclofenac, telmisartan

The co-administration may increase the risk of acute renal failure and hyperkalemia.

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.

Eplerenone, telmisartan [2] ---> SmPC of [2] of EMA

Fertility, telmisartan [2] ---> SmPC of [2] of EMA

In preclinical studies, no effects of telmisartan on male and female fertility were observed.

Furosemide, telmisartan [2] ---> SmPC of [2] of EMA

Prior treatment with high dose diuretics such as furosemide (loop diuretic) and hydrochlorothiazide (thiazide diuretic) may result in volume depletion and in a risk of hypotension when initiating therapy with telmisartan.

Heparin, telmisartan [2] ---> SmPC of [2] of EMA

Hydrochlorothiazide, telmisartan [2] ---> SmPC of [2] of EMA

Hyperkalemia, telmisartan [2] ---> SmPC of [2] of EMA

Lithium, telmisartan [2] ---> SmPC of [2] of EMA

Loop diuretics, telmisartan [2] ---> SmPC of [2] of EMA

Mycophenolate mofetil [1], telmisartan ---> SmPC of [1] of EMA

Concomitant administration of drugs affecting glucuronidation of MPA may change MPA exposure. Caution is therefore recommended when administering these drugs concomitantly with mycophenolate mofetil.

Narcotics, telmisartan [2] ---> SmPC of [2] of EMA

An orthostatic hypotension may be aggravated

NSAID, telmisartan [2] ---> SmPC of [2] of EMA

Potassium, telmisartan [2] ---> SmPC of [2] of EMA

Potassium-sparing diuretics, telmisartan [2] ---> SmPC of [2] of EMA

Pregnancy, telmisartan [2] ---> SmPC of [2] of EMA

The use of AIIRAs is not recommended during the first trimester of pregnancy. The use of AIIRAs is contraindicated during the second and third trimesters of pregnancy

Ramipril, telmisartan [2] ---> SmPC of [2] of EMA

In one study the co-administration of telmisartan and ramipril led to an increase of up to 2.5 fold in the AUC0-24 and Cmax of ramipril and ramiprilat. The clinical relevance of this observation is not known.

Spironolactone, telmisartan [2] ---> SmPC of [2] of EMA

Tacrolimus, telmisartan [2] ---> SmPC of [2] of EMA

Telmisartan [1], thiazides ---> SmPC of [1] of EMA

Telmisartan [1], triamterene ---> SmPC of [1] of EMA

Telmisartan [1], trimethoprim ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Telmisartan (Telmisartan Actavis)

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

- Second and third trimesters of pregnancy

- Biliary obstructive disorders

- Severe hepatic impairment

The concomitant use of Telmisartan Actavis with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m²)

https://www.ema.europa.eu/en/documents/product-information/telmisartan-actavis-epar-product-information_en.pdf 28/01/2025

Other trade names: Dinortes, Kinzalmono (previously Telmisartan Boehringer Ingelheim Pharma KG), Micardis, Pritor, Semintra, Telmisartan Actavis, Telmisartan Teva, Telmisartan Teva Pharma, Telspes, Tolura, Zanacodar,

Telmisartan/amlodipine (Twynsta)

Ability to drive, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Patients should be advised that they may experience adverse reactions such as syncope, somnolence, dizziness, or vertigo during treatment

ACE inhibitors, lithium ---> SmPC of [telmisartan/amlodipine] of EMA

ACE inhibitors, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Acetylsalicylic acid, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

NSAIDs (i.e. acetylsalicylic acid at anti-inflammatory dosage regimens, COX-2 inhibitors and non-selective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists.

AIIRA, diuretics ---> SmPC of [telmisartan/amlodipine] of EMA

Angiotensin II receptor blockers such as telmisartan, attenuate diuretic induced potassium loss.

AIIRA, lithium ---> SmPC of [telmisartan/amlodipine] of EMA

AIIRA, NSAID ---> SmPC of [telmisartan/amlodipine] of EMA

NSAIDs (i.e. acetylsalicylic acid at anti-inflammatory dosage regimens, COX-2 inhibitors and non-selective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists.

AIIRA, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Alcohol, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

An orthostatic hypotension may be aggravated by alcohol.

Aliskiren, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Amifostine, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Medicinal products with blood pressure lowering potential may potentiate the hypotensive effects of all antihypertensives

Amiloride, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Potassium sparing diuretics e.g. spirinolactone, eplerenone, triamterene, or amiloride, potassium supplements, or potassium-containing salt substitutes may lead to a significant increase in serum potassium.

Antidepressants, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Medicinal products with blood pressure lowering potential may potentiate the hypotensive effects of all antihypertensives

Antihypertensives, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

The blood pressure lowering effect of telmisartan/amlodipine can be increased by concomitant use of other antihypertensive medicinal products.

Azole antifungals, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure resulting in an increased risk of hypotension.

Baclofen, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Medicinal products with blood pressure lowering potential may potentiate the hypotensive effects of all antihypertensives

Breast-feeding, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

The use of during breastfeeding is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable

Calcium antagonists, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Due to risk of hyperkalemia, it is recommended that the coadministration of calcium channel blockers such as amlodipine be avoided in patients susceptible to malignant hyperthermia and in the management of malignant hyperthermia.

Clarithromycin, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure resulting in an increased risk of hypotension.

Corticosteroids, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Corticosteroids (systemic route) decrease the antihypertensive effect.

Coxibs, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

NSAIDs (i.e. acetylsalicylic acid at anti-inflammatory dosage regimens, COX-2 inhibitors and non-selective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists.

Cyclosporine, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Consideration should be given for monitoring cyclosporine levels in renal transplant patients on amlodipine, and cyclosporine dose reductions should be made as necessary.

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.

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

Diltiazem, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure resulting in an increased risk of hypotension.

Eplerenone, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Erythromycin, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure resulting in an increased risk of hypotension.

Everolimus, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

mTOR inhibitors such as sirolimus, temsirolimus, and everolimus are CYP3A substrates. Amlodipine is a weak CYP3A inhibitor. With concomitant use of mTOR inhibitors, amlodipine may increase exposure of mTOR inhibitors.

Fertility, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

In preclinical studies, no effects of telmisartan on male and female fertility were observed. In some patients treated by calcium channel blockers, reversible biochemical changes in the head of spermatozoa have been reported.

Grapefruit juice, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Administration of amlodipine with grapefruit or grapefruit juice is not recommended since bioavailability may be increased in certain patients resulting in increased blood pressure lowering effects.

Grapefruit, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Administration of amlodipine with grapefruit or grapefruit juice is not recommended since bioavailability may be increased in certain patients resulting in increased blood pressure lowering effects.

Heparin, telmisartan/amlodipine ---> SmPC of [telmisartan] of EMA

Hyperkalemia, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Itraconazol, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure resulting in an increased risk of hypotension.

Ketoconazole, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure resulting in an increased risk of hypotension.

Lithium, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inhibitors, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure resulting in an increased risk of hypotension.

MTOR inhibitors, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Neuroleptics, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Medicinal products with blood pressure lowering potential may potentiate the hypotensive effects of all antihypertensives

NSAID, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

NSAIDs (i.e. acetylsalicylic acid at anti-inflammatory dosage regimens, COX-2 inhibitors and non-selective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists.

Potassium, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Potassium-sparing diuretics, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Pregnancy, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

It is not recommended during the first trimester of pregnancy. Is contraindicated during the second and third trimesters of pregnancy.

Protease inhibitors, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure resulting in an increased risk of hypotension.

Ramipril, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Rifampicin, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Upon co-administration of known inducers of the CYP3A4, the plasma concentration of amlodipine may vary.

Ritonavir, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure resulting in an increased risk of hypotension.

Simvastatine, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Therefore, the dose of simvastatin in patients on amlodipine should be limited to 20 mg daily.

Sirolimus, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Spironolactone, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

St. John's wort, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Upon co-administration of known inducers of the CYP3A4, the plasma concentration of amlodipine may vary.

Strong CYP3A4 inductors, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Upon co-administration of known inducers of the CYP3A4, the plasma concentration of amlodipine may vary.

Strong CYP3A4 inhibitors, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure resulting in an increased risk of hypotension.

Tacrolimus, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

There is a risk of increased tacrolimus blood levels when co-administered with amlodipine but the pharmacokinetic mechanism of this interaction is not fully understood.

Telmisartan/amlodipine [1], temsirolimus ---> SmPC of [1] of EMA

Telmisartan/amlodipine [1], triamterene ---> SmPC of [1] of EMA

Telmisartan/amlodipine [1], trimethoprim ---> SmPC of [1] of EMA

Telmisartan/amlodipine [1], verapamil ---> SmPC of [1] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure resulting in an increased risk of hypotension.

CONTRAINDICATIONS of Telmisartan/amlodipine (Twynsta)

- Hypersensitivity to the active substances, to dihydropyridine derivatives, or to any of the excipients listed in section 6.1

- Second and third trimesters of pregnancy

- Biliary obstructive disorders and severe hepatic impairment

- Shock (including cardiogenic shock)

- Obstruction of the outflow tract of the left ventricle (e.g. high grade aortic stenosis)

- Haemodynamically unstable heart failure after acute myocardial infarction

The concomitant use of telmisartan/amlodipine with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m²)

https://www.ema.europa.eu/en/documents/product-information/twynsta-epar-product-information_en.pdf 28/04/2025

Telmisartan/hydrochlorothiazide (MicardisPlus)

Ability to drive, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

MicardisPlus can have influence on the ability to drive and use machines. Dizziness, syncope or vertigo may occasionally occur when taking antihypertensive therapy such as telmisartan/HCTZ.

ACE inhibitors, lithium ---> SmPC of [telmisartan/hydrochlorothiazide] of EMA

Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin converting enzyme inhibitors.

ACE inhibitors, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

ACTH, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Medicinal products associated with potassium loss and hypokalaemia: These medicinal products may potentiate the effect of hydrochlorothiazide on serum potassium

Alcohol, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Furthermore, orthostatic hypotension may be aggravated by alcohol, barbiturates, narcotics or antidepressants.

Aliskiren, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Allopurinol, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Dosage adjustment of uricosuric medications may be necessary as hydrochlorothiazide may raise the level of serum uric acid. Increase in dosage of probenecid or sulfinpyrazone may be necessary.

Amantadine, thiazides ---> SmPC of [telmisartan/hydrochlorothiazide] of EMA

Thiazides may increase the risk of adverse effects caused by amantadine.

Amifostine, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Based on their pharmacological properties it can be expected that the following medicinal products may potentiate the hypotensive effects of all antihypertensives including telmisartan: Baclofen, amifostine.

Amiodarone, 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

Amisulpride, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Amphotericin, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Medicinal products associated with potassium loss and hypokalaemia: These medicinal products may potentiate the effect of hydrochlorothiazide on serum potassium

Anticholinergics, thiazides ---> SmPC of [telmisartan/hydrochlorothiazide] of EMA

Anticholinergic agents (e.g. atropine, biperiden) may increase the bioavailability of thiazide-type diuretics by decreasing gastrointestinal motility and stomach emptying rate.

Antihypertensives, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Telmisartan may increase the hypotensive effect of other antihypertensive agents.

Atropine, thiazides ---> SmPC of [telmisartan/hydrochlorothiazide] of EMA

Anticholinergic agents (e.g. atropine, biperiden) may increase the bioavailability of thiazide-type diuretics by decreasing gastrointestinal motility and stomach emptying rate.

Baclofen, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Bepridil, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Betablockers, thiazides ---> SmPC of [telmisartan/hydrochlorothiazide] of EMA

The hyperglycaemic effect of beta-blockers and diazoxide may be enhanced by thiazides.

Biperiden, thiazides ---> SmPC of [telmisartan/hydrochlorothiazide] of EMA

Anticholinergic agents (e.g. atropine, biperiden) may increase the bioavailability of thiazide-type diuretics by decreasing gastrointestinal motility and stomach emptying rate.

Breast-feeding, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

The use of MicardisPlus during breast feeding is not recommended. If MicardisPlus is used during breast feeding, doses should be kept as low as possible.

Calcium salts, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Thiazide diuretics may increase serum calcium levels due to the decreased excretion. If calcium supplements or calcium sparing medicinal products (e.g. vitamin D therapy) must be prescribed

Calcium salts, thiazides ---> SmPC of [telmisartan/hydrochlorothiazide] of EMA

Thiazide diuretics may increase serum calcium levels due to the decreased excretion. If calcium supplements or calcium sparing medicinal products (e.g. vitamin D therapy) must be prescribed

Carbenoxolone, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Medicinal products associated with potassium loss and hypokalaemia: These medicinal products may potentiate the effect of hydrochlorothiazide on serum potassium

Catecholamines, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Hydrochlorothiazide may reduce the response to pressor amines

Chlorpromazine, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Cholestyramine, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins.

Cisapride, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Class IA antiarrhythmic agents, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Class III antiarrhythmic agents, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Colestipol, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins.

Corticosteroids, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Medicinal products associated with potassium loss and hypokalaemia: These medicinal products may potentiate the effect of hydrochlorothiazide on serum potassium

Coxibs, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

NSAIDs may reduce the diuretic, natriuretic and antihypertensive effects of thiazide diuretics and the antihypertensive effects of angiotensin II receptor antagonists.

Cyamemazine, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Cyclophosphamide, thiazides ---> SmPC of [telmisartan/hydrochlorothiazide] of EMA

Thiazides may reduce the renal excretion of cytotoxic medicinal products and potentiate their myelosuppressive effects.

Cyclosporine, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Medicinal products that may increase potassium levels or induce hyperkalaemia: Concomitant use of the these medicinal products may lead to increases in serum potassium and is, therefore, not recommended

Cytotoxic agents, thiazides ---> SmPC of [telmisartan/hydrochlorothiazide] of EMA

Thiazides may reduce the renal excretion of cytotoxic medicinal products and potentiate their myelosuppressive effects.

Diazoxide, thiazides ---> SmPC of [telmisartan/hydrochlorothiazide] of EMA

The hyperglycaemic effect of beta-blockers and diazoxide may be enhanced by thiazides.

Digital glycosides, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Thiazide-induced hypokalaemia or hypomagnesaemia favours the onset of digitalis-induced arrhythmia

Digital glycosides, thiazides ---> SmPC of [telmisartan/hydrochlorothiazide] of EMA

Thiazide-induced hypokalaemia or hypomagnesaemia favours the onset of digitalis-induced arrhythmia

Digoxin, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

When initiating, adjusting, and discontinuing telmisartan, monitor digoxin levels in order to maintain levels within the therapeutic range.

Diphemanil, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Disopyramide, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Dofetilide, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Droperidol, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Erythromycin, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Fertility, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

In preclinical studies, no effects of telmisartan and HCTZ on male and female fertility were observed.

Halofantrine, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Haloperidol, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Hydroquinidine, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Hyperkalemia, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Hypokalemia, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Medicinal products associated with potassium loss and hypokalaemia: These medicinal products may potentiate the effect of hydrochlorothiazide on serum potassium

Ibutilide, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Insulin, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Thiazides may alter glucose tolerance. Dose adjustment of the antidiabetic medicinal product may be necessary

Iodinated contrast media, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

In the event of dehydration caused by diuretics, there is an increased risk of acute functional renal failure, particularly during use of high doses of iodinated contrast products. Rehydration before administration of the iodinated product is required.

Kaliuretic medicines, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Medicinal products associated with potassium loss and hypokalaemia: These medicinal products may potentiate the effect of hydrochlorothiazide on serum potassium

Laxatives, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Medicinal products associated with potassium loss and hypokalaemia: These medicinal products may potentiate the effect of hydrochlorothiazide on serum potassium

Levomepromazine, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Lithium, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

The co-administration may reversibly increase the serum lithium concentration and toxicity. The coadministration is not recommended

Metformin, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Metformin should be used with precaution: risk of lactic acidosis induced by a possible functional renal failure linked to hydrochlorothiazide.

Methotrexate, thiazides ---> SmPC of [telmisartan/hydrochlorothiazide] of EMA

Thiazides may reduce the renal excretion of cytotoxic medicinal products and potentiate their myelosuppressive effects.

Mizolastine, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Muscle relaxants (non-depolarizing), telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

The effect of nondepolarizing skeletal muscle relaxants may be potentiated by hydrochlorothiazide.

Noradrenaline, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

The effect of pressor amines may be decreased.

NSAID, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

NSAIDs may reduce the diuretic, natriuretic and antihypertensive effects of thiazide diuretics and the antihypertensive effects of angiotensin II receptor antagonists.

Oral antidiabetics, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Thiazides may alter glucose tolerance. Dose adjustment of the antidiabetic medicinal product may be necessary

Penicillin G, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Medicinal products associated with potassium loss and hypokalaemia: These medicinal products may potentiate the effect of hydrochlorothiazide on serum potassium

Pentamidine, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Pimozide, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Potassium, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Potassium-sparing diuretics, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Pregnancy, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

The use of angiotensin II receptor antagonists is not recommended during the first trimester of pregnancy (see section 4.4). The use of angiotensin II receptor antagonists is contraindicated during the second and third trimesters of pregnancy

Pressor amines, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

The effect of pressor amines may be decreased.

Probenecide, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Dosage adjustment of uricosuric medications may be necessary as hydrochlorothiazide may raise the level of serum uric acid. Increase in dosage of probenecid or sulfinpyrazone may be necessary.

Quinidine, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Ramipril, telmisartan ---> SmPC of [telmisartan/hydrochlorothiazide] of EMA

Ramipril, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Salicylates, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Medicinal products associated with potassium loss and hypokalaemia: These medicinal products may potentiate the effect of hydrochlorothiazide on serum potassium

Salicylic acid, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Medicinal products associated with potassium loss and hypokalaemia: These medicinal products may potentiate the effect of hydrochlorothiazide on serum potassium

Sodium heparin, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Sotalol, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Sparfloxacin, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Sulfinpyrazone, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Dosage adjustment of uricosuric medications may be necessary as hydrochlorothiazide may raise the level of serum uric acid. Increase in dosage of probenecid or sulfinpyrazone may be necessary.

Sulpiride, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Sultopride, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Telmisartan/hydrochlorothiazide [1], terfenadine ---> SmPC of [1] of EMA

Telmisartan/hydrochlorothiazide [1], thioridazine ---> SmPC of [1] of EMA

Telmisartan/hydrochlorothiazide [1], tiapride ---> SmPC of [1] of EMA

Telmisartan/hydrochlorothiazide [1], torsades de pointes inducing drugs ---> SmPC of [1] of EMA

Telmisartan/hydrochlorothiazide [1], trifluoperazine ---> SmPC of [1] of EMA

Telmisartan/hydrochlorothiazide [1], tubocuranine ---> SmPC of [1] of EMA

The effect of nondepolarizing skeletal muscle relaxants may be potentiated by hydrochlorothiazide.

Telmisartan/hydrochlorothiazide [1], uricosuric agents ---> SmPC of [1] of EMA

Dosage adjustment of uricosuric medications may be necessary as hydrochlorothiazide may raise the level of serum uric acid. Increase in dosage of probenecid or sulfinpyrazone may be necessary.

Telmisartan/hydrochlorothiazide [1], vincamine ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Telmisartan/hydrochlorothiazide (MicardisPlus)

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

- Hypersensitivity to other sulphonamide-derived substances (since hydrochlorothiazide is a sulphonamide-derived medicinal product).

- Second and third trimesters of pregnancy (see sections 4.4 and 4.6).

- Cholestasis and biliary obstructive disorders.

- Severe hepatic impairment.

- Severe renal impairment (creatinine clearance < 30 ml/min), anuria.

- Refractory hypokalaemia, hypercalcaemia.

The concomitant use of MicardisPlus with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m²)

https://www.ema.europa.eu/en/documents/product-information/micardisplus-epar-product-information_en.pdf 03/10/2024

Other trade names: Actelsar HCT, Kinzalkomb, PritorPlus, Tolucombi,

Telotristat ethyl (Xermelo)

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

Fatigue may occur following administration of telotristat, patients with fatigue should be advised to refrain from driving or using machines until symptoms have subsided. (see section 4.8).

Amlodipine, telotristat ethyl [2] ---> SmPC of [2] of EMA

Concomitant use of Xermelo may decrease the efficacy of medicinal products that are CYP3A4 substrates (e.g. midazolam, everolimus, sunitinib, simvastatin, ethinyloestradiol, amlodipine, cyclosporine_) by decreasing their systemic exposure

Breast-feeding, telotristat ethyl [2] ---> SmPC of [2] of EMA

It is unknown whether telotristat ethyl and its metabolite are excreted in human breast milk. A risk to newborns/infants cannot be excluded. Xermelo should not be used during breast-feeding.

Bupropion, telotristat ethyl [2] ---> SmPC of [2] of EMA

Concomitant use of Xermelo may decrease the efficacy of medicinal products that are CYP2B6 substrates (e.g. valproic acid, bupropion, sertraline) by decreasing their systemic exposure.

Capecitabine, telotristat ethyl [2] ---> SmPC of [2] of EMA

Concomitant use of Xermelo may change the exposure of medicinal products that are CES2 substrates (e.g. prasugrel, irinotecan, capecitabine and flutamide) (see section 5.2).

Capivasertib [1], telotristat ethyl ---> SmPC of [1] of EMA

Co-administration of capivasertib with moderate CYP3A4 inducer has the potential to decrease the concentration of capivasertib. This may reduce the efficacy of TRUQAP. Co-administration of moderate CYP3A4 inducers should be avoided

Cyclosporine, telotristat ethyl [2] ---> SmPC of [2] of EMA

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/lamivudine/tenofovir disoproxil [1], telotristat ethyl ---> SmPC of [1] 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

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)

Drugs primarily metabolised by CYP2B6, telotristat ethyl [2] ---> SmPC of [2] of EMA

Concomitant use of Xermelo may decrease the efficacy of medicinal products that are CYP2B6 substrates (e.g. valproic acid, bupropion, sertraline) by decreasing their systemic exposure.

Drugs primarily metabolised by CYP3A4, telotristat ethyl [2] ---> SmPC of [2] of EMA

Ethinyl estradiol, telotristat ethyl [2] ---> SmPC of [2] of EMA

Everolimus, telotristat ethyl [2] ---> SmPC of [2] of EMA

Fertility, telotristat ethyl [2] ---> SmPC of [2] of EMA

No studies on the effect of telotristat on human fertility have been conducted. Telotristat had no effect on fertility in animal studies (see section 5.3).

Flutamide, telotristat ethyl [2] ---> SmPC of [2] of EMA

Concomitant use of Xermelo may change the exposure of medicinal products that are CES2 substrates (e.g. prasugrel, irinotecan, capecitabine and flutamide) (see section 5.2).

Foods, telotristat ethyl [2] ---> SmPC of [2] of EMA

Xermelo should be taken with food (see sections 5.1 and 5.2).

Irinotecan, telotristat ethyl [2] ---> SmPC of [2] of EMA

Concomitant use of Xermelo may change the exposure of medicinal products that are CES2 substrates (e.g. prasugrel, irinotecan, capecitabine and flutamide) (see section 5.2).

Loperamide, telotristat ethyl [2] ---> SmPC of [2] of EMA

The IC50 of the inhibition of loperamide on the metabolism of telotristat ethyl by CES2 was 5.2 然 (see section 5.2). In phase 3 clinical studies, telotristat was routinely combined with loperamide with no evidence of safety concerns.

Midazolam, telotristat ethyl [2] ---> SmPC of [2] of EMA

Octreotide, telotristat ethyl [2] ---> SmPC of [2] of EMA

Concomitant administration of short-acting octreotide with Xermelo significantly decreased the systemic exposure of telotristat ethyl and telotristat, the active metabolite

Prasugrel, telotristat ethyl [2] ---> SmPC of [2] of EMA

Concomitant use of Xermelo may change the exposure of medicinal products that are CES2 substrates (e.g. prasugrel, irinotecan, capecitabine and flutamide) (see section 5.2).

Pregnancy, telotristat ethyl [2] ---> SmPC of [2] of EMA

Xermelo is not recommended during pregnancy and in women of childbearing potential not using contraception.

Sertraline, telotristat ethyl [2] ---> SmPC of [2] of EMA

Concomitant use of Xermelo may decrease the efficacy of medicinal products that are CYP2B6 substrates (e.g. valproic acid, bupropion, sertraline) by decreasing their systemic exposure.

Simvastatine, telotristat ethyl [2] ---> SmPC of [2] of EMA

Sunitinib, telotristat ethyl [2] ---> SmPC of [2] of EMA

Telotristat ethyl [1], valproic acid ---> SmPC of [1] of EMA

Concomitant use of Xermelo may decrease the efficacy of medicinal products that are CYP2B6 substrates (e.g. valproic acid, bupropion, sertraline) by decreasing their systemic exposure.

CONTRAINDICATIONS of Telotristat ethyl (Xermelo)

- 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/xermelo-epar-product-information_en.pdf 08/12/2025

Temoporfin (Foscan)

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

To avoid photosensitivity problems, it is advised not to drive during the first 15 days after injection, and after under subdued lighting conditions

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

A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued for at least one month following injection of Foscan.

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

No other interactions have been observed. An in vitro study with human liver tissue has shown no potential for drug interaction through inhibition of cytochrome P-450 enzymes by temoporfin.

Fertility, temoporfin [2] ---> SmPC of [2] of EMA

The effects of Foscan on fertility in humans have not been studied.

Photosensitizing agents, temoporfin [2] ---> SmPC of [2] of EMA

There is potential for exacerbation of skin photosensitivity if temoporfin is used with other photosensitising active substances. Such a reaction has been reported with topical 5-fluorouracil.

Pregnancy, temoporfin [2] ---> SmPC of [2] of EMA

Foscan should not be used during pregnancy unless the clinical condition of the woman requires treatment with temoporfin.

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

Women of childbearing potential have to use effective contraception during and up 3 months after treatment.

CONTRAINDICATIONS of Temoporfin (Foscan)

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

- Porphyria or other diseases exacerbated by light.

- Hypersensitivity to porphyrins.

- Tumours known to be eroding into a major blood vessel in or adjacent to the illumination site.

- A planned surgical procedure within the next 30 days.

- Co-existing ophthalmic disease likely to require slit-lamp examination within the next 30 days.

- Existing therapy with a photosensitizing agent.

https://www.ema.europa.eu/en/documents/product-information/foscan-epar-product-information_en.pdf . 18/04/2016

Temozolomide (Temodal)

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

TMZ has minor influence on the ability to drive and use machines due to fatigue and somnolence (see section 4.8).

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

It is not known whether TMZ is excreted in human milk; thus, breast-feeding should be discontinued while receiving treatment with TMZ.

Carbamazepine, 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, 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.

Foods, temozolomide [2] ---> SmPC of [2] of EMA

As it cannot be excluded that the change in Cmax is clinically significant, Temodal should be administered without food.

Foods, temozolomide [2] ---> SmPC of [2] of EMA

Administration of TMZ with food resulted in a 33 % decrease in Cmax and a 9 % decrease in area under the curve (AUC).

H2 antagonists, 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.

Medicinal products, temozolomide [2] ---> SmPC of [2] of EMA

However, since TMZ does not undergo hepatic metabolism and exhibits low protein binding, it is unlikely that it would affect the pharmacokinetics of other medicinal products (see section 5.2).

Men, temozolomide [2] ---> SmPC of [2] of EMA

TMZ can have genotoxic effects. Therefore, men being treated with it should use effective contraceptive measures and be advised not to father a child for at least 3 months after receiving the last dose and to seek advice on cryoconservation of sperm prior to treatment, because of the possibility of irreversible infertility due to therapy with TMZ.

Myelosuppressive agents, temozolomide [2] ---> SmPC of [2] of EMA

Use of TMZ in combination with other myelosuppressive agents may increase the likelihood of myelosuppression.

Ondansetron, 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.

Phenobarbital, 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.

Phenytoin, 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.

Pregnancy, temozolomide [2] ---> SmPC of [2] of EMA

Temodal should not be administered to pregnant women. If use during pregnancy must be considered, the patient should be apprised of the potential risk to the foetus.

Prochlorperazine, 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.

Ranitidine, temozolomide [2] ---> SmPC of [2] of EMA

In a separate phase I study, administration of TMZ with ranitidine did not result in alterations in the extent of absorption of temozolomide or the exposure to its active metabolite monomethyl triazenoimidazole carboxamide (MTIC).

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

Co-administration with valproic acid was associated with a small but statistically significant decrease in clearance of TMZ.

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

Women of childbearing potential have to use effective contraception to avoid pregnancy while they are receiving TMZ, and for at least 6 months following completion of treatment.

Temozolomide, tiopronin

Blood count alterations

CONTRAINDICATIONS of Temozolomide (Temodal)

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

- Hypersensitivity to dacarbazine (DTIC).

- Severe myelosuppression

https://www.ema.europa.eu/en/documents/product-information/temodal-epar-product-information_en.pdf 23/02/2024

Other trade names: Temomedac, Temozolomide Accord, Temozolomide Hexal, Temozolomide Sandoz, Temozolomide Sun, Temozolomide Teva,

Temsirolimus (Torisel)

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

The amount of alcohol in this medicinal product may impair your ability to drive or use machines

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

An increased incidence of angioneurotic oedema has been observed in patients who received temsirolimus or other mTOR inhibitors in combination with an ACE inhibitor (e.g. ramipril) and/or a calcium channel blocker (e.g. amlodipine)

Alcohol, temsirolimus [2] ---> SmPC of [2] of EMA

The amount of alcohol in this medicinal product may alter the effects of other medicines. Harmful for those suffering from alcoholism.

Amiodarone, 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.

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

Amphiphilic agents, temsirolimus [2] ---> SmPC of [2] of EMA

It is possible that combined administration of temsirolimus with other amphiphilic agents could result in an increased risk of amphiphilic pulmonary toxicity.

Aprepitant, temsirolimus [2] ---> SmPC of [2] of EMA

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

It is possible that combined administration of temsirolimus with other amphiphilic agents such as amiodarone or statins could result in an increased risk of amphiphilic pulmonary toxicity.

Azole antifungals, temsirolimus [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inhibitors may increase blood concentrations of the active drug substances, temsirolimus and its metabolite, sirolimus. Therefore, concomitant treatment with agents that have strong CYP3A4 inhibition potential should be avoided.

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

Because of the potential for adverse reactions in breast-fed infants from temsirolimus, breast-feeding should be discontinued during therapy.

Calcium antagonists, temsirolimus [2] ---> SmPC of [2] of EMA

Cannabidiol, temsirolimus [2] ---> SmPC of [2] of EMA

Caution should be used when cannabidiol and temsirolimus are co-administered, closely monitoring for side effects and adjusting the temsirolimus dose as needed (see sections 4.2 and 4 4).

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

Agents such as carbamazepine, phenobarbital, phenytoin, rifampicin, and St. John's wort are strong inducers of CYP3A4/5 and may decrease composite exposure of the active drug substances, temsirolimus and its metabolite, sirolimus.

Cilazapril, temsirolimus ---> SmPC of [quinapril] of eMC

Concomitant use of ACE inhibitors with mTOR inhibitor therapy may lead to an increased risk for angioedema

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

Colchicine, 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.

CYP3A4 inhibitors, temsirolimus [2] ---> SmPC of [2] of EMA

The CYP3A4 inhibition may increase blood concentrations of the active moieties, temsirolimus and its metabolite, sirolimus. The co-treatment should be carried out with caution

Dabigatran, 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.

Desipramine, temsirolimus [2] ---> SmPC of [2] of EMA

In 23 healthy subjects the concentration of desipramine, a CYP2D6 substrate, was unaffected when 25 mg of temsirolimus was co-administered.

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.

Diltiazem, temsirolimus [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP2D6, temsirolimus [2] ---> SmPC of [2] of EMA

No clinically significant effect is anticipated when temsirolimus is co-administered with agents that are metabolised by CYP2D6.

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, temsirolimus [2] ---> SmPC of [2] of EMA

Therefore, caution is advised during concomitant administration of temsirolimus at a dose of 175 mg with medicinal products that are metabolised predominantly via CYP3A4/5 and that have a narrow therapeutic index.

Drugs primarily metabolised by CYP3A4, temsirolimus

Caution is advised during concomitant administration of temsirolimus (CYP3A4 inhibitor) with medicinal products metabolised via CYP3A4/5

Efavirenz, temsirolimus

May decrease the plasma levels of temsirolimus

Erythromycin, temsirolimus [2] ---> SmPC of [2] of EMA

Ethanol, temsirolimus [2] ---> SmPC of [2] of EMA

The ethanol content of this product should also be taken into account for pregnant women (see section 4.4).

Exposure to sunlight and ultraviolet light, temsirolimus [2] ---> SmPC of [2] of EMA

As usual for patients with increased risk for skin cancer, exposure to sunlight and ultraviolet (UV) light should be limited by wearing protective clothing and using a sunscreen with a high protection factor.

Fertility, temsirolimus [2] ---> SmPC of [2] of EMA

In male rats, decreased fertility and partly reversible reductions in sperm counts were reported (see section 5.3).

Fluconazole, temsirolimus [2] ---> SmPC of [2] of EMA

Grapefruit juice, temsirolimus [2] ---> SmPC of [2] of EMA

Indinavir, temsirolimus [2] ---> SmPC of [2] of EMA

Interferon alfa, temsirolimus [2] ---> SmPC of [2] of EMA

Cataracts have been observed in some patients who received the combination of temsirolimus and interferon-alpha (IFN-?).

Itraconazol, temsirolimus [2] ---> SmPC of [2] of EMA

Ketoconazole, temsirolimus [2] ---> SmPC of [2] of EMA

Lenalidomide, 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.

Men, temsirolimus [2] ---> SmPC of [2] of EMA

Men with partners of childbearing potential should use medically acceptable contraception while receiving Torisel (see section 5.3).

Moderate CYP3A4 inhibitors, temsirolimus [2] ---> SmPC of [2] of EMA

Nefazodone, temsirolimus [2] ---> SmPC of [2] of EMA

Nelfinavir, temsirolimus [2] ---> SmPC of [2] of EMA

P-glycoprotein substrates, 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.

Paclitaxel, 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.

Phenobarbital, temsirolimus [2] ---> SmPC of [2] of EMA

Phenytoin, temsirolimus [2] ---> SmPC of [2] of EMA

Pregnancy, temsirolimus [2] ---> SmPC of [2] of EMA

Torisel must not be used during pregnancy, unless the risk for the embryo is justified by the expected benefit for the mother.

Propylene glycol, temsirolimus [2] ---> SmPC of [2] of EMA

Administration of ?50 mg/kg/day propylene glycol to pregnant women should only be considered on a case by case basis.

Protease inhibitors, temsirolimus [2] ---> SmPC of [2] of EMA

Quinapril, temsirolimus

The co-administration of ACE inhibitors and mTOR inhibitors may increase the risk of angioedema

Ramipril, temsirolimus [2] ---> SmPC of [2] of EMA

Rifabutin, temsirolimus [2] ---> SmPC of [2] of EMA

Rifampicin, temsirolimus [2] ---> SmPC of [2] of EMA

Ritonavir, temsirolimus [2] ---> SmPC of [2] of EMA

St. John's wort, temsirolimus [2] ---> SmPC of [2] of EMA

Statins, temsirolimus [2] ---> SmPC of [2] of EMA

It is possible that combined administration of temsirolimus with other amphiphilic agents could result in an increased risk of amphiphilic pulmonary toxicity.

Strong CYP3A4 inductors, temsirolimus [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inhibitors, temsirolimus [2] ---> SmPC of [2] of EMA

Sunitinib, temsirolimus [2] ---> SmPC of [2] of EMA

The combination of temsirolimus and sunitinib resulted in dose-limiting toxicity.

Tacrolimus, temsirolimus

Possible decrease of tacrolimus plasma concentrations.

Temsirolimus [1], vaccinations ---> SmPC of [1] of EMA

Immunosuppressants may affect responses to vaccination. During treatment with temsirolimus, vaccination may be less effective.

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

The use of live vaccines should be avoided during treatment with temsirolimus.

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

Temsirolimus [1], vincristine ---> SmPC of [1] 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.

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

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

Due to the unknown risk related to potential exposure during early pregnancy, women of childbearing potential must be advised not to become pregnant while using Torisel.

CONTRAINDICATIONS of Temsirolimus (Torisel)

- Hypersensitivity to temsirolimus, its metabolites (including sirolimus), polysorbate 80, or to any of the excipients of Torisel listed in section 6.1.

- Use of temsirolimus in patients with MCL with moderate or severe hepatic impairment.

https://www.ema.europa.eu/en/documents/product-information/torisel-epar-product-information_en.pdf 09/07/2024

Tenecteplase (Metalyse)

Anticoagulants, tenecteplase [2] ---> SmPC of [2] of EMA

Medicinal products that affect coagulation or those that alter platelet function may increase the risk of bleeding prior to, during or after tenecteplase therapy.

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

Caution should be exercised when Metalyse is administered to a nursing woman and a decision must be made whether breast-feeding should be discontinued within the first 24 hours after administration of Metalyse.

Clopidogrel, tenecteplase [2] ---> SmPC of [2] of EMA

Medicinal products that affect coagulation or those that alter platelet function may increase the risk of bleeding prior to, during or after tenecteplase therapy.

Enoxaparin sodium [1], tenecteplase ---> SmPC of [1] of EMA

It is recommended that some agents which affect haemostasis should be discontinued prior to enoxaparin sodium therapy unless strictly indicated.

Eptifibatide [1], tenecteplase ---> SmPC of [1] of EMA

The combination of reduced dose tenecteplase and eptifibatide compared to placebo and eptifibatide significantly increased the risk of both major and minor bleeding when administered concomitantly in an acute ST-elevation myocardial infarction study.

Fertility, tenecteplase [2] ---> SmPC of [2] of EMA

Clinical data as well as nonclinical studies on fertility are not available for tenecteplase (Metalyse).

GP IIb/IIIa inhibitors, tenecteplase [2] ---> SmPC of [2] of EMA

Concomitant use of tenecteplase and GPIIb/IIIa antagonists increases bleeding risk.

Low molecular weight heparins, tenecteplase [2] ---> SmPC of [2] of EMA

Medicinal products that affect coagulation or those that alter platelet function may increase the risk of bleeding prior to, during or after tenecteplase therapy.

Myocardial infarction, tenecteplase [2] ---> SmPC of [2] of EMA

The benefit of treatment must be evaluated against the potential risks in case of myocardial infarction during pregnancy.

Platelet aggregation inhibitors, tenecteplase [2] ---> SmPC of [2] of EMA

Medicinal products that affect coagulation or those that alter platelet function may increase the risk of bleeding prior to, during or after tenecteplase therapy.

Pregnancy, tenecteplase [2] ---> SmPC of [2] of EMA

Nonclinical data performed with tenecteplase have shown bleeding with secondary mortality of dams due to the known pharmacological activity of the active substance

Tenecteplase [1], ticlopidine ---> SmPC of [1] of EMA

Medicinal products that affect coagulation or those that alter platelet function may increase the risk of bleeding prior to, during or after tenecteplase therapy.

CONTRAINDICATIONS of Tenecteplase

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or to gentamicin (a trace residue from the manufacturing process). If treatment with Metalyse is nevertheless considered to be necessary, facilities for resuscitation should be immediately available in case of need.

Furthermore, Metalyse is contraindicated in the following situations because thrombolytic therapy is associated with a higher risk of bleeding:

- Significant bleeding disorder either at present or within the past 6 months

- Patients receiving effective oral anticoagulant treatment, e.g. warfarin sodium (INR > 1.3) (see section 4.4, subsection "Bleeding")

- Any history of central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery)

- Known haemorrhagic diathesis

- Severe uncontrolled hypertension

- Major surgery, biopsy of a parenchymal organ, or significant trauma within the past 2 months (this includes any trauma associated with the current AMI)

- Recent trauma to the head or cranium

- Prolonged cardiopulmonary resuscitation (> 2 minutes) within the past 2 weeks

- Acute pericarditis and/or subacute bacterial endocarditis

- Acute pancreatitis

- Severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis

- Active peptic ulceration

- Arterial aneurysm and known arterial/venous malformation

- Neoplasm with increased bleeding risk

- Any known history of haemorrhagic stroke or stroke of unknown origin

- Known history of ischaemic stroke or transient ischaemic attack in the preceding 6 months

-Dementia

https://www.ema.europa.eu/en/documents/product-information/metalyse-epar-product-information_en.pdf 02/04/2024

Tenofovir alafenamide (Vemlidy)

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

Patients should be informed that dizziness has been reported during treatment with Vemlidy.

Activity of OATP1B1, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Tenofovir alafenamide is a substrate of OATP1B1 and OATP1B3 in vitro. The distribution of tenofovir alafenamide in the body may be affected by the activity of OATP1B1 and/or OATP1B3.

Activity of OATP1B3, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Tenofovir alafenamide is a substrate of OATP1B1 and OATP1B3 in vitro. The distribution of tenofovir alafenamide in the body may be affected by the activity of OATP1B1 and/or OATP1B3.

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

Co-administration is not recommended.

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

Co-administration is not recommended.

BCRP inhibitors, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Co-administration of Vemlidy with medicinal products that inhibit P-gp and/or BCRP may increase plasma concentration of tenofovir alafenamide. Co-administration of strong inhibitors of P-gp with Vemlidy is not recommended.

Breast-feeding, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

A risk to the breastfed child cannot be excluded; therefore, Vemlidy should not be used during breast-feeding.

Carbamazepine, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Medicinal products that are P-gp inducers are expected to decrease plasma concentrations of tenofovir alafenamide, which may lead to loss of therapeutic effect of Vemlidy. Co-administration is not recommended.

Co-administration, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Vemlidy should not be co-administered with products containing tenofovir alafenamide, tenofovir disoproxil fumarate or adefovir dipivoxil.

Darunavir/cobicistat, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Co-administration is not recommended.

Darunavir/ritonavir, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Co-administration is not recommended.

Dolutegravir, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No dose adjustment of Vemlidy or dolutegravir is required.

Dolutegravir/rilpivirine [1], tenofovir alafenamide ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], tenofovir alafenamide ---> SmPC of [1] of EMA

No dose adjustment is required.

Efavirenz, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No dose adjustment of Vemlidy or efavirenz is required.

Efavirenz/emtricitabine/tenofovir disoproxil [1], tenofovir alafenamide ---> SmPC of [1] of EMA

Atripla should not be administered concomitantly with adefovir dipivoxil or with medicinal products containing tenofovir alafenamide.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], tenofovir alafenamide ---> SmPC of [1] of EMA

Stribild should not be administered concomitantly with other medicinal products containing tenofovir alafenamide.

Ethinylestradiol/norgestimate, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No dose adjustment of Vemlidy or norgestimate/ethinylestradiol is required.

Fertility, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No human data on the effect of tenofovir alafenamide on fertility are available. Animal studies do not indicate harmful effects of tenofovir alafenamide on fertility.

Foods, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Vemlidy film-coated tablets should be taken with food.

Inhibitor, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Tenofovir alafenamide is not an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2D6 in vitro. It is not an inhibitor of CYP3A in vivo. Tenofovir alafenamide is not an inhibitor of human UGT 1A1 in vitro.

Itraconazol, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Co-administration of Vemlidy with strong inhibitors of P-gp (e.g. itraconazole and ketoconazole) may increase tenofovir alafenamide plasma concentrations. Co-administration is not recommended.

Ketoconazole, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Co-administration of Vemlidy with strong inhibitors of P-gp (e.g. itraconazole and ketoconazole) may increase tenofovir alafenamide plasma concentrations. Co-administration is not recommended.

Ledipasvir/sofosbuvir, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No dose adjustment of Vemlidy or ledipasvir/sofosbuvir is required.

Lenacapavir [1], tenofovir alafenamide ---> SmPC of [1] of EMA

No dose adjustment of tenofovir alafenamide is required.

Lopinavir/ritonavir, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Co-administration is not recommended.

Maraviroc, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No dose adjustment of Vemlidy or maraviroc is required.

Maribavir [1], tenofovir alafenamide ---> SmPC of [1] of EMA

No dose adjustment is required.

Midazolam, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No dose adjustment of midazolam (administered orally or IV) is required.

Nevirapine, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No dose adjustment of Vemlidy or nevirapine is required.

OATP1B1 substrates, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Tenofovir alafenamide is a substrate of OATP1B1 and OATP1B3 in vitro. The distribution of tenofovir alafenamide in the body may be affected by the activity of OATP1B1 and/or OATP1B3.

OATP1B3 substrates, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Tenofovir alafenamide is a substrate of OATP1B1 and OATP1B3 in vitro. The distribution of tenofovir alafenamide in the body may be affected by the activity of OATP1B1 and/or OATP1B3.

Oxcarbazepine, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

P-gp inhibitors, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Phenobarbital, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Phenytoin, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Pregnancy, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

The use of Vemlidy may be considered during pregnancy, if necessary.

Raltegravir, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No dose adjustment of Vemlidy or raltegravir is required.

Rifabutin, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Rifampicin, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Rifapentine, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Rilpivirine, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No dose adjustment of Vemlidy or rilpivirine is required.

Sertraline, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No dose adjustment of Vemlidy or sertraline is required.

Sofosbuvir, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No dose adjustment of Vemlidy or sofosbuvir is required.

Sofosbuvir/velpatasvir, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No dose adjustment of Vemlidy or ledipasvir/sofosbuvir is required.

St. John's wort, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Strong P-gp inductors, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Strong P-gp inhibitors, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Tenofovir alafenamide [1], tipranavir/ritonavir ---> SmPC of [1] of EMA

Co-administration is not recommended.

Tenofovir alafenamide, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Viread should not be administered concomitantly with other medicinal products containing tenofovir disoproxil or tenofovir alafenamide.

CONTRAINDICATIONS of Tenofovir alafenamide (Vemlidy)

- 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/vemlidy-epar-product-information_en.pdf 31/05/2023

Tenofovir disoproxil (Viread)

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

No studies on the effects on the ability to drive and use machines have been performed. However, patients should be informed that dizziness has been reported during treatment with tenofovir disoproxil.

Adefovir dipivoxil, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Viread should not be administered concomitantly with adefovir dipivoxil.

Aldesleukin, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Use of tenofovir should be avoided with recent or concurrent use of a nephrotoxic medicinal product

Aminoglycoside antibiotics, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Use of tenofovir should be avoided with concurrent or recent use of a nephrotoxic medicinal product

Amphotericin B, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Use of tenofovir should be avoided with concurrent or recent use of a nephrotoxic medicinal product

Atazanavir, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

No dose adjustment is recommended. The increased exposure of tenofovir could potentiate tenofovir-associated adverse events, including renal disorders. Renal function should be closely monitored renal disorders.

Atazanavir/cobicistat [1], tenofovir disoproxil ---> SmPC of [1] of EMA

Tenofovir may decrease the AUC and Cmin of atazanavir. When coadministered with tenofovir, it is recommended that EVOTAZ and tenofovir 300 mg be given together with food. Atazanavir increases tenofovir concentrations.

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

Breast-feeding, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

In order to avoid transmission of HIV to the infant it is recommended that mothers living with HIV do not breast-feed their infants.

Breast-feeding, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Generally, if the newborn is adequately managed for hepatitis B prevention at birth, a mother with hepatitis B may breast feed her infant.

Cidofovir, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Use of tenofovir should be avoided with concurrent or recent use of a nephrotoxic medicinal product

Cytochrome P450, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Based on the results of in vitro experiments and the known elimination pathway of tenofovir, the potential for CYP450-mediated interactions involving tenofovir with other medicinal products is low.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], tenofovir disoproxil ---> SmPC of [1] 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.

Darunavir/ritonavir, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Didanosine, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Co-administration of tenofovir disoproxil and didanosine is not recommended (see section 4.4 and Table 1).

Dolutegravir/rilpivirine [1], tenofovir disoproxil ---> 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/lamivudine/tenofovir disoproxil [1], tenofovir disoproxil ---> SmPC of [1] of EMA

No dose adjustment is required.

Efavirenz/emtricitabine/tenofovir disoproxil, sofosbuvir ---> SmPC of [tenofovir disoproxil] of EMA

No dose adjustment is required.

Elbasvir/grazoprevir [1], tenofovir disoproxil ---> SmPC of [1] of EMA

No dose adjustment is required.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [1], tenofovir disoproxil ---> SmPC of [1] of EMA

Genvoya should not be administered concomitantly with medicinal products containing tenofovir disoproxil (as fumarate), lamivudine or adefovir dipivoxil used for the treatment of HBV infection.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], tenofovir disoproxil ---> SmPC of [1] of EMA

Stribild should not be administered concomitantly with other medicinal products containing tenofovir disoproxil (as fumarate), lamivudine or adefovir dipivoxil used for the treatment of hepatitis B virus infection

Emtricitabine [1], tenofovir disoproxil ---> SmPC of [1] of EMA

There are no clinically significant interactions when emtricitabine is co-administered with indinavir, zidovudine, stavudine, famciclovir or tenofovir disoproxil fumarate.

Emtricitabine/rilpivirine/tenofovir alafenamide [1], tenofovir disoproxil ---> SmPC of [1] of EMA

Odefsey should not be co-administered with other medicinal products containing tenofovir alafenamide, lamivudine, tenofovir disoproxil (as fumarate) or adefovir dipivoxil

Emtricitabine/tenofovir alafenamide [1], tenofovir disoproxil ---> SmPC of [1] of EMA

Descovy should not be administered concomitantly with medicinal products containing tenofovir disoproxil (as fumarate), lamivudine or adefovir dipivoxil used for the treatment of HBV infection.

Fertility, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

There are limited clinical data with respect to the effect of tenofovir disoproxil on fertility. Animal studies do not indicate harmful effects of tenofovir disoproxil on fertility.

Foods, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Tenofovir must be taken with food, as food enhances the bioavailability of tenofovir

Foscarnet, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Use of tenofovir should be avoided with recent or concurrent use of a nephrotoxic medicinal product

Fostemsavir [1], tenofovir disoproxil ---> SmPC of [1] of EMA

No dose adjustment of either medicinal product is necessary.

Ganciclovir, nephrotoxic substances ---> SmPC of [tenofovir disoproxil] of EMA

Use of ganciclovir should be avoided with recent or concurrent use of a nephrotoxic medicinal product

Ganciclovir, tenofovir ---> SmPC of [tenofovir disoproxil] of EMA

Use of tenofovir should be avoided with recent or concurrent use of a nephrotoxic medicinal product

Ganciclovir, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Use of tenofovir should be avoided with recent or concurrent use of a nephrotoxic medicinal product

Gentamicin, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Use of tenofovir should be avoided with concurrent or recent use of a nephrotoxic medicinal product

Interleukin-2, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Use of tenofovir should be avoided with recent or concurrent use of a nephrotoxic medicinal product

Ledipasvir/sofosbuvir, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Co-administration of tenofovir disoproxil fumarate with ledipasvir/sofosbuvir has been shown to increase plasma concentrations of tenofovir, especially when used together with an HIV regimen containing tenofovir disoproxil fumarate and a pharmacokinetic enhancer (ritonavir or cobicistat)

Lopinavir/ritonavir, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Maribavir [1], tenofovir disoproxil ---> SmPC of [1] of EMA

No dose adjustment is required.

Mitochondrial function, 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.

Nephrotoxic substances, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Use of tenofovir should be avoided with concurrent or recent use of a nephrotoxic medicinal product

NSAID, tenofovir disoproxil

Concomitant administration of tenofovir disoproxil fumarate and NSAIDs may increase the risk of renal failure.

NSAID, tenofovir disoproxil ---> SmPC of [efavirenz/emtricitabine/tenofovir disoproxil] of EMA

Cases of acute renal failure after initiation of high dose or multiple non-steroidal anti-inflammatory drugs (NSAIDs) have been reported in patients treated with tenofovir disoproxil fumarate and with risk factors for renal dysfunction.

Pentamidine, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Use of tenofovir should be avoided with concurrent or recent use of a nephrotoxic medicinal product

Pharmacokinetics, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

There were no clinically significant pharmacokinetic interactions when tenofovir disoproxil fumarate was co-administered with emtricitabine, lamivudine, indinavir, efavirenz, nelfinavir, saquinavir (ritonavir boosted), methadone, ribavirin, rifampicin, tacrolimus, or the hormonal contraceptive norgestimate/ethinyl oestradiol.

Pregnancy, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

The use of tenofovir disoproxil fumarate may be considered during pregnancy, if necessary.

Saquinavir/ritonavir, tenofovir disoproxil ---> SmPC of [saquinavir] of EMA

No dose adjustment required.

Sofosbuvir [1], tenofovir disoproxil ---> SmPC of [1] of EMA

No dose adjustment of sofosbuvir or tenofovir disoproxil is required when sofosbuvir and tenofovir disoproxil are used concomitantly.

Sofosbuvir/velpatasvir [1], tenofovir disoproxil ---> SmPC of [1] of EMA

Epclusa has been shown to increase tenofovir exposure (P-gp-inhibition).

Sofosbuvir/velpatasvir, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

The combination should be used with caution with frequent renal monitoring (see section 4.4).

Stavudine, 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.

Tacrolimus, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Given that tacrolimus can affect renal function, close monitoring is recommended when it is co-administered with tenofovir disoproxil.

Telaprevir [1], tenofovir disoproxil ---> SmPC of [1] of EMA

Increased plasma concentrations of tenofovir. Increased clinical and laboratory monitoring are warranted

Tenofovir alafenamide, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Viread should not be administered concomitantly with other medicinal products containing tenofovir disoproxil or tenofovir alafenamide.

Tenofovir disoproxil [1], tenofovir disoproxil ---> SmPC of [1] of EMA

Viread should not be administered concomitantly with other medicinal products containing tenofovir disoproxil or tenofovir alafenamide.

Tenofovir disoproxil [1], tubular secretion ---> SmPC of [1] of EMA

Since tenofovir is primarily eliminated by the kidneys, co-administration of tenofovir disoproxil with medicinal products that reduce renal function or compete for active tubular secretion via transport proteins hOAT 1, hOAT 3 or MRP 4 (e.g. cidofovir) may increase serum concentrations of tenofovir and/or the co-administered medicinal products.

Tenofovir disoproxil [1], vancomycin ---> SmPC of [1] of EMA

Use of tenofovir should be avoided with recent or concurrent use of a nephrotoxic medicinal product

Tenofovir disoproxil [1], zidovudine ---> SmPC of [1] of EMA

Nucleos(t)ide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine.

Tenofovir, vancomycin ---> SmPC of [tenofovir disoproxil] of EMA

Use of tenofovir should be avoided with recent or concurrent use of a nephrotoxic medicinal product

CONTRAINDICATIONS of Tenofovir disoproxil (Viread)

- 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/viread-epar-product-information_en.pdf 29/02/2024

Other trade names: Tenofovir disoproxil Mylan, Tenofovir disoproxil Viatris (previously Tenofovir disoproxil Mylan), Tenofovir disoproxil Zentiva,

Tenoxicam

Ability to drive, tenoxicam

Rotatory vertigo or vision disorders may occur

ACE inhibitors, tenoxicam

Tenoxicam may decrease the activity of alfa-adrenergic receptor blockers and ACE inhibitors

Alfa-adrenergic receptor blockers, tenoxicam

Tenoxicam may decrease the activity of alfa-adrenergic receptor blockers and ACE inhibitors

Antihypertensives, tenoxicam ---> SmPC of [celecoxib] of

Tenoxicam and other NSAIDs can reduce the effects of anti-hypertensive drugs.

Breast-feeding, tenoxicam

A decision must be made to either discontinue breast-feeding or to discontinue/abstain from therapy

Cardiac glycosides, tenoxicam ---> SmPC of [ibuprofen] of

NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels when co-administered with cardiac glycosides.

Cholestyramine, tenoxicam

Decreased elimination half-life of oxicame. Therefore, the cholestyramine should not be taken within 1 hour if maximal analgesia is required.

Corticosteroids, tenoxicam [2] ---> SmPC of [2] of eMC

As with all NSAIDs, caution should be taken when co-administering tenoxicam and corticosteroids because of the increased risk of GI bleeding.

Coumarin anticoagulants, tenoxicam ---> SmPC of [naproxen/esomeprazole] of

NSAIDs may enhance the effects of oral anti-coagulants (e.g. warfarin, dicoumarol)

Cyclosporine, tenoxicam [2] ---> SmPC of [2] of eMC

As with all NSAIDs caution is advised when cyclosporin is co-administered because of the increased risk of nephrotoxicity.

Diuretics, tenoxicam [2] ---> SmPC of [2] of eMC

Non-steroidal anti-inflammatory drugs may cause sodium, potassium and fluid retention and may interfere with the natriuretic action of diuretic agents, which can increase the risk of nephrotoxicity of NSAIDs.

Hydrochlorothiazide, tenoxicam

Decreased hypotensive effect of hydrochlorothiazide.

Lithium, tenoxicam [2] ---> SmPC of [2] of eMC

Non-steroidal anti-inflammatory drugs have been reported to decrease elimination of lithium.

Methotrexate, tenoxicam [2] ---> SmPC of [2] of eMC

Caution is advised where methotrexate is given concurrently because of possible enhancement of its toxicity, since NSAIDs have been reported to decrease elimination of methotrexate.

NSAID, tenoxicam [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.

Platelet aggregation inhibitors, tenoxicam

The co-administration may increase the risk of bleeding

Potassium-sparing diuretics, tenoxicam [2] ---> SmPC of [2] of eMC

Concomitant administration of NSAIDs and potassium-sparing agents may cause hyperkalemia

Pregnancy, tenoxicam

Strict indication in the first and second trimester. Contraindicated in the third trimester

Salicylates, tenoxicam [2] ---> SmPC of [2] of eMC

Salicylates can displace tenoxicam from protein-binding sites. Co-treatment with salicylates or NSAID should be avoided because of the increased risk of adverse reactions (particularly gastro-intestinal).

SSRI, tenoxicam

The co-administration may increase the risk of gastrointestinal haemorrhage or ulcera

Tenoxicam, ticlopidine

Concomitant use with ticlopidine should be avoided

CONTRAINDICATIONS of Tenoxicam

1. Active peptic ulceration and a past history of peptic ulceration, gastrointestinal bleeding (melaena, haematemesis) or severe gastritis.

2. Hypersensitivity to Mobiflex. Mobiflex should also be avoided in cases where the patient has suffered a hypersensitivity reaction (symptoms of asthma, rhinitis, angioedema or urticaria) to other nonsteroidal anti-inflammatory drugs, including aspirin, as the potential exists for cross-sensitivity to Mobiflex.

3. Severe heart failure

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

Tepotinib (Tepmetko)

Aliskiren, tepotinib [2] ---> SmPC of [2] of EMA

Caution and monitoring for adverse reactions of other P-gp-dependent substances with a narrow therapeutic index (e.g. digoxin, aliskiren, everolimus, sirolimus) is recommended during co-administration with TEPMETKO.

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

Tepotinib can inhibit the transport of substrates of the BCRP in vitro. Monitoring for adverse reactions of sensitive BCRP substrates (e.g. rosuvastatin, methotrexate, topotecan) is recommended during coadministration with TEPMETKO.

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

Breast-feeding should be discontinued during treatment with TEPMETKO and for at least 1 week after the last dose.

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

In healthy participants, co-administration of a single 450 mg tepotinib dose with the strong inducer carbamazepine (300 mg twice daily for 14 days) decreased tepotinib AUCinf by 35% and Cmax by 11% compared to administration of tepotinib alone.

CYP3A4 substrates, tepotinib [2] ---> SmPC of [2] of EMA

Multiple administrations of 450 mg tepotinib orally once daily had no clinically relevant effect on the pharmacokinetics of the sensitive CYP3A4 substrate midazolam.

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.

Digoxin, tepotinib [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP3A4, tepotinib [2] ---> SmPC of [2] of EMA

Multiple administrations of 450 mg tepotinib orally once daily had no clinically relevant effect on the pharmacokinetics of the sensitive CYP3A4 substrate midazolam.

Everolimus, tepotinib [2] ---> SmPC of [2] of EMA

Fertility, tepotinib [2] ---> SmPC of [2] of EMA

Except for reduced secretion in seminal vesicles of male rats at comparable human clinical exposure (see section 5.3).

Foods, tepotinib [2] ---> SmPC of [2] of EMA

The tablet(s) should be taken with food and should be swallowed whole to ensure that the full dose is administered.

Hormonal contraceptives, tepotinib [2] ---> SmPC of [2] of EMA

Women using systemically acting hormonal contraceptives should add a barrier method during TEPMETKO treatment and for at least 1 week after the last dose

Itraconazol, tepotinib [2] ---> SmPC of [2] of EMA

Co-administration of a single 450 mg tepotinib dose with the strong CYP3A inhibitor and P-gp inhibitor itraconazole (200 mg once daily for 11 days) increased tepotinib AUCinf by 22% with no change in tepotinib Cmax compared to administration alone.

MATE1 substrates, tepotinib [2] ---> SmPC of [2] of EMA

Based on in vitro data, tepotinib or its metabolite may have the potential to alter the exposure of substrates of the transporters OCT1 and 2 and MATE1 and 2

MATE2 substrates, tepotinib [2] ---> SmPC of [2] of EMA

Based on in vitro data, tepotinib or its metabolite may have the potential to alter the exposure of substrates of the transporters OCT1 and 2 and MATE1 and 2

Men, tepotinib [2] ---> SmPC of [2] of EMA

Male patients with female partners of childbearing potential should use barrier contraception during TEPMETKO treatment and for at least 1 week after the last dose.

Metformin, tepotinib [2] ---> SmPC of [2] of EMA

The most clinically relevant example of substrates of these transporters is metformin. Monitoring of the clinical effects of metformin is recommended during co-administration with TEPMETKO.

Methotrexate, tepotinib [2] ---> SmPC of [2] of EMA

Midazolam, tepotinib [2] ---> SmPC of [2] of EMA

Multiple administrations of 450 mg tepotinib orally once daily had no clinically relevant effect on the pharmacokinetics of the sensitive CYP3A4 substrate midazolam.

OCT1 substrates, tepotinib [2] ---> SmPC of [2] of EMA

Based on in vitro data, tepotinib or its metabolite may have the potential to alter the exposure of substrates of the transporters OCT1 and 2 and MATE1 and 2

Omeprazole, tepotinib [2] ---> SmPC of [2] of EMA

Co-administration of omeprazole under fed conditions had no clinically relevant effect on the pharmacokinetic profile of a single dose of tepotinib 450 mg and its metabolites

P-glycoprotein and CYP3A4 inhibitors, tepotinib [2] ---> SmPC of [2] of EMA

Also for P-gp inhibitors that are not strong inhibitors of CYP3A (e.g. quinidine, verapamil) an increase in exposure for tepotinib cannot be excluded.

P-glycoprotein substrates with small therapeutic index, tepotinib [2] ---> SmPC of [2] of EMA

Pregnancy, tepotinib [2] ---> SmPC of [2] of EMA

Tepotinib can cause foetal harm when administered to pregnant women. Pregnancy testing is recommended in women of childbearing potential prior to initiating treatment with TEPMETKO.

QT interval prolonging drugs, tepotinib [2] ---> SmPC of [2] of EMA

QTc prolongation was reported in a limited number of patients

Quinidine, tepotinib [2] ---> SmPC of [2] of EMA

Also for P-gp inhibitors that are not strong inhibitors of CYP3A (e.g. quinidine, verapamil) an increase in exposure for tepotinib cannot be excluded.

Rosuvastatin, tepotinib [2] ---> SmPC of [2] of EMA

Sirolimus, tepotinib [2] ---> SmPC of [2] of EMA

Strong CYP inducers, tepotinib [2] ---> SmPC of [2] of EMA

Tepotinib is a substrate for P-glycoprotein (P-gp) (see section 5.2). Strong CYP inducers may also decrease tepotinib exposure.

Strong CYP3A4 and P-glycoprotein-inhibitors, tepotinib [2] ---> SmPC of [2] of EMA

Therefore, CYP3A and P-gp inhibitors are not expected to influence tepotinib exposure.

Strong P-gp inductors, tepotinib [2] ---> SmPC of [2] of EMA

Tepotinib is a substrate for P-glycoprotein (P-gp) (see section 5.2). Strong P-gp inducers may have the potential to decrease tepotinib exposure.

Tepotinib [1], topotecan ---> SmPC of [1] of EMA

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

Also for P-gp inhibitors that are not strong inhibitors of CYP3A (e.g. quinidine, verapamil) an increase in exposure for tepotinib cannot be excluded.

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

Women of childbearing potential should use effective contraception during TEPMETKO treatment and for at least 1 week after the last dose.

CONTRAINDICATIONS of Tepotinib (Tepmetko)

- 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/tepmetko-epar-product-information_en.pdf 21/05/2024

Teprotumumab (Tepezza)

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

TEPEZZA has a minor influence on the ability to drive and use machines. Fatigue and headaches have been reported with the use of teprotumumab (see section 4.8).

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

It is unknown whether teprotumumab is excreted in human milk. Teprotumumab induced developmental toxicity in animals (see section 5.3). Thus, as a precautionary measure, teprotumumab should not be used during breast-feeding.

Fertility, teprotumumab [2] ---> SmPC of [2] of EMA

Among female participants of childbearing potential, menstrual disorders (Amenorrhea, Dysmenorrhoea, Heavy menstrual bleeding, Hypomenorrhoea, Menstruation irregular) have been reported during clinical trials (see section 4.8).

Medicinal products, teprotumumab [2] ---> SmPC of [2] of EMA

Since teprotumumab is cleared from the circulation by proteolytic catabolism, no metabolic interactions with other medicinal products are expected.

Pregnancy, teprotumumab [2] ---> SmPC of [2] of EMA

Teprotumumab may cause congenital malformations such as foetal growth retardation and developmental anomalies when administered during pregnancy (see section 5.3). Therefore, TEPEZZA is contraindicated during pregnancy (see section 4.3).

Risk to the unborn child, teprotumumab [2] ---> SmPC of [2] of EMA

If a patient becomes pregnant while taking TEPEZZA, therapy should be discontinued, and the patient advised of the potential risk to the foetus.

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

Women of childbearing potential should use effective contraception (methods that result in less than 1% pregnancy rates) prior to initiation, during treatment and for 6 months after the last administration of teprotumumab.

CONTRAINDICATIONS of Teprotumumab (Tepezza)

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

- Pregnancy (see section 4.6).

https://www.ema.europa.eu/en/documents/product-information/tepezza-epar-product-information_en.pdf 14/07/2025

Terazosine

Ability to drive, terazosine [2] ---> SmPC of [2] of eMC

Dizziness, light-headedness or drowsiness may occur with the initial dose

Alfa1-adrenergic receptor blockers, terazosine [2] ---> SmPC of [2] of eMC

Combination of terazosin with other alpha-receptor blockers is not recommended.

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

Caution is required when prescribing terazosin with other antihypertensive agents as significant hypotension has been observed.

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

Caution should be exercised when terazosin is administered to a breast-feeding woman.

Carteolol, terazosine

Increased antihypertensive effect, increased risk of orthostatic hypotension

Clonidine, terazosine [2] ---> SmPC of [2] of eMC

Terazosin may reduce the anti-hypertensive effect of intravenously administered clonidine.

Dopamine, terazosine [2] ---> SmPC of [2] of eMC

Terazosin may reduce blood pressure and vasculare reactions to dopamine

Ephedrine, terazosine [2] ---> SmPC of [2] of eMC

Terazosina puede disminuir la presión arterial y las reacciones vasculares a la efedrina

Epinephrine, terazosine [2] ---> SmPC of [2] of eMC

Terazosin may reduce blood pressure and vasculare reactions to epinephrine

Estrogens, terazosine [2] ---> SmPC of [2] of eMC

Estrogens may reduce the antihypertensive effect of terazosin.

Metaraminol, terazosine [2] ---> SmPC of [2] of eMC

Terazosin may reduce blood pressure and vasculare reactions to metaraminol

Methoxamine, terazosine [2] ---> SmPC of [2] of eMC

Terazosin may reduce blood pressure and vasculare reactions to methoxamine

NSAID, terazosine [2] ---> SmPC of [2] of eMC

Non-steroidal antirheumatics may reduce the antihypertensive effect of terazosin.

PDE5 inhibitors, terazosine [2] ---> SmPC of [2] of eMC

Concomitant use of phosphodiesterase-5-inhibitors and terazosin may lead to symptomatic hypotension in some patients

Phenylephrine, terazosine [2] ---> SmPC of [2] of eMC

Terazosin may reduce blood pressure and vasculare reactions to phenylephrine

Pregnancy, terazosine [2] ---> SmPC of [2] of eMC

Terazosin should not be used in pregnancy unless the potential benefit out weighs the risk.

Ramipril [1], terazosine ---> SmPC of [1] of eMC

Potentiation of the risk of hypotension is to be anticipated. Caution is recommended

Sildenafil, terazosine [2] ---> SmPC of [2] of eMC

Concomitant use of phosphodiesterase-5-inhibitors and terazosin may lead to symptomatic hypotension in some patients

Sympathomimetics, terazosine [2] ---> SmPC of [2] of eMC

Sympathomimetics may reduce the antihypertensive effect of terazosin.

Tadalafil, terazosine [2] ---> SmPC of [2] of eMC

Concomitant use of phosphodiesterase-5-inhibitors and terazosin may lead to symptomatic hypotension in some patients

Terazosine, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of terazosin thus increasing risk of toxicity

Terazosine, vardenafil [2] ---> SmPC of [2] of EMA

The concomitant use may lead to symptomatic hypotension in some patients. A time separation of dosing should be considered

Terazosine, verapamil ---> SmPC of [trandolapril/verapamil] of

Verapamil may increase the plasma concentrations of terazosin thus increasing risk of toxicity

Terazosine, xipamide

Increased hypotensive effect. Risk of orthostatic hypotension

CONTRAINDICATIONS of Terazosine

Terazosin is contra-indicated:

- in patients with known hypersensitivity to the active ingredient, terazosin, to other quinazolines (e.g. prazosin, doxazosin, alfuzosin, indoramin or tamsulosin) or to any of the excipients.

- history of micturition syncope

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

Terbinafine

Ability to drive, terbinafine [2] ---> SmPC of [2] of eMC

Patients who experience dizziness as an undesirable effect should avoid driving vehicles or using machines.

Amiodarone, terbinafine [2] ---> SmPC of [2] of eMC

Co-administration of terbinafine with drugs that inhibit CYP2C9 and CYP3A4 may increase the exposure to terbinafine

Atomoxetine, terbinafine

The CYP2D6 inhibition may increase the AUC of atomoxetine ca. 6- to 8-fold. There is the potential for an increased risk of QT interval prolongation

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

Terbinafine is excreted in breast milk and therefore mothers should not receive treatment whilst breastfeeding.

Caffeine, terbinafine [2] ---> SmPC of [2] of eMC

Terbinafine decreased the clearance of caffeine administered intravenously by 21%.

Cimetidine, terbinafine [2] ---> SmPC of [2] of eMC

Cimetidine decreases the clearance of terbinafine and may increase the effect or plasma concentration of terbinafine

Cotrimoxazole, terbinafine [2] ---> SmPC of [2] of eMC

There was no clinically relevant interaction between terbinafine and the potential comedications cotrimoxazole (trimethoprim and sulfamethoxazole)

Cyclosporine, terbinafine [2] ---> SmPC of [2] of eMC

Terbinafine increased the clearance of ciclosporin by 15%.

CYP3A4 and CYP2C9 inhibitors, terbinafine [2] ---> SmPC of [2] of eMC

Co-administration of terbinafine with drugs that inhibit CYP2C9 and CYP3A4 may increase the exposure to terbinafine

Darifenacin [1], terbinafine ---> SmPC of [1] of EMA

Concomitant treatment with potent CYP2D6 inhibitors results in an increase in darifenacin exposure

Desipramine, terbinafine [2] ---> SmPC of [2] of eMC

Terbinafine decreased the clearance of desipramine by 82%.

Digoxin, terbinafine [2] ---> SmPC of [2] of eMC

Terbinafine does not interfere with the clearance of digoxin.

Drugs primarily metabolised by CYP2D6 with narrow therapeutic index, terbinafine [2] ---> SmPC of [2] of eMC

In vitro and in vivo studies have shown that terbinafine inhibits the CYP2D6-mediated metabolism. This finding may be of clinical relevance for patients receiving compounds predominantly metabolised by CYP2D6 and also have a narrow therapeutic window

Drugs primarily metabolised by CYP2D6, terbinafine [2] ---> SmPC of [2] of eMC

Terbinafine, strong CYP2D6 inhibitor, may increase the plasma concentrations of the medicinal products primarily metabolised by CYP2D6. Patients should be closely monitored

Eliglustat [1], terbinafine ---> SmPC of [1] 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

Enzyme inductors, terbinafine [2] ---> SmPC of [2] of eMC

The enzymatic induction may decrease the plasma levels and the effect of terbinafine.

Enzyme inhibitors, terbinafine [2] ---> SmPC of [2] of eMC

The enzymatic inhibitor may increase the plasma levels of terbinafine

Felodipine/metoprolol, terbinafine

CYP2D6 inhibitors may increase the plasma levels of metoprolol

Flecainide [1], terbinafine ---> SmPC of [1] of eMC

Terbinafine may increase plasma concentrations of flecainide resulting from its inhibition of CYP2D6 activity.

Fluconazole, terbinafine [2] ---> SmPC of [2] of eMC

Co-administration of terbinafine with drugs that inhibit CYP2C9 and CYP3A4 may increase the exposure to terbinafine

Fluvoxamine, terbinafine

Terbinafine may increase the plasma levels of fluvoxamine.

Imipramine, terbinafine

Concomitant use of imipramine and terbinafine, strong CYP2D6 inhibitor, may increase the exposition and accumulation of imipramine and terbinafine. Dose adjustment may be required

Ketoconazole, terbinafine [2] ---> SmPC of [2] of eMC

Co-administration of terbinafine with drugs that inhibit CYP2C9 and CYP3A4 may increase the exposure to terbinafine

Mequitazine, terbinafine

Mequitazine should not be used with CYP2D6 inhibitor drugs. The increased plasma levels of mequitazine may increase the risk of QT interval prolongation

Metoprolol [1], terbinafine ---> SmPC of [1] of eMC

Enzyme inhibitors may increase plasma concentrations of hepatically metabolised beta-blockers.

Nebivolol [1], terbinafine ---> SmPC of [1] of eMC

The CYP2D6 inhibition may lead to increased plasma levels of nebivolol (metabolized by CYP2D6) that is associated with an increased risk of excessive bradycardia and adverse events.

Oral contraceptives, terbinafine [2] ---> SmPC of [2] of eMC

Some cases of menstrual disturbance (breakthrough bleeding and irregular cycle) have been reported in patients taking terbinafine concomitantly with oral contraceptives

Pitolisant [1], terbinafine ---> SmPC of [1] 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.

Pregnancy, terbinafine [2] ---> SmPC of [2] of eMC

Terbinafine should not be used during pregnancy unless clinical condition of the woman requires treatment with oral terbinafine and the potential benefits for the mother outweigh any potential risks for the foetus.

Rifampicin, terbinafine [2] ---> SmPC of [2] of eMC

Rifampicin increases the clearance of terbinafine and may decrease the effect or plasma concentration of terbinafine

Terbinafine [1], warfarin ---> SmPC of [1] of eMC

Rare cases of changes in INR and/or prothrombin time have been reported in patients receiving terbinafine concomitantly with warfarin.

Terbinafine [1], zidovudine ---> SmPC of [1] of eMC

There was no clinically relevant interaction between terbinafine and the potential comedications zidovudine

Terbinafine, 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.

Terbinafine, theophylline [2] ---> SmPC of [2] of eMC

There was no clinically relevant interaction between terbinafine and the potential comedications theophylline

Terbinafine, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

CONTRAINDICATIONS of Terbinafine

- Known hypersensitivity to Lamisil or to any of the excipients

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

Terbutaline

Ability to drive, terbutaline

The ability to drive and use machines may be reduced

Alcohol, terbutaline

Alcohol may enhance the cardiac and circulatory regulator sympathomimetics effects of terbutaline

Antiarrhythmics, terbutaline

The co-administration may cause cardiac rhythm disorders

Anticholinergics, terbutaline

The co-administration may enhance the antiobstruktive effect of terbutaline

Antidiabetics, terbutaline [2] ---> SmPC of [2] of eMC

Due to the hyperglycaemic effects of beta2-agonists, additional blood glucose controls are recommended initially in diabetic patients.

Beta-adrenergic agonists, terbutaline

The co-administration of terbutaline and other beta- sympathomimetic agents may enhance the antiobstruktive effect of terbutaline. Adverse reactions may also increase, e. g. heart rhythm disorders

Betablockers, terbutaline [2] ---> SmPC of [2] of eMC

Beta-blocking agents (including eye drops), especially the non-selective ones such as propranolol, may partially or totally inhibit the effect of beta-stimulants.

Bleomycin, terbutaline

Incompatibility

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

Terbutaline is secreted into breast milk, but any effect on the infant is unlikely at therapeutic doses.

Corticosteroids, terbutaline [2] ---> SmPC of [2] of eMC

Hypokalaemia may result from beta2-agonist therapy and may be potentiated by concomitant treatment with corticosteroids

Digital glycosides, terbutaline

The co-administration may cause cardiac rhythm disorders

Diuretics, terbutaline [2] ---> SmPC of [2] of eMC

Hypokalaemia may result from beta2-agonist therapy and may be potentiated by concomitant treatment with diuretics

Gliclazide [1], terbutaline ---> SmPC of [1] of eMC

The administration of gliclazide and i.v. terbutaline increases the blood glucose levels due to beta-2 agonist effects

Halogenated anaesthetics, terbutaline

The co-administration may increase the risk of arrythmias

Hypokalemia, terbutaline [2] ---> SmPC of [2] of eMC

Potentially serious hypokalaemia may result from beta2-agonist therapy. The hypokalaemic effect may be potentiated by concomitant treatments. It is recommended that serum potassium levels are monitored in such situations.

IMAOs, terbutaline

The co-administration may enhance the effect of terbutaline on the cardiovascular system

Insulin glargin [1], terbutaline ---> SmPC of [1] of EMA

Reduced blood-glucose-lowering effect

Insulin glargine/lixisenatide [1], terbutaline ---> SmPC of [1] of EMA

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

Insulin glulisin [1], terbutaline ---> SmPC of [1] of EMA

Possible decrease in blood-glucose-lowering activity

Insulin lispro [1], terbutaline ---> SmPC of [1] of EMA

Insulin requirements may be increased by medicinal products with hyperglycaemic activity

Levodopa, terbutaline

Levodopa may enhance the cardiac and circulatory regulator sympathomimetics effects of terbutaline

Levothyroxine, terbutaline

L-thyroxine may enhance the cardiac and circulatory regulator sympathomimetics effects of terbutaline

Non-selective betablockers, terbutaline [2] ---> SmPC of [2] of eMC

Beta-blocking agents (including eye drops), especially the non-selective ones such as propranolol, may partially or totally inhibit the effect of beta-stimulants.

Oxytocin, terbutaline

Oxytocin may enhance the cardiac and circulatory regulator sympathomimetics effects of terbutaline

Pregnancy, terbutaline [2] ---> SmPC of [2] of eMC

Terbutaline should only be administered with caution during the first trimester of pregnancy.

Propranolol, terbutaline [2] ---> SmPC of [2] of eMC

Beta-blocking agents (including eye drops), especially the non-selective ones such as propranolol, may partially or totally inhibit the effect of beta-stimulants.

Quinidine, terbutaline

The co-administration may cause cardiac rhythm disorders

Suxamethonium [1], terbutaline ---> SmPC of [1] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Sympathomimetics, terbutaline [2] ---> SmPC of [2] of eMC

Terbutaline should be used with caution in patients receiving other sympathomimetics.

Tadalafil [1], terbutaline ---> SmPC of [1] of EMA

Tadalafil has been demonstrated to produce an increase in the oral bioavailability of ethinylestradiol; a similar increase may be expected with oral administration of terbutaline

Terbutaline [1], xanthines ---> SmPC of [1] of eMC

Hypokalaemia may result from beta2-agonist therapy and may be potentiated by concomitant treatment with xanthine derivatives

Terbutaline, tricyclic antidepressant

The co-administration may enhance the effect of terbutaline on the cardiovascular system

CONTRAINDICATIONS of Terbutaline

history of hypersensitivity to any of the ingredients.

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

Teriflunomide (Aubagio)

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

In the case of adverse reactions such as dizziness, which has been reported with leflunomide, the parent compound, the patient's ability to concentrate and to react properly may be impaired.

Activated charcoal, teriflunomide [2] ---> SmPC of [2] of EMA

It is recommended that patients receiving teriflunomide are not treated with cholestyramine or activated charcoal because this leads to a rapid and significant decrease in plasma concentration unless an accelerated elimination is desired.

Alcohol, teriflunomide [2] ---> SmPC of [2] of EMA

The medicinal product should be used with caution in patients who consume substantial quantities of alcohol.

Alosetron, 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.

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

For other substrates of BCRP and the OATP family especially HMG-Co reductase inhibitors concomitant administration of teriflunomide should also be undertaken with caution.

BCRP substrates, 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

Benzylpenicillin, teriflunomide [2] ---> SmPC of [2] of EMA

When teriflunomide (OAT3 inhibitor) is coadministered with substrates of OAT3 caution is recommended.

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

Animal studies have shown excretion of teriflunomide in milk. Teriflunomide is contraindicated during breast-feeding (see section 4.3).

Caffeine, 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.

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

Rifampicin und andere bekannte starke CYP und Transporter-Induktoren, wie etwa Carbamazepin, Phenobarbital, Phenytoin und Johanniskraut, sollten während der Behandlung mit Teriflunomid mit Vorsicht angewendet werden.

Cefaclor, teriflunomide [2] ---> SmPC of [2] of EMA

When teriflunomide (OAT3 inhibitor) is coadministered with substrates of OAT3 caution is recommended.

Cholestyramine, teriflunomide [2] ---> SmPC of [2] of EMA

Cimetidine, teriflunomide [2] ---> SmPC of [2] of EMA

When teriflunomide (OAT3 inhibitor) is coadministered with substrates of OAT3 caution is recommended.

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

When teriflunomide (OAT3 inhibitor) is coadministered with substrates of OAT3 caution is recommended.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, teriflunomide ---> SmPC of [dasabuvir] of EMA

Teriflunomide may increase dasabuvir exposures and should be used with caution.

Dasabuvir [1], teriflunomide ---> SmPC of [1] 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

Daunorubicin, 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, 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

Drugs primarily metabolised by CYP1A2, 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.

Drugs primarily metabolised by CYP2C8, teriflunomide [2] ---> SmPC of [2] of EMA

Teriflunomide, CYP2C8 inhibitor, increases teriflunomide AUC. Medicinal products metabolised by CYP2C8 should be used with caution during treatment with teriflunomide.

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.

Enzyme inductors, teriflunomide [2] ---> SmPC of [2] of EMA

Ethinyl estradiol, teriflunomide [2] ---> SmPC of [2] of EMA

There was an increase in mean ethinylestradiol Cmax and AUC0-24 (1.58- and 1.54-fold, respectively) and levonorgestrel Cmax and AUC0-24 (1.33- and 1.41-fold, respectively) following repeated doses of teriflunomide.

Fertility, teriflunomide [2] ---> SmPC of [2] of EMA

Results of studies in animals have not shown an effect on fertility (see section 5.3). Although human data are lacking, no effect on male and female fertility is anticipated.

Fingolimod [1], teriflunomide ---> SmPC of [1] of EMA

Caution should also be exercised when switching patients from long-acting therapies with immune effects such as natalizumab, teriflunomide or mitoxantrone (see section 4.4).

Furosemide, teriflunomide [2] ---> SmPC of [2] of EMA

When teriflunomide (OAT3 inhibitor) is coadministered with substrates of OAT3 caution is recommended.

Indometacin, teriflunomide [2] ---> SmPC of [2] of EMA

When teriflunomide (OAT3 inhibitor) is coadministered with substrates of OAT3 caution is recommended.

Ketoprofen, teriflunomide [2] ---> SmPC of [2] of EMA

When teriflunomide (OAT3 inhibitor) is coadministered with substrates of OAT3 caution is recommended.

Leflunomide, teriflunomide [2] ---> SmPC of [2] of EMA

As leflunomide is the parent compound of teriflunomide, co-administration of teriflunomide with leflunomide is not recommended.

Levonorgestrel, teriflunomide [2] ---> SmPC of [2] of EMA

Men, teriflunomide [2] ---> SmPC of [2] of EMA

The risk of male-mediated embryo-foetal toxicity through teriflunomide treatment is considered low (see section 5.3).

Menstruation, teriflunomide [2] ---> SmPC of [2] of EMA

Female children and/or parents/caregivers of female children should be informed about the need to contact the treating physician once the female child under AUBAGIO treatment experiences menses.

Methotrexate, teriflunomide [2] ---> SmPC of [2] of EMA

When teriflunomide (OAT3 inhibitor) is coadministered with substrates of OAT3 caution is recommended.

Nateglinide, teriflunomide [2] ---> SmPC of [2] of EMA

For other substrates of BCRP and the OATP family especially HMG-Co reductase inhibitors concomitant administration of teriflunomide should also be undertaken with caution.

OAT3 substrates, teriflunomide [2] ---> SmPC of [2] of EMA

When teriflunomide (OAT3 inhibitor) is coadministered with substrates of OAT3 caution is recommended.

OATP substrates, teriflunomide [2] ---> SmPC of [2] of EMA

For other substrates of BCRP and the OATP family especially HMG-Co reductase inhibitors concomitant administration of teriflunomide should also be undertaken with caution.

Oral contraceptives, teriflunomide [2] ---> SmPC of [2] of EMA

While the interaction of teriflunomide is not expected to adversely impact the efficacy of oral contraceptives, consideration should be given to the type or dose of oral contraceptives used in combination with teriflunomide.

Paclitaxel, teriflunomide [2] ---> SmPC of [2] of EMA

Teriflunomide, CYP2C8 inhibitor, increases teriflunomide AUC. Medicinal products metabolised by CYP2C8 should be used with caution during treatment with teriflunomide.

Penicillin G, teriflunomide [2] ---> SmPC of [2] of EMA

When teriflunomide (OAT3 inhibitor) is coadministered with substrates of OAT3 caution is recommended.

Phenobarbital, teriflunomide [2] ---> SmPC of [2] of EMA

Phenytoin, teriflunomide [2] ---> SmPC of [2] of EMA

Pioglitazone, teriflunomide [2] ---> SmPC of [2] of EMA

Teriflunomide, CYP2C8 inhibitor, increases teriflunomide AUC. Medicinal products metabolised by CYP2C8 should be used with caution during treatment with teriflunomide.

Pravastatine, teriflunomide [2] ---> SmPC of [2] of EMA

For other substrates of BCRP and the OATP family especially HMG-Co reductase inhibitors concomitant administration of teriflunomide should also be undertaken with caution.

Pregnancy, teriflunomide [2] ---> SmPC of [2] of EMA

Studies in animals have shown reproductive toxicity (see section 5.3). Teriflunomide may cause serious birth defects when administered during pregnancy. Teriflunomide is contraindicated in pregnancy (see section 4.3).

Repaglinide, teriflunomide [2] ---> SmPC of [2] of EMA

For other substrates of BCRP and the OATP family especially HMG-Co reductase inhibitors concomitant administration of teriflunomide should also be undertaken with caution.

Repaglinide, teriflunomide [2] ---> SmPC of [2] of EMA

Teriflunomide, CYP2C8 inhibitor, increases teriflunomide AUC. Medicinal products metabolised by CYP2C8 should be used with caution during treatment with teriflunomide.

Rifampicin, teriflunomide [2] ---> SmPC of [2] of EMA

For other substrates of BCRP and the OATP family especially HMG-Co reductase inhibitors concomitant administration of teriflunomide should also be undertaken with caution.

Rifampicin, teriflunomide [2] ---> SmPC of [2] of EMA

Rosiglitazone, teriflunomide [2] ---> SmPC of [2] of EMA

Teriflunomide, CYP2C8 inhibitor, increases teriflunomide AUC. Medicinal products metabolised by CYP2C8 should be used with caution during treatment with teriflunomide.

Rosuvastatin, teriflunomide [2] ---> SmPC of [2] of EMA

There was an increase in mean rosuvastatin Cmax and AUC (2.65-and 2.51-fold, respectively), following repeated doses of teriflunomide. For rosuvastatin, a dose reduction by 50% is recommended for coadministration with teriflunomide.

Selexipag [1], teriflunomide ---> SmPC of [1] of EMA

The total daily dose of Uptravi should be decreased by reducing each dose to half when co-administered with moderate CYP2C8 inhibitors (e.g., clopidogrel, deferasirox, teriflunomide).

Simvastatine, teriflunomide [2] ---> SmPC of [2] of EMA

For other substrates of BCRP and the OATP family especially HMG-Co reductase inhibitors concomitant administration of teriflunomide should also be undertaken with caution.

St. John's wort, teriflunomide [2] ---> SmPC of [2] of EMA

Sulfasalazine, 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

Teriflunomide [1], theophylline ---> SmPC of [1] 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.

Teriflunomide [1], tizanidine ---> SmPC of [1] 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.

Teriflunomide [1], topotecan ---> SmPC of [1] of EMA

Teriflunomide, BCRP inhibitor, may increase the AUC of BCRP substrate. The co-administration should be undertaken with caution

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

The use of live attenuated vaccines may carry a risk of infections and should therefore be avoided.

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

When warfarin is co-administered with teriflunomide, close INR follow-up and monitoring is recommended.

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

Women of childbearing potential have to use effective contraception during treatment and after treatment as long as teriflunomide plasma concentration is above 0.02 mg/l.

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

Counselling should be provided to the new patients of child-bearing potential about contraception and the potential risk to the foetus. Referral to a gynaecologist should be considered.

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

When teriflunomide (OAT3 inhibitor) is coadministered with substrates of OAT3 caution is recommended.

Teriflunomide, vadadustat [2] ---> SmPC of [2] of EMA

If co-administration with strong or moderate OAT1 or OAT3 inhibitors (e.g. benzylpenicillin, teriflunomide or p-aminohippuric acid) occurs, patients should be managed cautiously and evaluated for excessive effects of vadadustat.

CONTRAINDICATIONS of Teriflunomide (Aubagio)

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

- Patients with severe hepatic impairment (Child-Pugh class C).

- Pregnant women, or women of childbearing potential who are not using reliable contraception during treatment with teriflunomide and thereafter as long as its plasma levels are above 0.02 mg/l. Pregnancy must be excluded before start of treatment

- Breast-feeding women

- Patients with severe immunodeficiency states, e.g. AIDS.

- Patients with significantly impaired bone marrow function or significant anaemia, leucopenia, neutropenia or thrombocytopenia.

- Patients with severe active infection until resolution

- Patients with severe renal impairment undergoing dialysis, because insufficient clinical experience is available in this patient group.

- Patients with severe hypoproteinaemia, e.g. in nephrotic syndrome.

https://www.ema.europa.eu/en/documents/product-information/aubagio-epar-product-information_en.pdf 09/12/2025

Other trade names: Teriflunomide Accord,Teriflunomide Mylan, Teriflunomide Viatris (previously Teriflunomide Mylan),

Teriparatide (Forsteo)

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

Transient, orthostatic hypotension or dizziness was observed in some patients. These patients should refrain from driving or the use of machines until symptoms have subsided.

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

FORSTEO is contraindicated for use during breast-feeding. It is not known whether teriparatide is excreted in human milk.

Digital glycosides, 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, teriparatide [2] ---> SmPC of [2] of EMA

Fertility, teriparatide [2] ---> SmPC of [2] of EMA

Studies in rabbits have shown reproductive toxicity (see section 5.3). The effect of teriparatide on human foetal development has not been studied. The potential risk for humans is unknown.

Hormone replacement therapy, teriparatide [2] ---> SmPC of [2] of EMA

Co-administration of raloxifene or hormone replacement therapy with FORSTEO did not alter the effects of FORSTEO on serum or urine calcium or on clinical adverse events.

Hydrochlorothiazide, teriparatide [2] ---> SmPC of [2] of EMA

FORSTEO has been evaluated in pharmacodynamic interaction studies with hydrochlorothiazide. No clinically significant interactions were noted.

Pregnancy, teriparatide [2] ---> SmPC of [2] of EMA

FORSTEO is contraindicated for use during pregnancy

Raloxifene, teriparatide [2] ---> SmPC of [2] of EMA

Co-administration of raloxifene or hormone replacement therapy with FORSTEO did not alter the effects of FORSTEO on serum or urine calcium or on clinical adverse events.

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

Women of childbearing potential should use effective methods of contraception during use of FORSTEO. If pregnancy occurs, FORSTEO should be discontinued.

CONTRAINDICATIONS of Teriparatide (Forsteo)

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

- Pregnancy and breast-feeding

- Pre-existing hypercalcaemia

- Severe renal impairment

- Metabolic bone diseases (including hyperparathyroidism and Paget's disease of the bone) other than primary osteoporosis or glucorticoid-induced osteoporosis.

- Unexplained elevations of alkaline phosphatase

- Prior external beam or implant radiation therapy to the skeleton

- Patients with skeletal malignancies or bone metastases should be excluded from treatment with teriparatide.

https://www.ema.europa.eu/en/documents/product-information/forsteo-epar-product-information_en.pdf 20/01/2022

Other trade names: Livogiva, Movymia, Qutavina, Terrosa,

Terlipressin

Antihypertensives, terlipressin

The co-administration weakens the hypotensive effect

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

Terlipressin should not be used in breast feeding women.

Class IA antiarrhythmic agents, terlipressin

Terlipressin can cause ventricular arrhythmias (incl. torsades de pointes). The combination with drugs that prolong the QT interval should be done with extreme caution

Class III antiarrhythmic agents, terlipressin

Terlipressin can cause ventricular arrhythmias (incl. torsades de pointes). The combination with drugs that prolong the QT interval should be done with extreme caution

Drugs inducing bradycardia, terlipressin [2] ---> SmPC of [2] of eMC

Concomitant treatment of terlipressin with medicinal products with a known bradycardic effect may lower the heart rate and cardiac output.

Erythromycin, terlipressin

Terlipressin can cause ventricular arrhythmias (incl. torsades de pointes). The combination with drugs that prolong the QT interval should be done with extreme caution

Hypokalemia, terlipressin

Terlipressin can cause ventricular arrhythmias. The combination with drugs that can origin electrolyte disorders should be done with extreme caution

Hypomagnesemia, terlipressin

Terlipressin can cause ventricular arrhythmias. The combination with drugs that can origin electrolyte disorders should be done with extreme caution

Non-potassium-sparing diuretics, terlipressin

Terlipressin can cause ventricular arrhythmias. The combination with drugs that can origin electrolyte disorders should be done with extreme caution

Non-selective betablockers, terlipressin [2] ---> SmPC of [2] of eMC

The hypotensive effect of non-selective beta-blockers on the portal vein is increased with terlipressin.

Pregnancy, terlipressin [2] ---> SmPC of [2] of eMC

Treatment with terlipressin during pregnancy is contraindicated

Propofol, terlipressin [2] ---> SmPC of [2] of eMC

Concomitant treatment of terlipressin with medicinal products with a known bradycardic effect may lower the heart rate and cardiac output.

QT interval prolonging drugs, terlipressin

Terlipressin can cause ventricular arrhythmias (incl. torsades de pointes). The combination with drugs that prolong the QT interval should be done with extreme caution

Sufentanil, terlipressin [2] ---> SmPC of [2] of eMC

Concomitant treatment of terlipressin with medicinal products with a known bradycardic effect may lower the heart rate and cardiac output.

Terlipressin, tricyclic antidepressant

Terlipressin can cause ventricular arrhythmias (incl. torsades de pointes). The combination with drugs that prolong the QT interval should be done with extreme caution

Terlipressin, vasoconstrictors

The co-administration has a synergistic effect on the blood pressure

CONTRAINDICATIONS of Terlipressin

- Contraindicated in pregnancy.

- Hypersensitivity to terlipressin acetate or any of the excipients

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

Testosterone undecanoate

ACTH, testosterone undecanoate [2] ---> SmPC of [2] of eMC

The concurrent administration of testosterone with ACTH may enhance oedema formation

Barbiturates, testosterone undecanoate [2] ---> SmPC of [2] of eMC

Concurrent administration of liver enzyme inducing may decrease the effect of testosterone undecanoate.

Breast-feeding, testosterone undecanoate [2] ---> SmPC of [2] of eMC

It should not be used during lactation.

Carbamazepine, testosterone undecanoate [2] ---> SmPC of [2] of eMC

Concurrent administration of liver enzyme inducing may decrease the effect of testosterone undecanoate.

Corticosteroids, testosterone ---> SmPC of [testosterone undecanoate] of

The concurrent administration of testosterone or corticosteroids may enhance oedema formation

Corticosteroids, testosterone undecanoate [2] ---> SmPC of [2] of eMC

The concurrent administration of testosterone or corticosteroids may enhance oedema formation

Enzyme inductors, testosterone undecanoate [2] ---> SmPC of [2] of eMC

Concurrent administration of liver enzyme inducing may decrease the effect of testosterone undecanoate.

Foods, testosterone undecanoate [2] ---> SmPC of [2] of eMC

Testosterone undecanoate be taken with a normal meal to ensure absorption.

Insulin, testosterone undecanoate ---> SmPC of [testosterone] of

In diabetic patients the metabolic effects of testosterone may decrease blood glucose and therefore insulin requirements.

Oral anticoagulants, testosterone undecanoate [2] ---> SmPC of [2] of eMC

High doses of androgens may enhance the anticoagulant action of coumarine type agents and additional monitoring of INR and adjustment of anticoagulant dose may need to be considered.

Oral antidiabetics, testosterone undecanoate ---> SmPC of [testosterone] of

In diabetic patients the metabolic effects of testosterone may decrease blood glucose and therefore insulin requirements.

Phenylbutazone, testosterone undecanoate [2] ---> SmPC of [2] of eMC

Concurrent administration of liver enzyme inducing may decrease the effect of testosterone undecanoate.

Phenytoin, testosterone undecanoate [2] ---> SmPC of [2] of eMC

Concurrent administration of liver enzyme inducing may decrease the effect of testosterone undecanoate.

Pregnancy, testosterone undecanoate [2] ---> SmPC of [2] of eMC

There are no adequate data for the use in pregnant women. In view of the risk of virilisation of the foetus, it should not be used during pregnancy.

Primidone, testosterone undecanoate [2] ---> SmPC of [2] of eMC

Concurrent administration of liver enzyme inducing may decrease the effect of testosterone undecanoate.

Rifampicin, testosterone undecanoate [2] ---> SmPC of [2] of eMC

Concurrent administration of liver enzyme inducing may decrease the effect of testosterone undecanoate.

CONTRAINDICATIONS of Testosterone undecanoate

- Pregnancy

- Breast feeding

- Known or suspected prostatic or mammary carcinoma;

- History of liver tumours

- Hypersensitivity to the active substance or to any of the excipients.

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

Testosterone (Livensa)

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

Livensa has no influence on the ability to drive and use machines. However, patients should be informed that migraine, insomnia, disturbance in attention and diplopia have been reported during treatment with Livensa.

ACTH, testosterone ---> SmPC of [testosterone undecanoate] of eMC

The concurrent administration of testosterone with ACTH may enhance oedema formation

Anticoagulants, testosterone [2] ---> SmPC of [2] of EMA

When testosterone is given concomitantly with anticoagulants, the anticoagulant effect may increase. Patients receiving oral anticoagulants require close monitoring, especially when testosterone therapy is started or stopped.

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

Livensa must not be used by breast-feeding women.

Corticosteroids, testosterone ---> SmPC of [testosterone undecanoate] of eMC

The concurrent administration of testosterone or corticosteroids may enhance oedema formation

Enzyme inhibitors, testosterone

The enzymatic inhibition may increase the plasma levels of testosterone

Fertility, testosterone [2] ---> SmPC of [2] of EMA

No data is available of the effect of Livensa on fertility.

Glibenclamide [1], testosterone ---> SmPC of [1] of EMA

The co-administration may enhance the hypoglycemic effect

Glimepiride [1], testosterone ---> SmPC of [1] of eMC

Potentiation of the blood-sugar-lowering effect and possible hypoglycaemia

Gliquidone, testosterone

Hypoglycemic reactions may occur as expression of enhancement effect of gliquidone with gliquidone is co-administered with testosterone.

Insulin, testosterone undecanoate

In diabetic patients the metabolic effects of testosterone may decrease blood glucose and therefore insulin requirements.

Insulin, testosterone [2] ---> SmPC of [2] of EMA

In diabetic patients the metabolic effects of testosterone may decrease blood glucose and therefore insulin requirements.

Lenacapavir [1], testosterone ---> SmPC of [1] of EMA

Plasma concentrations of these medicinal products may be increased when co-administered with lenacapavir. No dose adjustment of these gender affirming hormones is required.

Oral anticoagulants, testosterone [2] ---> SmPC of [2] of EMA

Oral antidiabetics, testosterone undecanoate

In diabetic patients the metabolic effects of testosterone may decrease blood glucose and therefore insulin requirements.

Oral antidiabetics, testosterone [2] ---> SmPC of [2] of EMA

In diabetic patients the metabolic effects of testosterone may decrease blood glucose and therefore insulin requirements.

Oxyphenbutazone, testosterone

The serum levels of oxyphenbutazone may increase

Pioglitazone/glimepiride [1], testosterone ---> SmPC of [1] of EMA

Potentiation of the blood-glucose-lowering effect and, thus, in some instances hypoglycaemia may occur

Pregnancy, testosterone [2] ---> SmPC of [2] of EMA

Testosterone may induce virilising effects on the female foetus when administered to a pregnant woman. Studies in animals have shown reproductive toxicity (see section 5.3).

Pregnancy, testosterone [2] ---> SmPC of [2] of EMA

Livensa must not be used in women who are or may become pregnant. In case of inadvertent exposure during pregnancy, use of Livensa must be discontinued.

Somapacitan [1], testosterone ---> SmPC of [1] of EMA

The metabolic effects of somapacitan can also be influenced by concomitant therapy with other hormones, e.g. testosterone and thyroid hormones

Sulfonylureas, testosterone

Potentiation of the blood-sugar-lowering effect and possible hypoglycaemia

CONTRAINDICATIONS of Testosterone (Livensa)

- Hypersensitivity to the active substance or to any of the excipients.

- Known, suspected or past history of cancer of the breast or known or suspected estrogen-dependent neoplasia, or any other condition consistent with the contraindications for the use of estrogen.

https://www.ema.europa.eu/en/documents/product-information/livensa-epar-product-information_en.pdf 16/04/2012 (withdrawn)

Tetrabenazine

Ability to drive, tetrabenazine

Patients should be advised that tetrabenazine may cause drowsiness

Alcohol, tetrabenazine

The co-administration of tetrabenazine with CNS depressant drugs may have an additive sedative effect

Amiodarone, tetrabenazine [2] ---> SmPC of [2] of eMC

Tetrabenazine should be used with caution with drugs known to prolong QTc

Amitriptyline, tetrabenazine [2] ---> SmPC of [2] of eMC

In vitro studies indicate that tetrabenazine may be a CYP2D6 inhibitor and therefore cause increased plasma concentrations of medicinal products metabolised by CYP2D6.

Antihypertensives, tetrabenazine

The co-administration of tetrabenazine with antihypertensive drugs may increase the risk of orthostatic hypotension

Benperidol [1], tetrabenazine ---> SmPC of [1] of eMC

The risk of extrapyramidal side effects is increased if tetrabenazine is used concomitantly with benperidol.

Betablockers, tetrabenazine

The co-administration of tetrabenazine with betablockers may increase the risk of orthostatic hypotension

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

Tetrabenazine is contraindicated during lactation

Chlorpromazine, tetrabenazine

The co-administration may cause significant dopamine depletion. Tetrabenazine should be used with caution with other medicinal products with the potential to prolong QT interval

Class IA antiarrhythmic agents, tetrabenazine [2] ---> SmPC of [2] of eMC

Tetrabenazine should be used with caution with drugs known to prolong QTc

Class III antiarrhythmic agents, tetrabenazine [2] ---> SmPC of [2] of eMC

Tetrabenazine should be used with caution with drugs known to prolong QTc

CNS depressants, tetrabenazine

The co-administration of tetrabenazine with CNS depressant drugs may have an additive sedative effect

Digoxin, tetrabenazine

Tetrabenazin has no effect on the bioavailability of digoxin

Dopamine antagonists, tetrabenazine

The adverse reactions of tetrabenazine, like QTc prolongation, NMS and extrapyramidal disorders, may be enhanced with the concomitant use of dopamine antagonists

Dopaminergic antiparkinsonian agents, tetrabenazine

Concomitant use with tetrabenazine is not recommended, as there is antagonism between dopaminergic antiparkinsonian agents and tetrabenazine

Drugs primarily metabolised by CYP2D6, tetrabenazine [2] ---> SmPC of [2] of eMC

In vitro studies indicate that tetrabenazine may be a CYP2D6 inhibitor and therefore cause increased plasma concentrations of medicinal products metabolised by CYP2D6.

Duloxetine, tetrabenazine [2] ---> SmPC of [2] of eMC

Fluoxetine, tetrabenazine [2] ---> SmPC of [2] of eMC

Gatifloxacin, tetrabenazine [2] ---> SmPC of [2] of eMC

Tetrabenazine should be used with caution with drugs known to prolong QTc

Haloperidol, tetrabenazine

The co-administration may cause significant dopamine depletion

Hypnotics, tetrabenazine

The co-administration of tetrabenazine with CNS depressant drugs may have an additive sedative effect

IMAOs, tetrabenazine

Possible state of central excitement and hypertension. Contraindicated. It is recommended an interval of at least 2 weeks between each one

Imipramine, tetrabenazine [2] ---> SmPC of [2] of eMC

In vitro studies indicate that tetrabenazine may be a CYP2D6 inhibitor and therefore cause increased plasma concentrations of medicinal products metabolised by CYP2D6.

Levodopa, tetrabenazine [2] ---> SmPC of [2] of eMC

Levodopa should be administered with caution in the presence of tetrabenazine.

Metoclopramide, tetrabenazine

The co-administration may cause significant dopamine depletion

Metoprolol, tetrabenazine [2] ---> SmPC of [2] of eMC

In vitro studies indicate that tetrabenazine may be a CYP2D6 inhibitor and therefore cause increased plasma concentrations of medicinal products metabolised by CYP2D6.

Moxifloxacin, tetrabenazine [2] ---> SmPC of [2] of eMC

Tetrabenazine should be used with caution with drugs known to prolong QTc

Neuroleptics, tetrabenazine

The co-administration may cause significant dopamine depletion

Opiates, tetrabenazine

The co-administration of tetrabenazine with CNS depressant drugs may have an additive sedative effect

Paroxetine, tetrabenazine [2] ---> SmPC of [2] of eMC

Phenothiazines, tetrabenazine

Coadministration of phenothiazines with tetrabenazine increases the risk of extrapyramidal effects.

Piribedil, tetrabenazine

Concomitant use of piribedil with tetrabenazine is not recommended, as there is antagonism between dopaminergic antiparkinsonian agents and tetrabenazine

Pregnancy, tetrabenazine

Tetrabenazine should not be used during pregnancy unless no other treatment is available.

Procainamide, tetrabenazine [2] ---> SmPC of [2] of eMC

Tetrabenazine should be used with caution with drugs known to prolong QTc

QT interval prolonging drugs, tetrabenazine [2] ---> SmPC of [2] of eMC

Tetrabenazine should be used with caution with drugs known to prolong QTc

Quinidine, tetrabenazine [2] ---> SmPC of [2] of eMC

Reserpine, tetrabenazine [2] ---> SmPC of [2] of eMC

Tetrabenazine should not be used concomitantly with reserpine

Risperidone, tetrabenazine [2] ---> SmPC of [2] of eMC

In vitro studies indicate that tetrabenazine may be a CYP2D6 inhibitor and therefore cause increased plasma concentrations of medicinal products metabolised by CYP2D6.

Sertraline, tetrabenazine [2] ---> SmPC of [2] of eMC

Sotalol, tetrabenazine [2] ---> SmPC of [2] of eMC

Tetrabenazine should be used with caution with drugs known to prolong QTc

Strong CYP2D6 inhibitors, tetrabenazine [2] ---> SmPC of [2] of eMC

Terbinafine, tetrabenazine [2] ---> SmPC of [2] of eMC

Tetrabenazine [1], thioridazine ---> SmPC of [1] of eMC

Tetrabenazine should be used with caution with drugs known to prolong QTc

CONTRAINDICATIONS of Tetrabenazine

- Hypersensitivity to the active substance or to any of the excipients

- Tetrabenazine can block the action of reserpine. Thus these substances should not be taken concomitantly.

- Use of monoamine oxidase inhibitors

- Presence of a hypokinetic-rigid-syndrome (Parkinsonism)

- Depression

- Breast feeding

- Pheochromocytoma

- Prolactin-dependent tumours, e.g. pituitary or breast cancer.

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

Tetracaine

Anticholinesterase, tetracaine

The anticholinesterase may inhibit the metabolism of ester-type local anaesthetic agent and increase the risk of systemic toxicity

Betablockers, tetracaine

Decreased effect of betablocker

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

Safety for use in lactation has not been established, therefore, use only when considered essential by the physician.

Pregnancy, tetracaine [2] ---> SmPC of [2] of eMC

Safety for use in pregnancy has not been established, therefore, use only when considered essential by the physician.

Sulphamides, tetracaine [2] ---> SmPC of [2] of eMC

Tetracaine should not be used in patients being treated with sulphonamides

Sulphonamides, tetracaine [2] ---> SmPC of [2] of eMC

Tetracaine should not be used in patients being treated with sulphonamides

Sympathomimetics, tetracaine

Increased effect of sympathomimetic agent

CONTRAINDICATIONS of Tetracaine

- Not to be used in patients with a known hypersensitivity to the product.

- Tetracaine is hydrolysed in the body to p-amino-benzoic acid and should not therefore be used in patients being treated with sulphonamides.

- In view of the immaturity of the enzyme system which metabolises the ester type local anaesthetics in premature babies, tetracaine should be avoided in these patients.

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

Tetrazepam

Ability to drive, tetrazepam

The sedative effect affects the ability to drive or use machines

Alcohol, tetrazepam

The co-administration may enhance mutually the effects. It is recommended not to take alcohol

Barbiturates, tetrazepam

The co-administration may mutually enhance the CNS depressant effects

Benzodiazepines, tetrazepam

Tetrazepam should not be administrated with other benzodiazepines due to the risk of further increase of dependence development and abstinence symptoms

Breast-feeding, tetrazepam

Breast feeding in not recommended during administration of benzodiazepines.

CNS depressants, tetrazepam

The co-administration may mutually enhance the CNS depressant effects

Cisapride, tetrazepam

The co-administration may enhance and prolong the effect of tetrazepam

Clonidine, tetrazepam

The co-administration may mutually enhance the CNS depressant effects

Clozapine, tetrazepam

Particular caution is advised when clozapine therapy is initiated in patients who are receiving a benzodiazepine or any other psychotropic agent. These patients may have an increased risk of circulatory collapse,

Guanfacin, tetrazepam

The co-administration may mutually enhance the CNS depressant effects

Methyldopa, tetrazepam

The co-administration may mutually enhance the CNS depressant effects

Moxonidine, tetrazepam

The co-administration may mutually enhance the CNS depressant effects

Muscle relaxants, tetrazepam

The co-administration may enhance the muscle relaxant effect

Omeprazole, tetrazepam

The co-administration may enhance and prolong the effect of tetrazepam

Opiates, tetrazepam

The co-administration may mutually enhance the CNS depressant effects

Phenothiazines, tetrazepam

The co-administration may mutually enhance the CNS depressant effects

Pregnancy, tetrazepam

During pregnancy, a benzodiazepine may be administered only if there is a compelling indication.

Sedating antihistamines, tetrazepam

The co-administration may mutually enhance the CNS depressant effects

Tezacaftor/ivacaftor (Symkevi)

Ability to drive, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Patients experiencing dizziness should be advised not to drive or use machines until symptoms abate.

BCRP inhibitors, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Co-administration of BCRP inhibitors is not expected to alter exposure of ivacaftor and M1-IVA, while any potential changes in M6-IVA exposures are not expected to be clinically relevant.

Breast-feeding, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

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.

Carbamazepine, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Co-administration with strong CYP3A inducers is not recommended.

Ciprofloxacin, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Co-administration of ciprofloxacin did not affect the exposure of ivacaftor or tezacaftor. No dose adjustment is required when Symkevi is co-administered with ciprofloxacin.

Clarithromycin, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

The dose of Symkevi should be adjusted when co-administered with strong CYP3A inhibitors (see Table 2 in section 4.2).

CYP3A4 substrates, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

No dose adjustment of CYP3A substrates is required when co-administered with Symkevi in combination with ivacaftor.

Digoxin, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

When used concomitantly with digoxin or other substrates of P-gp with a narrow therapeutic index, such as ciclosporin, everolimus, sirolimus, and tacrolimus, caution and appropriate monitoring should be used.

Erythromycin, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

The dose of Symkevi and ivacaftor should be adjusted when co-administered with moderate CYP3A inhibitors (see Table 2 in section 4.2).

Fertility, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Tezacaftor had no effects on fertility and reproductive performance indices in male and female rats at doses up to 100 mg/kg/day. Ivacaftor had an effect on fertility in rats (see section 5.3).

Fluconazole, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

The dose of Symkevi and ivacaftor should be adjusted when co-administered with moderate CYP3A inhibitors (see Table 2 in section 4.2).

Foods, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

The morning and evening dose should be taken approximately 12 hours apart with fat-containing food

Glimepiride, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Other medicinal products for which exposure may be increased include glimepiride and glipizide; these medicinal products should be used with caution.

Glipizide, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Other medicinal products for which exposure may be increased include glimepiride and glipizide; these medicinal products should be used with caution.

Grapefruit juice, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Co-administration with grapefruit juice, which contains one or more components that moderately inhibit CYP3A, may increase exposure of ivacaftor and tezacaftor

Grapefruit, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Food or drink containing grapefruit should be avoided during treatment (see

Itraconazol, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Co-administration with itraconazole, a strong CYP3A inhibitor, increased tezacaftor exposure (measured as AUC) by 4-fold and increased ivacaftor AUC by 15.6-fold.

Ketoconazole, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

When co-administered with strong CYP3A inhibitors, the dose should be adjusted to one Symkevi tablet twice a week, taken approximately 3 to 4 days apart.

Midazolam, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Co-administration with (oral) midazolam, a sensitive CYP3A substrate, did not affect midazolam exposure. No dose adjustment of CYP3A substrates is required when co-administered with Symkevi in combination with ivacaftor.

Moderate CYP3A4 inhibitors, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

The dose of Symkevi and ivacaftor should be adjusted when co-administered with moderate CYP3A inhibitors (see Table 2 in section 4.2).

Nirmatrelvir/ritonavir [1], tezacaftor/ivacaftor ---> SmPC of [1] of EMA

Reduce dosage when coadministered with Paxlovid. Refer to individual SmPCs for more information.

OATP1B1 substrates, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

No dose adjustment of OATP1B1 substrates is required when co-administered with Symkevi.

Oral contraceptives, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Symkevi in combination with ivacaftor has been studied with an estrogen/progesterone oral contraceptive and was found to have no significant effect on the exposures of the hormonal contraceptive.

P-glycoprotein substrates with small therapeutic index, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

P-glycoprotein substrates, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Administration of Symkevi in combination with ivacaftor may increase systemic exposure of medicinal products that are sensitive substrates of P-gp, which may increase or prolong their therapeutic effect and adverse reactions.

P-gp inhibitors, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Caution should be used when P-gp inhibitors are used with Symkevi

Phenobarbital, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Co-administration with strong CYP3A inducers is not recommended.

Phenytoin, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Co-administration with strong CYP3A inducers is not recommended.

Pitavastatin, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Symkevi in combination with ivacaftor has been studied with pitavastatin, an OATP1B1 substrate, and was found to have no clinically relevant effect on the exposure of pitavastatin (1.24-fold increased exposure based on AUC).

Posaconazole, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

The dose of Symkevi should be adjusted when co-administered with strong CYP3A inhibitors (see Table 2 in section 4.2).

Pregnancy, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

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

Rifabutin, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Co-administration with strong CYP3A inducers is not recommended.

Rifampicin, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Co-administration of ivacaftor with rifampicin, a strong CYP3A inducer, significantly decreased ivacaftor exposure (area under the curve [AUC]) by 89%.

St. John's wort, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Co-administration with strong CYP3A inducers is not recommended.

Strong CYP3A4 inductors, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Exposure to tezacaftor and ivacaftor may be reduced by the concomitant use of CYP3A inducers, potentially resulting in reduced efficacy of Symkevi and ivacaftor. Therefore, co-administration with strong CYP3A inducers is not recommended

Strong CYP3A4 inhibitors, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

When co-administered with strong CYP3A inhibitors, the dose should be adjusted to one Symkevi tablet twice a week, taken approximately 3 to 4 days apart.

Telithromycin, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

The dose of Symkevi should be adjusted when co-administered with strong CYP3A inhibitors (see Table 2 in section 4.2).

Tezacaftor/ivacaftor [1], voriconazole ---> SmPC of [1] of EMA

The dose of Symkevi should be adjusted when co-administered with strong CYP3A inhibitors (see Table 2 in section 4.2).

Tezacaftor/ivacaftor [1], warfarin ---> SmPC of [1] of EMA

Ivacaftor may inhibit CYP2C9; therefore, monitoring of the international normalized ratio (INR) is recommended during co-administration of warfarin with Symkevi given in combination with ivacaftor.

Tezacaftor/ivacaftor, verapamil [2] ---> SmPC of [2] of EMA

The dose of Symkevi and ivacaftor should be adjusted when co-administered with moderate CYP3A inhibitors (see Table 2 in section 4.2).

CONTRAINDICATIONS of Tezacaftor/ivacaftor (Symkevi)

- 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/symkevi-epar-product-information_en.pdf 08/12/2025

Thalidomide (Thalidomide BMS)

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

Patients should be instructed not to drive cars, use machines or perform hazardous tasks while being treated with thalidomide if they feel tired, dizzy, sleepy or have blurred vison.

Alcohol, thalidomide [2] ---> SmPC of [2] of EMA

Thalidomide has sedative properties, thus may enhance the sedation induced by anxiolytics, hypnotics, antipsychotics, H1 antihistamines, opiate derivatives, barbiturates and alcohol.

Anticholinesterase, thalidomide [2] ---> SmPC of [2] of EMA

Due to thalidomide 's potential to induce bradycardia, caution should be exercised with medicinal products having the same pharmacodynamic effect

Antihistamines, thalidomide [2] ---> SmPC of [2] of EMA

Thalidomide has sedative properties, thus may enhance the sedation induced by anxiolytics, hypnotics, antipsychotics, H1 antihistamines, opiate derivatives, barbiturates and alcohol.

Anxiolytics, thalidomide [2] ---> SmPC of [2] of EMA

Thalidomide has sedative properties, thus may enhance the sedation induced by anxiolytics, hypnotics, antipsychotics, H1 antihistamines, opiate derivatives, barbiturates and alcohol.

Barbiturates, thalidomide [2] ---> SmPC of [2] of EMA

Thalidomide has sedative properties, thus may enhance the sedation induced by anxiolytics, hypnotics, antipsychotics, H1 antihistamines, opiate derivatives, barbiturates and alcohol.

Betablockers, thalidomide [2] ---> SmPC of [2] of EMA

Due to thalidomide 's potential to induce bradycardia, caution should be exercised with medicinal products having the same pharmacodynamic effect

Bortezomib, thalidomide [2] ---> SmPC of [2] of EMA

Medicinal products known to be associated with peripheral neuropathy (e.g. vincristine and bortezomib) should be used with caution in patients receiving thalidomide.

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

Breast-feeding should be discontinued during therapy with thalidomide.

Contraceptives, thalidomide [2] ---> SmPC of [2] of EMA

Combined hormonal contraceptives are not recommended due to the increased risk of venous thrombo-embolic disease

CYP450 substrates, thalidomide [2] ---> SmPC of [2] of EMA

Thalidomide is a poor substrate for cytochrome P450 isoenzymes and therefore clinically important interactions with medicinal products that are inhibitors and/or inducers of this enzyme system are unlikely.

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

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

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.

Drugs inducing bradycardia, thalidomide [2] ---> SmPC of [2] of EMA

Due to thalidomide 's potential to induce bradycardia, caution should be exercised with medicinal products having the same pharmacodynamic effect

Ethinyl estradiol, thalidomide [2] ---> SmPC of [2] of EMA

Combined hormonal contraceptives are not recommended due to the increased risk of venous thrombo-embolic disease

Fertility, thalidomide [2] ---> SmPC of [2] of EMA

A study in rabbits demonstrated no effect on fertility indices in males or females although testicular degeneration was observed in males.

Hypnotics, thalidomide [2] ---> SmPC of [2] of EMA

Thalidomide has sedative properties, thus may enhance the sedation induced by anxiolytics, hypnotics, antipsychotics, H1 antihistamines, opiate derivatives, barbiturates and alcohol.

Levomepromazine, thalidomide

The co-administration of levomepromazine with other central nervous depressants will cause a greater depressant effect on central nervous system

Men, thalidomide [2] ---> SmPC of [2] of EMA

If pregnancy occurs in a partner of a male patient taking thalidomide, the female partner should be referred to a physician specialised or experienced in teratology for evaluation and advice.

Men, thalidomide [2] ---> SmPC of [2] of EMA

As thalidomide is found in semen, as a precaution all male patients must use condoms during treatment, during dose interruption and for at least 7 days following discontinuation of treatment when

Midazolam [1], thalidomide ---> SmPC of [1] of EMA

The co-administration of midazolam with other sedative/hypnotic agents and CNS depressants, including alcohol, is likely to result in enhanced sedation and respiratory depression.

Neuroleptics, thalidomide [2] ---> SmPC of [2] of EMA

Thalidomide has sedative properties, thus may enhance the sedation induced by anxiolytics, hypnotics, antipsychotics, H1 antihistamines, opiate derivatives, barbiturates and alcohol.

Non-enzymatic hydrolysis, thalidomide [2] ---> SmPC of [2] of EMA

Non-enzymatic hydrolysis of thalidomide, being the primary clearance mechanism, suggests that the potential for drug-drug interactions with thalidomide is low.

Norethindrone, thalidomide [2] ---> SmPC of [2] of EMA

Combined hormonal contraceptives are not recommended due to the increased risk of venous thrombo-embolic disease

Opiate agonists, thalidomide [2] ---> SmPC of [2] of EMA

Thalidomide has sedative properties, thus may enhance the sedation induced by anxiolytics, hypnotics, antipsychotics, H1 antihistamines, opiate derivatives, barbiturates and alcohol.

Pamidronate [1], thalidomide ---> SmPC of [1] of eMC

In multiple myeloma patients, the risk of renal dysfunction may be increased when pamidronate is used in combination with thalidomide.

Pamidronic acid [1], thalidomide ---> SmPC of [1] of eMC

In multiple myeloma patients, the risk of renal dysfunction may be increased when pamidronate is used in combination with thalidomide.

Peripheral neuropathy, thalidomide [2] ---> SmPC of [2] of EMA

Medicinal products known to be associated with peripheral neuropathy (e.g. vincristine and bortezomib) should be used with caution in patients receiving thalidomide.

Pregnancy, thalidomide [2] ---> SmPC of [2] of EMA

Thalidomide is contraindicated during pregnancy and in women of childbearing potential unless all the conditions of the Pregnancy Prevention Programme are met

Thalidomide [1], torsades de pointes inducing drugs ---> SmPC of [1] of EMA

Due to thalidomide 's potential to induce bradycardia, caution should be exercised with medicinal products having the same pharmacodynamic effect

Thalidomide [1], vincristine ---> SmPC of [1] of EMA

Medicinal products known to be associated with peripheral neuropathy (e.g. vincristine and bortezomib) should be used with caution in patients receiving thalidomide.

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

Close monitoring of INR values is advised during thalidomide-prednisone combination treatment as well as during the first weeks after ending these treatments.

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

Women of childbearing potential must use one effective method of contraception for at least 4 weeks before start of treatment, during treatment including during dose interruptions, and until at least 4 weeks after thalidomide treatment (see section 4.4).

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

If pregnancy occurs in a woman treated with thalidomide, treatment must be stopped immediately and the patient should be referred to a physician specialised or experienced in teratology for evaluation and advice

Thalidomide, tiapride

Enhancement of CNS depressant effect

Thalidomide, tramadol [2] ---> SmPC of [2] of eMC

Concomitant administration of tramadol with other centrally acting drugs may potentiate CNS depressant effects.

Thalidomide, zoledronic acid [2] ---> SmPC of [2] of EMA

Reports of ONJ have been received in patients treated with zoledronic acid and concomitant anti-angiogenic medicinal products.

CONTRAINDICATIONS of Thalidomide (Thalidomide BMS)

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

- Women who are pregnant (see section 4.6).

- Women of childbearing potential unless all the conditions of the Pregnancy Prevention Programme are met (see sections 4.4 and 4.6).

- Male patients unable to follow or comply with the required contraceptive measures (see section 4.4).

https://www.ema.europa.eu/en/documents/product-information/thalidomide-bms-previously-thalidomide-celgene-epar-product-information_en.pdf. 22/01/2025

Talimogene laherparepvec (Imlygic)

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

Because of potential adverse reactions such as dizziness and confusional state (see section 4.8), patients should be advised to use caution when driving or operating machinery

Aciclovir, talimogene laherparepvec [2] ---> SmPC of [2] of EMA

Acyclovir and other anti-viral agents may interfere with the effectiveness of Imlygic if administered systemically or topically directly to the injection site.

Breast-feeding, talimogene laherparepvec [2] ---> SmPC of [2] of EMA

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

Condom, talimogene laherparepvec [2] ---> SmPC of [2] of EMA

All patients should be advised to use a latex condom during sexual contact to prevent possible

Fertility, talimogene laherparepvec [2] ---> SmPC of [2] of EMA

No clinical studies have been performed to evaluate the effects of talimogene laherparepvec on fertility (see section 5.3).

Hepatic haemorrhage, talimogene laherparepvec [2] ---> SmPC of [2] of EMA

Imlygic is not indicated for transcutaneous intrahepatic route of administration. In clinical studies, cases of hepatic haemorrhage resulting in hospitalisation and death have been reported in patients receiving transcutaneous intrahepatic Imlygic inject

Herpes infection, talimogene laherparepvec [2] ---> SmPC of [2] of EMA

Consider the risks and benefits of Imlygic treatment before administering acyclovir or other anti-viral agents indicated for management of herpetic infection.

Impaired healing, talimogene laherparepvec [2] ---> SmPC of [2] of EMA

Imlygic may increase the risk of impaired healing in patients with underlying risk factors (e.g. previous radiation at the injection site, or lesions in poorly vascularised areas).

Infection, talimogene laherparepvec [2] ---> SmPC of [2] of EMA

The occurrence of latent infection with talimogene laherparepvec cannot be excluded.

Obstructive airway disorder, talimogene laherparepvec [2] ---> SmPC of [2] of EMA

Obstructive airway disorder has been reported following Imlygic treatment. Caution should be used when injecting lesions close to major airways.

Plasmacytoma, talimogene laherparepvec [2] ---> SmPC of [2] of EMA

Plasmacytoma has been reported in proximity to the injection site after administration of Imlygic. The risks and benefits of Imlygic should be considered in patients with multiple myeloma or in whom plasmacytoma develops during treatment.

Pregnancy, talimogene laherparepvec [2] ---> SmPC of [2] of EMA

If Imlygic is used during pregnancy, or if the patient becomes pregnant while taking the medicinal product, the patient should be apprised of the potential hazards to the foetus and/or neonate.

Pregnancy, talimogene laherparepvec [2] ---> SmPC of [2] of EMA

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

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

Women of childbearing potential should be advised to use an effective method of contraception to prevent pregnancy during treatment.

CONTRAINDICATIONS of Talimogene laherparepvec (Imlygic)

- Patients with a history of hypersensitivity to talimogene laherparepvec or any of its excipients.

- Patients who are severely immunocompromised (e.g. patients with severe congenital or acquired cellular and/or humoral immune deficiency) (see section 4.4).

https://www.ema.europa.eu/en/documents/product-information/imlygic-epar-product-information_en.pdf 06/10/2025

Theophylline

Ability to drive, theophylline [2] ---> SmPC of [2] of eMC

No known effects.

Aciclovir, theophylline

Aciclovir reduces clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

ACTH, theophylline

Enhancement of steroidal effect of ACTH

Adenosine [1], theophylline ---> SmPC of [1] of eMC

The theophylline, adenosine antagonist, decreases the adenosine effect. The co-administration should be avoided for 24 hours prior to use of adenosine.

Adrenaline [1], theophylline ---> SmPC of [1] of eMC

Drugs which cause potassium loss (corticosteroids, potassium-depleting diuretic, aminophylline, theophylline) increase the risk of hypokalemia.

Agomelatine [1], theophylline ---> SmPC of [1] of EMA

No evidence of pharmacokinetic or pharmacodynamic interaction was found in phase I clinical trials

Allopurinol, theophylline [2] ---> SmPC of [2] of eMC

Allopurinol reduces clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Allopurinol/lesinurad [1], theophylline ---> SmPC of [1] of EMA

Inhibition of the metabolism of theophylline by allopurinol has been reported. Theophylline levels should be monitored in patients undergoing Duzallo therapy.

Aluminium, theophylline

The aluminium salt decreases the absorption of the co-administered active principle. Separate administration by at least 2 hours

Aminoglutethimide, theophylline [2] ---> SmPC of [2] of eMC

The aminoglutethimide increases clearance of theophylline and it may be necessary to increase dosage to ensure a therapeutic effect

Aminophylline, barbiturates ---> SmPC of [theophylline] of

The barbiturates increase clearance of theophylline and it may be necessary to increase dosage to ensure a therapeutic effect

Aminophylline, pentobarbital ---> SmPC of [theophylline] of

The barbiturates increase clearance of theophylline and it may be necessary to increase dosage to ensure a therapeutic effect

Aminophylline, phenobarbital ---> SmPC of [theophylline] of

Antiepileptics may decrease plasma theophylline concentrations

Aminophylline, primidone ---> SmPC of [theophylline] of

Antiepileptics may decrease plasma theophylline concentrations

Anagrelide [1], theophylline ---> SmPC of [1] of EMA

Anagrelide demonstrates some limited inhibitory activity towards CYP1A2 which may present a theoretical potential for interaction with other co-administered medicinal products sharing that clearance mechanism

Antacids, theophylline

The antacid may decrease the absorption of theophylline

Atenolol/nifedipine, theophylline

The co-administration may increase the plasma levels of theophylline

Axitinib [1], theophylline ---> SmPC of [1] of EMA

In vitro studies indicated that axitinib has a potential to inhibit CYP1A2. Therefore, co-administration of axitinib with CYP1A2 substrates may result in increased plasma concentrations of CYP1A2 substrates

Azithromycin, theophylline [2] ---> SmPC of [2] of eMC

The macrolide antibiotics reduce clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Bamethane, theophylline

Possible enhancement of sympathomimetic effect

Barbiturates, theophylline [2] ---> SmPC of [2] of eMC

The barbiturates increase clearance of theophylline and it may be necessary to increase dosage to ensure a therapeutic effect

Benzodiazepines, theophylline [2] ---> SmPC of [2] of eMC

There is a pharmacological interaction with benzodiazepines and these drugs should be used with caution.

Beta-adrenergic agonists, theophylline

Theophylline acts synergistic with beta-adrenergic agents

Betablockers, theophylline [2] ---> SmPC of [2] of eMC

Co-administration of theophylline with beta-blockers may cause antagonism

Binimetinib [1], theophylline ---> 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, theophylline [2] ---> SmPC of [2] of eMC

Theophylline is secreted in breast milk, and may be associated with irritability in the infant, therefore it should only be given to breast feeding women when the anticipated benefits outweigh the risk to the child.

Bupropion [1], theophylline ---> SmPC of [1] of eMC

There is an increased risk of seizures occurring with the use of bupropion in the presence of predisposing risk factors which lower the seizure threshold.

Caffeine [1], theophylline ---> SmPC of [1] of EMA

Inter-conversion between caffeine and theophylline occurs in preterm newborn infants. These active substances should not be used concurrently.

Calcium antagonists, 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

Carbaldrate, theophylline

The aluminium salt decreases the absorption of the co-administered active principle. Separate administration by at least 2 hours

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

The carbamazepine increases clearance of theophylline and it may be necessary to increase dosage to ensure a therapeutic effect

Cimetidine, theophylline [2] ---> SmPC of [2] of eMC

Cimetidine reduces clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Ciprofloxacin [1], theophylline ---> SmPC of [1] of eMC

Ciprofloxacin inhibits CYP1A2 and thus may cause increased serum concentration of concomitantly administered substances metabolised by this enzyme

Clarithromycin, theophylline [2] ---> SmPC of [2] of eMC

The macrolide antibiotics reduce clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Clenbuterol, theophylline

The co-administration may increase the effect of clenbuterol

Clopidogrel [1], theophylline ---> SmPC of [1] of EMA

The pharmacokinetics of digoxin or theophylline were not modified by the co-administration of clopidogrel.

Clopidogrel/acetylsalicylic acid [1], theophylline ---> SmPC of [1] of EMA

The pharmacokinetics of digoxin or theophylline were not modified by the co-administration of clopidogrel.

Cobimetinib [1], theophylline ---> SmPC of [1] of EMA

In vitro, cobimetinib is a potential inducer of CYP1A2 and may therefore reduce the exposure of substrates of this enzyme e.g., theophylline.

CYP1A2 inductors, theophylline

The CYP1A2 induction may decrease plasma concentrations of theophylline

CYP1A2 inhibitors, theophylline

The CYP1A2 inhibition may increase plasma concentrations of theophylline

Dasabuvir with ombitasvir/paritaprevir/ritonavir, theophylline ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of

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).

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.

Diazepam, theophylline

Counteraction of the pharmacodynamic effects of diazepam, e.g. reduction of sedation and psychomotor effects. Special caution is recommended

Digital glycosides, theophylline

Theophylline may enhance the toxicity of digitalis

Digitoxin, theophylline

The co-administration may increase the digitoxin effect and promote heart rhythm disorders

Digoxin, theophylline

Phosphodiesterase inhibitors may increase the risk of cardiac arrhythmias

Dihydropyridines, theophylline

The co-administration may increase the theophylline plasma levels

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

Dipyridamole, theophylline

Xanthines may weaken the vasodilator efect of dipyridamole

Disopyramide [1], theophylline ---> SmPC of [1] 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.

Disulfiram, theophylline [2] ---> SmPC of [2] of eMC

Disulfiram inhibits the metabolism of many drugs which are converted in the liver and thereby enhances efficacy.

Diuretics, theophylline

Theophylline enhances the diuretic effect

Doxapram [1], theophylline ---> SmPC of [1] of eMC

Clinical data suggest that concurrent use of theophylline and doxapram may be associated with increased CNS stimulation, agitation, muscle fasciculation and hyperactivity.

Dronedarone [1], theophylline ---> SmPC of [1] of EMA

Dronedarone 400 mg twice daily does not increase the steady state theophylline exposure.

Duloxetine [1], theophylline ---> SmPC of [1] of EMA

The pharmacokinetics of theophylline, a CYP1A2 substrate, were not significantly affected by co-administration with duloxetine

Enoxacin, theophylline [2] ---> SmPC of [2] of eMC

Quinolone reduce clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Ephedrine [1], theophylline ---> SmPC of [1] of eMC

Concomitant administration of ephedrine and theophylline may result in insomnia, nervousness and gastrointestinal complaints.

Epinephrine [1], theophylline ---> SmPC of [1] of eMC

Drugs which cause potassium loss (corticosteroids, potassium-depleting diuretic, aminophylline, theophylline) increase the risk of hypokalemia.

Erythromycin, theophylline [2] ---> SmPC of [2] of eMC

The macrolide antibiotics reduce clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Esketamine, theophylline

The co-administration may decrease the convulsant threshold. The combination is contraindicated.

Estriol [1], theophylline ---> SmPC of [1] of eMC

Estriol may possibly increase the pharmacological effects of theophyllines

Estrogens, theophylline

This may lead to a plasma increase of the theophylline up to toxic levels.

Ethinyl estradiol, theophylline ---> SmPC of [ethinylestradiol/chlormadinone] of

The inhibition of hepatic microsomal enzymes by ethinylestradiol may increase the plasma levels of theophylline

Ethinylestradiol/chlormadinone, theophylline

Ethinylestradiol may inhibit the hepatic microsomal enzymes and increase plasma concentrations of theophylline

Ethinylestradiol/norgestimate [1], theophylline ---> SmPC of [1] of eMC

Combination hormonal contraceptives with theophylline may increase plasma levels (due to CYP inhibition) of theophylline

Etintidine, theophylline

Increased plasma concentration of theophylline

Febuxostat [1], theophylline ---> SmPC of [1] of EMA

The results of a study showed that the co-administration of febuxostat 80 mg QD with theophylline 400 mg single dose has no effect on the pharmacokinetics or safety of theophylline.

Felodipine, theophylline ---> SmPC of [felodipine/ramipril] of

Concomitant administration of felodipine and oral theophylline reduces theophylline absorption by approximately 20%. This is probably of minor clinical importance.

Felodipine/ramipril [1], theophylline ---> SmPC of [1] of eMC

Concomitant administration of felodipine and oral theophylline reduces theophylline absorption by approximately 20%. This is probably of minor clinical importance.

Fenoterol, theophylline

The co-administration may increase the bronchodilator effect

Fluconazole [1], theophylline ---> SmPC of [1] of eMC

In a placebo controlled interaction study, the administration of fluconazole 200 mg for 14 days resulted in an 18% decrease in the mean plasma clearance rate of theophylline.

Flurazepam, theophylline

The use of theophylline or aminophylline may decrease the sedative effects of benzodiazepines

Flutamide, theophylline

The co-administration may increase the plasma levels of theophylline

Fluvoxamine, theophylline [2] ---> SmPC of [2] of eMC

Fluvoxamine reduces clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Formoterol, theophylline

The co-administration may mutually potentiate the effects and also the side effects such as cardiac dysrhythmia

Fosphenytoin [1], theophylline ---> SmPC of [1] of eMC

Theophylline may decrease phenytoin serum levels. Blood levels and/or effects of theophylline may be altered by phenytoin (CYP1A2 induction)

Furosemide, theophylline [2] ---> SmPC of [2] of eMC

Furosemide may potentiate the effects of theophylline.

Gallopamil, theophylline

Increased plasma levels of theophylline

Halothane, theophylline [2] ---> SmPC of [2] of eMC

There is a pharmacological interaction with halothane and these drugs should be used with caution.

Idrocilamide, theophylline

The enzymatic inhibition may decrease the metabolism of theophylline and increase its plasma levels and effect

Imipenem, theophylline

Imipenem reduces clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Indinavir [1], theophylline ---> SmPC of [1] of EMA

Indinavir and theophylline can be co-administered without dose adjustment.

Influenza vaccine, theophylline [2] ---> SmPC of [2] of eMC

There are conflicting reports concerning the potentiation of theophylline by influenza vaccine and physicians should be aware that interaction may occur.

Interferon alfa, theophylline [2] ---> SmPC of [2] of eMC

Interferon alfa reduces clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Interferon alfa-2a, theophylline

Decreased clearance of theophylline

Interferon alfa-2b [1], theophylline ---> SmPC of [1] of EMA

Interferons may affect the oxidative metabolic process. This must be considered during concomitant therapy with medicinal products metabolised by this route, such as the xanthine derivatives theophylline or aminophylline.

Interferon, theophylline

Caution should be used when administering interferon with medicines mainly metabolised by hepatic cytochrome P450 and have a narrow therapeutic window

Isoniazid, theophylline [2] ---> SmPC of [2] of eMC

Isoniazid is known to inhibit certain cytochrome P-450 enzymes and can inhibit the hepatic metabolism of theophylline

Isoprenaline, theophylline

Isoprenaline increases the elimination of theophylline (bronchodilator) and can enhance the hypokaliemia, hyperglycaemia, tachycardia and hypertension

Isradipine, theophylline

The co-administration may increase the theophylline plasma levels

Josamycin, theophylline [2] ---> SmPC of [2] of eMC

The macrolide antibiotics reduce clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Ketamine [1], theophylline ---> SmPC of [1] of eMC

When ketamine and theophylline are given concurrently, a clinically significant reduction in the seizure threshold is observed. Unpredictable extensor-type seizures have been reported with concurrent administration of these agents.

Lansoprazole [1], theophylline ---> SmPC of [1] of eMC

Lansoprazole reduces the plasma concentration of theophylline, which may decrease the expected clinical effect at the dose. Caution is advised when combining the two medicinal products.

Leflunomide [1], theophylline ---> SmPC of [1] of EMA

A771726 may be a weak inducer of CYP1A2 in vivo. Therefore, medicinal products metabolised by CYP1A2 should be used with caution during treatment, as it could lead to the reduction of the efficacy of these products.

Levofloxacin [1], theophylline ---> SmPC of [1] of EMA

A pronounced lowering of the cerebral seizure threshold may occur when quinolones are given concurrently with theophylline, non-steroidal anti-inflammatory drugs, or other substances which lower the seizure threshold

Lithium carbonate, theophylline

Theophylline may decrease the effect of lithium carbonate if they are given together

Lithium, theophylline

Theophylline may decrease the effect of lithium carbonate if they are given together

Lomustine [1], theophylline ---> SmPC of [1] of eMC

Lomustine use in combination with theophylline may potentiate bone marrow toxicity.

Lorazepam [1], theophylline ---> SmPC of [1] of eMC

Theophylline increases metabolism of lorazepam which possibly reduces the effect

Macrolide antibiotics, theophylline [2] ---> SmPC of [2] of eMC

The macrolide antibiotics reduce clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Medazepam, theophylline

The co-administration may decrease the sedative effects of the benzodiazepine

Methotrexate [1], theophylline ---> SmPC of [1] of EMA

Methotrexate may reduce theophylline clearance. Therefore, theophylline blood levels should be monitored under concomitant methotrexate administration.

Metildigoxin, theophylline

Increased risk of cardiac arrhythmias

Metreleptin [1], theophylline ---> SmPC of [1] of EMA

The effect of metreleptin on CYP450 enzymes may be clinically relevant for CYP450 substrates with narrow therapeutic index, where the dose is individually adjusted.

Mexiletine, theophylline [2] ---> SmPC of [2] of eMC

Mexiletine reduces clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Minocycline, theophylline

The co-administration may increase the adverse effects of theophylline

Naltrexone/bupropion [1], theophylline ---> SmPC of [1] of EMA

Caution should be used when prescribing naltrexone/bupropion to patients with predisposing factors that may increase the risk of seizure

Nicotine, theophylline [2] ---> SmPC of [2] of eMC

Smoking can increase clearance of theophylline.

Nifedipine, theophylline

The co-administration may increase the plasma levels of theophylline

Nilutamide, theophylline

Nilutamide may inhibit the hepatic metabolism of theophylline and increase its plasma levels

Niraparib [1], theophylline ---> SmPC of [1] of EMA

Caution is recommended when niraparib is combined with active substances the metabolism of which is CYP1A2-dependent and, notably, those having a narrow therapeutic range (e.g. clozapine, theophylline, and ropinirole).

Noradrenaline, theophylline

The use of noradrenaline with theophylline is not recommended because severe, prolonged hypertension and possible arrhythmias may result

Norepinephrine, theophylline

The use of noradrenaline with theophylline is not recommended because severe, prolonged hypertension and possible arrhythmias may result

Norfloxacin, theophylline [2] ---> SmPC of [2] of eMC

Quinolone reduce clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Obeticholic acid [1], theophylline ---> SmPC of [1] of EMA

Therapeutic monitoring of CYP1A2 substrates with narrow therapeutic index (e.g. theophylline and tizanidine) is recommended.

Ofloxacin [1], theophylline ---> SmPC of [1] of eMC

There may be a further lowering of the cerebral seizure threshold when quinolones are given concurrently with other drugs which lower the seizure threshold

Olanzapine [1], theophylline ---> SmPC of [1] 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

Ombitasvir/paritaprevir/ritonavir [1], theophylline ---> SmPC of [1] of EMA

Oral contraceptives, theophylline [2] ---> SmPC of [2] of eMC

The oral contraceptives reduce clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Orciprenaline, theophylline

Concomitant treatment with theophylline may enhance the effect of orciprenaline

Oxetacaine, theophylline

Decreased absorption of theophylline

Oxipurinol, theophylline

The inhibition of xanthine oxidase increases theophylline levels. Caution should be exercised

Pancuronium [1], theophylline ---> SmPC of [1] of eMC

Decreased duration of action of pancuronium and the intensity of neuromuscular block.

Pantoprazole [1], theophylline ---> SmPC of [1] of EMA

No clinically significant interactions were observed

Pefloxacine, theophylline [2] ---> SmPC of [2] of eMC

Quinolone reduce clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Peginterferon alfa-2a [1], theophylline ---> SmPC of [1] of EMA

Peginterferon alfa-2a, CYP1A2 inhibitor, may increase the plasma levels of theophylline

Peginterferon alfa-2b [1], theophylline ---> SmPC of [1] of EMA

Co-administration of theophylline with the product (PegIntron) may increase the blood concentrations of theophylline. Metabolism of theophylline is suppressed by inhibitory action of the product (PegIntron) on CYP1A2.

Pentobarbital, theophylline [2] ---> SmPC of [2] of eMC

The pentobarbital increases clearance of theophylline and it may be necessary to increase dosage to ensure a therapeutic effect

Pentoxifylline [1], theophylline ---> SmPC of [1] of eMC

Concomitant administration of pentoxifylline and theophylline may increase theophylline levels in some patients.

Phenobarbital, theophylline [2] ---> SmPC of [2] of eMC

The phenobarbital increases clearance of theophylline and it may be necessary to increase dosage to ensure a therapeutic effect

Phenylpropanolamine, theophylline

Phenylpropanolamine reduces clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Phenytoin, theophylline [2] ---> SmPC of [2] of eMC

The phenytoin increases clearance of theophylline and it may be necessary to increase dosage to ensure a therapeutic effect

Pipemidic acid, theophylline

The co-administration increases the plasma levels of theophylline

Piperaquine/artenimol [1], theophylline ---> SmPC of [1] of EMA

DHA administration may result in a slight decrease in CYP1A2 activity. Caution is therefore, advised when Eurartesim is administered concomitantly with medicinal products metabolised by this enzyme that have a narrow therapeutic index

Pixantrone [1], theophylline ---> SmPC of [1] of EMA

When co-administering the narrow-therapeutic index medicinal product theophylline, which is primarily metabolised by CYP1A2, there is a theoretical concern that this substrate may increase in concentration resulting in theophylline toxicity.

Prazepam, theophylline

Theophylline may decrease the effect of benzodiazepines

Prednisone, theophylline

Corticosteroid may inhibit the theophylline metabolism and increase its effect and/or toxicity

Pregnancy, theophylline [2] ---> SmPC of [2] of eMC

Theophylline should not be administered during pregnancy unless clearly necessary.

Primidone, theophylline [2] ---> SmPC of [2] of eMC

The primidone increases clearance of theophylline and it may be necessary to increase dosage to ensure a therapeutic effect

Probenecide, theophylline

Probenecid increases the exposure to theophylline

Propafenone, theophylline [2] ---> SmPC of [2] of eMC

Propafenone reduces clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Propranolol, theophylline [2] ---> SmPC of [2] of eMC

Propranolol reduces clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Protirelin, theophylline

Enhancement of TSH-increase

Prulifloxacin, theophylline [2] ---> SmPC of [2] of eMC

Quinolone reduce clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Quinolones, theophylline ---> SmPC of [levofloxacin] of

Ranitidine, theophylline

Ranitidine reduces clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Regadenoson [1], theophylline ---> SmPC of [1] of EMA

Methylxanthines are non-specific adenosine receptor antagonists and may interfere with the vasodilation activity of regadenoson.

Rifabutin [1], theophylline ---> SmPC of [1] of eMC

No significant interaction may be expected with ethambutol, theophylline, sulphonamides, pyrazinamide and zalcitabine

Rifampicin, theophylline [2] ---> SmPC of [2] of eMC

The rifampicin increases clearance of theophylline and it may be necessary to increase dosage to ensure a therapeutic effect

Rifapentine, theophylline [2] ---> SmPC of [2] of eMC

The rifapentine increases clearance of theophylline and it may be necessary to increase dosage to ensure a therapeutic effect

Riluzole [1], theophylline ---> SmPC of [1] 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

Ritonavir [1], theophylline ---> SmPC of [1] of EMA

An increased dose of theophylline may be required when co-administered with ritonavir, due to induction of CYP1A2.

Rofecoxib, theophylline

Rofecoxib reduces clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Roflumilast [1], theophylline ---> SmPC of [1] of EMA

Co-administration with theophylline resulted in an increase of 8% of the total PDE4 inhibitory activity. No dose adjustment is necessary

Ropinirole [1], theophylline ---> SmPC of [1] of eMC

A pharmacokinetic interaction study between ropinirole and theophylline, a substrate of CYP1A2, revealed no change in the pharmacokinetics of either ropinirole or theophylline.

Roxithromycin, theophylline [2] ---> SmPC of [2] of eMC

The macrolide antibiotics reduce clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Rucaparib [1], theophylline ---> SmPC of [1] of EMA

When co-administering medicinal products metabolized by CYP1A2, particularly medicines which have a narrow therapeutic index (e.g., tizanidine, theophylline), dose adjustments may be considered based on appropriate clinical monitoring.

Salbutamol [1], theophylline ---> SmPC of [1] of eMC

There is an increased risk of hypokalaemia if high doses of theophylline are given with higher doses of salbutamol.

Sildenafil [1], theophylline ---> SmPC of [1] of EMA

There are no data on the interaction of sildenafil and non-specific phosphodiesterase inhibitors such as theophylline or dipyridamole.

Spiramycin, theophylline [2] ---> SmPC of [2] of eMC

The macrolide antibiotics reduce clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

St. John's wort, theophylline [2] ---> SmPC of [2] of eMC

The St John's Wort increases clearance of theophylline and it may be necessary to increase dosage to ensure a therapeutic effect. St. John's Wort should be avoided

Stiripentol [1], theophylline ---> SmPC of [1] of EMA

Data on the potential for inhibition of CYP1A2 are limited. Interactions with theophylline and caffeine cannot be excluded because of the increased plasma levels of theophylline and caffeine may potentially lead to toxicity.

Strong CYP1A2 inhibitors, theophylline

The strong CYP1A2 inhibition may increase plasma concentrations of theophylline

Sucralfate [1], theophylline ---> SmPC of [1] of eMC

Concomitant administration of sucralfate may reduce the bioavailability of theophylline. The bioavailability may be restored by separating the administration from sucralfate by 2 hours.

Sulfinpyrazone, theophylline [2] ---> SmPC of [2] of eMC

The sulfinpyrazone increases clearance of theophylline and it may be necessary to increase dosage to ensure a therapeutic effect

Tadalafil [1], theophylline ---> SmPC of [1] of EMA

Telithromycin [1], theophylline ---> SmPC of [1] of EMA

The co-administration of both medicinal products should be separated by one hour in order to avoid possible digestive side effects such as nausea and vomiting.

Terbinafine, theophylline [2] ---> SmPC of [2] of eMC

There was no clinically relevant interaction between terbinafine and the potential comedications theophylline

Teriflunomide [1], theophylline ---> SmPC of [1] 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.

Tetracosactide, theophylline

Enhancement of steroidal effect of ACTH

Tetracyclines, theophylline

The co-administration of theophylline and tetracyclines may increase the gastrointestinal adverse effects

Tezacaftor/ivacaftor [1], theophylline ---> SmPC of [1] of EMA

Caution and appropriate monitoring should be used when Symkevi is administered concomitantly with narrow therapeutic index substrates of CYP1A2 (such as theophylline) or CYP2B6 (such as bupropion).

Theophylline [1], tiabendazole ---> SmPC of [1] of eMC

Tiabendazole reduces clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

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

Ticlopidine reduces clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Theophylline [1], troleandomycin ---> SmPC of [1] of eMC

The macrolide antibiotics reduce clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Theophylline [1], verapamil ---> SmPC of [1] of eMC

Calcium antagonists reduce clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Theophylline [1], zafirlukast ---> SmPC of [1] of eMC

In clinical trials co-administration with theophylline resulted in decreased plasma levels of zafirlukast, by ca. 30%. However, during post-marketing surveillance, there have been rare cases of patients experiencing increased theophylline levels

Theophylline, thiopurinol

The inhibition of xanthine oxidase increases theophylline levels. Caution should be exercised

Theophylline, tiagabine [2] ---> SmPC of [2] of eMC

Tiagabine does not have any clinically significant effect on the plasma concentrations of theophylline

Theophylline, tipranavir/ritonavir ---> SmPC of [tipranavir] of

Tipranavir/r, CYP1A2 inductors, may decrease the plasma concentrations of theophylline

Theophylline, tocilizumab [2] ---> SmPC of [2] of EMA

When starting or stopping therapy with tocilizumab, patients taking medicinal products which are individually adjusted and are metabolised via CYP450 3A4, 1A2 or 2C9 should be monitored as doses may need to be increased to maintain therapeutic effect.

Theophylline, torasemid [2] ---> SmPC of [2] of eMC

The action of theophylline can be potentiated by torasemide.

Theophylline, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of theophylline thus increasing risk of toxicity

Theophylline, tuberculosis vaccine

The enzymatic inhibition may decrease the metabolism of theophylline and increase its plasma levels and effect

Theophylline, 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.

Theophylline, varenicline [2] ---> SmPC of [2] of EMA

Physiological changes resulting from smoking cessation, with or without treatment with varenicline, may alter the pharmacokinetics or pharmacodynamics of some medicinal products, for which dosage adjustment may be necessary

Theophylline, 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.

Theophylline, viloxazine

Viloxazine reduces clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Theophylline, xanthine oxidase inhibitors

The inhibition of xanthine oxidase increases plasma levels of theophylline. Caution should be exercised

Theophylline, xanthines

Theophylline acts synergistic with other xanthines

Theophylline, zileuton

Zileuton reduces clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

CONTRAINDICATIONS of Theophylline

- Porphyria;

- hypersensitivity to xanthines or any of the tablet constituents;

- concomitant administration with ephedrine in children.

- Theophylline should not be administered to children under 6 months of age.

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

Tetryzoline

Ability to drive, tetryzoline

Blurred vision may occur

Breast-feeding, tetryzoline

Due to possible systemic effects, it is recommended not to use this product during breastfeeding

Guanethidine, tetryzoline

The systemic administration of the guanethidine can enhance the mydriasis of sympathomimetic agent and cause ocular hypertension

Guanidine derivatives, tetryzoline

The systemic administration of the guanidine derivative can enhance the mydriasis of sympathomimetic agent and cause ocular hypertension

Monoamine oxidase inhibitors, tetryzoline

Concomitant use of tetryzoline with MAO inhibitors may enhance the vasoconstrictor effect and increase the blood pressure. The co-administration is contraindicated

Pregnancy, tetryzoline

Due to possible systemic effects, it is recommended not to use this product during pregnancy

Tetryzoline, tricyclic antidepressants

Concomitant use of tetryzoline with tricyclic antidepressants may enhance the vasoconstrictor effect and increase the blood pressure

Thiamazole

Breast-feeding, thiamazole

Breast-feeding is possible during treatment with thiamazole, however only small doses can be used (up to 10 mg/day) without additional administration of thyroid hormones

Pregnancy, thiamazole

Thiamazole crosses the placenta barrier. Strict indication. The combination of thiamazole with thyroid hormones is contraindicated in the pregnancy

Propiverine, thiamazole

Clinically relevant increases in serum propiverine may cause the coadministration of propiverine with inhibitors of flavin monooxygenase (e. g. methimazole)

Sodium perchlorate, thiamazole

The co-administration may potentiate the thyreostatic effect and cause a positive perchlorate discharge test by inhibition of iodine organification

Thioguanine

Aminosalicylates, thioguanine [2] ---> SmPC of [2] of eMC

As there is in vitro evidence that aminosalicylate derivatives inhibit the TPMT enzyme, they should be administered with caution to patients receiving concurrent tioguanine therapy

Antigout preparations, thioguanine

Tioguanine may increase plasma levels of uric acid. Dosage adjustment of the antigout medicinal product may be necessary

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

It is suggested that mothers receiving tioguanine should not breast feed.

Busulfan, thioguanine

The co-administration may develop nodular regenerative hyperplasia, portal hypertension and esophageal varices

Medicines with myelotoxic effects, thioguanine

The co-administration may increase the risk of bone marrow depression

Mesalazine, thioguanine [2] ---> SmPC of [2] of eMC

As there is in vitro evidence that aminosalicylate derivatives inhibit the TPMT enzyme, they should be administered with caution to patients receiving concurrent tioguanine therapy

Olsalazine, thioguanine [2] ---> SmPC of [2] of eMC

The coadministration of olsalazine and thioguanine may result in an increased risk of myelosuppression.

Pregnancy, thioguanine [2] ---> SmPC of [2] of eMC

Its use should be avoided whenever possible during pregnancy, particularly during the first trimester.

Radiotherapy, thioguanine

Concomitant use of radiation therapy may enhance the myelotoxicity of thioguanine

Sulfasalazine, thioguanine [2] ---> SmPC of [2] of eMC

As there is in vitro evidence that aminosalicylate derivatives inhibit the TPMT enzyme, they should be administered with caution to patients receiving concurrent tioguanine therapy

Thioguanine [1], vaccinations with live organism vaccines ---> SmPC of [1] of eMC

Vaccinations with live organism vaccines are not recommended in immunocompromised individuals

Thioguanine, thiopurine methyl transferase inhibitors

The inhibition of the thiopurine methyl transferase (TPMT) may increase the plasma concentrations of thioguanine. They should be administered with caution

Thioguanine, vindesine

The co-administration may enhance the haematopoietic disorders y neutropenia. Special caution is recommended

CONTRAINDICATIONS of Thioguanine

- In view of the seriousness of the indications there are no absolute contra-indications.

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

Thiotepa (Tepadina)

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

TEPADINA may have major influence on the ability to drive and use machines. It is likely that certain adverse reactions of thiotepa like dizziness, headache and blurred vision could affect these functions.

Alkylator, metabolised by plasma cholinesterase ---> SmPC of [thiotepa] of EMA

Alkylating chemotherapeutic agents inhibit plasma pseudocholinesterase by 35% to 70%.

Anticoagulants, thiotepa [2] ---> SmPC of [2] of EMA

Patients treated with anticoagulant and antineoplastic agents should be monitored more frequently

Azole antifungals, thiotepa [2] ---> SmPC of [2] of EMA

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

It is unknown whether thiotepa is excreted in human milk. Due to its pharmacological properties and its potential toxicity for breast-fed newborns/infants, breast-feeding is contraindicated during treatment with thiotepa.

Bupropion, thiotepa [2] ---> SmPC of [2] of EMA

Thiotepa is a weak inhibitor for CYP2B6, and may thereby potentially increase plasma levels of substances metabolised via CYP2B6. Co-administration of thiotepa may lead to decreased concentrations of the active 4-OHCP.

Busulfan, thiotepa [2] ---> SmPC of [2] of EMA

The concomitant use of thiotepa and other myelosuppressive or myelotoxic agents may potentiate the risk of haematologic adverse reactions due to overlapping toxicity profiles of these medicinal products.

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

Co-administration of inducers of Cytochrome P450 may increase the metabolism of thiotepa leading to increased plasma concentrations of the active metabolite.

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

Clopidogrel, thiotepa [2] ---> SmPC of [2] of EMA

Coagulation, thiotepa [2] ---> SmPC of [2] of EMA

Due to the increase of thrombotic risk in case of malignancy, the use of anticoagulative treatment is frequent.

Cyclophosphamide, thiotepa [2] ---> SmPC of [2] of EMA

Thiotepa must not be concurrently administered with cyclophosphamide when both medicinal products are present in the same conditioning treatment. TEPADINA must be delivered after the completion of any cyclophosphamide infusion.

Cyclophosphamide, thiotepa [2] ---> SmPC of [2] of EMA

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

Excessive immunosuppression with risk of lymphoproliferation

CYP2B6 inhibitors, thiotepa [2] ---> SmPC of [2] of EMA

CYP3A4 inductors, thiotepa

The CYP3A4 induction may decrease the plasma concentrations of thiotepa and increase the concentrations of the active metabolite TEPA

CYP3A4 inhibitors, thiotepa [2] ---> SmPC of [2] of EMA

Cytotoxic agents, thiotepa [2] ---> SmPC of [2] of EMA

Patients treated with anticoagulant and antineoplastic agents should be monitored more frequently

Drugs metabolised by CYP2B6, thiotepa [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP2B6, thiotepa [2] ---> SmPC of [2] of EMA

Efavirenz, thiotepa [2] ---> SmPC of [2] of EMA

Enzyme inductors, thiotepa [2] ---> SmPC of [2] of EMA

Co-administration of inducers of Cytochrome P450 may increase the metabolism of thiotepa leading to increased plasma concentrations of the active metabolite.

Erythromycin, thiotepa [2] ---> SmPC of [2] of EMA

Fertility, thiotepa [2] ---> SmPC of [2] of EMA

As most alkylating agents, thiotepa might impair male and female fertility. Male patients should seek for sperm cryopreservation before therapy is started (see section 5.3).

Fludarabine, thiotepa [2] ---> SmPC of [2] of EMA

Fospropofol, thiotepa

Thiotepa, weak inhibitor for CYP2B6, may increase plasma concentrations of fospropofol

Hydantoins, thiotepa

Decrease of hydantoin digestive absorption by thiotepa effect and increased hepatic metabolism of thiotepa by hydantoin

Ifosfamide, thiotepa [2] ---> SmPC of [2] of EMA

Immunosuppressives, vaccinations with live organism vaccines ---> SmPC of [thiotepa] of EMA

Live virus and bacterial vaccines must not be administered to a patient receiving an immunosuppressive chemotherapeutic agent and at least three months must elapse between discontinuation of therapy and vaccination.

Irinotecan, thiotepa

Thiotepa, weak inhibitor for CYP2B6, may increase plasma concentrations of irinotecan

Live attenuated vaccines, thiotepa [2] ---> SmPC of [2] of EMA

An inactivated virus vaccine should be used instead, whenever possible (poliomyelitis).

Live attenuated vaccines, thiotepa [2] ---> SmPC of [2] of EMA

Concomitant use not recommended Live attenuated vaccines (except yellow fever): risk of systemic, possibly fatal disease. This risk is increased in subjects who are already immunosuppressed by their underlying disease.

Macrolide antibiotics, thiotepa [2] ---> SmPC of [2] of EMA

Medicines with myelotoxic effects, thiotepa [2] ---> SmPC of [2] of EMA

Melphalan, thiotepa [2] ---> SmPC of [2] of EMA

Men, thiotepa [2] ---> SmPC of [2] of EMA

Male patients should not father a child while treated and during the year after cessation of treatment (see section 5.3).

Metabolised by plasma cholinesterase, thiotepa [2] ---> SmPC of [2] of EMA

Alkylating chemotherapeutic agents, including thiotepa, inhibit plasma pseudocholinesterase by 35% to 70%.

Myelosuppressive agents, thiotepa [2] ---> SmPC of [2] of EMA

Natalizumab, thiotepa

Thiotepa may increase the adverse effects of natalizumab

Phenobarbital, thiotepa [2] ---> SmPC of [2] of EMA

Co-administration of inducers of Cytochrome P450 may increase the metabolism of thiotepa leading to increased plasma concentrations of the active metabolite.

Phenytoin, thiotepa [2] ---> SmPC of [2] of EMA

Risk of exacerbation of convulsions resulting from the decrease of phenytoin digestive absorption by cytotoxic product or risk of toxicity enhancement and loss of efficacy of the cytotoxic product due to increased hepatic metabolism by phenytoin.

Pregnancy, thiotepa [2] ---> SmPC of [2] of EMA

In pre-clinical studies thiotepa, as most alkylating agents, has been shown to cause embryofoetal lethality and teratogenicity (see section 5.3). Therefore, thiotepa is contraindicated during pregnancy.

Protease inhibitors, thiotepa [2] ---> SmPC of [2] of EMA

Rifampicin, thiotepa [2] ---> SmPC of [2] of EMA

Co-administration of inducers of Cytochrome P450 may increase the metabolism of thiotepa leading to increased plasma concentrations of the active metabolite.

Strong CYP2B6 inhibitors, thiotepa [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inductors, thiotepa [2] ---> SmPC of [2] of EMA

Co-administration of inducers of Cytochrome P450 may increase the metabolism of thiotepa leading to increased plasma concentrations of the active metabolite.

Succinylcholine, thiotepa [2] ---> SmPC of [2] of EMA

The action of succinyl-choline can be prolonged by 5 to 15 minutes.

Suxamethonium, thiotepa [2] ---> SmPC of [2] of EMA

The action of succinyl-choline can be prolonged by 5 to 15 minutes.

Tacrolimus, thiotepa [2] ---> SmPC of [2] of EMA

Excessive immunosuppression with risk of lymphoproliferation

Tamoxifen, thiotepa [2] ---> SmPC of [2] of EMA

Telithromycin, thiotepa [2] ---> SmPC of [2] of EMA

Thiotepa [1], ticlopidine ---> SmPC of [1] of EMA

Thiotepa [1], treosulfan ---> SmPC of [1] of EMA

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

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

Women of childbearing potential have to use effective contraception during treatment and a pregnancy test should be performed before treatment is started.

Thiotepa [1], yellow fever vaccine ---> SmPC of [1] of EMA

Risk of fatal generalized vaccine-induced disease. The co-administration is contraindicated

Thiotepa, trastuzumab

Trastuzumab may increase the risk of neutropenia and anemia

CONTRAINDICATIONS of Thiotepa (Tepadina)

- Hypersensitivity to active substance

- Pregnancy and lactation

- Concomitant use with yellow fever vaccine and with live virus and bacterial vaccines

https://www.ema.europa.eu/en/documents/product-information/tepadina-epar-product-information_en.pdf 07/10/2025

Other trade names: Thiotepa Riemser,

Thyrotropin alfa (Thyrogen)

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

Thyrogen may reduce the ability to drive or use machines, since dizziness and headaches have been reported.

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

It is unknown whether thyrotropin alfa /metabolites are excreted in human milk. A risk to the suckling child cannot be excluded. Thyrogen should not be used during breast-feeding.

Fertility, thyrotropin alfa [2] ---> SmPC of [2] of EMA

It is not known whether Thyrogen can affect fertility in humans.

Interactions, thyrotropin alfa [2] ---> SmPC of [2] of EMA

In clinical trials, no interactions were observed between Thyrogen and the thyroid hormones triiodothyronine (T3) and thyroxine (T4) when administered concurrently.

Pregnancy, thyrotropin alfa [2] ---> SmPC of [2] of EMA

Thyrogen in combination with diagnostic radioiodine whole body scintigraphy is contra-indicated in pregnancy (see section 4.3), because of the consequent exposure of the foetus to a high dose of radioactive material.

Renal function, thyrotropin alfa [2] ---> SmPC of [2] of EMA

Data on radioiodine kinetics indicate that the clearance of radioiodine is approximately 50% greater while euthyroid than during the hypothyroid state when renal function is decreased

CONTRAINDICATIONS of Thyrotropin alfa (Thyrogen)

- Hypersensitivity to bovine or human thyroid stimulating hormone or to any of the excipients listed in section 6.1.

- Pregnancy

https://www.ema.europa.eu/en/documents/product-information/thyrogen-epar-product-information_en.pdf 31/01/2024

Tezepelumab (Tezspire)

Antasthmatic, tezepelumab [2] ---> SmPC of [2] of EMA

A clinically relevant effect of tezepelumab on the pharmacokinetics of co-administered asthma medicinal products is not expected.

Anthelmintics, tezepelumab [2] ---> SmPC of [2] of EMA

If patients become infected while receiving treatment and do not respond to anti-helminth treatment, therapy with tezepelumab should be discontinued until infection resolves.

Asthma medicine, tezepelumab [2] ---> SmPC of [2] of EMA

Based on the population pharmacokinetic analysis, commonly co-administered asthma medicinal products (including leukotriene receptor antagonists, theophylline/aminophylline and oral corticosteroids) had no effect on tezepelumab clearance.

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

Human IgGs are known to be excreted in breast milk during the first few days after birth, which decreases to low concentrations soon afterwards; consequently, a risk to the breast-fed child cannot be excluded during this short period.

Cardiac event, tezepelumab [2] ---> SmPC of [2] of EMA

Patients should be advised of signs or symptoms suggestive of a cardiac event (for example, chest pain, dyspnoea, malaise, feeling lightheaded or faint) and to seek immediate medical attention if such symptoms occur.

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

Fertility, tezepelumab [2] ---> SmPC of [2] of EMA

There are no fertility data in humans. Animal studies showed no adverse effects of tezepelumab treatment on fertility (see section 5.3).

Infection, tezepelumab [2] ---> SmPC of [2] of EMA

Blocking thymic stromal lymphopoietin (TSLP) may theoretically increase the risk of serious infections. In placebo-controlled studies, no increase in serious infections was observed with tezepelumab.

Pregnancy, tezepelumab [2] ---> SmPC of [2] of EMA

As a precautionary measure, it is preferable to avoid the use of Tezspire during pregnancy unless the expected benefit to the pregnant mother is greater than any possible risk to the foetus.

Tezepelumab [1], vaccinations ---> SmPC of [1] of EMA

The use of live attenuated vaccines should be avoided in patients receiving tezepelumab.

CONTRAINDICATIONS of Tezepelumab (Tezspire)

- 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/tezspire-epar-product-information_en.pdf 22/10/2025

Tiagabine

Ability to drive, tiagabine [2] ---> SmPC of [2] of eMC

Tiagabine may cause dizziness or other CNS related symptoms, especially during initial treatment.

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

As a precautionary measure, it is preferable not to use tiagabine during breast-feeding unless in the opinion of the physician, the potential benefits of treatment outweigh the potential risks.

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

Anti-epileptic agents that induce hepatic enzymes enhance the metabolism of tiagabine.

Cimetidine, tiagabine [2] ---> SmPC of [2] of eMC

Cimetidine increases the bioavailability of tiagabine by about 5%. This finding isn't considered clinically important and do not warrant a dose modification

Digoxin, tiagabine [2] ---> SmPC of [2] of eMC

Tiagabine does not have any clinically significant effect on the plasma concentrations of digoxine

Enzyme inductors, tiagabine [2] ---> SmPC of [2] of eMC

Following a given dose of tiagabine, the estimated plasma concentration in non-induced patients is more than twice that in patients receiving enzyme-inducing agents.

Oral contraceptives, tiagabine [2] ---> SmPC of [2] of eMC

Tiagabine does not have any clinically significant effect on the plasma concentrations of hormones from oral contraceptive pills.

Phenobarbital, tiagabine [2] ---> SmPC of [2] of eMC

Anti-epileptic agents that induce hepatic enzymes enhance the metabolism of tiagabine.

Phenytoin, tiagabine [2] ---> SmPC of [2] of eMC

Anti-epileptic agents that induce hepatic enzymes enhance the metabolism of tiagabine.

Pregnancy, tiagabine [2] ---> SmPC of [2] of eMC

As a precautionary measure, it is preferable not to use tiagabine during pregnancy unless in the opinion of the physician, the potential benefits of treatment outweigh the potential risks.

Primidone, tiagabine [2] ---> SmPC of [2] of eMC

Anti-epileptic agents that induce hepatic enzymes enhance the metabolism of tiagabine.

Rifampicin, tiagabine

Rifampicin, enzymatic inductor, may accelerate the metabolism of tiagabine and decrease its plasma levels and effect

Stiripentol [1], tiagabine ---> SmPC of [1] of EMA

Inhibition of CYP450 isoenzyme CYP2C19 and CYP3A4 may provoke pharmacokinetic interactions. The consequences are increased plasma levels of the anticonvulsant with potential risk of overdose.

Strong CYP3A4 inductors, tiagabine

The strong CYP3A4 induction enhances the metabolism of tiagabine

Theophylline, tiagabine [2] ---> SmPC of [2] of eMC

Tiagabine does not have any clinically significant effect on the plasma concentrations of theophylline

Tiagabine [1], valproate ---> SmPC of [1] of eMC

Tiagabine does not have any clinically significant effect on the plasma concentrations of valproate

Tiagabine [1], warfarin ---> SmPC of [1] of eMC

Tiagabine does not have any clinically significant effect on the plasma concentrations of warfarin

CONTRAINDICATIONS of Tiagabine

- Gabitril should not be given to patients with a history of hypersensitivity to tiagabine or one of the excipients.

- Severely impaired liver function.

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

Tiapride

Ability to drive, tiapride

Tiapride acts on the central nervous system and can cause somnolence, dizziness, visual alterations and decreased ability to react

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

Alcohol enhances the sedative effect of neuroleptics. Association not recommended

Amantadine, tiapride

Concomitant use of tiapride and dopaminergic agonists, except levodopa, is not recommended in patients with Parkinson disease due to mutual antagonism between dopaminergic agonists and neuroleptics

Amiodarone [1], tiapride ---> 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

Amitriptyline, tiapride

Enhancement of CNS depressant effect

Amphotericin B, tiapride

It is not recommended the combination of cisapride with amphotericin IV (can induce hypokaliemia)

Anticholinergics, tiapride

Anticholinergic agents may weaken the effect of tiapride

Anticholinesterase, tiapride

Bradycardia-inducing medicinal products increase the risk of ventricular arrhythmias, particularly torsades de pointes. Clinical and electrocardiographic monitoring

Antihypertensives, tiapride

Antihypertensive effect and increased risk of orthostatic hypotension (additive effect)

Anxiolytics, tiapride

Enhancement of CNS depressant effect

Apomorphine, tiapride

Concomitant use of tiapride and dopaminergic agonists, except levodopa, is not recommended in patients with Parkinson disease due to mutual antagonism between dopaminergic agonists and neuroleptics

Baclofen, tiapride

Enhancement of CNS depressant effect

Barbiturates, tiapride

Enhancement of CNS depressant effect

Benzodiazepines, tiapride

Enhancement of CNS depressant effect

Bepridil, 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

Betablockers, tiapride

Bradycardia-inducing medicinal products increase the risk of ventricular arrhythmias, particularly torsades de pointes. Clinical and electrocardiographic monitoring

Bisoprolol, tiapride

Tiapride with betablockers given in heart failure increases the risk of ventricular arrhythmias, particularly torsades de pointes. Clinical and electrocardiographic monitoring is necessary

Breast-feeding, tiapride

Breast-feeding is not recommended during the treatment with tiapride

Bromocriptine, tiapride

Concomitant use of tiapride and dopaminergic agonists, except levodopa, is not recommended in patients with Parkinson disease due to mutual antagonism between dopaminergic agonists and neuroleptics

Cabergoline, tiapride

The combination of dopaminergic agonists, except in case of Parkinson disease, and tiapride is contraindicated due to mutual antagonism between dopaminergic agonists and neuroleptics

Cardiac glycosides, tiapride

Bradycardia-inducing medicinal products increase the risk of ventricular arrhythmias, particularly torsades de pointes. Clinical and electrocardiographic monitoring

Carteolol, tiapride

The co-administration increases the risk of heart rhythm disorders, particularly torsades de pointes

Carvedilol, tiapride

Tiapride with betablockers given in heart failure increases the risk of ventricular arrhythmias, particularly torsades de pointes. Clinical and electrocardiographic monitoring is necessary

Centrally-acting antihypertensives, tiapride

Enhancement of CNS depressant effect

Chlorpromazine, 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

Cisapride, 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

Class IA antiarrhythmic agents, 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

Class III antiarrhythmic agents, 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

Clonidine, 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

CNS depressants, tiapride

Enhancement of CNS depressant effect

Cyamemazine, 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

Diphemanil, 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, 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, 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

Dopamine agonists, neuroleptics ---> SmPC of [tiapride] of

The combination of dopaminergic agonists, except in case of Parkinson disease, and neuroleptics is contraindicated due to mutual antagonism between dopaminergic agonists and neuroleptics

Dopamine agonists, tiapride

The combination of dopaminergic agonists, except in case of Parkinson disease, and tiapride is contraindicated due to mutual antagonism between dopaminergic agonists and neuroleptics

Dopaminergic drugs, neuroleptics ---> SmPC of [tiapride] of

The combination of dopaminergic agonists, except in case of Parkinson disease, and tiapride is contraindicated due to mutual antagonism between dopaminergic agonists and neuroleptics

Doxepin, tiapride

Enhancement of CNS depressant effect

Droperidol, tiapride [2] ---> SmPC of [2] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Drugs inducing bradycardia, 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

Electrolyte imbalance, tiapride

Hypokaliemia-inducing medicinal products increase the risk of ventricular arrhythmias, particularly torsades de pointes. The combination is not recommended

Entacapone, tiapride

Concomitant use of tiapride and dopaminergic agonists, except levodopa, is not recommended in patients with Parkinson disease due to mutual antagonism between dopaminergic agonists and neuroleptics

Erythromycin, tiapride

It is not recommended the combination of cisapride with erythromycin IV due to both active principles can induce torsades de pointes or prolong the QT-interval

Flupentixol, 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

Fluphenazine, 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

Glucocorticoids, tiapride

Hypokaliemia-inducing medicinal products increase the risk of ventricular arrhythmias, particularly torsades de pointes. The combination is not recommended

Guanfacin, 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

Halofantrine, 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

Haloperidol, 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

Hydrochlorothiazide, tiapride ---> SmPC of [losartan/hydrochlorothiazide] of

Periodic monitoring of serum potassium and ECG is recommended, when hydrochlorothiazide is administered with drugs which may induce torsades de pointes

Hydroquinidine, tiapride

Concomitant use is not recommended due to increased risk of heart rhythm disorders (torsades de pointes)

Hypnotics, tiapride

Enhancement of CNS depressant effect

Hypokalemia, tiapride

Hypokaliemia-inducing medicinal products increase the risk of ventricular arrhythmias, particularly torsades de pointes. The combination is not recommended

Ibutilide, 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

Imipramine, 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

Indapamide [1], tiapride ---> SmPC of [1] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Levodopa, neuroleptics ---> SmPC of [tiapride] of

Reciprocal antagonism of effects between levodopa and neuroleptics. Association contra-indicated

Levodopa, tiapride

Reciprocal antagonism of effects between levodopa and neuroleptics. Association contra-indicated

Levodopa/carbidopa, neuroleptics ---> SmPC of [tiapride] of

Reciprocal antagonism of effects between levodopa and neuroleptics. Association contra-indicated

Levodopa/carbidopa/entacapone, neuroleptics ---> SmPC of [tiapride] of

Reciprocal antagonism of effects between levodopa and neuroleptics. Association contra-indicated

Levomepromazine, 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

Lisuride, tiapride

Concomitant use of tiapride and dopaminergic agonists, except levodopa, is not recommended in patients with Parkinson disease due to mutual antagonism between dopaminergic agonists and neuroleptics

Lithium, 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

Losartan/hydrochlorothiazide [1], tiapride ---> SmPC of [1] of eMC

Periodic monitoring of serum potassium and ECG is recommended when losartan/hydrochlorothiazide is administered with torsades de pointes-inducing medicinal products

Lumefantrine, 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

Methadone, 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

Metoprolol, tiapride

Tiapride with betablockers given in heart failure increases the risk of ventricular arrhythmias, particularly torsades de pointes. Clinical and electrocardiographic monitoring is necessary

Mianserin, tiapride

Enhancement of CNS depressant effect

Mirtazapine, tiapride

Enhancement of CNS depressant effect

Mizolastine, 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

Moxifloxacin, 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

Narcotics, tiapride

Enhancement of CNS depressant effect

Nebivolol, tiapride

Tiapride with betablockers given in heart failure increases the risk of ventricular arrhythmias, particularly torsades de pointes. Clinical and electrocardiographic monitoring is necessary

Neuroleptics, tiapride

Enhancement of CNS depressant effect

Pasireotide [1], tiapride ---> SmPC of [1] of EMA

Pasireotide should be used with caution in patients who are concomitantly receiving medicinal products that prolong the QT interval

Pentamidine, 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

Pergolide, tiapride

Concomitant use of tiapride and dopaminergic agonists, except levodopa, is not recommended in patients with Parkinson disease due to mutual antagonism between dopaminergic agonists and neuroleptics

Pilocarpine, tiapride

Bradycardia-inducing medicinal products increase the risk of ventricular arrhythmias, particularly torsades de pointes. Clinical and electrocardiographic monitoring

Pimozide, 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

Pipamperone, 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

Pipotiazine, 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

Piribedil, tiapride

Concomitant use of tiapride and dopaminergic agonists, except levodopa, is not recommended in patients with Parkinson disease due to mutual antagonism between dopaminergic agonists and neuroleptics

Pizotifen, tiapride

Enhancement of CNS depressant effect

Pramipexole, tiapride

Concomitant use of tiapride and dopaminergic agonists, except levodopa, is not recommended in patients with Parkinson disease due to mutual antagonism between dopaminergic agonists and neuroleptics

Pregnancy, tiapride

It can be considered the use of tiapride during the whole pregnancy. Close monitoring of the newborn

QT interval prolonging drugs, 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

Quinagolide, tiapride

The combination of dopaminergic agonists, except in case of Parkinson disease, and tiapride is contraindicated due to mutual antagonism between dopaminergic agonists and neuroleptics

Quinidine, 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

Rivastigmine [1], tiapride ---> SmPC of [1] 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.

Ropinirole, tiapride

Concomitant use of tiapride and dopaminergic agonists, except levodopa, is not recommended in patients with Parkinson disease due to mutual antagonism between dopaminergic agonists and neuroleptics

Sedating antihistamines, tiapride

Enhancement of CNS depressant effect

Sedative antidepressants, tiapride

Enhancement of CNS depressant effect

Selegiline, tiapride

Concomitant use of tiapride and dopaminergic agonists, except levodopa, is not recommended in patients with Parkinson disease due to mutual antagonism between dopaminergic agonists and neuroleptics

Sertindole, 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

Sotalol, tiapride [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 is contraindicated

Sparfloxacin, 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

Spiramycin, tiapride

It is not recommended the combination of cisapride with spiramycin IV due to both active principles can induce torsades de pointes or prolong the QT-interval

Stimulant laxatives, tiapride

Hypokaliemia-inducing medicinal products increase the risk of ventricular arrhythmias, particularly torsades de pointes. The combination is not recommended

Sulpiride, 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

Sultopride, 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

Telmisartan/hydrochlorothiazide [1], tiapride ---> SmPC of [1] of EMA

Thalidomide, tiapride

Enhancement of CNS depressant effect

Thioridazine, 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

Tiapride, torsades de pointes inducing and QT interval prolonging drugs

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

Tiapride, torsades de pointes inducing drugs

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

Tiapride, tricyclic antidepressant

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

Tiapride, trifluoperazine

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

Tiapride, trimipramine

Enhancement of CNS depressant effect

Tiapride, veralipride

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

Tiapride, verapamil

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

Tiapride, vincamine

It is not recommended the combination of cisapride with vincamine IV due to both active principles can induce torsades de pointes or prolong the QT-interval

Tiapride, xipamide

The combination increases the risk of ventricular arrhythmias, particularly torsades de pointes (favored by hypokaliemia). It is recommended a special caution

Tiapride, zuclopenthixol

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

Tibolone

Anticoagulants, tibolone [2] –––> SmPC of [2] of eMC

Since tibolone may increase blood fibrinolytic activity, it may enhance the effect of anticoagulants. This effect has been demonstrated with warfarin.

Barbiturates, tibolone [2] –––> SmPC of [2] of eMC

CYP3A4 inducing compounds such as barbiturates, carbamazepine, hydantoins and rifampicin may enhance the metabolism of tibolone and thus affect its therapeutic effect.

Breast–feeding, tibolone [2] –––> SmPC of [2] of eMC

Tibolone is contraindicated during lactation

Carbamazepine, tibolone [2] –––> SmPC of [2] of eMC

CYP3A4 inducing compounds such as barbiturates, carbamazepine, hydantoins and rifampicin may enhance the metabolism of tibolone and thus affect its therapeutic effect.

Drugs primarily metabolised by CYP3A4, tibolone [2] –––> SmPC of [2] of eMC

An in vivo study showed that simultaneous treatment of tibolone affects pharmacokinetics of the cytochrome P450 3A4 substrate midazolam to a moderate extent. Based on this, drug interactions with other CYP3A4 substrates might be expected

Hydantoins, tibolone [2] –––> SmPC of [2] of eMC

CYP3A4 inducing compounds such as barbiturates, carbamazepine, hydantoins and rifampicin may enhance the metabolism of tibolone and thus affect its therapeutic effect.

Midazolam, tibolone [2] –––> SmPC of [2] of eMC

Pregnancy, tibolone [2] –––> SmPC of [2] of eMC

Tibolone is contraindicated during pregnancy. If pregnancy occurs during medication with tibolone, treatment should be withdrawn immediately.

Rifampicin, tibolone [2] –––> SmPC of [2] of eMC

CYP3A4 inducing compounds such as barbiturates, carbamazepine, hydantoins and rifampicin may enhance the metabolism of tibolone and thus affect its therapeutic effect.

St. John's wort, tibolone [2] –––> SmPC of [2] of eMC

St. John's wort may induce the metabolism of oestrogens and progestogens via CYP3A4. Clinically, an increased metabolism of oestrogens and progestogens may lead to decreased effect and changes in the uterine bleeding profile.

Strong CYP3A4 inductors, tibolone [2] –––> SmPC of [2] of eMC

CYP3A4 inducing compounds such as barbiturates, carbamazepine, hydantoins and rifampicin may enhance the metabolism of tibolone and thus affect its therapeutic effect.

Tibolone [1], warfarin –––> SmPC of [1] of eMC

Since tibolone may increase blood fibrinolytic activity, it may enhance the effect of anticoagulants. This effect has been demonstrated with warfarin.

CONTRAINDICATIONS of Tibolone

– Pregnancy and lactation

– Known, past or suspected breast cancer – tibolone increased the risk of breast cancer recurrence in a placebo controlled trial.

– Known or suspected oestrogen–dependent malignant tumours (e.g. endometrial cancer)

– Undiagnosed genital bleeding

– Untreated endometrial hyperplasia

– Previous or current venous thromboembolism (deep venous thrombosis, pulmonary embolism)

– Known thrombophilic disorders (e.g. protein C, protein S, or antithrombin deficiency)

– Any history of arterial thromboembolic disease (e.g. angina, myocardial infarction, stroke or TIA)

– Acute liver disease, or a history of liver disease as long as liver function tests have failed to return to normal

– Known hypersensitivity to the active substance or to any of the excipients

– Porphyria

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

Ticagrelor (Brilique)

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

During treatment with ticagrelor, dizziness and confusion have been reported. Therefore, patients who experience these symptoms should be cautious while driving or using machines.

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

No evidence of clinically significant adverse interactions with these medicinal products was observed.

Acetylsalicylic acid, ticagrelor [2] ---> SmPC of [2] of EMA

Co-administration of ticagrelor with heparin, enoxaparin and ASA or desmopressin did not have any effect on the pharmacokinetics of ticagrelor or the active metabolite or on ADP-induced platelet aggregation compared with ticagrelor alone.

Adagrasib [1], ticagrelor ---> SmPC of [1] of EMA

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

No evidence of clinically significant adverse interactions with these medicinal products was observed.

Aminocaproic acid, ticagrelor [2] ---> SmPC of [2] of EMA

Antifibrinolytic therapy and/or recombinant factor VIIa may increase haemostasis. Ticagrelor may be resumed after the cause of bleeding has been identified and controlled.

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

Other moderate CYP3A4 inhibitors (e.g. amprenavir, aprepitant, erythromycin and fluconazole) would be expected to have a similar effect and can as well be co-administered with ticagrelor.

Antifibrinolytics, ticagrelor [2] ---> SmPC of [2] of EMA

Antifibrinolytic therapy and/or recombinant factor VIIa may increase haemostasis. Ticagrelor may be resumed after the cause of bleeding has been identified and controlled.

Aprepitant, ticagrelor [2] ---> SmPC of [2] of EMA

Other moderate CYP3A4 inhibitors (e.g. amprenavir, aprepitant, erythromycin and fluconazole) would be expected to have a similar effect and can as well be co-administered with ticagrelor.

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

Other strong inhibitors of CYP3A4 (clarithromycin, nefazodone, ritonavir and atazanavir) would be expected to have similar effects and therefore concomitant use of strong CYP3A4 inhibitors with ticagrelor is contraindicated (see section 4.3).

Atazanavir/cobicistat [1], ticagrelor ---> 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.

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

Co-administration of atorvastatin and ticagrelor increased atorvastatin acid Cmax by 23% and AUC by 36%. These increases are not considered clinically significant.

Betablockers, ticagrelor [2] ---> SmPC of [2] of EMA

No evidence of clinically significant adverse interactions with these medicinal products was observed.

Betablockers, ticagrelor [2] ---> SmPC of [2] of EMA

No evidence of clinically significant adverse reactions was observed after coadministration with one or more medicines known to induce bradycardia (e.g. 96% beta blockers, 33% calcium channel blockers diltiazem and verapamil and 4% digoxin).

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

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

Calcium antagonists, ticagrelor [2] ---> SmPC of [2] of EMA

Cangrelor [1], ticagrelor ---> SmPC of [1] of EMA

A pharmacodynamic interaction study has been conducted with cangrelor and ticagrelor. No interaction on cangrelor was observed. Patients can be transitioned from cangrelor to ticagrelor without interruption of antiplatelet effect.

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

Other CYP3A inducers (e.g. phenytoin, carbamazepine and phenobarbital) would be expected to decrease the exposure to ticagrelor as well.

Cisapride, ticagrelor [2] ---> SmPC of [2] of EMA

Ticagrelor is a mild CYP3A4 inhibitor. Co-administration of ticagrelor and CYP3A4 substrates with narrow therapeutic indices is not recommended, as ticagrelor may increase the exposure to these medicinal products

Citalopram, ticagrelor [2] ---> SmPC of [2] of EMA

Due to reports of cutaneous bleeding abnormalities with SSRIs, caution is advised when administering SSRIs with ticagrelor as this may increase the risk of bleeding.

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

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

Co-administration of cyclosporine with ticagrelor increased ticagrelor Cmax and AUC. The AUC of the active metabolite was increased and Cmax was decreased. If the association cannot be avoided, their concomitant use should be made with caution

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

The inhibition of P-glycoprotein may increase the bioavailability of dabigatran. Caution is recommended

Darunavir/cobicistat [1], ticagrelor ---> SmPC of [1] 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

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], ticagrelor ---> SmPC of [1] of EMA

Co-administration is contraindicated due to the potential for serious and/or life-threatening adverse reactions

Darunavir/ritonavir, ticagrelor ---> 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

Dasabuvir with ombitasvir/paritaprevir/ritonavir, ticagrelor ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of E

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

Desmopressin, ticagrelor [2] ---> SmPC of [2] of EMA

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

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

Diltiazem, ticagrelor [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inhibitors - Co-administration of diltiazem with ticagrelor increased the ticagrelor Cmax by 69% and AUC to 2.7-fold and decreased the active metabolite Cmax by 38% and AUC was unchanged.

Drugs inducing bradycardia, ticagrelor [2] ---> SmPC of [2] of EMA

Due to observations of mostly asymptomatic ventricular pauses and bradycardia, caution should be exercised when administering ticagrelor concomitantly with medicinal products known to induce bradycardia

Drugs metabolised by CYP2C9, ticagrelor [2] ---> SmPC of [2] of EMA

Ticagrelor is not a CYP2C9 inhibitor and unlikely to alter the CYP2C9 mediated metabolism of medicinal products like warfarin and tolbutamide.

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, ticagrelor [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP3A4, ticagrelor

Ticagrelor, weak CYP3A4 inhibitor, may increase the plasma concentrations of the medicinal products metabolized by CYP3A4

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.

Enoxaparin, ticagrelor [2] ---> SmPC of [2] of EMA

Ergot derivatives, ticagrelor [2] ---> SmPC of [2] of EMA

Ergotamine, ticagrelor [2] ---> SmPC of [2] of EMA

Erythromycin, ticagrelor [2] ---> SmPC of [2] of EMA

Other moderate CYP3A4 inhibitors (e.g. amprenavir, aprepitant, erythromycin and fluconazole) would be expected to have a similar effect and can as well be co-administered with ticagrelor.

Fertility, ticagrelor [2] ---> SmPC of [2] of EMA

Ticagrelor had no effect on male or female fertility in animals (see section 5.3).

Fluconazole, ticagrelor [2] ---> SmPC of [2] of EMA

Other moderate CYP3A4 inhibitors (e.g. amprenavir, aprepitant, erythromycin and fluconazole) would be expected to have a similar effect and can as well be co-administered with ticagrelor.

Grapefruit juice, ticagrelor [2] ---> SmPC of [2] of EMA

A 2-fold increase of ticagrelor exposure was observed after daily consumption of large quantities of grapefruit juice (3 x 200 ml). This magnitude of increased exposure is not expected to be clinically relevant to most patients.

Heparin, ticagrelor [2] ---> SmPC of [2] of EMA

Co-administration of ticagrelor with heparin, enoxaparin or desmopressin had no effect on activated partial thromboplastin time (aPTT), activated coagulation time (ACT) or factor Xa assays

Heparin, ticagrelor [2] ---> SmPC of [2] of EMA

Ketoconazole, ticagrelor [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inhibitors - Co-administration of ketoconazole with ticagrelor increased the ticagrelor Cmax and AUC equal to 2.4-fold and 7.3-fold, respectively.

Levonorgestrel/ethinylestradiol, ticagrelor [2] ---> SmPC of [2] of EMA

Co-administration of ticagrelor and levonorgestrel and ethinyl estradiol increased ethinyl estradiol exposure approximately 20% but did not alter the pharmacokinetics of levonorgestrel.

Lomitapide [1], ticagrelor ---> SmPC of [1] of EMA

Weak CYP3A4 inhibitors are expected to increase the exposure of lomitapide when taken simultaneously. Separate the dose of the medications by 12 hours OR decrease the dose of Lojuxta by half.

Lovastatine, ticagrelor [2] ---> SmPC of [2] of EMA

The concomitant use of ticagrelor with doses of lovastatin greater than 40 mg is not recommended

Moderate CYP3A4 inhibitors, ticagrelor [2] ---> SmPC of [2] of EMA

Other moderate CYP3A4 inhibitors (e.g. amprenavir, aprepitant, erythromycin and fluconazole) would be expected to have a similar effect and can as well be co-administered with ticagrelor.

Morphine, ticagrelor [2] ---> SmPC of [2] of EMA

A delayed and decreased exposure to oral P2Y12 inhibitors, including ticagrelor and its active metabolite, has been observed in patients with ACS treated with morphine (35% reduction in ticagrelor exposure).

Morphine, ticagrelor [2] ---> SmPC of [2] of EMA

In patients with ACS, in whom morphine cannot be withheld and fast P2Y12 inhibition is deemed crucial, the use of a parenteral P2Y12 inhibitor may be considered.

Nefazodone, ticagrelor [2] ---> SmPC of [2] of EMA

NSAID, ticagrelor [2] ---> SmPC of [2] of EMA

If clinically indicated, ticagrelor should be used with caution in the patients with coadministration of medicines that may increase the risk of bleeding within 24 hours of ticagrelor dosing.

Ombitasvir/paritaprevir/ritonavir [1], ticagrelor ---> SmPC of [1] of EMA

Oral anticoagulants, ticagrelor [2] ---> SmPC of [2] of EMA

If clinically indicated, ticagrelor should be used with caution in the patients with coadministration of medicines that may increase the risk of bleeding within 24 hours of ticagrelor dosing.

Oral contraceptives, ticagrelor [2] ---> SmPC of [2] of EMA

No clinically relevant effect on oral contraceptive efficacy is expected when levonorgestrel and ethinyl estradiol are co-administered with ticagrelor.

P-glycoprotein substrates with small therapeutic index, 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

P-glycoprotein substrates, ticagrelor [2] ---> SmPC of [2] of EMA

Ticagrelor is also a P-glycoprotein (P-gp) substrate and a weak P-gp inhibitor and may increase the exposure of P-gp substrates.

Paroxetine, ticagrelor [2] ---> SmPC of [2] of EMA

Due to reports of cutaneous bleeding abnormalities with SSRIs, caution is advised when administering SSRIs with ticagrelor as this may increase the risk of bleeding.

Phenobarbital, ticagrelor [2] ---> SmPC of [2] of EMA

Other CYP3A inducers (e.g. phenytoin, carbamazepine and phenobarbital) would be expected to decrease the exposure to ticagrelor as well.

Phenytoin, ticagrelor [2] ---> SmPC of [2] of EMA

Other CYP3A inducers (e.g. phenytoin, carbamazepine and phenobarbital) would be expected to decrease the exposure to ticagrelor as well.

Potent P-glycoprotein inhibitors and moderate CYP3A4 inhibitors, ticagrelor [2] ---> SmPC of [2] of EMA

Concomitant use of ticagrelor with drugs that are potent P-glycoprotein inhibitors and moderate CYP3A4 inhibitors may increase ticagrelor exposure. If the association cannot be avoided, their concomitant use should be made with caution

Pregnancy, ticagrelor [2] ---> SmPC of [2] of EMA

There are no or limited amount of data from the use of ticagrelor in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Ticagrelor is not recommended during pregnancy.

Proton pump inhibitors, ticagrelor [2] ---> SmPC of [2] of EMA

No evidence of clinically significant adverse interactions with these medicinal products was observed.

Quinidine, ticagrelor [2] ---> SmPC of [2] of EMA

Rifampicin, ticagrelor [2] ---> SmPC of [2] of EMA

Co-administration of rifampicin with ticagrelor decreased ticagrelor Cmax and AUC by 73% and 86%, respectively. The Cmax of the active metabolite was unchanged and the AUC was decreased by 46%, respectively.

Ritonavir, ticagrelor [2] ---> SmPC of [2] of EMA

Rosuvastatin, ticagrelor [2] ---> SmPC of [2] of EMA

Ticagrelor might affect renal excretion of rosuvastatin, increasing the risk for rosuvastatin accumulation. In some cases, concomitant use of ticagrelor and rosuvastatin led to renal function decrease, increased CPK level and rhabdomyolysis.

Sertraline, ticagrelor [2] ---> SmPC of [2] of EMA

Due to reports of cutaneous bleeding abnormalities with SSRIs, caution is advised when administering SSRIs with ticagrelor as this may increase the risk of bleeding.

Simvastatine, ticagrelor [2] ---> SmPC of [2] of EMA

Co-administration of ticagrelor with doses of simvastatin exceeding 40 mg daily could cause adverse effects of simvastatin and should be weighed against potential benefits

SSRI, ticagrelor [2] ---> SmPC of [2] of EMA

Due to reports of cutaneous bleeding abnormalities with SSRIs, caution is advised when administering SSRIs with ticagrelor as this may increase the risk of bleeding.

Statins metabolised by CYP3A4, ticagrelor [2] ---> SmPC of [2] of EMA

A similar effect on other statins metabolised by CYP3A4 cannot be excluded. Patients in PLATO receiving ticagrelor took a variety of statins, with no concern of an association with statin safety among the 93% of the PLATO cohort

Statins, ticagrelor [2] ---> SmPC of [2] of EMA

No evidence of clinically significant adverse interactions with these medicinal products was observed.

Strong CYP3A4 inductors, ticagrelor [2] ---> SmPC of [2] of EMA

Co-administration of ticagrelor with potent CYP3A inducers may decrease exposure and efficacy of ticagrelor, therefore, their concomitant use with ticagrelor is discouraged.

Strong CYP3A4 inhibitors, ticagrelor [2] ---> SmPC of [2] of EMA

Strong P-gp inhibitors, ticagrelor

The strong inhibition of P-glycoprotein may increase ticagrelor exposure. The concomitant use should be made with caution

Thrombolytics, ticagrelor [2] ---> SmPC of [2] of EMA

If clinically indicated, ticagrelor should be used with caution in the patients with coadministration of medicines that may increase the risk of bleeding within 24 hours of ticagrelor dosing.

Ticagrelor [1], tolbutamide ---> SmPC of [1] of EMA

Ticagrelor is not a CYP2C9 inhibitor and unlikely to alter the CYP2C9 mediated metabolism of medicinal products like warfarin and tolbutamide.

Ticagrelor [1], tranexamic acid ---> SmPC of [1] of EMA

Antifibrinolytic therapy and/or recombinant factor VIIa may increase haemostasis. Ticagrelor may be resumed after the cause of bleeding has been identified and controlled.

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

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

Ticagrelor is not a CYP2C9 inhibitor and unlikely to alter the CYP2C9 mediated metabolism of medicinal products like warfarin and tolbutamide.

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

Women of childbearing potential should use appropriate contraceptive measures to avoid pregnancy during ticagrelor therapy.

Ticagrelor, vorapaxar [2] ---> SmPC of [2] of EMA

When vorapaxar was co-administered with prasugrel, no clinically significant pharmacokinetic interaction was demonstrated. Vorapaxar should not be used with prasugrel or ticagrelor

CONTRAINDICATIONS of Ticagrelor (Brilique)

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

- Active pathological bleeding.

- History of intracranial haemorrhage

- Severe hepatic impairment

- Co-administration of ticagrelor with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, nefazodone, ritonavir, and atazanavir) is contraindicated, as co-administration may lead to a substantial increase in exposure to ticagrelor

https://www.ema.europa.eu/en/documents/product-information/brilique-epar-product-information_en.pdf 24/04/2025

Ticlopidine

Ability to drive, ticlopidine

Dizziness may occur

Acenocoumarol, ticlopidine

Increased bleeding risk (combination of the anticoagulant and platelet aggregation inhibitor effect)

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

It is considered unsafe to take NSAIDs in combination with platelet aggregation inhibitors due to increased risk of bleeding. If coadministration is unavoidable, patient should be closely monitored.

Aminophylline, ticlopidine

Ticlopidine reduces clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Antacids, ticlopidine

The co-administration of ticlopidine and antacids decreases the plasma levels of ticlopidine about 20-30%.

Bemiparin, ticlopidine

The concomitant administration of bemiparin and ticlopidine is not advisable. Increased risk of bleeding.

Breast-feeding, ticlopidine

Ticlopidine should not be used during breast-feeding unless clearly necessary.

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

Co-administration of medicinal products that may affect the metabolism of bupropion via CYP2B6 isoenzyme may result in increased bupropion plasma levels and lower levels of active metabolite hydroxy-bupropion.

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

The plasma concentrations of carbamazepine may be increased

Certoparin, ticlopidine

The co-administration may enhance the pharmacological effects of certoparin

Cimetidine, ticlopidine

The chronic administration of cimetidine increases significantly the plasma levels of ticlopidine

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

The co-administration may increase the bleeding risk. The CYP2C19 inhibition may increase the plasma levels of citalopram

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

The potent CYP2C19 inhibition may increase the exposure to the active metabolite of clobazam. Dosage adjustment of clobazam may be necessary

Clopidogrel [1], ticlopidine ---> SmPC of [1] of EMA

Since clopidogrel is metabolised to its active metabolite partly by CYP2C19, use of medicinal products that inhibit the activity of this enzyme would be expected to result in reduced drug levels of the active metabolite of clopidogrel.

Clopidogrel/acetylsalicylic acid [1], ticlopidine ---> SmPC of [1] of EMA

Cyclophosphamide, ticlopidine

The CYP2B6 and CYP3A4 inhibition may decrease the efficacy of cyclophosphamide (prodrug)

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

Decreased cyclosporine plasma levels.

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

The co-administration may increase the risk of bleeding

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

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

Desirudin [1], ticlopidine ---> SmPC of [1] of EMA

Desirudin should be used with caution in conjunction with medicinal products which affect platelet function

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.

Digoxin, ticlopidine

Concomitant use of ticlopidine and digoxin reduces the plasma concentrations of digoxin (ca. 15 %). Changing of digoxin effects are not expected

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.

Drotrecogin alfa [1], ticlopidine ---> SmPC of [1] of EMA

Caution should be employed when using drotrecogin alfa with other drugs that affect haemostasis

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

The co-administration may enhance the pharmacologic effect and increase the bleeding risk. A close clinical and laboratory monitoring is recommended

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

Caution should be exercised when used escitalopram concomitantly with CYP2C19 inhibitors. A reduction in the dose of escitalopram may be necessary based on monitoring of side-effects during concomitant treatment.

Fondaparinux [1], ticlopidine ---> SmPC of [1] of EMA

Other antiplatelet medicinal products and NSAIDs should be used with caution. If co-administration is essential, close monitoring is necessary.

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

CYP2C9/2C19 inhibition may increase plasma phenytoin concentrations

Heparin, ticlopidine

Increased bleeding risk (combination of the anticoagulant and platelet aggregation inhibitor effect)

Ibuprofen, ticlopidine [2] ---> SmPC of [2] of eMC

It is considered unsafe to take NSAIDs in combination with platelet aggregation inhibitors due to increased risk of bleeding. If coadministration is unavoidable, patient should be closely monitored.

Iloprost [1], ticlopidine ---> SmPC of [1] of EMA

Since iloprost inhibits platelet function its use with anticoagulants or other inhibitors of platelet aggregation may increase the risk of bleeding. A careful monitoring of the patients is recommended.

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

Increased risk of bleeding

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

There is an increased risk of gastrointestinal bleeding when anti-platelet agents are combined with NSAIDs.

Melagatran, ticlopidine

The co-administration may significantly increase the bleeding risk

Naltrexone/bupropion [1], ticlopidine ---> SmPC of [1] of EMA

Co-administration of medicinal products that may inhibit the metabolism of bupropion via CYP2B6 isoenzyme may result in increased bupropion plasma levels and lower levels of active metabolite hydroxybupropion.

NSAID, ticlopidine [2] ---> SmPC of [2] of eMC

It is considered unsafe to take NSAIDs in combination with platelet aggregation inhibitors due to increased risk of bleeding. If coadministration is unavoidable, patient should be closely monitored.

Oral anticoagulants, ticlopidine

Increased bleeding risk (combination of the anticoagulant and platelet aggregation inhibitor effect)

Parnaparin, ticlopidine

Increased bleeding risk (combination of the anticoagulant and platelet aggregation inhibitor effect)

Phenobarbital, ticlopidine

Chronic administration of phenobarbital showed no effect on the inhibition of platelet aggregation by ticlopidine

Phenytoin, ticlopidine ---> SmPC of [fosphenytoin] of

CYP2C9/2C19 inhibition may increase plasma phenytoin concentrations

Platelet aggregation inhibitors, ticlopidine

Increased bleeding risk (enhancement of platelet aggregation inhibitor effect)

Pregnancy, ticlopidine

Ticlopidine should not be used during pregnancy unless clearly necessary.

Reteplase [1], ticlopidine ---> SmPC of [1] of EMA

Caution should be employed when used reteplase with other medicinal products affecting haemostasis

Salicylates, ticlopidine [2] ---> SmPC of [2] of eMC

It is considered unsafe to take NSAIDs in combination with platelet aggregation inhibitors due to increased risk of bleeding. If coadministration is unavoidable, patient should be closely monitored.

Sertraline [1], ticlopidine ---> SmPC of [1] of EMA

The risk of bleeding may be increased when medicines acting on platelet function or other medicines that might increase bleeding risk are concomitantly administered with SSRIs

SSRI, ticlopidine ---> SmPC of [sertraline] of

The risk of bleeding may be increased when medicines acting on platelet function or other medicines that might increase bleeding risk are concomitantly administered with SSRIs

Tenecteplase [1], ticlopidine ---> SmPC of [1] of EMA

Medicinal products that affect coagulation or those that alter platelet function may increase the risk of bleeding prior to, during or after tenecteplase therapy.

Tenoxicam, ticlopidine

Concomitant use with ticlopidine should be avoided

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

Ticlopidine reduces clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Thiotepa [1], ticlopidine ---> SmPC of [1] of EMA

Tiaprofenic acid, ticlopidine [2] ---> SmPC of [2] of eMC

It is considered unsafe to take NSAIDs in combination with platelet aggregation inhibitors due to increased risk of bleeding. If coadministration is unavoidable, patient should be closely monitored.

Ticlopidine, tizanidine [2] ---> SmPC of [2] of eMC

Concomitant administration of drugs known to inhibit the activity of CYP1A2 may increase the plasma levels of tizanidine. Co-administration of tizanidine inhibitors of CYP1A2 is not recommended

Ticlopidine, urokinase [2] ---> SmPC of [2] of eMC

Due to increased risk of haemorrhage, concomitant use of urokinase and active substances that affect platelet function should be avoided

Ticlopidine, venlafaxine

Possible prolongation of bleeding time. Caution is recommended

Ticlopidine, warfarin

The co-administration may enhance the anticoagulant effect

Ticlopidine, ximelagatran

The co-administration may significantly increase the bleeding risk

Tigecycline (Tygacil)

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

Dizziness may occur and this may have an effect on driving and use of machines

Antibiotics, oral contraceptives ---> SmPC of [tigecycline] of EMA

Concurrent use of antibiotics with oral contraceptives may render oral contraceptives less effective.

Antibiotics, tigecycline [2] ---> SmPC of [2] of EMA

In in vitro studies, no antagonism has been observed between tigecycline and other commonly used antibiotic classes.

Anticoagulants, tigecycline [2] ---> SmPC of [2] of EMA

Since tigecycline may prolong both prothrombin time (PT) and activated partial thromboplastin time (aPTT), the relevant coagulation tests should be closely monitored when tigecycline is co-administered with anticoagulants

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

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

Calcineurin inhibitors, tigecycline [2] ---> SmPC of [2] of EMA

Concomitant use of tigecycline and calcineurin inhibitors such as tacrolimus or cyclosporine may lead to an increase in serum trough concentrations of the calcineurin inhibitors.

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

Concomitant use of tigecycline and calcineurin inhibitors such as tacrolimus or cyclosporine may lead to an increase in serum trough concentrations of the calcineurin inhibitors.

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

Coadministration of P-gp inhibitors could affect the pharmacokinetics of tigecycline

CYP450, tigecycline [2] ---> SmPC of [2] of EMA

In vitro, tigecycline is neither a competitive inhibitor nor an irreversible inhibitor of CYP450 enzymes

CYP450, tigecycline [2] ---> SmPC of [2] of EMA

Tigecycline is not extensively metabolised. Therefore, clearance of tigecycline is not expected to be affected by active substances that inhibit or induce the activity of the CYP450 isoforms.

Digoxin, tigecycline [2] ---> SmPC of [2] of EMA

No dosage adjustment is necessary when tigecycline is administered with digoxin.

Fertility, tigecycline [2] ---> SmPC of [2] of EMA

The effects of tigecycline on fertility in humans have not been studied. Nonclinical studies conducted with tigecycline in rats do not indicate harmful effects with respect to fertility or reproductive performance.

Ketoconazole, tigecycline [2] ---> SmPC of [2] of EMA

Based on an in vitro study tigecycline is a P-gp substrate. Co-administration of P-gp inhibitors (e.g., ketoconazole or cyclosporine) or P-gp inducers (e.g., rifampicin) could affect the pharmacokinetics of tigecycline

Oral contraceptives, tigecycline [2] ---> SmPC of [2] of EMA

Concurrent use of antibiotics with oral contraceptives may render oral contraceptives less effective.

P-gp inductors, tigecycline [2] ---> SmPC of [2] of EMA

P-gp inhibitors, tigecycline [2] ---> SmPC of [2] of EMA

Pregnancy, tigecycline [2] ---> SmPC of [2] of EMA

Tigecycline should not be used during pregnancy unless the clinical condition of the woman requires treatment with tigecycline.

Rifampicin, tigecycline [2] ---> SmPC of [2] of EMA

Tacrolimus, tigecycline [2] ---> SmPC of [2] of EMA

Concomitant use of tigecycline and calcineurin inhibitors such as tacrolimus or cyclosporine may lead to an increase in serum trough concentrations of the calcineurin inhibitors.

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

Warfarin did not affect the pharmacokinetic profile of tigecycline.

CONTRAINDICATIONS of Tigecycline (Tygacil)

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

- Patients hypersensitive to tetracycline class antibiotics may be hypersensitive to tigecycline.

https://www.ema.europa.eu/en/documents/product-information/tygacil-epar-product-information_en.pdf 22/10/2025

Other trade names: Tigecycline Accord,

Tildrakizumab (Ilumetri)

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

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

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

Concomitant medicinal products affecting tildrakizumab pharmacokinetics are not expected since it is cleared from the body by general protein catabolism processes with no contribution of cytochrome P450 (CYP450) enzymes

Fertility, tildrakizumab [2] ---> SmPC of [2] of EMA

The effect of Ilumetri on human fertility has not been evaluated. Animal studies do not indicate direct or indirect harmful effects with respect to fertility (see section 5.3).

Immunosuppressives, tildrakizumab [2] ---> SmPC of [2] of EMA

The safety and efficacy of tildrakizumab in combination with other immunosupressive agents, including biologics, or phototherapy has not been evaluated.

Pharmacokinetics, tildrakizumab [2] ---> SmPC of [2] of EMA

Furthermore, tildrakizumab does not impact the pharmacokinetics of concomitant medicinal products metabolised by CYP450 enzymes either through direct or indirect mechanisms (see section 5.2).

Pregnancy, tildrakizumab [2] ---> SmPC of [2] of EMA

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

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

Patients treated with Ilumetri should not receive live vaccines during treatment and for at least 17 weeks after treatment

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

Women of childbearing potential should use an effective method of contraception during treatment and for at least 17 weeks after treatment.

CONTRAINDICATIONS of Tildrakizumab (Ilumetri)

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

- Clinically important active infection, e.g. active tuberculosis (see section 4.4).

https://www.ema.europa.eu/en/documents/product-information/ilumetri-epar-product-information_en.pdf 01/07/2024

Tilmanocept (Lymphoseek)

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

If administration is considered necessary, breast-feeding should be interrupted for 24 hours post injection and the expressed feeds discarded.

Fertility, tilmanocept [2] ---> SmPC of [2] of EMA

Animal fertility studies have not been conducted with Lymphoseek.

Pregnancy, tilmanocept [2] ---> SmPC of [2] of EMA

Radionuclide procedures carried out on pregnant women also involve radiation dose to the foetus. Only essential investigations should therefore be carried out during pregnancy, when the likely benefit far exceeds the risk

Tilmanocept [1], tracing agents ---> SmPC of [1] of EMA

Additional tracing agents should not be injected within 30 minutes of Lymphoseek administration.

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

When an administration of radiopharmaceuticals to a woman of childbearing potential is intended, it is important to determine whether or not she is pregnant. Any woman who has missed a period should be assumed to be pregnant until proven otherwise.

CONTRAINDICATIONS of Tilmanocept (Lymphoseek)

- Hypersensitivity to the active substance, to any of the excipients listed in section 6.1 or to any of the components of the radiolabelled product.

https://www.ema.europa.eu/en/documents/product-information/lymphoseek-epar-product-information_en.pdf 19/04/2024

Timolol

Ability to drive, timolol [2] ---> SmPC of [2] of eMC

When driving vehicles or operating machines it should be taken into account that occasionally dizziness or fatigue may occur.

Acetazolamide, timolol

The co-administration can enhance the effect of acetazolamide

Acetohexamide, timolol

Timolol may decrease symptoms of hypoglycemia.

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

Alcohol induces increased plasma levels of hepatically metabolised beta blockers

Aminophylline, timolol

Antagonism and increased effect of theophylline

Amiodarone, timolol ---> SmPC of [bimatoprost/timolol] of

There is a potential for additive effects resulting in hypotension, and/or marked bradycardia when ophthalmic beta-blockers solution is administered concomitantly with oral anti-arrhythmics (including amiodarone)

Anaesthetics, timolol [2] ---> SmPC of [2] of eMC

Concomitant use of beta blockers and anaesthetics may attenuate reflex tachycardia and increase the risk of hypotension.

Antiarrhythmics, timolol ---> SmPC of [bimatoprost/timolol] of

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

Concomitant administration of timolol with antihypertensive agents may increase the blood pressure lowering effect.

Atazanavir/cobicistat [1], timolol ---> SmPC of [1] of EMA

Concentrations of the beta-blocker may be increased when coadministered with EVOTAZ. The mechanism of interaction is inhibition of CYP2D6 by cobicistat. A dose reduction of the beta-blocker may be necessary.

Barbiturates, timolol [2] ---> SmPC of [2] of eMC

Concomitant administration of timolol with barbiturates may increase the blood pressure lowering effect.

Beta-adrenergic receptor blockers [1], timolol ---> SmPC of [1] of EMA

There is a potential for additive effects resulting in hypotension and/or marked bradycardia

Beta2-adrenergic agonists, timolol

Decrease of beta2-adrenergic agonist effect and possible induction of severe bronchospasms

Betablockers, timolol ---> SmPC of [bimatoprost/timolol] of

Breast-feeding, timolol

Beta-blockers are excreted in breast milk. However, at therapeutic doses of timolol in eye drops it is not likely that sufficient amounts would be present in breast milk to produce clinical symptoms

Calcium antagonists, timolol ---> SmPC of [bimatoprost/timolol] of

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

Catecholamine depleting drugs, timolol

The potential exists for additive effects and production of hypotension and/or marked bradycardia.

Centrally-acting antihypertensives, timolol

Enhancement of hypotensive effect and additional bradycardia

Cimetidine, timolol [2] ---> SmPC of [2] of eMC

The bioavailability of timolol will be increased by co-administration with cimetidine

Clonidine, timolol [2] ---> SmPC of [2] of eMC

Beta blockers increase the risk of "rebound hypertension" when taken with clonidine.

Cobicistat [1], timolol ---> SmPC of [1] of EMA

The co-administration with cobicistat may increase the concentrations of betablocker

Darunavir/cobicistat, timolol ---> SmPC of [darunavir] of

Boosted darunavir is expected to increase betablocker plasma concentrations. (CYP2D6 inhibition)

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/ritonavir, timolol ---> SmPC of [darunavir] of

Boosted darunavir is expected to increase betablocker plasma concentrations. (CYP2D6 inhibition)

Digital glycosides, timolol [2] ---> SmPC of [2] of

Concurrent administration of timolol und digitalis glycosides may increase the atrio-ventricular conduction time.

Dihydropyridines, timolol [2] ---> SmPC of [2] of eMC

Concomitant administration of timolol with dihydropyridine derivatives (e. g. nifedipine) may increase the blood pressure lowering effect.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [1], timolol ---> SmPC of [1] of EMA

Concentrations of the beta-blocker may be increased when co-administered with cobicistat.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], timolol ---> SmPC of [1] of EMA

The co-administration with cobicistat may increase the concentrations of betablocker

Fluoxetine, timolol ---> SmPC of [travoprost/timolol] of

Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors and timolol.

Guanethidine, timolol ---> SmPC of [bimatoprost/timolol] of

There is a potential for additive effects resulting in hypotension, and/or marked bradycardia when ophthalmic beta-blockers solution is administered concomitantly with oral guanethidine

Hydralazine, timolol [2] ---> SmPC of [2] of eMC

The bioavailability of timolol will be increased by co-administration with hydralazine

IMAOs, timolol

The potential exists for additive effects and production of hypotension and/or marked bradycardia.

Insulin, timolol ---> SmPC of [brinzolamide/timolol] of

The beta-blocker may increase the hypoglycaemic effect of antidiabetic agent. Blockade of beta-adrenoreceptors may mask the symptoms of hypoglycaemia

Latanoprost, timolol

Enhancement of hypotensive effect of latanoprost on intraocular pressure

Methyldopa, timolol

Possible hypertensive crisis

Methysergide, timolol

Ischemia with risk of gangrene

Oral antidiabetics, timolol ---> SmPC of [brinzolamide/timolol] of

The beta-blocker may increase the hypoglycaemic effect of antidiabetic agent. Blockade of beta-adrenoreceptors may mask the symptoms of hypoglycaemia

Oxtriphylline, timolol

Antagonism and increased effect of theophylline

Parasympathomimetics, timolol ---> SmPC of [bimatoprost/timolol] of

There is a potential for additive effects resulting in hypotension, and/or marked bradycardia when ophthalmic beta-blockers solution is administered concomitantly with oral parasympathomimetics

Paroxetine, timolol ---> SmPC of [travoprost/timolol] of

Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors and timolol.

Phenothiazines, timolol [2] ---> SmPC of [2] of eMC

Concomitant administration of timolol with phenothiazines may increase the blood pressure lowering effect.

Phenylephrine, timolol

The co-administration may decrease the timolol absorption

Pilocarpine, timolol

The co-administration may increase the ocular hypotensor effect of timolol

Pregnancy, timolol [2] ---> SmPC of [2] of eMC

Timolol should not be used during pregnancy unless clearly necessary.

Quinidine, timolol ---> SmPC of [travoprost/timolol] of

Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors and timolol.

Rifampicin, timolol [2] ---> SmPC of [2] of eMC

The bioavailability of timolol will be reduced by co-administration with rifampicin.

SSRI, timolol

The CYP2D6 inhibition may increase plasma concentrations of timolol

Stiripentol [1], timolol ---> SmPC of [1] 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

Strong CYP2D6 inhibitors, timolol ---> SmPC of [bimatoprost/timolol] of

Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors and timolol.

Sympathomimetics, timolol [2] ---> SmPC of [2] of eMC

The effect of sympathomimetic agents, e.g. isoprenaline, salbutamol, will be reduced by concomitant use of beta blockers. In addition, sympathomimetics may counteract the effect of beta blocking agents.

Timolol, tricyclic antidepressant [2] ---> SmPC of [2] of eMC

Concomitant administration of timolol with tricyclic antidepressants may increase the blood pressure lowering effect.

CONTRAINDICATIONS of Timolol

- Hypersensitivity to timolol or to any of the excipients.

- Heart failure, unless adequately controlled, sinus bradycardia (< 45 - 50 bpm) or heart block. Cardiogenic shock.

- History of bronchospasm and bronchial asthma.

- Chronic obstructive pulmonary disease.

- Patients receiving monoamine oxidase inhibitors.

- Pregnancy.

- Sick sinus syndrome (including sino-atrial block), severe peripheral vascular disease or Raynaud's disease.

- Prinzmetal's angina.

- Untreated phaeochromocytoma.

- Metabolic acidosis.

- Hypotension.

- Severe peripheral circulatory disturbances.

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

Tinzaparin

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

Patients are advised to stop breast-feeding while receiving tinzaparin

Dextran, tinzaparin [2] ---> SmPC of [2] of eMC

The anticoagulant effect of tinzaparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Direct Factor Xa inhibitors, tinzaparin [2] ---> SmPC of [2] of eMC

The anticoagulant effect of tinzaparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Hyperkalemia, tinzaparin

The combination may lead to hyperkalemia, particularly in renal failure. Co-administration is not recommended

NSAID, tinzaparin [2] ---> SmPC of [2] of eMC

The anticoagulant effect of tinzaparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Platelet aggregation inhibitors, tinzaparin [2] ---> SmPC of [2] of eMC

The anticoagulant effect of tinzaparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Pregnancy, tinzaparin [2] ---> SmPC of [2] of eMC

Although these animal studies show no hazard, as a precaution tinzaparin should not be used in pregnancy unless no safer alternative is available.

Propranolol, tinzaparin

Enhanced propranolol effect due to displacement from protein binding sites

Salicylates, tinzaparin [2] ---> SmPC of [2] of eMC

The anticoagulant effect of tinzaparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Thrombolytics, tinzaparin [2] ---> SmPC of [2] of eMC

The anticoagulant effect of tinzaparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

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

The anticoagulant effect of tinzaparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

CONTRAINDICATIONS of Tinzaparin

- Known hypersensitivity to constituents.

- Current or history of heparin]induced thrombocytopenia.

- Generalised or local haemorrhagic tendency, including uncontrolled severe hypertension, severe liver insufficiency, active peptic ulcer, acute or subacute septic endocarditis, intracranial haemorrhage, or injuries and operations on the central nervous system, eyes and ears, and in women with abortus imminens.

- The innohep® 10,000 IU/ml vial formulation contains 10 mg/ml of the preservative benzyl alcohol. This formulation must not be given to premature babies or neonates.

The innohep® 10,000 IU/ml syringe formulation does not contain the preservative benzyl alcohol.

- An epidural anaesthesia during birth in pregnant women treated with low molecular weight heparin is contraindicated

- In patients receiving heparin for treatment rather than prophylaxis, locoregional anaesthesia in elective surgical procedures is contra-indicated because the use of heparin may be very rarely associated with epidural or spinal haematoma resulting in prolonged or permanent paralysis.

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

Tioconazole

Amlodipine, tioconazole ---> SmPC of [amlodipine/valsartan] 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.

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

Nursing should be temporarily discontinued while tioconazole is administered.

Pregnancy, tioconazole [2] ---> SmPC of [2] of eMC

The use is contra-indicated throughout pregnancy.

CONTRAINDICATIONS of Tioconazole

- Hypersensitivity to the active substance or to any of the excipients

- Trosyl Nail Solution is contraindicated in individuals who have been shown to be hypersensitive to imidazole antifungal agents.

- Use is contraindicated during pregnancy

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

Tiotropium

Ability to drive, tiotropium [2] ---> SmPC of [2] of eMC

The occurrence of dizziness, blurred vision, or headache may influence the ability to drive and use machinery.

Anticholinergics, tiotropium [2] ---> SmPC of [2] of eMC

The co-administration of tiotropium bromide with other anticholinergic-containing drugs has not been studied and is therefore not recommended

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

A decision on whether to continue/discontinue breastfeeding or to continue/discontinue therapy should be made

Butylscopolamine [1], tiotropium ---> SmPC of [1] of eMC

The anticholinergic effect may be intensified by hyoscine butylbromide

Pregnancy, tiotropium [2] ---> SmPC of [2] of eMC

Tiotropium should only be used during pregnancy when clearly indicated.

Scopolamine, tiotropium

Scopolamine may enhance the anticholinergic effect

CONTRAINDICATIONS of Tiotropium

- Tiotropium bromide inhalation powder is contraindicated in patients with a hypersensitivity to tiotropium bromide, atropine or its derivatives, e.g. ipratropium or oxitropium or to the excipient lactose monohydrate which contains milk protein.

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

Tipranavir

Abacavir, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

The concomitant use of tipranavir, co-administered with low dose ritonavir, with zidovudine or abacavir, results in a significant decrease in plasma concentration of these nucleoside reverse transcriptase inhibitors

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

Dizziness, somnolence, and fatigue have been reported in some patients

Ability to drive, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Dizziness, somnolence, and fatigue have been reported in some patients

Alfuzosin, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Tipranavir and ritonavir, CYP3A4 inhibitors, may increase the plasma concentrations of alfuzosin. Concomitant therapy is contraindicated.

Aluminium, tipranavir

Decreased AUC and Cmax of tipranavir. The dosing should be separated by at least a 2 hours time interval

Aluminium, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Decreased AUC and Cmax of tipranavir. The dosing should be separated by at least a 2 hours time interval

Amiodarone, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Co-administration of tipranavir with low dose ritonavir, 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.

Amlodipine, tipranavir ---> SmPC of [amlodipine/valsartan] 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.

Amprenavir/ritonavir, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

The concomitant use of Aptivus, coadministered with low dose ritonavir, with amprenavir/ritonavir is not recommended. If the combination is nevertheless considered necessary, a monitoring of the plasma levels of amprenavir is strongly encouraged

Astemizole, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Atazanavir/ritonavir, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Significant decrease in plasma concentrations of atazanavir and a marked increase of tipranavir concentrations. Concomitant use is not recommended

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

The CYP3A4 inhibition may increase the plasma levels of atorvastatin. Concomitant use is not recommended

Atorvastatin, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Tipranavir, co-administered with low dose ritonavir (inhibition of CYP 3A4 by tipranavir/ritonavir), increases the plasma concentrations of atorvastatin. The combination is not recommended.

Bepridil, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Boceprevir, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

In a pharmacokinetic study of healthy volunteers, boceprevir decreased the exposure of ritonavir. Coadministration of boceprevir with tipranavir/ritonavir is not recommended

Bosentan, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Due to the marked hepatotoxicity of bosentan and the potential for increasing the liver toxicity associated with tipranavir, co-administered with low dose ritonavir, this combination is not recommended.

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

Consistent with the recommendation that HIV-infected mothers should not breast-feed their infants under any circumstances to avoid risking postnatal transmission of HIV, mothers should discontinue breast-feeding if they are receiving Aptivus.

Buprenorphine/naloxone, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Decreased plasma concentrations of norbuprenorphine. Patients should be monitored for opiate withdrawal syndrome.

Bupropion, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Decreased plasma concentrations of bupropion (induction of CYP2B6 and UGT activity by ritonavir)

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

Carbamazepine, CYP3A4 inductor, may decrease the plasma concentrations of tipranavir. Caution should be used when prescribing

Carbamazepine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Carbamazepine, CYP3A4 inductor, may decrease the plasma concentrations of tipranavir. Caution should be used when prescribing

Cisapride, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

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

Decreased 14-OH metabolite AUC of clarithromycin and increased Cmin of tipranavir

Clarithromycin, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

CYP 3A4 inhibition by tipranavir/ritonavir and P-gp (an intestinal efflux transporter) inhibition by clarithromycin

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

When co-administered, tipranavir and cobicistat exposures are much lower compared to that of tipranavir when boosted with low dose ritonavir. Tipranavir/ritonavir should not be administered concomitantly with cobicistat or cobicistat-containing products.

Cobicistat, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Colchicine, tipranavir [2] ---> SmPC of [2] of EMA

The inhibition of CYP3A4 and P-glycoprotein may increase the exposition to colchicine. The coadministration is not recommended. Co-administration is contraindicated in case of renal or hepatic insufficiency

Colchicine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

In patients with renal or hepatic impairment, co-administration of colchicine in patients on Aptivus/ritonavir is contraindicated

Cyclosporine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Concentrations of ciclosporin cannot be predicted when co-administered with tipranavir/ritonavir. More frequent concentration monitoring of these medicinal products is recommended

CYP3A4 and P-glycoprotein inductors, tipranavir [2] ---> SmPC of [2] of EMA

Co-administration of tipranavir and medicinal products that induce CYP3A and/or P-gp may decrease tipranavir plasma concentrations.

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.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, tipranavir ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of E

Deflazacort, tipranavir

Increased plasma levels of glucocorticoid metabolized by CYP3A4 with risk of systemic corticosteroid effects. Concomitant use not recommended

Desipramine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

The CYP2D6 inhibition by tipranavir/r may increase the plasma concentrations of desipramine. Dosage reduction and concentration monitoring of desipramine is 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

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

Dihydroergotamine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Drugs primarily metabolised by CYP2D6, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

The co-administration of tipranavir and low dose ritonavir with drugs that are highly dependent on CYP2D6 for clearance is contraindicated

Drugs primarily metabolised by CYP3A4, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Co-administration of tipranavir and low dose ritonavir with agents primarily metabolised by CYP3A may result in changed plasma concentrations of tipranavir or the other agents, which could alter their therapeutic and undesirable effects

Efavirenz, tipranavir [2] ---> SmPC of [2] of EMA

No clinically significant interaction is observed. No dosage adjustment necessary

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

Increased eliglustat exposition would be expected for strong inhibitors of CYP3A. Caution should be used with strong CYP3A inhibitors in intermediate and extensive metabolisers.

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

Co-administration of OATP1B1 inhibitors with eluxadoline may increase exposure to eluxadoline. Eluxadoline should not be administered concomitantly with such medicinal products

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

Due to insufficient clinical data, the combination of elvitegravir with tipranavir is not recommended

Emtricitabine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

No dosage adjustment necessary in patients with normal renal function. In case of concomitant administration of emtricitabine and tipranavir/ritonavir, renal function should be evaluated before initiating the co-administration.

Enfuvirtide, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

The clinical data available from the RESIST trials did not suggest any significant alteration of the tipranavir with ritonavir safety profile when combined with enfuvirtide as compared to patients treated with tipranavir with ritonavir without enfuvirtid

Ergometrine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Ergonovine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Ergot derivatives, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Ergotamine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Esomeprazole, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

The CYP2C19 induction by tipranavir/ritonavir may decrease the plasma concentrations of omeprazole. Concomitant use is not recommended

Estrogens, tipranavir

Decreased plasma concentrations of estrogen. Concomitant use not recommended

Estrogens, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Decreased plasma concentrations of estrogen. Concomitant use not recommended

Ethinyl estradiol, tipranavir

Decreased plasma concentrations of ethinyl estradiol. Concomitant use not recommended

Ethinylestradiol/norethindrone, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Decreased plasma concentrations of ethinyl estradiol. Concomitant use not recommended

Etravirine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Concomitant use of tipranavir/ritonavir caused a decrease of etravirine exposure that could significantly impair the virologic response to etravirine. Co-administration is not recommended.

Flecainide, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

The co-administration of tipranavir and low dose ritonavir with drugs that are highly dependent on CYP2D6 for clearance is contraindicated

Fluconazole, tipranavir [2] ---> SmPC of [2] of EMA

Increased plasma concentrations of tipranavir. No dosage adjustments are recommended. Fluconazole doses > 200 mg/day are not recommended.

Flunitrazepam, tipranavir

Substances that inhibit hepatic enzymes may enhance the effect of benzodiazepines. Interactions with strong CYP3A4 inhibitors cannot be excluded

Fluticasone, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Concomitant use of tipranavir, co-administered with low dose ritonavir, and fluticasone or other glucocorticoids that are metabolised by CYP3A4 is not recommended

Foods, tipranavir [2] ---> SmPC of [2] of EMA

Should be given with food

Glucocorticoids metabolized by CYP3A4, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Concomitant use of tipranavir, co-administered with low dose ritonavir and glucocorticoids that are metabolised by CYP3A4 is not recommended

Glucocorticoids, tipranavir

Increased plasma levels of glucocorticoid metabolized by CYP3A4 with risk of systemic corticosteroid effects. Concomitant use not recommended

H2 antagonists, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

An increase in gastric pH that may result from H2-receptor antagonist therapy is not expected to have an impact on tipranavir plasma concentrations.

Halofantrine, tipranavir

Possible increase of plasma concentrations of halofantrine. Inherent risk of inducing torsades de pointes. The co-administration is not recommended

Halofantrine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Due to their metabolic profile and inherent risk of inducing torsades de pointes, administration of halofantrine and lumefantrine with tipranavir co-administered with low dose ritonavir, is not recommended.

Itraconazol, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Based on theoretical considerations tipranavir, is expected to increase plasma concentrations of the active principles

Ketoconazole, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Based on theoretical considerations tipranavir, is expected to increase plasma concentrations of the active principles

Lamivudine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

No clinically significant interaction is observed. No dosage adjustment necessary.

Lansoprazole, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

The plasma concentrations of lansoprazole are difficult to predict due to inhibition of CYP3A4 and induction of CYP2C19. The combined use of tipranavir/ritonavir with proton pump inhibitors is not recommended

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

Lapatinib is predominantly metabolised by CYP3A. The strong CYP3A4 inhibition increases the exposition to lapatinib. Co-administration of lapatinib with strong inhibitors of CYP3A4 should be avoided.

Loperamide, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

A pharmacodynamic interaction study in healthy volunteers demonstrated that administration of loperamide and tipranavir/ritonavir does not cause any clinically relevant change in the respiratory response to carbon dioxide.

Lopinavir, tipranavir

Decreased plasma concentrations of lopinavir

Lopinavir/ritonavir, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

The concomitant use of Aptivus, coadministered with low dose ritonavir, with lopinavir/ritonavir is not recommended. If the combination is nevertheless considered necessary, a monitoring of the plasma levels of lopinavir is strongly encouraged

Lovastatine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Lumefantrine, tipranavir

Possible increase of plasma concentrations of lumefantrine. Inherent risk of inducing torsades de pointes. The co-administration is not recommended

Lumefantrine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Lurasidone, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Magnesium, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Decreased AUC and Cmax of tipranavir. The dosing should be separated by at least a 2 hours time interval

Meperidine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Decreased plasma concentrations of meperidine and increased plasma concentrations of normeperidine. Concomitant use is not recommended

Methadone, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Decreased plasma concentrations of methadone. Patients should be monitored for opiate withdrawal syndrome

Methylergometrine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Methylergonovine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Metoprolol, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

The co-administration of tipranavir and low dose ritonavir with drugs that are highly dependent on CYP2D6 for clearance is contraindicated

Midazolam, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Concomitant use of tipranavir/ritonavir and oral midazolam is contra-indicated. If tipranavir/ritonavir is administered with parenteral midazolam, close clinical monitoring for respiratory depression and/or prolonged sedation should be instituted

Nevirapine, tipranavir [2] ---> SmPC of [2] of EMA

No clinically significant interaction is observed. No dosage adjustment necessary.

Nevirapine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

No clinically significant interaction is observed. No dosage adjustment necessary.

Ombitasvir/paritaprevir/ritonavir [1], tipranavir ---> SmPC of [1] of EMA

Omeprazole, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

The CYP2C19 induction by tipranavir/ritonavir may decrease the plasma concentrations of esomeprazole. Concomitant use is not recommended

Oral contraceptives, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Alternative or additional contraceptive measures are to be used when oestrogen based oral contraceptives are co-administered with tipranavir co-administered with low dose ritonavir

P-glycoprotein and CYP3A4 inhibitors, tipranavir [2] ---> SmPC of [2] of EMA

The P-glycoprotein and CYP3A4 inhibition may increase the plasma concentrations of tipranavir

P-glycoprotein and CYP3A4 inhibitors, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

It is difficult to predict the net effect of tipranavir co-administered with low dose ritonavir on oral bioavailability and plasma concentrations of agents that are dual substrates of CYP3A and P-gp.

Pantoprazole, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

The plasma concentrations of pantoprazole are difficult to predict due to inhibition of CYP3A4 and induction of CYP2C19. The combined use of tipranavir/ritonavir with proton pump inhibitors is not recommended

PDE5 inhibitors, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Coadministration of tipranavir/ritonavir (CYP3A4 inhibition) with PDE5 inhibitors is expected to increase PDE5 concentrations and may result in an increase in PDE5 inhibitor-associated adverse events including hypotension, visual changes and priapism.

Phenobarbital, tipranavir [2] ---> SmPC of [2] of EMA

The CYP3A4 induction may decrease the plasma concentrations of tipranavir. Caution should be used when prescribing

Phenobarbital, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

The CYP3A4 induction may decrease the plasma concentrations of tipranavir. Caution should be used when prescribing

Phenytoin, tipranavir [2] ---> SmPC of [2] of EMA

The CYP3A4 induction may decrease the plasma concentrations of tipranavir. Caution should be used when prescribing

Phenytoin, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

The CYP3A4 induction may decrease the plasma concentrations of tipranavir. Caution should be used when prescribing

Pimozide, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Pravastatine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

The coadministration may increase pravastatine exposure

Pregnancy, tipranavir [2] ---> SmPC of [2] of EMA

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

Propafenone, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

The co-administration of tipranavir and low dose ritonavir with drugs that are highly dependent on CYP2D6 for clearance is contraindicated

Protease inhibitors, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

According to current treatment guidelines, dual therapy with protease inhibitors is generally not recommended

Proton pump inhibitors, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

The combined use of tipranavir, coadministered with low dose ritonavir, with proton pump inhibitors is not recommended

Quetiapine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Quinidine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Rabeprazole, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Rabeprazole plasma concentrations might decrease as a result of induction of CYP2C19 by tipranavir/ritonavir. The combined use of tipranavir/ritonavir with proton pump inhibitors is not recommended

Raltegravir, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Small decrease in plasma concentrations of raltegravir. The mechanism of action is thought to be induction of glucuronosyltransferase by tipranavir/ritonavir. No dosage adjustment necessary.

Rifabutin, tipranavir [2] ---> SmPC of [2] of EMA

The inhibition of CYP 3A4 by tipranavir may increase rifabutin concentration

Rifabutin, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

The inhibition of CYP 3A4 by tipranavir/ritonavir may increase rifabutin concentration

Rifampicin, tipranavir [2] ---> SmPC of [2] of EMA

Co-administration of protease inhibitors with rifampicin substantially decreases protease inhibitor concentrations.

Rifampicin, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Concomitant use of rifampicin with tipranavir/ritonavir is expected to result in sub-optimal levels of tipranavir which may lead to loss of virologic response and possible resistance to tipranavir. Concomitant use is contraindicated

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

Ritonavir increases the serum levels of tipranavir as a result of CYP3A inhibition. Tipranavir must be given with low dose ritonavir to ensure its therapeutic effect.

Rosuvastatin, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Co-administration of Aptivus, coadministered with low dose ritonavir, and rosuvastatin should be initiated with the lowest dose (5 mg/day) of rosuvastatin, titrated to treatment response, and accompanied with careful clinical monitoring for rosuvastatin

Salmeterol, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

The concurrent administration of tipranavir/ritonavir (inhibition of CYP 3A4 by tipranavir/ritonavir) may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations and sinus tachycardia.

Sertindole, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Sildenafil, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Tipranavir, CYP3A4 inhibitor, may increase sildenafil plasma levels. Increased potential for adverse events (visual disturbances, hypotension, prolonged erection, and syncope). Co-administration to treat pulmonary arterial hypertension is contraindicated

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

The CYP3A4 enzyme induction or inhibition may alter plasma concentrations of simeprevir. It is not recommended to co-administer simeprevir with any HIV PI, with or without ritonavir.

Simvastatine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Sirolimus, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Concentrations of sirolimus cannot be predicted when co-administered with tipranavir/ritonavir. More frequent concentration monitoring of these medicinal products is recommended

St. John's wort, tipranavir [2] ---> SmPC of [2] of EMA

Plasma concentrations of tipranavir can be reduced by concomitant use of the herbal preparation St John's wort (Hypericum perforatum). This is due to induction of drug metabolising enzymes by St John's wort.

St. John's wort, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

St. John's wort must not be combined with tipranavir/ritonavir. Combination is expected to substantially decrease tipranavir and ritonavir levels and may result in suboptimal levels of tipranavir (loss of virologic response and possible resistance)

Stavudine, tipranavir [2] ---> SmPC of [2] of EMA

No clinically significant interaction is observed. No dosage adjustment necessary.

Stavudine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

No clinically significant interaction is observed. No dosage adjustment necessary.

Strong CYP3A4 inductors, tipranavir [2] ---> SmPC of [2] of EMA

Co-administration of tipranavir and medicinal products that induce CYP3A may decrease tipranavir plasma concentrations.

Strong CYP3A4 inhibitors, tipranavir [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the plasma concentrations of tipranavir

Strong P-gp inductors, tipranavir [2] ---> SmPC of [2] of EMA

Co-administration of tipranavir and medicinal products that induce P-gp may decrease tipranavir plasma concentrations.

Strong P-gp inhibitors, tipranavir [2] ---> SmPC of [2] of EMA

Co-administration of tipranavir and medicinal products that inhibit P-gp may increase tipranavir plasma concentrations.

Tacrolimus, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Concentrations of tacrolimus cannot be predicted when co-administered with tipranavir/ritonavir. More frequent concentration monitoring of these medicinal products is recommended

Tadalafil, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

It is recommended to prescribe tadalafil after at least 7 days of tipranavir/ritonavir dosing.

Telaprevir, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Tenofovir, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

No clinically significant interaction is observed. No dosage adjustment necessary.

Terfenadine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Theophylline, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Tipranavir/r, CYP1A2 inductors, may decrease the plasma concentrations of theophylline

Tipranavir, topiramate

The strong CYP3A4 induction may decrease the plasma levels of tipranavir

Tipranavir, valproic acid

Tipranavir decreases the plasma concentrations of valproic acid.

Tipranavir, voriconazole

The mutual inhibition of CYP3A4 may increase the plasma concentrations of both principle actives

Tipranavir/ritonavir, tolterodine ---> SmPC of [tipranavir] of EMA

The CYP3A4 and CYP2D6 inhibition by tipranavir/ritonavir may increase the plasma concentrations of tolterodine. Concomitant use is not recommended

Tipranavir/ritonavir, trazodone ---> SmPC of [tipranavir] of EMA

Increased plasma concentrations of trazodone. The combination should be used with caution and a lower dose of trazodone should be considered.

Tipranavir/ritonavir, triazolam ---> SmPC of [tipranavir] of EMA

Tipranavir/ritonavir, valaciclovir ---> SmPC of [tipranavir] of EMA

Valaciclovir and tipranavir with low dose ritonavir, may be co-administered without dose adjustment

Tipranavir/ritonavir, vardenafil ---> SmPC of [tipranavir] of EMA

Tipranavir/ritonavir, CYP3A4 inhibitors, may increase vardenafil plasma levels. There is increased potential for PDE5 inhibitor-associated adverse events (which include visual disturbances, hypotension, prolonged erection, and syncope).

Tipranavir/ritonavir, voriconazole ---> SmPC of [tipranavir] of EMA

Due to multiple CYP isoenzyme systems involved in voriconazole metabolism, it is difficult to predict the interaction with tipranavir, co-administered with low-dose ritonavir. The co-administration of tipranavir/r and voriconazole should be avoided

Tipranavir/ritonavir, warfarin ---> SmPC of [tipranavir] of EMA

Aptivus, co-administered with low dose ritonavir, when combined with warfarin may be associated with changes in INR (International Normalised Ratio) values, and may affect anticoagulation (thrombogenic effect) or increase the risk of bleeding.

Tipranavir/ritonavir, zidovudine ---> SmPC of [tipranavir] of EMA

CONTRAINDICATIONS of Tipranavir

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

- Patients with moderate or severe (Child-Pugh B or C) hepatic impairment.

- Combination of rifampicin with Aptivus with concomitant low dose ritonavir is contraindicated

- Herbal preparations containing St John's wort (Hypericum perforatum) must not be used while taking Aptivus due to the risk of decreased plasma concentrations and reduced clinical effects of tipranavir

- Co-administration of Aptivus with low dose ritonavir, 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. These active substances include antiarrhythmics (such as amiodarone, bepridil, quinidine), antihistamines (such as astemizole, terfenadine), ergot derivatives (such as dihydroergotamine, ergonovine, ergotamine, methylergonovine), gastrointestinal motility agents (such as cisapride), antipsychotics (such as pimozide, sertindole, quetiapine, lurasidone), sedatives/hypnotics (such as orally administered midazolam and triazolam) and HMG-CoA reductase inhibitors (such as simvastatin and lovastatin) (see section 4.5). Also contraindicated is the use of the alpha-1 adrenoceptor antagonist alfuzosin, and sildenafil when used for the treatment of pulmonary arterial hypertension. In addition, co-administration of Aptivus with low dose ritonavir, and medicinal products that are highly dependent on CYP2D6 for clearance, such as the antiarrhythmics flecainide, propafenone and metoprolol given in heart failure, is contraindicated (see section 4.5).

- Co-administration of colchicine with Aptivus/ritonavir is contraindicated in patients with renal or hepatic impairment

https://www.ema.europa.eu/documents/product-information/aptivus-epar-product-information_en.pdf.

Tiratricol (Emcitate)

Activated charcoal, tiratricol [2] ---> SmPC of [2] of EMA

Antacids, charcoal, calcium, cationic resins (e.g. cholestyramine), iron, sucralphate, and other gastrointestinal agents may interfere with the gastrointestinal absorption of tiratricol.

Alfentanyl, tiratricol [2] ---> SmPC of [2] of EMA

Based on in vitro data there is an indication that tiratricol may induce CYP3A4 at a gut level and therefore medicinal products with narrow therapeutic indices that are dependent on CYP3A4

Amphetamine, tiratricol [2] ---> SmPC of [2] of EMA

Administration of psychostimulants (e.g. caffeine, norepinephrine-dopamine reuptake inhibitors (NDRIs), and amphetamines) in combination with high doses of tiratricol may lead to increased heart rate and blood pressure.

Anabolic steroids, tiratricol [2] ---> SmPC of [2] of EMA

Anabolic steroids and glucocorticoids are known to decrease serum Thyroxine-Binding Globulin (TBG) concentration and may result in lower T3 and tiratricol serum concentration.

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

Antacids, charcoal, calcium, cationic resins (e.g. cholestyramine), iron, sucralphate, and other gastrointestinal agents may interfere with the gastrointestinal absorption of tiratricol.

Anticoagulants, tiratricol [2] ---> SmPC of [2] of EMA

The effect of anti-coagulant therapy may be increased during treatment with tiratricol. This may increase the risk of haemorrhage. The dose of anti-coagulant therapy may have to be adjusted if administered concomitantly with tiratricol.

Anticoagulants, tiratricol [2] ---> SmPC of [2] of EMA

Salicylates, anti-coagulants, anti-inflammatory and anti-convulsant medicinal products may cause protein binding site displacement of T3, and potentially tiratricol, from (TBG) and thereby altering serum levels of thyroid hormones

Antidiabetics, tiratricol [2] ---> SmPC of [2] of EMA

Tiratricol may reduce blood glucose levels. The dose of anti-diabetic agents may need to be adjusted if administered concomitantly with tiratricol. Periodic monitoring of blood glucose is necessary (see section 4.4).

Antiinflammatory, tiratricol [2] ---> SmPC of [2] of EMA

Antimalarial agents, tiratricol [2] ---> SmPC of [2] of EMA

Concomitant use of tiratricol and antimalarial medicinal products may cause clinical hypothyroidism. Monitoring of serum levels of T3 and dose adjustment of tiratricol may be necessary during and after treatment with antimalarial medicinal products.

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

Based on in vitro data there is an indication that tiratricol may induce CYP3A4 at a gut level and therefore medicinal products with narrow therapeutic indices that are dependent on CYP3A4

BCRP substrates with narrow therapeutic range, tiratricol [2] ---> SmPC of [2] of EMA

Medicinal products that are substrates of P-glycoprotein (P-gp) or Breast Cancer Resistance Protein (BCRP) efflux transporters with narrow therapeutic indices should also be used with caution.

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

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Emcitate therapy considering the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Caffeine, tiratricol [2] ---> SmPC of [2] of EMA

Calcium, tiratricol [2] ---> SmPC of [2] of EMA

These treatments should be taken before or after tiratricol (more than 2 hours before or after if possible).

Calcium, tiratricol [2] ---> SmPC of [2] of EMA

Antacids, charcoal, calcium, cationic resins (e.g. cholestyramine), iron, sucralphate, and other gastrointestinal agents may interfere with the gastrointestinal absorption of tiratricol.

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

Medicinal products that can induce the enzyme system in the liver, such as barbiturates, phenytoin carbamazepine, rifabutin, rifampicin or products containing St. John's wort (Hypericum perforatum) may increase the hepatic clearance of tiratricol.

Carbimazole, tiratricol [2] ---> SmPC of [2] of EMA

Taking tiratricol in combination with other thyromimetic medicines other used to treat thyroid conditions (e.g. levothyroxine, propylthiouracil, and carbimazole) may increase the risk of symptoms of hyperthyroidism or hypothyroidism.

Cationic resins, tiratricol [2] ---> SmPC of [2] of EMA

Antacids, charcoal, calcium, cationic resins (e.g. cholestyramine), iron, sucralphate, and other gastrointestinal agents may interfere with the gastrointestinal absorption of tiratricol.

Chloroquine, tiratricol [2] ---> SmPC of [2] of EMA

Cholestyramine, tiratricol [2] ---> SmPC of [2] of EMA

In the case of cholestyramine, tiratricol should be taken 1 hour before or 4 hours after the resin dose. Adjustment of the tiratricol dose may be required to obtain the desired effect.

Cisapride, tiratricol [2] ---> SmPC of [2] of EMA

Based on in vitro data there is an indication that tiratricol may induce CYP3A4 at a gut level and therefore medicinal products with narrow therapeutic indices that are dependent on CYP3A4

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

Based on in vitro data there is an indication that tiratricol may induce CYP3A4 at a gut level and therefore medicinal products with narrow therapeutic indices that are dependent on CYP3A4

CYP3A4 substrates with narrow therapeutic index, tiratricol [2] ---> SmPC of [2] of EMA

Based on in vitro data there is an indication that tiratricol may induce CYP3A4 at a gut level and therefore medicinal products with narrow therapeutic indices that are dependent on CYP3A4

Enzyme inductors, tiratricol [2] ---> SmPC of [2] of EMA

Ergotamine, tiratricol [2] ---> SmPC of [2] of EMA

Based on in vitro data there is an indication that tiratricol may induce CYP3A4 at a gut level and therefore medicinal products with narrow therapeutic indices that are dependent on CYP3A4

Estrogens, tiratricol [2] ---> SmPC of [2] of EMA

Non-contraceptive oestrogen and oestrogen containing products (including hormone replacement therapy) may increase the requirement of tiratricol treatment dose.

Fentanyl, tiratricol [2] ---> SmPC of [2] of EMA

Based on in vitro data there is an indication that tiratricol may induce CYP3A4 at a gut level and therefore medicinal products with narrow therapeutic indices that are dependent on CYP3A4

Fertility, tiratricol [2] ---> SmPC of [2] of EMA

A study in rats showed no impact on fertility and mating ability (see section 5.3).

Glucocorticoids, tiratricol [2] ---> SmPC of [2] of EMA

Anabolic steroids and glucocorticoids are known to decrease serum Thyroxine-Binding Globulin (TBG) concentration and may result in lower T3 and tiratricol serum concentration.

Immunoassay, tiratricol [2] ---> SmPC of [2] of EMA

Tiratricol cross-reacts with T3 if assessed by immunoassay, which may cause unreliable test results. It is recommended to use an LC/MS/MS method to measure T3 levels. Care should be taken if an immunoassay method is used.

Levothyroxine, tiratricol [2] ---> SmPC of [2] of EMA

Lovastatine, tiratricol [2] ---> SmPC of [2] of EMA

Based on in vitro data there is an indication that tiratricol may induce CYP3A4 at a gut level and therefore medicinal products with narrow therapeutic indices that are dependent on CYP3A4

Norepinephrine and dopamine reuptake inhibitors, tiratricol [2] ---> SmPC of [2] of EMA

Omeprazole, tiratricol [2] ---> SmPC of [2] of EMA

Serum concentrations of T3 should be monitored and dose adjustment of tiratricol considered when initiating, changing or discontinuing PPI treatment.

Orlistat, tiratricol [2] ---> SmPC of [2] of EMA

Tiratricol should not be taken for weight reduction. It may cause serious or life-threatening undesirable effects, particularly in combination with orlistat (see section 4.5 under "Orlistat").

P-glycoprotein substrates with small therapeutic index, tiratricol [2] ---> SmPC of [2] of EMA

Medicinal products that are substrates of P-glycoprotein (P-gp) or Breast Cancer Resistance Protein (BCRP) efflux transporters with narrow therapeutic indices should also be used with caution.

Phenytoin, tiratricol [2] ---> SmPC of [2] of EMA

Pimozide, tiratricol [2] ---> SmPC of [2] of EMA

Based on in vitro data there is an indication that tiratricol may induce CYP3A4 at a gut level and therefore medicinal products with narrow therapeutic indices that are dependent on CYP3A4

Pregnancy, tiratricol [2] ---> SmPC of [2] of EMA

Emcitate is contraindicated during pregnancy (see section 4.3).

Proguanil, tiratricol [2] ---> SmPC of [2] of EMA

Propylthiouracil, tiratricol [2] ---> SmPC of [2] of EMA

Proton pump inhibitors, tiratricol [2] ---> SmPC of [2] of EMA

Co-administration with PPIs may cause a decrease in the absorption of the thyroid hormones, due to the increase of the intragastric pH caused by PPIs such as omeprazole, esomeprazole, pantoprazole, rabeprazole and lansoprazole.

Psychostimulants, tiratricol [2] ---> SmPC of [2] of EMA

Quinidine, tiratricol [2] ---> SmPC of [2] of EMA

Based on in vitro data there is an indication that tiratricol may induce CYP3A4 at a gut level and therefore medicinal products with narrow therapeutic indices that are dependent on CYP3A4

Rifabutin, tiratricol [2] ---> SmPC of [2] of EMA

Rifampicin, tiratricol [2] ---> SmPC of [2] of EMA

Salicylates, tiratricol [2] ---> SmPC of [2] of EMA

Sevelamer, tiratricol [2] ---> SmPC of [2] of EMA

Sevelamer may decrease the concentration of thyroid hormones and result in reduced efficacy of tiratricol. Sevelamer should be taken more than 2 hours before or after administration of tiratricol.

Simvastatine, tiratricol [2] ---> SmPC of [2] of EMA

Based on in vitro data there is an indication that tiratricol may induce CYP3A4 at a gut level and therefore medicinal products with narrow therapeutic indices that are dependent on CYP3A4

Sirolimus, tiratricol [2] ---> SmPC of [2] of EMA

Based on in vitro data there is an indication that tiratricol may induce CYP3A4 at a gut level and therefore medicinal products with narrow therapeutic indices that are dependent on CYP3A4

Tacrolimus, tiratricol [2] ---> SmPC of [2] of EMA

Based on in vitro data there is an indication that tiratricol may induce CYP3A4 at a gut level and therefore medicinal products with narrow therapeutic indices that are dependent on CYP3A4

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

Women of childbearing potential have to use effective contraception during treatment.

CONTRAINDICATIONS of Tiratricol (Emcitate)

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

- Hyperthyroidism for other reasons than MCT8 deficiency (e.g. Grave’s Disease).

- Pregnancy (see section 4.6).

https://www.ema.europa.eu/en/documents/product-information/emcitate-epar-product-information_en.pdf 11/03/2025

Tirbanibulin (Klisyri)

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

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from tirbanibulin ointment therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Fertility, tirbanibulin [2] ---> SmPC of [2] of EMA

In a non-clinical fertility and early embryonic development study in rats, changes considered indicative of male fertility toxicity occurred

Pregnancy, tirbanibulin [2] ---> SmPC of [2] of EMA

Tirbanibulin ointment is not recommended during pregnancy and in women of childbearing potential not using contraception.

CONTRAINDICATIONS of Tirbanibulin (Klisyri)

- 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/klisyri-epar-product-information_en.pdf 19/09/2024

Tirofiban

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

The concomitant administration of tirofiban and ASA increases the inhibition of platelet aggregation

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

A decision must be made whether to discontinue breastfeeding or to discontinue therapy

Cangrelor [1], tirofiban ---> SmPC of [1] of EMA

In clinical studies, cangrelor has been co-administered with bivalirudin, low molecular weight heparin, fondaparinux, and GP IIb/IIIa inhibitors with no apparent effect upon the pharmacokinetics or pharmacodynamics of cangrelor.

Desirudin [1], tirofiban ---> SmPC of [1] of EMA

Desirudin should be used with caution in conjunction with medicinal products which affect platelet function

Dextran, tirofiban [2] ---> SmPC of [2] of eMC

Concurrent use of tirofiban with drugs that increase the risk of bleeding to a relevant degree is not recommended

Drotrecogin alfa [1], tirofiban ---> SmPC of [1] of EMA

Caution should be employed when using drotrecogin alfa with other drugs that affect haemostasis

GP IIb/IIIa inhibitors, tirofiban [2] ---> SmPC of [2] of eMC

Concurrent use of tirofiban with drugs that increase the risk of bleeding to a relevant degree is not recommended

Heparin, tirofiban [2] ---> SmPC of [2] of eMC

The use of platelet aggregation inhibitors with heparin increases the risk of bleeding

Iloprost [1], tirofiban ---> SmPC of [1] of EMA

Oral anticoagulants, tirofiban [2] ---> SmPC of [2] of eMC

Concurrent use of tirofiban with drugs that increase the risk of bleeding to a relevant degree is not recommended

Platelet aggregation inhibitors, tirofiban [2] ---> SmPC of [2] of eMC

The use of several platelet aggregation inhibitors increases the risk of bleeding

Pregnancy, tirofiban [2] ---> SmPC of [2] of eMC

Tirofiban is not recommended during pregnancy

Retinol, tirofiban

Concomitant use of antiplatelet drugs with vitamin A may increase the anticoagulant effect and the risk of bleeding

Thrombolytics, tirofiban [2] ---> SmPC of [2] of eMC

The use of platelet aggregation inhibitors with thrombolytics increases the risk of bleeding

Tirofiban [1], warfarin ---> SmPC of [1] of eMC

The use of platelet aggregation inhibitors with warfarin increases the risk of bleeding

Tirofiban, vitamin A

Concomitant use of antiplatelet drugs with vitamin A may increase the anticoagulant effect and the risk of bleeding

CONTRAINDICATIONS of Tirofiban

Aggrastat is contra-indicated in patients who are hypersensitive to the active substance or to any of the excipients of the preparation listed in section 6.1 or who developed thrombocytopenia during earlier use of a GP IIb/IIIa receptor antagonist.

- Since inhibition of platelet aggregation increases the bleeding risk, Aggrastat is contra-indicated in patients with:

- History of stroke within 30 days or any history of haemorrhagic stroke.

- Known history of intracranial disease (e.g. neoplasm, arteriovenous malformation, aneurysm).

- Active or recent (within the previous 30 days of treatment) clinically relevant bleeding (e.g. gastro-intestinal bleeding).

- Malignant hypertension.

- Relevant trauma or major surgical intervention within the past six weeks.

- Thrombocytopenia (platelet count <100,000/mm³), disorders of platelet function.

- Clotting disturbances (e.g. prothrombin time >1.3 times normal or INR [International Normalised Ratio] >1.5).

- Severe liver failure.

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

Tirzepatide (Mounjaro)

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

When tirzepatide is used in combination with a sulphonylurea or insulin, patients should be advised to take precautions to avoid hypoglycaemia while driving and using machines

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

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

Digoxin, tirzepatide [2] ---> SmPC of [2] of EMA

It is recommended to monitor patients on oral medicinal products with a narrow therapeutic index (e.g., warfarin, digoxin), especially at initiation of -tirzepatide treatment and following dose increase.

Fertility, tirzepatide [2] ---> SmPC of [2] of EMA

The effect of tirzepatide on fertility in humans is unknown. Animal studies with tirzepatide did not indicate direct harmful effects with respect to fertility (see section 5.3).

Gastric emptying, tirzepatide [2] ---> SmPC of [2] of EMA

Tirzepatide delays gastric emptying and thereby has the potential to impact the rate of absorption of concomitantly administered oral medicinal products.

Oral contraceptives, tirzepatide [2] ---> SmPC of [2] of EMA

This reduction in exposure after a single dose of tirzepatide is not considered clinically relevant. No dose adjustment of oral contraceptives is required.

Paracetamol, tirzepatide [2] ---> SmPC of [2] of EMA

The effect of tirzepatide on the oral absorption of paracetamol is dose and time dependent. No dose adjustment of paracetamol is necessary when administered with tirzepatide.

Pregnancy, tirzepatide [2] ---> SmPC of [2] of EMA

If a patient wishes to become pregnant, or pregnancy occurs, tirzepatide should be discontinued. Tirzepatide should be discontinued at least 1 month before a planned pregnancy due to the long half-life (see section 5.2).

Pregnancy, tirzepatide [2] ---> SmPC of [2] of EMA

Tirzepatide is not recommended during pregnancy and in women of childbearing potential not using contraception.

Rapid onset of effect, tirzepatide [2] ---> SmPC of [2] of EMA

The risk of delayed effect should also be considered for oral medicinal products for which a rapid onset of effect is of importance.

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

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

Women of childbearing potential are recommended to use contraception when treated with tirzepatide.

CONTRAINDICATIONS of Tirzepatide (Mounjaro)

- 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/mounjaro-epar-product-information_en.pdf 26/02/2026

Tisagenlecleucel (Kymriah)

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

Due to the potential for neurological events, including altered mental status or seizures, patients receiving Kymriah are at risk for altered or decreased consciousness or coordination in the 8 weeks following infusion.

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

It is unknown whether tisagenlecleucel cells are excreted in human milk. A risk to the breast-fed infant cannot be excluded. Women who are breast-feeding should be advised of the potential risk to the breast-fed infant.

Duration of contraception, tisagenlecleucel [2] ---> SmPC of [2] of EMA

There are insufficient exposure data to provide a recommendation concerning duration of contraception following treatment with Kymriah.

Fertility, tisagenlecleucel [2] ---> SmPC of [2] of EMA

There are no data on the effect of Kymriah on fertility. Effects of Kymriah on male and female fertility have not been evaluated in animal studies.

Lymphodepleting chemotherapy, tisagenlecleucel [2] ---> SmPC of [2] of EMA

See the prescribing information for lymphodepleting chemotherapy for information on the need for effective contraception in patients who receive the lymphodepleting chemotherapy.

Pregnancy, tisagenlecleucel [2] ---> SmPC of [2] of EMA

Pregnant women who have received Kymriah may have hypogammaglobulinaemia. Assessment of immunoglobulin levels is indicated in newborns of mothers treated with Kymriah.

Pregnancy, tisagenlecleucel [2] ---> SmPC of [2] of EMA

Kymriah is not recommended during pregnancy and in women of childbearing potential not using contraception. Pregnant women should be advised on the potential risks to the foetus.

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

As a precautionary measure, vaccination with live vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during Kymriah treatment, and until immune recovery following treatment.

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

Pregnancy status for females of child-bearing age should be verified prior to starting treatment with Kymriah.

CONTRAINDICATIONS of Tisagenlecleucel (Kymriah)

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

- Contraindications of the lymphodepleting chemotherapy must be considered.

https://www.ema.europa.eu/en/documents/product-information/kymriah-epar-product-information_en.pdf 20/03/2024

Tislelizumab (Tevimbra)

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

Tevimbra has minor influence on the ability to drive and use machines. In some patients, fatigue has been reported following administration of tislelizumab (see section 4.8).

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

Because of the potential for serious adverse drug reactions in breast-fed newborns/infants from Tevimbra, women should be advised not to breast-feed during treatment and for at least 4 months after the last dose of Tevimbra.

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

Corticosteroids can also be used as pre-medication when tislelizumab is used in combination with chemotherapy, as antiemetic prophylaxis and/or to alleviate chemotherapy-related adverse reactions.

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

The use of systemic corticosteroids and other immunosuppressants at baseline, before starting tislelizumab, except for physiological doses of systemic corticosteroid (10 mg/day prednisone or equivalent), should be avoided.

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

As monoclonal antibodies are not metabolised by cytochrome P450 enzymes or other drug-metabolising enzymes, inhibition or induction of these enzymes by co-administered medicinal products is not anticipated to affect the pharmacokinetics of tislelizumab.

Fertility, tislelizumab [2] ---> SmPC of [2] of EMA

There were no notable effects in the male and female reproductive organs in cynomolgus monkeys when tislelizumab was given at doses of 3, 10 or 30 mg/kg every 2 weeks for 13 weeks (7 dose administrations) (see section 5.3).

Pregnancy, tislelizumab [2] ---> SmPC of [2] of EMA

Tislelizumab should not be used during pregnancy unless the clinical condition of the woman requires treatment with tislelizumab.

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

Women of childbearing potential should use effective contraception (methods that result in less than 1% pregnancy rates) during treatment and for at least 4 months following the last dose of tislelizumab.

CONTRAINDICATIONS of Tislelizumab (Tevimbra)

- 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/tevimbra-epar-product-information_en.pdf 15/05/2025

Other trade names: Tizveni (withdrawn)

Tisotumab vedotin (Tivdak)

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

The clinical status of the patient should be considered when assessing the patient's ability to perform tasks that require judgement, motor, or cognitive skills.

Boceprevir, tisotumab vedotin [2] ---> SmPC of [2] of EMA

Caution is advised in case of treatment with strong CYP3A4 inhibitors. Patients should be closely monitored for adverse reactions when tisotumab vedotin is given concomitantly with strong CYP3A4 inhibitors

Breast-feeding, tisotumab vedotin [2] ---> SmPC of [2] of EMA

A risk to breast-fed children cannot be excluded. Breast-feeding should be discontinued during treatment with Tivdak and for at least 3 weeks after the last dose.

Clarithromycin, tisotumab vedotin [2] ---> SmPC of [2] of EMA

Cobicistat, tisotumab vedotin [2] ---> SmPC of [2] of EMA

Drugs metabolised by CYP3A4, tisotumab vedotin [2] ---> SmPC of [2] of EMA

Similarly, tisotumab vedotin is not expected to alter the exposure of drugs that are metabolised by CYP3A4 enzymes.

Embryo-foetal harm, tisotumab vedotin [2] ---> SmPC of [2] of EMA

Based on its mechanism of action and findings from animal studies, tisotumab vedotin could cause embryo-foetal harm when administered to a pregnant woman, including embryo-foetal toxicity and structural malformations (see section 5.3).

Fertility, tisotumab vedotin [2] ---> SmPC of [2] of EMA

Based on findings from animal studies, tisotumab vedotin may impair fertility in males and females (see section 5.3).

Indinavir, tisotumab vedotin [2] ---> SmPC of [2] of EMA

Itraconazol, tisotumab vedotin [2] ---> SmPC of [2] of EMA

Ketoconazole, tisotumab vedotin [2] ---> SmPC of [2] of EMA

Men, tisotumab vedotin [2] ---> SmPC of [2] of EMA

Males with female partners of reproductive potential should be advised to use effective contraception during treatment and for at least 4 months after the last dose of Tivdak.

Midazolam, tisotumab vedotin [2] ---> SmPC of [2] of EMA

Another ADC that contains MMAE co-administered with midazolam (a sensitive CYP3A4 substrate) did not affect the exposure of midazolam.

Nefazodone, tisotumab vedotin [2] ---> SmPC of [2] of EMA

Nelfinavir, tisotumab vedotin [2] ---> SmPC of [2] of EMA

Posaconazole, tisotumab vedotin [2] ---> SmPC of [2] of EMA

Pregnancy, tisotumab vedotin [2] ---> SmPC of [2] of EMA

Tivdak should not be used during pregnancy unless the clinical condition of the woman requires treatment with tisotumab vedotin.

Rifampicin, tisotumab vedotin [2] ---> SmPC of [2] of EMA

Rifampicin (a strong CYP3A4 inducer) co-administered with another ADC that contains MMAE decreased MMAE exposure, with no change in ADC exposure

Ritonavir, tisotumab vedotin [2] ---> SmPC of [2] of EMA

Saquinavir, tisotumab vedotin [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inductors, tisotumab vedotin [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inducers: rifampicin (a strong CYP3A4 inducer) co-administered with another ADC that contains MMAE decreased MMAE exposure, with no change in ADC exposure

Strong CYP3A4 inhibitors, tisotumab vedotin [2] ---> SmPC of [2] of EMA

Telaprevir, tisotumab vedotin [2] ---> SmPC of [2] of EMA

Telithromycin, tisotumab vedotin [2] ---> SmPC of [2] of EMA

Tisotumab vedotin [1], voriconazole ---> SmPC of [1] of EMA

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

The pregnancy status of women of childbearing potential should be verified prior to initiating Tivdak treatment.

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

Females of childbearing potential should be advised to use effective contraception during treatment and for at least 2 months after stopping treatment.

CONTRAINDICATIONS of Tisotumab vedotin (Tivdak)

- 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/tivdak-epar-product-information_en.pdf 24/02/2026

Tivozanib (Fotivda)

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

Patients should be advised to be cautious when driving or using machines if they experience asthenia, fatigue, and/or dizziness during treatment with tivozanib

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

Patients taking an oral BCRP substrate with a clinically-relevant efflux interaction in the gut should ensure that a suitable time window (e.g. 2 hours) is applied between administration of tivozanib and the BCRP substrate.

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

It is unknown whether tivozanib is excreted in human milk, but the potential exists. Because of the potential for tivozanib-mediated adverse reactions in breastfed infants, women should not breast-feed while taking tivozanib.

Fertility, tivozanib [2] ---> SmPC of [2] of EMA

Hormonal contraceptives, tivozanib [2] ---> SmPC of [2] of EMA

It is currently unknown whether tivozanib may reduce the effectiveness of hormonal contraceptives and therefore women using hormonal contraceptives should add a barrier method.

Ketoconazole, tivozanib [2] ---> SmPC of [2] of EMA

The co-administration of tivozanib with a potent CYP3A4 inhibitor, ketoconazole (400 mg once daily), had no influence on tivozanib serum concentrations (Cmax or AUC); therefore, tivozanib exposure is unlikely to be altered by CYP3A4 inhibitors.

Moderate CYP3A4 inductors, tivozanib [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inducers are not expected to have a clinically relevant effect on tivozanib exposure.

Pregnancy, tivozanib [2] ---> SmPC of [2] of EMA

Tivozanib should not be used during pregnancy. If tivozanib is used during pregnancy, or if the patient becomes pregnant while receiving tivozanib, the potential hazard to the foetus must be explained to the patient.

Rifampicin, tivozanib [2] ---> SmPC of [2] of EMA

It is recommended that concomitant administration of tivozanib with strong CYP3A4 inducers, if used, should be undertaken with caution.

Rosuvastatin, tivozanib [2] ---> SmPC of [2] of EMA

Tivozanib inhibits the transporter protein BCRP in vitro, but the clinical relevance of this finding is unknown. Caution should be exercised if tivozanib is co-administered with rosuvastatin.

St. John's wort, tivozanib [2] ---> SmPC of [2] of EMA

Herbal preparations containing St. John's wort (Hypericum perforatum) are contraindicated. The inducing effect of St John's wort may persist for at least 2 weeks after cessation of treatment with St John's wort

Strong CYP3A4 inductors, tivozanib [2] ---> SmPC of [2] of EMA

It is recommended that concomitant administration of tivozanib with strong CYP3A4 inducers, if used, should be undertaken with caution.

Strong CYP3A4 inhibitors, tivozanib [2] ---> SmPC of [2] of EMA

CONTRAINDICATIONS of Tivozanib (Fotivda)

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

- Co-administration with herbal preparations containing St. John’s wort (Hypericum perforatum) (see section 4.5).

https://www.ema.europa.eu/en/documents/product-information/fotivda-epar-product-information_en.pdf 17/07/2023

Tixagevimab + cilgavimab (Evusheld)

Breast-feeding, tixagevimab + cilgavimab [2] ---> SmPC of [2] of EMA

In view of low systemic absorption after oral ingestion of antibodies, administration of EVUSHELD whilst breast-feeding can be considered when clinically indicated.

Cytochrome P450, tixagevimab + cilgavimab [2] ---> SmPC of [2] of EMA

Interactions with medicinal products that are renally excreted or that are substrates, inducers, or inhibitors of CYP enzymes are unlikely.

Fertility, tixagevimab + cilgavimab [2] ---> SmPC of [2] of EMA

There are no data on the effects of tixagevimab and cilgavimab on human fertility. Effects on male and female fertility have not been evaluated in animal studies.

Pharmacokinetics, tixagevimab + cilgavimab [2] ---> SmPC of [2] of EMA

Based on PK modelling, COVID-19 vaccination following EVUSHELD administration had no clinically relevant impact on the clearance of EVUSHELD. Immunocompromised condition had no clinically relevant impact on the clearance of EVUSHELD.

Pregnancy, tixagevimab + cilgavimab [2] ---> SmPC of [2] of EMA

Human immunoglobulin G1 (IgG1) antibodies are known to cross the placenta. EVUSHELD should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the foetus.

CONTRAINDICATIONS of Tixagevimab + cilgavimab (Evusheld)

- 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/evusheld-epar-product-information_en.pdf 14/10/2025 (withdrawn)

Tizanidine

Ability to drive, tizanidine [2] ---> SmPC of [2] of eMC

Patients experiencing somnolence, dizziness or any signs or symptoms of hypotension should refrain from activities requiring a high degree of alertness, e.g. driving a vehicle or operating machines.

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

Alcohol may enhance the sedative action of tizanidine.

Alfa2-adrenergic agonists, tizanidine

The co-administration of tizanidine with other alfa2-adrenergic agonists (e. g. clonidine) should be avoided due to additive hypotensive effects

Amiodarone, tizanidine [2] ---> SmPC of [2] of eMC

Concomitant administration of drugs known to inhibit the activity of CYP1A2 may increase the plasma levels of tizanidine. Co-administration of tizanidine inhibitors of CYP1A2 is not recommended

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

As tizanidine may induce hypotension it may potentiate the effect of antihypertensive products, including diuretics, and caution should therefore be exercised in patients receiving blood pressure lowering products.

Baclofen, tizanidine [2] ---> SmPC of [2] of eMC

Sedatives may enhance the sedative action of tizanidine.

Benzodiazepines, tizanidine [2] ---> SmPC of [2] of eMC

Sedatives may enhance the sedative action of tizanidine.

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

Tizanidine should not be taken by women who are breast-feeding.

Cimetidine, tizanidine [2] ---> SmPC of [2] of eMC

Concomitant administration of drugs known to inhibit the activity of CYP1A2 may increase the plasma levels of tizanidine. Co-administration of tizanidine inhibitors of CYP1A2 is not recommended

Ciprofloxacin [1], tizanidine ---> SmPC of [1] of eMC

Tizanidine must not be administered together with ciprofloxacin. Increased serum tizanidine concentration is associated with a potentiated hypotensive and sedative effect.

Clonidine, tizanidine

The co-administration of tizanidine with other alfa2-adrenergic agonists (e. g. clonidine) should be avoided due to additive hypotensive effects

CYP1A2 inductors, tizanidine

The co-administration of tizanidine with inductors of CYP1A2 may decrease the plasma levels of tizanidine. Decreased plasma levels of tizanidine may reduce the therapeutic effect of tizanidine

CYP1A2 inhibitors, tizanidine [2] ---> SmPC of [2] of eMC

Concomitant administration of drugs known to inhibit the activity of CYP1A2 may increase the plasma levels of tizanidine. Co-administration of tizanidine inhibitors of CYP1A2 is not recommended

Deferasirox [1], tizanidine ---> SmPC of [1] of EMA

Concomitant use of deferasirox with substances that are predominantly metabolised by CYP1A2 and that have a narrow therapeutic index is not recommended.

Digoxin, tizanidine

The co-administration may enhance the antihypertensive effect and a bradycardia. Caution is recommended

Diuretics, tizanidine [2] ---> SmPC of [2] of eMC

Enoxacin, tizanidine [2] ---> SmPC of [2] of eMC

Concomitant administration of drugs known to inhibit the activity of CYP1A2 may increase the plasma levels of tizanidine. Co-administration of tizanidine inhibitors of CYP1A2 is not recommended

Ethinylestradiol/norgestimate [1], tizanidine ---> SmPC of [1] of eMC

Combination hormonal contraceptives with tizanidine may increase plasma levels (due to CYP inhibition) of tizanidine

Fluvoxamine, tizanidine [2] ---> SmPC of [2] of eMC

Concomitant administration of drugs known to inhibit the activity of CYP1A2 may increase the plasma levels of tizanidine. Concomitant use of tizanidine with fluvoxamine, CYP450 1A2 inhibitor in man, is contraindicated

Hydralazine, tizanidine

Concurrent treatment of hydralazine with other antihypertensives may potentate the effects

Interferon, tizanidine

Caution should be used when administering interferon with medicines mainly metabolised by hepatic cytochrome P450 and have a narrow therapeutic window

Leflunomide [1], tizanidine ---> SmPC of [1] of EMA

Methyldopa [1], tizanidine ---> SmPC of [1] of eMC

Concomitant use of methyldopa and tizanidine may enhance the hypotensive effect.

Mexiletine, tizanidine [2] ---> SmPC of [2] of eMC

Concomitant administration of drugs known to inhibit the activity of CYP1A2 may increase the plasma levels of tizanidine. Co-administration of tizanidine inhibitors of CYP1A2 is not recommended

Midostaurin [1], tizanidine ---> SmPC of [1] of EMA

Medicinal products with a narrow therapeutic range that are substrates of CYP1A2 (e.g. tizanidine) should be used with caution when administered concomitantly with midostaurin and may need dose adjustment to maintain optimal exposure

Muscle relaxants, tizanidine

The combination of tizanidine with other muscle relaxants may cause mutual enhancement of effect

Nicotine, tizanidine

The administration of tizanidine to smokers (> 10 cigarettes/day) decreases the systemic exposition of tizanidine

Norfloxacin, tizanidine [2] ---> SmPC of [2] of eMC

Concomitant administration of drugs known to inhibit the activity of CYP1A2 may increase the plasma levels of tizanidine. Co-administration of tizanidine inhibitors of CYP1A2 is not recommended

Obeticholic acid [1], tizanidine ---> SmPC of [1] of EMA

Therapeutic monitoring of CYP1A2 substrates with narrow therapeutic index (e.g. theophylline and tizanidine) is recommended.

Oral contraceptives, tizanidine [2] ---> SmPC of [2] of eMC

Pharmacokinetic data following single and multiple doses of tizanidine suggested that clearance of tizanidine was reduced by approximately 50% in women who were concurrently taking oral contraceptives.

Pefloxacine, tizanidine [2] ---> SmPC of [2] of eMC

Concomitant administration of drugs known to inhibit the activity of CYP1A2 may increase the plasma levels of tizanidine. Co-administration of tizanidine inhibitors of CYP1A2 is not recommended

Pregnancy, tizanidine [2] ---> SmPC of [2] of eMC

Tizanidine should not be used during pregnancy unless the benefit clearly outweighs the risk.

Propafenone, tizanidine [2] ---> SmPC of [2] of eMC

Concomitant administration of drugs known to inhibit the activity of CYP1A2 may increase the plasma levels of tizanidine. Co-administration of tizanidine inhibitors of CYP1A2 is not recommended

QT interval prolonging drugs, tizanidine [2] ---> SmPC of [2] of eMC

The increased plasma levels of tizanidine may result in overdose symptoms such as QT(c) prolongation. Concomitant use of tizanidine (in high doses) with other products that could cause QT (c) prolongation is not recommended.

Rifampicin, tizanidine

The combination of tizanidine with rifampicin may decrease the plasma levels and the therapeutic effect or tizanidine

Rofecoxib, tizanidine [2] ---> SmPC of [2] of eMC

Concomitant administration of drugs known to inhibit the activity of CYP1A2 may increase the plasma levels of tizanidine. Co-administration of tizanidine inhibitors of CYP1A2 is not recommended

Rucaparib [1], tizanidine ---> SmPC of [1] of EMA

Sedatives, tizanidine [2] ---> SmPC of [2] of eMC

Sedatives may enhance the sedative action of tizanidine.

Strong CYP1A2 inductors, tizanidine

The co-administration of tizanidine with inductors of CYP1A2 may decrease the plasma levels of tizanidine. Decreased plasma levels of tizanidine may reduce the therapeutic effect of tizanidine

Strong CYP1A2 inhibitors, tizanidine [2] ---> SmPC of [2] of eMC

Concomitant administration of drugs known to inhibit the activity of CYP1A2 may increase the plasma levels of tizanidine. Co-administration of tizanidine inhibitors of CYP1A2 is not recommended

Teriflunomide [1], tizanidine ---> SmPC of [1] 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.

Ticlopidine, tizanidine [2] ---> SmPC of [2] of eMC

Concomitant administration of drugs known to inhibit the activity of CYP1A2 may increase the plasma levels of tizanidine. Co-administration of tizanidine inhibitors of CYP1A2 is not recommended

Tizanidine, 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.

CONTRAINDICATIONS of Tizanidine

- The use of tizanidine in patients with significantly impaired hepatic function is contraindicated, because tizanidine is extensively metabolised by the liver.

- Concomitant use of tizanidine with strong inhibitors of CYP1A2 such as fluvoxamine or ciprofloxacin is contraindicated

- Hypersensitivity to tizanidine or to any of the excipients.

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

Tobramycin (Tobi Podhaler)

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

On the basis of the pharmacodynamic profile and reported adverse drug reactions, TOBI Podhaler is not expected to adversely affect the ability to drive and use machines.

Aminoglycoside antibiotics, tobramycin [2] ---> SmPC of [2] of EMA

The co-administration with parenteral aminoglycoside therapy should be monitored taking into account the risk of cumulative toxicity

Amphotericin B, tobramycin [2] ---> SmPC of [2] of EMA

Increased potential toxicity of parenterally administered aminoglycosides

Anticholinesterase, tobramycin [2] ---> SmPC of [2] of EMA

Neuromuscular effects

Aztreonam [1], tobramycin ---> SmPC of [1] of EMA

No evidence of any drug interactions were identified from clinical studies in which Cayston was taken

Beta-lactam antibiotics, tobramycin

Significant mutual inactivation

Botulinus toxin, tobramycin [2] ---> SmPC of [2] of EMA

Increased potential toxicity of parenterally administered aminoglycosides (neuromuscular effects)

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

Because of the potential for ototoxicity and nephrotoxicity in infants, a decision should be made whether to terminate breast-feeding or discontinue treatment with TOBI Podhaler, taking into account the importance of the treatment to the mother.

Bronchodilatators, tobramycin [2] ---> SmPC of [2] of EMA

No evidence of drug interactions with these medicines was identified.

Cefalotin, tobramycin [2] ---> SmPC of [2] of EMA

Increased potential toxicity of parenterally administered aminoglycosides

Cisplatin, tobramycin [2] ---> SmPC of [2] of EMA

Risk of increased nephrotoxicity and ototoxicity

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

Care should be taken when using ciclosporin together with other active substances that exhibit nephrotoxic synergy

Daptomycin [1], tobramycin ---> SmPC of [1] of EMA

Caution is warranted when Cubicin is co-administered with tobramycin.

Diuretics, tobramycin [2] ---> SmPC of [2] of EMA

Concomitant use of tobramycin with diuretic compounds is not recommended. Such compounds can enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue.

Dornase alfa, tobramycin [2] ---> SmPC of [2] of EMA

No evidence of drug interactions with these medicines was identified.

Ethacrynic acid, tobramycin [2] ---> SmPC of [2] of EMA

Concomitant use of tobramycin with diuretic compounds is not recommended. Such compounds can enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue.

Ether, tobramycin

Enhancement of a neuromuscular block or respiratory paralysis

Fertility, tobramycin [2] ---> SmPC of [2] of EMA

No effect on male or female fertility was observed in animal studies after subcutaneous administration (see section 5.3).

Furosemide, tobramycin [2] ---> SmPC of [2] of EMA

Concomitant use of tobramycin with diuretic compounds is not recommended. Such compounds can enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue.

Inhaled corticosteroid, tobramycin [2] ---> SmPC of [2] of EMA

No evidence of drug interactions with these medicines was identified.

Macrolide antibiotics, tobramycin [2] ---> SmPC of [2] of EMA

No evidence of drug interactions with these medicines was identified.

Mannitol, tobramycin [2] ---> SmPC of [2] of EMA

Concomitant use of tobramycin with diuretic compounds is not recommended. Such compounds can enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue.

Muscle relaxants, tobramycin

The aminoglycoside antibiotic may enhance the effect of muscle relaxant agent

Nephrotoxic substances, tobramycin [2] ---> SmPC of [2] of EMA

Based on the interaction profile for tobramycin following intravenous and aerosolised administration, concurrent and/or sequential use of TOBI Podhaler is not recommended with other medicinal products with nephrotoxic or ototoxic potential.

Ototoxic agents, tobramycin [2] ---> SmPC of [2] of EMA

Pharmacological interactions, tobramycin [2] ---> SmPC of [2] of EMA

In clinical studies, patients receiving TOBI Podhaler continued to take dornase alfa, bronchodilators, inhaled corticosteroids and macrolides, no evidence of drug interactions with these medicines was identified.

Piperacillin, tobramycin ---> SmPC of [piperacillin/tazobactam] of eMC

The inactivation of tobramycin by piperacillin has been demonstrated in patients with severe renal impairment.

Piperacillin/tazobactam [1], tobramycin ---> SmPC of [1] of eMC

The inactivation of tobramycin by piperacillin has been demonstrated in patients with severe renal impairment.

Platinum compounds, tobramycin [2] ---> SmPC of [2] of EMA

The co-administration may potentiate the nephrotoxic and ototoxic effects of both active principles

Polymyxin, tobramycin [2] ---> SmPC of [2] of EMA

Increased risk of nephrotoxicity

Pregnancy, tobramycin [2] ---> SmPC of [2] of EMA

TOBI Podhaler should not be used during pregnancy unless clearly necessary

Tacrolimus, tobramycin [2] ---> SmPC of [2] of EMA

Increased potential toxicity of parenterally administered aminoglycosides

Tobramycin [1], urea ---> SmPC of [1] of EMA

Concomitant use of tobramycin with diuretic compounds is not recommended. Such compounds can enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue.

Tobramycin, valsartan

Increased risk of nephrotoxicity

Tobramycin, vancomycin [2] ---> SmPC of [2] of eMC

The administration concurrent or sequential of vancomycin with other potentially nephrotoxic or ototoxic drugs may increase the nephrotoxicity and/or ototoxicity

CONTRAINDICATIONS of Tobramycin (Tobi Podhaler)

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

https://www.ema.europa.eu/en/documents/product-information/tobi-podhaler-epar-product-information_en.pdf 13/05/2025

Other trade names: Bramitob, Nebris, Tobrex, Tobrexan, Tobramycin PARI, Ursitan, Vantobra (previously Tobramycin PARI),

Tocilizumab (RoActemra)

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

RoActemra has minor influence on the ability to drive and use machines (see section 4.8, dizziness).

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

Benzodiazepines, tocilizumab [2] ---> SmPC of [2] of EMA

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

A decision must be made to either discontinue breast-feeding or to discontinue/abstain from therapy

Calcium antagonists, tocilizumab [2] ---> SmPC of [2] of EMA

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

Population pharmacokinetic analyses did not detect any effect of MTX, non-steroidal anti-inflammatory drugs (NSAIDs) or corticosteroids on tocilizumab clearance.

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

CYP450, strong cytokine inhibitors ---> SmPC of [tocilizumab] of EMA

The expression of hepatic CYP450 enzymes is suppressed by cytokines, such as IL-6, that stimulate chronic inflammation. Thus, CYP450 expression may be reversed when potent cytokine inhibitory therapy, such as tocilizumab, is introduced.

CYP450, tocilizumab [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP1A2, tocilizumab [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP2C9, tocilizumab [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP3A4, tocilizumab [2] ---> SmPC of [2] of EMA

Enzyme expression, tocilizumab [2] ---> SmPC of [2] of EMA

In vitro studies with cultured human hepatocytes demonstrated that IL-6 caused a reduction in CYP1A2, CYP2C9, CYP2C19 and CYP3A4 enzyme expression. Tocilizumab normalises expression of these enzymes.

Fertility, tocilizumab [2] ---> SmPC of [2] of EMA

Available non-clinical data do not suggest an effect on fertility under tocilizumab treatment.

Half-life, tocilizumab [2] ---> SmPC of [2] of EMA

Given its long elimination half-life (t1/2), the effect of tocilizumab on CYP450 enzyme activity may persist for several weeks after stopping therapy.

Methotrexate, tocilizumab [2] ---> SmPC of [2] of EMA

Concomitant administration of a single dose of 10 mg/kg tocilizumab with 10-25 mg MTX once weekly had no clinically significant effect on MTX exposure.

NSAID, tocilizumab [2] ---> SmPC of [2] of EMA

Population pharmacokinetic analyses did not detect any effect of MTX, non-steroidal anti-inflammatory drugs (NSAIDs) or corticosteroids on tocilizumab clearance.

Phenprocoumon, tocilizumab [2] ---> SmPC of [2] of EMA

Phenytoin, tocilizumab [2] ---> SmPC of [2] of EMA

Pregnancy, tocilizumab [2] ---> SmPC of [2] of EMA

RoActemra should not be used during pregnancy unless clearly necessary

Simvastatine, tocilizumab [2] ---> SmPC of [2] of EMA

In a study in RA patients, levels of simvastatin (CYP3A4) were decreased by 57% one week following a single dose of tocilizumab, to the level similar to, or slightly higher than, those observed in healthy subjects.

Theophylline, tocilizumab [2] ---> SmPC of [2] of EMA

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

Live and live attenuated vaccines should not be given concurrently with tocilizumab as clinical safety has not been established.

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

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

Women of childbearing potential must use effective contraception during and up to 3 months after treatment.

CONTRAINDICATIONS of Tocilizumab (RoActemra)

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

- Active, severe infections with the exception of COVID-19 (see section 4.4).

https://www.ema.europa.eu/en/documents/product-information/roactemra-epar-product-information_en.pdf 06/05/2025

Other trade names: Tofidence, Tyenne,

Tocofersolan (Vedrop)

Antibiotics, tocofersolan [2] ---> SmPC of [2] of EMA

Antihistamines, tocofersolan [2] ---> SmPC of [2] of EMA

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

A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy should be made taking into account the benefit of breast-feeding to the child and the benefit of tocofersolan therapy to the woman.

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

Fat-soluble vitamins, tocofersolan [2] ---> SmPC of [2] of EMA

Fertility, tocofersolan [2] ---> SmPC of [2] of EMA

No data is available

Lipophilic medicinal products, tocofersolan [2] ---> SmPC of [2] of EMA

Pregnancy, tocofersolan [2] ---> SmPC of [2] of EMA

Caution should be exercised when prescribing to pregnant women.

Steroids, tocofersolan [2] ---> SmPC of [2] of EMA

Tacrolimus, tocofersolan [2] ---> SmPC of [2] of EMA

Tocofersolan [1], vitamin A ---> SmPC of [1] of EMA

Tocofersolan [1], vitamin D ---> SmPC of [1] of EMA

Tocofersolan [1], vitamin E ---> SmPC of [1] of EMA

Tocofersolan [1], vitamin K ---> SmPC of [1] of EMA

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

It is recommended to monitor the coagulation function when tocofersolan administered with anti-vitamins K treatment

CONTRAINDICATIONS of Tocofersolan (Vedrop)

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

- Vedrop must not be used in preterm newborn infants.

https://www.ema.europa.eu/en/documents/product-information/vedrop-epar-product-information_en.pdf 16/12/2024

Tofacitinib (Xeljanz)

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

As a precautionary measure, the use of tofacitinib during breast-feeding is contraindicated

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

Coadministration with tacrolimus (mild CYP3A4 inhibitor) and cyclosporine (moderate CYP3A4 inhibitor) increased XELJANZ AUC

Fertility, tofacitinib [2] ---> SmPC of [2] of EMA

Formal studies of the potential effect on human fertility have not been conducted. Tofacitinib impaired female fertility but not male fertility in rats (see section 5.3).

Fluconazole, tofacitinib [2] ---> SmPC of [2] of EMA

Tofacitinib exposure is increased when one or more concomitant medications results in both moderate inhibition of CYP3A4 and potent inhibition of CYP2C19 (e.g., fluconazole)

Ketoconazole, tofacitinib [2] ---> SmPC of [2] of EMA

Tofacitinib exposure is increased when coadministered with potent inhibitors of CYP3A4 (e.g., ketoconazole)

Metformin, tofacitinib [2] ---> SmPC of [2] of EMA

Coadministration of XELJANZ did not have an effect on the PK of metformin, indicating that tofacitinib does not interfere with the organic cationic transporter (OCT2) in healthy volunteers.

Methotrexate, tofacitinib [2] ---> SmPC of [2] of EMA

Concomitant administration with MTX 15-25 mg once weekly had no effect on the PK of tofacitinib in RA patients (see Figure 1).

Midazolam, tofacitinib [2] ---> SmPC of [2] of EMA

These in vitro results were confirmed by a human drug interaction study showing no changes in the PK of midazolam, a highly sensitive CYP3A4 substrate, when coadministered with XELJANZ.

Oral contraceptives, tofacitinib [2] ---> SmPC of [2] of EMA

Coadministration of tofacitinib did not have an effect on the PK of oral contraceptives, levonorgestrel and ethinyl estradiol, in healthy female volunteers.

Pregnancy, tofacitinib [2] ---> SmPC of [2] of EMA

As a precautionary measure, the use of tofacitinib during pregnancy is contraindicated

Rifampicin, tofacitinib [2] ---> SmPC of [2] of EMA

Tofacitinib exposure is decreased when coadministered with potent CYP inducers (e.g., rifampicin). Coadministration of potent inducers of CYP3A4 with XELJANZ is not recommended.

Strong CYP2C19 and moderate CYP3A4 inhibitors, tofacitinib [2] ---> SmPC of [2] of EMA

Tofacitinib exposure is increased when one or more concomitant medications results in both moderate inhibition of CYP3A4 and potent inhibition of CYP2C19 (e.g., fluconazole)

Strong CYP3A4 inductors, tofacitinib [2] ---> SmPC of [2] of EMA

Tofacitinib exposure is decreased when coadministered with potent CYP inducers (e.g., rifampicin). Coadministration of potent inducers of CYP3A4 with XELJANZ is not recommended.

Strong CYP3A4 inhibitors, tofacitinib [2] ---> SmPC of [2] of EMA

Tofacitinib exposure is increased when coadministered with potent inhibitors of CYP3A4 (e.g., ketoconazole)

Tacrolimus, tofacitinib [2] ---> SmPC of [2] of EMA

Coadministration with tacrolimus (mild CYP3A4 inhibitor) and cyclosporine (moderate CYP3A4 inhibitor) increased tofacitinib AUC

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

It is recommended that live vaccines not be given concurrently with tofacitinib.

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

Women of childbearing potential should be advised to use effective contraception during treatment with tofacitinib and for at least 4 weeks after the last dose.

CONTRAINDICATIONS of Tofacitinib (Xeljanz)

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

- Active tuberculosis (TB), serious infections such as sepsis, or opportunistic infections (see section 4.4).

- Severe hepatic impairment (see section 4.2).

- Pregnancy and lactation (see section 4.6).

https://www.ema.europa.eu/en/documents/product-information/xeljanz-epar-product-information_en.pdf 20/10/2025

Tofersen (Qalsody)

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

Tofersen has minor influence on the ability to drive and use machines. Patients who develop visual disturbance under tofersen should be cautioned to avoid driving or operating machinery.

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

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

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

Tofersen is not an inducer or inhibitor of CYP450-mediated oxidative metabolism; therefore, it should not interfere with other medicinal products that interact with these metabolic pathways.

Fertility, tofersen [2] ---> SmPC of [2] of EMA

There are no data available on the potential effects on fertility in humans. Toxicity studies in animals have indicated that tofersen would not appear to have harmful effects on male or female fertility (see section 5.3).

Pregnancy, tofersen [2] ---> SmPC of [2] of EMA

Tofersen is not recommended during pregnancy and in women of childbearing potential not using contraception.

CONTRAINDICATIONS of Tofersen (Qalsody)

- 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/qalsody-epar-product-information_en.pdf 14/06/2024

Tolcapone (Tasmar)

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

The ability to drive and operate machines may be compromised due to the Parkinson's disease symptoms. Levodopa has been associated with somnolence and episodes of sudden sleep onset.

Adrenaline, tolcapone [2] ---> SmPC of [2] of EMA

Tolcapone, COMT inhibitor, may increase the plasma concentrations of drugs metabolised by COMT

Alpha-methyldopa, tolcapone [2] ---> SmPC of [2] of EMA

Tolcapone, COMT inhibitor, may increase the plasma concentrations of drugs metabolised by COMT

Apomorphine, tolcapone [2] ---> SmPC of [2] of EMA

Tolcapone, COMT inhibitor, may increase the plasma concentrations of drugs metabolised by COMT

Benserazide, tolcapone [2] ---> SmPC of [2] of EMA

An interaction was observed with benserazide, which may lead to increased levels of benserazide and its active metabolite.

Benserazide/levodopa, tolcapone [2] ---> SmPC of [2] of EMA

The plasma concentrations of benserazide observed after co-administration of tolcapone and benserazide-25 mg/levodopa were still within the range of values observed with levodopa/benserazide alone.

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

The safety of tolcapone in infants is unknown; therefore, women should not breast-feed during treatment with Tasmar.

Carbidopa, tolcapone [2] ---> SmPC of [2] of EMA

An interaction was observed with benserazide, which may lead to increased levels of benserazide and its active metabolite.

Catecholamine-O-methyltransferase inhibitors, levodopa ---> SmPC of [tolcapone] of EMA

The consequent increase in dopaminergic stimulation can lead to the dopaminergic adverse reactions observed after treatment with COMT inhibitors.

Catecholamine-O-methyltransferase inhibitors, levodopa/carbidopa ---> SmPC of [tolcapone] of EMA

COMT inhibitors are known to increase the bioavailability of the co-administered levodopa.

Catecholamines, tolcapone [2] ---> SmPC of [2] of EMA

Drugs that increase catecholamines: Since tolcapone interferes with the metabolism of catecholamines, interactions with other drugs affecting catecholamine levels are theoretically possible.

Cytochrome CYP2C9, tolcapone [2] ---> SmPC of [2] of EMA

In an interaction study, tolcapone did not change the pharmacokinetics of tolbutamide. Therefore, clinically relevant interactions involving cytochrome CYP2C9 appear unlikely.

Desipramine, tolcapone [2] ---> SmPC of [2] of EMA

Therefore, caution should be exercised when potent noradrenaline uptake inhibitors such as desipramine, maprotiline, or venlafaxine are administered to Parkinson's disease patients being treated with Tasmar and levodopa preparations.

Doubutamine, tolcapone [2] ---> SmPC of [2] of EMA

Tolcapone, COMT inhibitor, may increase the plasma concentrations of drugs metabolised by COMT

Drugs metabolised by catechol-O-methyltransferase, tolcapone [2] ---> SmPC of [2] of EMA

Tolcapone, COMT inhibitor, may increase the plasma concentrations of drugs metabolised by COMT

Fertility, tolcapone [2] ---> SmPC of [2] of EMA

In rats and rabbits, embryo-foetal toxicity was observed after tolcapone administration (see section 5.3). The potential risk for humans is unknown.

IMAO B, tolcapone [2] ---> SmPC of [2] of EMA

Selective MAO-B inhibitors should not be used at higher than recommended doses (e.g. selegiline 10 mg/day) when co-administered with Tasmar.

Isoprenaline, tolcapone [2] ---> SmPC of [2] of EMA

Tolcapone, COMT inhibitor, may increase the plasma concentrations of drugs metabolised by COMT

Levodopa preparation, tolcapone [2] ---> SmPC of [2] of EMA

In clinical trials, patients receiving Tasmar/levodopa preparations reported a similar adverse reaction profile independent of whether or not they were also concomitantly administered selegiline (a MAO-B inhibitor).

Levodopa, tolcapone [2] ---> SmPC of [2] of EMA

Tasmar, as a COMT inhibitor, is known to increase the bioavailability of the co-administered levodopa. The consequent increase in dopaminergic stimulation can lead to the dopaminergic adverse reactions observed after treatment with COMT inhibitors.

Levodopa/benserazide, tolcapone [2] ---> SmPC of [2] of EMA

Since Tasmar should be used only in combination with levodopa/benserazide and levodopa/carbidopa, the prescribing information for these levodopa preparations is also applicable to their concomitant use with Tasmar.

Levodopa/carbidopa, tolcapone [2] ---> SmPC of [2] of EMA

Maprotiline, tolcapone [2] ---> SmPC of [2] of EMA

Non-selective MAO-inhibitors, tolcapone [2] ---> SmPC of [2] of EMA

The combination of MAO-A and MAO-B inhibitors is equivalent to non-selective MAO-inhibition, therefore they should not both be given concomitantly with Tasmar and levodopa preparations (see also section 4.5).

Non-selective MAO-inhibitors, tolcapone [2] ---> SmPC of [2] of EMA

No se administrará Tasmar junto con inhibidores no selectivos de la monoamino oxidasa (MAO) (ej. fenelzina y tranilcipromina).

Pharmacokinetics of other drugs, tolcapone [2] ---> SmPC of [2] of EMA

The effect of tolcapone on the pharmacokinetics of other drugs metabolised by COMT such as alpha-methyldopa, dobutamine, apomorphine, adrenaline and isoprenaline have not been evaluated.

Phenelzine, tolcapone [2] ---> SmPC of [2] of EMA

No se administrará Tasmar junto con inhibidores no selectivos de la monoamino oxidasa (MAO) (ej. fenelzina y tranilcipromina).

Pregnancy, tolcapone [2] ---> SmPC of [2] of EMA

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

Selegiline, tolcapone [2] ---> SmPC of [2] of EMA

Selective MAO-B inhibitors should not be used at higher than recommended doses (e.g. selegiline 10 mg/day) when co-administered with Tasmar.

Tolbutamide, tolcapone [2] ---> SmPC of [2] of EMA

In an interaction study, tolcapone did not change the pharmacokinetics of tolbutamide. Therefore, clinically relevant interactions involving cytochrome CYP2C9 appear unlikely.

Tolcapone [1], tranylcypromine ---> SmPC of [1] of EMA

No se administrará Tasmar junto con inhibidores no selectivos de la monoamino oxidasa (MAO) (ej. fenelzina y tranilcipromina).

Tolcapone [1], venlafaxine ---> SmPC of [1] of EMA

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

Since clinical information is limited regarding the combination of warfarin and tolcapone, coagulation parameters should be monitored when these drugs are co-administered.

CONTRAINDICATIONS of Tolcapone (Tasmar)

- Hypersensitivity to tolcapone or any of its other ingredients listed in section 6.1.

- Evidence of liver disease or increased liver enzymes

- Severe dyskinesia

- A previous history of Neuroleptic Malignant Syndrome (NMS) Symptom Complex and /or non-traumatic Rhabdomyolysis or Hyperthermia.

- Phaeochromocytoma.

- Treatment with non-selective mono amino oxidase (MAO) inhibitors

https://www.ema.europa.eu/en/documents/product-information/tasmar-epar-product-information_en.pdf 08/11/2024

Tolterodine

Ability to drive, tolterodine [2] ---> SmPC of [2] of eMC

Since this drug may cause accommodation disturbances and influence reaction time, the ability to drive and use machines may be negatively affected.

Amiodarone, tolterodine [2] ---> SmPC of [2] of eMC

Tolterodine should be used with caution in patients with risk factors for QT-prolongation

Antimuscarinic agents, tolterodine [2] ---> SmPC of [2] of eMC

Concomitant medication of tolterodine with other drugs that possess antimuscarinic properties may result in more pronounced therapeutic effect and side-effects.

Aprepitant, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

Azole antifungals, tolterodine [2] ---> SmPC of [2] of eMC

Concomitant systemic medication with potent CYP3A4 inhibitors is not recommended due to increased serum concentrations of tolterodine in poor CYP2D6 metabolisers with (subsequent) risk of overdosage

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

Tolterodine should be avoided during lactation.

Chlorpromazine, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

Cholinergic agents, tolterodine [2] ---> SmPC of [2] of eMC

The therapeutic effect of tolterodine may be reduced by concomitant administration of muscarinic cholinergic receptor agonists.

Cisapride, tolterodine [2] ---> SmPC of [2] of eMC

The effect of prokinetics may be decreased by tolterodine.

Clarithromycin, tolterodine [2] ---> SmPC of [2] of eMC

Concomitant systemic medication with potent CYP3A4 inhibitors is not recommended due to increased serum concentrations of tolterodine in poor CYP2D6 metabolisers with (subsequent) risk of overdosage

Class IA antiarrhythmic agents, tolterodine [2] ---> SmPC of [2] of eMC

Tolterodine should be used with caution in patients with risk factors for QT-prolongation

Class III antiarrhythmic agents, tolterodine [2] ---> SmPC of [2] of eMC

Tolterodine should be used with caution in patients with risk factors for QT-prolongation

Cocaine, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

Conivaptan, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

CYP2D6 and CYP3A4 inhibitor, tolterodine

The CYP3A4 and CYP2D6 inhibition may increase the plasma concentrations of tolterodine. Concomitant use is not recommended

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.

Drugs inducing bradycardia, tolterodine [2] ---> SmPC of [2] of eMC

Tolterodine should be used with caution in patients with risk factors for QT-prolongation

Efavirenz, tolterodine

May increase the plasma levels of tolterodine

Electrolyte imbalance, tolterodine [2] ---> SmPC of [2] of eMC

Tolterodine should be used with caution in patients with risk factors for QT-prolongation

Erythromycin, tolterodine [2] ---> SmPC of [2] of eMC

Concomitant systemic medication with potent CYP3A4 inhibitors is not recommended due to increased serum concentrations of tolterodine in poor CYP2D6 metabolisers with (subsequent) risk of overdosage

Etravirine, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

Fluoxetine, tolterodine [2] ---> SmPC of [2] of eMC

Concomitant treatment with fluoxetine (a potent CYP2D6 inhibitor) does not result in a clinically significant interaction since tolterodine and its CYP2D6-dependent metabolite, 5-hydroxymethyl tolterodine are equipotent.

Fosaprepitant, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

Haloperidol, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

Hypocalcemia, tolterodine [2] ---> SmPC of [2] of eMC

Tolterodine should be used with caution in patients with risk factors for QT-prolongation

Hypokalemia, tolterodine [2] ---> SmPC of [2] of eMC

Tolterodine should be used with caution in patients with risk factors for QT-prolongation

Hypomagnesemia, tolterodine [2] ---> SmPC of [2] of eMC

Tolterodine should be used with caution in patients with risk factors for QT-prolongation

Imatinib, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

Isoniazid, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

Itraconazol, tolterodine [2] ---> SmPC of [2] of eMC

Concomitant systemic medication with potent CYP3A4 inhibitors is not recommended due to increased serum concentrations of tolterodine in poor CYP2D6 metabolisers with (subsequent) risk of overdosage

Ketoconazole, tolterodine [2] ---> SmPC of [2] of eMC

Concomitant systemic medication with potent CYP3A4 inhibitors is not recommended due to increased serum concentrations of tolterodine in poor CYP2D6 metabolisers with (subsequent) risk of overdosage

Lapatinib, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

Macrolide antibiotics, tolterodine [2] ---> SmPC of [2] of eMC

Concomitant systemic medication with potent CYP3A4 inhibitors is not recommended due to increased serum concentrations of tolterodine in poor CYP2D6 metabolisers with (subsequent) risk of overdosage

Metoclopramide, tolterodine [2] ---> SmPC of [2] of eMC

The effect of prokinetics may be decreased by tolterodine.

Metronidazole, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

Muscarinic agents, tolterodine [2] ---> SmPC of [2] of eMC

The therapeutic effect of tolterodine may be reduced by concomitant administration of muscarinic cholinergic receptor agonists.

Nicardipine, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

Norfloxacin, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

Oral contraceptives, tolterodine [2] ---> SmPC of [2] of eMC

Drug interaction studies have shown no interactions with combined oral contraceptives (ethinyl estradiol/levonorgestrel)

Pergolide, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

Pregnancy, tolterodine [2] ---> SmPC of [2] of eMC

Tolterodine is not recommended during pregnancy.

Procainamide, tolterodine [2] ---> SmPC of [2] of eMC

Tolterodine should be used with caution in patients with risk factors for QT-prolongation

Prokinetics, tolterodine [2] ---> SmPC of [2] of eMC

The effect of prokinetics may be decreased by tolterodine.

Protease inhibitors, tolterodine [2] ---> SmPC of [2] of eMC

Concomitant systemic medication with potent CYP3A4 inhibitors is not recommended due to increased serum concentrations of tolterodine in poor CYP2D6 metabolisers with (subsequent) risk of overdosage

QT interval prolonging drugs, tolterodine [2] ---> SmPC of [2] of eMC

Tolterodine should be used with caution in patients with risk factors for QT-prolongation

Quinidine, tolterodine [2] ---> SmPC of [2] of eMC

Tolterodine should be used with caution in patients with risk factors for QT-prolongation

Rivastigmine [1], tolterodine ---> SmPC of [1] of EMA

Rivastigmine might interfere with the activity of the anticholinergic medicinal product

Sertraline, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

Sotalol, tolterodine [2] ---> SmPC of [2] of eMC

Tolterodine should be used with caution in patients with risk factors for QT-prolongation

Strong CYP2D6 inhibitors, tolterodine [2] ---> SmPC of [2] of eMC

Strong CYP3A4 inhibitors, tolterodine [2] ---> SmPC of [2] of eMC

Concomitant systemic medication with potent CYP3A4 inhibitors is not recommended due to increased serum concentrations of tolterodine in poor CYP2D6 metabolisers with (subsequent) risk of overdosage

Terbinafine, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

Tetracyclines, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

Tipranavir/ritonavir, tolterodine ---> SmPC of [tipranavir] of EMA

The CYP3A4 and CYP2D6 inhibition by tipranavir/ritonavir may increase the plasma concentrations of tolterodine. Concomitant use is not recommended

Tolterodine [1], warfarin ---> SmPC of [1] of eMC

Drug interaction studies have shown no interactions with warfarin

Tolterodine, verapamil

The co-administration may increase the plasma concentrations of tolterodine

Tolterodine, vinblastine

The co-administration may increase the plasma concentrations of tolterodine

CONTRAINDICATIONS of Tolterodine

Tolterodine is contraindicated in patients with

- Urinary retention

- Uncontrolled narrow angle glaucoma

- Myasthenia gravis

- Known hypersensitivity to tolterodine or excipients

- Severe ulcerative colitis

- Toxic megacolon

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

Tolvaptan (Samsca)

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

When driving vehicles or using machines it should be taken into account that occasionally dizziness, asthenia or syncope may occur.

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

In healthy subjects, tolvaptan, a CYP3A4 substrate, had no effect on the plasma concentrations of some other CYP3A4 substrates (e.g., warfarin or amiodarone).

Barbiturates, tolvaptan [2] ---> SmPC of [2] of EMA

Tolvaptan plasma concentrations have been decreased by up to 87 % (AUC) after the administration of CYP3A4 inducers. Caution has to be exercised in co-administering CYP3A4 inducers (e.g., rifampicin, barbiturates) with tolvaptan.

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

If BCRP substrates (e.g., sulfasalazine) are co-administered with tolvaptan, patients must be managed cautiously and evaluated for excessive effects of these medicinal products.

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

The potential risk for humans is unknown. Samsca is contraindicated during breast-feeding (see section 4.3).

Cabozantinib [1], tolvaptan ---> 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.

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

Patients receiving digoxin or other narrow therapeutic index P-gp substrates (e.g., dabigatran etexilate) must therefore be managed cautiously and evaluated for excessive effects when treated with tolvaptan.

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.

Digoxin, tolvaptan [2] ---> SmPC of [2] of EMA

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.

Drugs primarily metabolised by CYP3A4, tolvaptan [2] ---> SmPC of [2] of EMA

Tolvaptan increased plasma levels of lovastatin by 1.3 to 1.5-fold. Even though this increase has no clinical relevance, it indicates tolvaptan can potentially increase exposure to CYP3A4 substrates.

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.

Effervescent analgesics, tolvaptan [2] ---> SmPC of [2] of EMA

Medicinal products with high sodium content such as effervescent analgesic preparations and certain sodium containing treatments for dyspepsia may also increase serum sodium concentration.

Fertility, tolvaptan [2] ---> SmPC of [2] of EMA

Studies in animals showed effects on fertility (see section 5.3). The potential risk for humans is unknown.

Grapefruit juice, tolvaptan [2] ---> SmPC of [2] of EMA

Co-administration of grapefruit juice and tolvaptan resulted in a 1.8-fold increase in exposure to tolvaptan. Patients taking tolvaptan should avoid ingesting grapefruit juice.

Hypertonic saline solution, tolvaptan [2] ---> SmPC of [2] of EMA

Higher risk for developing rapid correction of serum sodium

Hyponatremia, tolvaptan [2] ---> SmPC of [2] of EMA

There is no experience from controlled clinical trials with concomitant use of Samsca and other treatments for hyponatremia such as hypertonic sodium chloride solution, oral sodium formulations, and medicinal products that increase serum sodium level.

Ketoconazole [1], tolvaptan --> SmPC of [1] of EMA

The coadministration of ketoconazole with tolvaptan used for a specific disease called "syndrome of inappropriate antidiuretic hormone secretion" is contraindicated.

Ketoconazole, 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.

Lomitapide [1], tolvaptan ---> SmPC of [1] of EMA

Weak CYP3A4 inhibitors are expected to increase the exposure of lomitapide when taken simultaneously. Separate the dose of the medications by 12 hours OR decrease the dose of Lojuxta by half.

Loop diuretics, tolvaptan [2] ---> SmPC of [2] of EMA

Each class of agent has the potential to lead to severe dehydration, which constitutes a risk factor for renal dysfunction.

Lovastatine, tolvaptan [2] ---> SmPC of [2] of EMA

Tolvaptan increased plasma levels of lovastatin by 1.3 to 1.5-fold. Even though this increase has no clinical relevance, it indicates tolvaptan can potentially increase exposure to CYP3A4 substrates.

Macrolide antibiotics, 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.

Metformin, tolvaptan [2] ---> SmPC of [2] of EMA

If OCT1 substrates (e.g., metformin) are co-administered with tolvaptan, patients must be managed cautiously and evaluated for excessive effects of these medicinal products.

Nirmatrelvir/ritonavir [1], tolvaptan ---> SmPC of [1] of EMA

Coadministration is contraindicated due to potential for dehydration, hypovolemia and hyperkalemia (see section 4.3).

OCT1 substrates, tolvaptan [2] ---> SmPC of [2] of EMA

If OCT1 substrates (e.g., metformin) are co-administered with tolvaptan, patients must be managed cautiously and evaluated for excessive effects of these medicinal products.

P-glycoprotein substrates with small therapeutic index, tolvaptan [2] ---> SmPC of [2] of EMA

Pregnancy, tolvaptan [2] ---> SmPC of [2] of EMA

Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Samsca is contraindicated during pregnancy (see section 4.3).

Rifampicin, tolvaptan [2] ---> SmPC of [2] of EMA

Rosuvastatin, tolvaptan [2] ---> SmPC of [2] of EMA

If BCRP substrates (e.g., sulfasalazine) are co-administered with tolvaptan, patients must be managed cautiously and evaluated for excessive effects of these medicinal products.

Sodium, tolvaptan [2] ---> SmPC of [2] of EMA

Co-administration of tolvaptan with other treatments for hyponatraemia, and medications that increase serum sodium concentration, is not recommended

Strong CYP3A4 inductors, tolvaptan [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inhibitors, 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.

Sulfasalazine, tolvaptan [2] ---> SmPC of [2] of EMA

If BCRP substrates (e.g., sulfasalazine) are co-administered with tolvaptan, patients must be managed cautiously and evaluated for excessive effects of these medicinal products.

Thiazides, tolvaptan [2] ---> SmPC of [2] of EMA

Each class of agent has the potential to lead to severe dehydration, which constitutes a risk factor for renal dysfunction.

Tolvaptan [1], vasopressin and analogues ---> SmPC of [1] 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.

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

In healthy subjects, tolvaptan, a CYP3A4 substrate, had no effect on the plasma concentrations of some other CYP3A4 substrates (e.g., warfarin or amiodarone).

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

Women of childbearing potential have to use effective contraception during tolvaptan treatment.

Tolvaptan, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to significantly increase the plasma concentrations of tolvaptan. The co-administration is Contraindicated.

CONTRAINDICATIONS of Tolvaptan (Samsca)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or to benzazepine or benzazepine derivatives (see section 4.4)

- Anuria

- Hypovolemia

- Hypovolaemic hyponatraemia

- Hypernatremia

- Patients who cannot perceive thirst

- Pregnancy

- Breast-feeding

https://www.ema.europa.eu/en/documents/product-information/samsca-epar-product-information_en.pdf 26/03/2025

Other trade names: Jinarc,

Topiramate

Ability to drive, topiramate [2] ---> SmPC of [2] of eMC

Topiramate acts on the central nervous system and may produce drowsiness, dizziness or other related symptoms.

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

It is recommended that topiramate not be used concomitantly with alcohol

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

A decision must be made whether to suspend breast-feeding or to discontinue/ abstain from topiramate therapy

Carbamazepine [1], topiramate ---> SmPC of [1] of eMC

Carbamazepine decreases the plasma concentration of topiramate.

CNS depressants, topiramate [2] ---> SmPC of [2] of eMC

It is recommended that topiramate not be used concomitantly with other CNS depressant medicinal products.

Cyproterone/ethinylestradiol [1], topiramate ---> SmPC of [1] of eMC

Drugs which induce hepatic enzymes (especially cytochrome P450 3A4) increase the metabolism of contraceptive steroids and hence may result in breakthrough bleeding and pregnancy.

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

Diazepam, topiramate [2] ---> SmPC of [2] of eMC

Topiramate inhibits the enzyme CYP 2C19 and may interfere with other substances metabolized via this enzyme

Dienogest, topiramate

The enzymatic induction may decrease the plasma levels of dienogest

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.

Drugs primarily metabolised by CYP2C19, topiramate [2] ---> SmPC of [2] of eMC

Topiramate inhibits the enzyme CYP 2C19 and may interfere with other substances metabolized via this enzyme

Eslicarbazepine [1], topiramate ---> SmPC of [1] of EMA

No dose adjustment is required.

Estradiol valerate/norgestrel [1], topiramate ---> SmPC of [1] of eMC

The metabolism of oestrogens and progestagens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes

Ethinyl estradiol, topiramate ---> SmPC of [ethinylestradiol/chlormadinone] of eMC

Interactions can occur with drugs that induce hepatic enzymes which can result in increased clearance of sex hormones

Ethinylestradiol/chlormadinone [1], topiramate ---> SmPC of [1] of eMC

Interactions can occur with drugs that induce hepatic enzymes which can result in increased clearance of sex hormones

Ethinylestradiol/desogestrel [1], topiramate ---> SmPC of [1] of eMC

Interactions can occur with drugs that induce microsomal enzymes, which can result in increased clearance of sex hormones

Ethinylestradiol/drospirenone [1], topiramate ---> SmPC of [1] of eMC

Interactions can occur with drugs that induce hepatic enzymes which can result in increased clearance of sex hormones

Ethinylestradiol/etonogestrel [1], topiramate ---> SmPC of [1] of eMC

Interactions can occur with drugs that induce hepatic enzymes which can result in increased clearance of sex hormones

Ethinylestradiol/gestodene [1], topiramate ---> SmPC of [1] of eMC

Drugs which induce hepatic enzymes (especially cytochrome P450 3A4) increase the metabolism of contraceptive steroids and hence may result in breakthrough bleeding and pregnancy.

Ethinylestradiol/norgestimate [1], topiramate ---> SmPC of [1] of eMC

Drugs or herbal products that induce enzymes, especially CYP3A4, may decrease the plasma concentrations of contraceptive hormones, and may decrease their effectiveness and/or increase breakthrough bleeding.

Etonogestrel [1], topiramate ---> SmPC of [1] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, specifically cytochrome P450 enzymes, which can result in increased clearance of sex hormones

Glyburide, topiramate [2] ---> SmPC of [2] of eMC

When topiramate is added to glyburide therapy or glyburide is added to topiramate therapy, careful attention should be given to the routine monitoring of patients for adequate control of their diabetic disease state.

Hydrochlorothiazide, topiramate [2] ---> SmPC of [2] of eMC

The results of a study indicate that topiramate Cmax increased by 27% and AUC increased by 29% when HCTZ was added to topiramate. The addition of HCTZ to topiramate therapy may require an adjustment of the topiramate dose.

Imipramine, topiramate [2] ---> SmPC of [2] of eMC

Topiramate inhibits the enzyme CYP 2C19 and may interfere with other substances metabolized via this enzyme

Lamotrigine [1], topiramate ---> SmPC of [1] of eMC

Topiramate resulted in no change in plasma concentrations of lamotrigine. Administration of lamotrigine resulted in a 15% increase in topiramate concentrations.

Levonorgestrel/ethinylestradiol [1], topiramate ---> SmPC of [1] of eMC

Interactions of enzyme inducers with oral contraceptives may lead to breakthrough bleeding and/or contraceptive failure: Women should temporarily use a barrier method in addition to the COC or choose another method of contraception.

Lithium, topiramate [2] ---> SmPC of [2] of eMC

Lithium levels should be monitored when co-administered with topiramate.

Metformin, topiramate [2] ---> SmPC of [2] of eMC

When topiramate is added or withdrawn in patients on metformin therapy, careful attention should be given to the routine monitoring for adequate control of their diabetic disease state.

Moclobemide, topiramate [2] ---> SmPC of [2] of eMC

Topiramate inhibits the enzyme CYP 2C19 and may interfere with other substances metabolized via this enzyme

Nephrolithiasis, topiramate [2] ---> SmPC of [2] of eMC

Topiramate, when used concomitantly with other agents predisposing to nephrolithiasis, may increase the risk of nephrolithiasis. While using topiramate, agents like these should be avoided

Nomegestrol/estradiol [1], topiramate ---> SmPC of [1] of EMA

Interactions between oral contraceptives and enzyme-inducing medicinal products may lead to breakthrough bleeding and even contraceptive failure.

Norelgestromin/ethinylestradiol [1], topiramate ---> SmPC of [1] of EMA

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

Norgestimate, topiramate

The CYP3A4 induction may accelerate the norgestimate metabolism and decrease its plasma levels and effect. The induction lasts at least 4 weeks after dose interruption

Norgestrel, topiramate

The enzymatic induction may accelerate the metabolism of steroid hormones and decrease their plasma levels and effect.

Omeprazole, topiramate [2] ---> SmPC of [2] of eMC

Topiramate inhibits the enzyme CYP 2C19 and may interfere with other substances metabolized via this enzyme

Oral contraceptives, topiramate [2] ---> SmPC of [2] of eMC

The possibility of decreased contraceptive efficacy and increased breakthrough bleeding should be considered in patients taking combination oral contraceptive products with topiramate.

Phenobarbital, topiramate [2] ---> SmPC of [2] of eMC

The addition of topiramate to phenobarbital has no effect on their steady-state plasma concentrations of phenobarbital

Phenytoin, topiramate [2] ---> SmPC of [2] of eMC

Phenytoin decreases the plasma concentration of topiramate. The addition of topiramate to phenytoin in occasional patients may result in an increase of plasma concentrations of phenytoin.

Pioglitazone, topiramate [2] ---> SmPC of [2] of eMC

When topiramate is added to pioglitazone therapy or pioglitazone is added to topiramate therapy, careful attention should be given to the routine monitoring of patients for adequate control of their diabetic disease state.

Pregnancy, topiramate [2] ---> SmPC of [2] of eMC

It is recommended that women of child bearing potential use adequate contraception and consider alternative therapeutic options.

Primidone, topiramate [2] ---> SmPC of [2] of eMC

The addition of topiramate to primidone has no effect on their steady-state plasma concentrations of primidone

Proguanil, topiramate [2] ---> SmPC of [2] of eMC

Topiramate inhibits the enzyme CYP 2C19 and may interfere with other substances metabolized via this enzyme

Retigabine [1], topiramate ---> SmPC of [1] of EMA

Based on these pooled data, retigabine did not cause clinically significant effects on the plasma trough concentrations of this antiepileptic medicinal product. The antiepileptic had no clinically significant effects on retigabine pharmacokinetics

Risperidone, topiramate [2] ---> SmPC of [2] of eMC

There were no significant changes in the systemic exposure of the risperidone total active moiety or of topiramate.

Rufinamide [1], topiramate ---> SmPC of [1] of EMA

Rufinamide appears not to have clinically relevant effect on topiramate steady state concentrations

Sodium oxybate [1], topiramate ---> SmPC of [1] of EMA

There have been clinical observation(s) of coma and increased plasma GHB concentration after co-administration of sodium oxybate with topiramate. Therefore, patients should be warned against the use of topiramate in conjunction with sodium oxybate

Sodium valproate [1], topiramate ---> SmPC of [1] of eMC

Concomitant administration of valproate and topiramate has been associated with encephalopathy and/or hyperammonaemia.

St. John's wort, topiramate [2] ---> SmPC of [2] of eMC

A risk of decreased plasma concentrations resulting in a loss of efficacy could be observed with coadministration of topiramate and St John's Wort.

Strong CYP3A4 inductors, topiramate

The strong CYP3A4 induction enhances the metabolism of topiramate

Tipranavir, topiramate

The strong CYP3A4 induction may decrease the plasma levels of tipranavir

Topiramate, valproic acid [2] ---> SmPC of [2] of eMC

Concomitant administration of valproate and topiramate has been associated with encephalopathy and/or hyperammonaemia.

Topiramate, zonisamide [2] ---> SmPC of [2] of EMA

Zonegran should be used with caution in patients treated concomitantly with carbonic anhydrase inhibitors

CONTRAINDICATIONS of Topiramate

- Hypersensitivity to the active substance or to any of the excipients.

- Migraine prophylaxis in pregnancy and in women of childbearing potential if not using effective methods of contraception

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

Topotecan (Hycamtin)

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

Caution should be observed when driving or operating machines if fatigue and asthenia persist.

Alectinib [1], topotecan ---> 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.

Antineoplastics, topotecan [2] ---> SmPC of [2] of EMA

In combining topotecan with other chemotherapy agents, reduction of the doses of each medicinal product may be required to improve tolerability.

BCRP inhibitors, topotecan

The BCRP inhibition can increase the bioavailability of topotecan

Boceprevir, topotecan

The inhibition of the transporters of the P-glycoprotein and breast cancer resistant protein (BCRP) may increase the plasma concentrations of boceprevir.

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

Topotecan is contraindicated during breast-feeding (see section 4.3). Although it is not known whether topotecan is excreted in human breast milk, breast-feeding should be discontinued at the start of therapy.

Carboplatin, topotecan [2] ---> SmPC of [2] of EMA

If either cisplatin or carboplatin is given on day 1 of the topotecan dosing, compared to the dose of each agent which can be given if the platinum agent is given on day 5 of the topotecan dosing.

Ceritinib [1], topotecan ---> SmPC of [1] of EMA

Based on in vitro data, ceritinib is predicted to inhibit intestinal BCRP. Therefore, ceritinib may have the potential to increase plasma concentrations of co-administered medicinal products transported by BCRP.

Chemotherapeutic agents, topotecan [2] ---> SmPC of [2] of EMA

When combining topotecan with other chemotherapy agents, reduction of the doses of each medicinal product may be required to improve tolerability.

Cisplatin, topotecan [2] ---> SmPC of [2] of EMA

If either cisplatin or carboplatin is given on day 1 of the topotecan dosing, compared to the dose of each agent which can be given if the platinum agent is given on day 5 of the topotecan dosing.

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

In a population study using the intravenous route, the co-administration of granisetron, ondansetron, morphine or corticosteroids did not appear to have a significant effect on the pharmacokinetics of total topotecan (active and inactive form).

Eltrombopag [1], topotecan ---> SmPC of [1] of EMA

Concomitant administration of eltrombopag (OATP1B1 and BCRP inhibitor) and OATP1B1 (e.g. methotrexate) and BCRP (e.g. topotecan and methotrexate) substrates should be undertaken with caution

Entrectinib [1], topotecan ---> SmPC of [1] of EMA

Caution is advised when sensitive oral BCRP substrates (e.g. methotrexate, mitoxantrone, topotecan, lapatinib) are co-administered with entrectinib, due to the risk of increased absorption.

Fertility, topotecan [2] ---> SmPC of [2] of EMA

As with other cytotoxic medicinal products, topotecan is genotoxic and effects on fertility, including male fertility, cannot be excluded.

Granisetron, topotecan [2] ---> SmPC of [2] of EMA

Hematotoxic drugs, topotecan

The risk of hematologic toxicity may increase

Isavuconazole [1], topotecan ---> SmPC of [1] 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.

Leflunomide [1], topotecan ---> SmPC of [1] 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

Lomitapide [1], topotecan ---> SmPC of [1] of EMA

Coadministration of Lojuxta with P gp may increase the absorption of P gp substrates. Dose reduction of the P gp substrate should be considered when used concomitantly with Lojuxta.

Men, topotecan [2] ---> SmPC of [2] of EMA

As with all cytotoxic chemotherapy, patients being treated with topotecan must be advised that they or their partner must use an effective method of contraception.

Morphine, topotecan [2] ---> SmPC of [2] of EMA

Ondansetron, topotecan [2] ---> SmPC of [2] of EMA

Oxaliplatin, topotecan

May increase the risk of neutropenia and thrombocytopenia.

P-gp inhibitors, topotecan

The inhibition of P-glycoprotein may increase the bioavailability of oral topotecan

P450, topotecan [2] ---> SmPC of [2] of EMA

Topotecan hemmt die menschlichen P450-Enzyme nicht

Pazopanib, topotecan

Care should be taken when pazopanib (BCRP and P-gp inhibitor) is co-administered with other oral BCRP and P-gp substrates

Platinum compounds, topotecan [2] ---> SmPC of [2] of EMA

If either cisplatin or carboplatin is given on day 1 of the topotecan dosing, compared to the dose of each agent which can be given if the platinum agent is given on day 5 of the topotecan dosing.

Pregnancy, topotecan [2] ---> SmPC of [2] of EMA

If topotecan is used during pregnancy, or if the patient becomes pregnant during therapy with topotecan, the patient must be warned of the potential hazards to the foetus.

Rolapitant [1], topotecan ---> SmPC of [1] of EMA

Rolapitant is an inhibitor of Breast-Cancer-Resistance Protein (BCRP). Increased plasma concentrations of BCRP substrates may result in potential adverse reactions.

Safinamide [1], topotecan ---> SmPC of [1] of EMA

It is recommended to monitor patients when safinamide is taken with medicinal products that are BCRP substrates (e.g., rosuvastatin, pitavastatin, pravastatin, ciprofloxacin, methotrexate, topotecan, diclofenac or glyburide)

Sonidegib [1], topotecan ---> SmPC of [1] of EMA

Sonidegib is a breast cancer resistance protein (BCRP) inhibitor. BCRP substrates with narrow therapeutic range (e.g. methotrexate, mitoxantrone, irinotecan, topotecan) should be avoided.

Sotorasib [1], topotecan ---> SmPC of [1] of EMA

When LUMYKRAS is co-administered with a BCRP substrate, monitor for adverse reactions of the BCRP substrate and reduce the BCRP substrate dose in accordance with its current summary of product characteristics.

Sunitinib, topotecan

Sunitinib, P-glycoprotein inhibitor, may increase the plasma concentrations of topotecan. Concomitant use should be avoided

Tacrolimus, topotecan

The inhibition of P-glycoprotein may increase the bioavailability of oral topotecan

Tedizolid [1], topotecan ---> SmPC of [1] of EMA

Tepotinib [1], topotecan ---> SmPC of [1] of EMA

Teriflunomide [1], topotecan ---> SmPC of [1] of EMA

Teriflunomide, BCRP inhibitor, may increase the AUC of BCRP substrate. The co-administration should be undertaken with caution

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

As with other cytotoxic medicinal products, topotecan may cause foetal harm and therefore women of childbearing potential should be advised to avoid becoming pregnant during therapy with topotecan.

Topotecan, trastuzumab

Trastuzumab may increase the risk of neutropenia and anemia.

Topotecan, vadadustat [2] ---> SmPC of [2] of EMA

In addition to sulfasalazine, simvastatin, and rosuvastatin, monitor for signs of excessive effects of coadministered BCRP substrates such as fluvastatin, nelfinavir, pitavastatin, and topotecan, and for the need of their dose reduction.

Topotecan, vemurafenib [2] ---> SmPC of [2] of EMA

Caution should be exercised when dosing vemurafenib concurrently with P-gp substrates and dose reduction of the concomitant medicinal product may be considered, if clinically indicated.

Topotecan, vismodegib [2] ---> SmPC of [2] of EMA

Vismodegib, BCRP inhibitor, may increase exposure of medicinal products transported by this protein. The co-administration should be undertaken with caution

CONTRAINDICATIONS of Topotecan (Hycamtin)

- Severe hypersensitivity to the active substance or to any of the excipients.

- Breast-feeding (see section 4.6).

- Severe bone marrow depression prior to starting first course, as evidenced by baseline neutrophils <1.5 x 109/l and/or a platelet count of <100 x 109/l.

https://www.ema.europa.eu/en/documents/product-information/hycamtin-epar-product-information_en.pdf 27/09/2024

Other trade names: Evotopin, Potactasol, Topotecan Actavis, Topotecan Hospira, Topotecan Teva,

Torasemid

Ability to drive, torasemid [2] ---> SmPC of [2] of eMC

As for other drugs which produce changes in blood pressure, patients taking torasemide should be warned not to drive or operate machinery if they experience dizziness or related symptoms.

ACE inhibitors, torasemid [2] ---> SmPC of [2] of eMC

Sequential or combined treatment, or starting a new co-medication with an ACE inhibitor may result in transient hypotension.

Adrenaline, torasemid [2] ---> SmPC of [2] of eMC

Torasemide may decrease arterial responsiveness to pressor agents

Aliskiren [1], torasemid ---> SmPC of [1] of EMA

Since aliskiren has been shown to be a substrate for the OATP1A2, there is a potential for aliskiren to reduce plasma torasemide exposure by an interference with the absorption process.

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

Since aliskiren has been shown to be a substrate for the OATP1A2, there is a potential for aliskiren to reduce plasma torasemide exposure by an interference with the absorption process.

Aliskiren/hydrochlorothiazide, torasemid ---> SmPC of [aliskiren] of EMA

Since aliskiren has been shown to be a substrate for the OATP1A2, there is a potential for aliskiren to reduce plasma torasemide exposure by an interference with the absorption process.

Aminoglycoside antibiotics, torasemid [2] ---> SmPC of [2] of eMC

Torasemide, especially at high doses, may potentiate the toxicity of aminoglycoside antibiotics

Antidiabetics, torasemid [2] ---> SmPC of [2] of eMC

The action of anti-diabetic drugs may be reduced by torasemide

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

As with other diuretics, the effect of antihypertensive drugs given concomitantly may be potentiated.

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

Torasemide is contra-indicated in lactation.

Cardiac glycosides, torasemid [2] ---> SmPC of [2] of eMC

When used simultaneously with cardiac glycosides, a potassium and/or magnesium deficiency may increase sensitivity of the cardiac muscle to such drugs.

Catecholamines, torasemid [2] ---> SmPC of [2] of eMC

Torasemide may decrease arterial responsiveness to pressor agents

Cephalosporins, torasemid [2] ---> SmPC of [2] of eMC

Torasemide, especially at high doses, may potentiate the nephrotoxic effects of cephalosporins

Cholestyramine, torasemid [2] ---> SmPC of [2] of eMC

Decreased oral absorption of torasemide

Curare-type muscle relaxants, torasemid [2] ---> SmPC of [2] of eMC

The action of curare-containing muscle relaxants can be potentiated by torasemide.

CYP2C9 inhibitors, torasemid

The CYP2C9 inhibition may increase the plasma concentrations of torasemide

Ethacrynic acid, torasemid

Torasemide, especially at high doses, may potentiate the toxicity of etacrynic acid

Gentamicin, torasemid [2] ---> SmPC of [2] of eMC

Torasemide, especially at high doses, may potentiate the toxicity of aminoglycoside antibiotics

Glucocorticoids, torasemid [2] ---> SmPC of [2] of eMC

The kaliuretic effect of glucocorticoids may be increased by torasemide

Indometacin, torasemid [2] ---> SmPC of [2] of eMC

Non-steroidal anti-inflammatory drugs may reduce the diuretic and hypotensive effect of torasemide.

Laxatives, torasemid [2] ---> SmPC of [2] of eMC

The kaliuretic effect of laxatives may be increased by torasemide

Lithium, torasemid [2] ---> SmPC of [2] of eMC

Torasemide, especially at high doses, may potentiate the cardio- and neurotoxic effect of lithium.

Noradrenaline, torasemid [2] ---> SmPC of [2] of eMC

Torasemide may decrease arterial responsiveness to pressor agents

NSAID, torasemid [2] ---> SmPC of [2] of eMC

Non-steroidal anti-inflammatory drugs may reduce the diuretic and hypotensive effect of torasemide.

Platinum compounds, torasemid [2] ---> SmPC of [2] of eMC

Torasemide, especially at high doses, may potentiate the toxicity of cisplatin preparations

Pregnancy, torasemid [2] ---> SmPC of [2] of eMC

Torasemide is contra-indicated in pregnancy

Probenecide, torasemid [2] ---> SmPC of [2] of eMC

Probenecid may reduce the diuretic and hypotensive effect of torasemide.

Proteolytic enzymes enriched in bromelain [1], torasemid ---> SmPC of [1] of EMA

NexoBrid, when absorbed, is an inhibitor of CYP2C8 and CYP2C9. This should be taken into account if it is used in patients receiving CYP2C8 substrates

Salicylates, torasemid [2] ---> SmPC of [2] of eMC

In patients receiving high doses of salicylates, salicylate toxicity may be increased.

Strong CYP2C9 inhibitors, torasemid

The potent CYP2C9 inhibition may increase the plasma concentrations of torasemide

Theophylline, torasemid [2] ---> SmPC of [2] of eMC

The action of theophylline can be potentiated by torasemide.

Torasemid, vasoconstrictors

Torasemide may decrease arterial responsiveness to pressor agents

CONTRAINDICATIONS of Torasemid

- Renal failure with anuria;

- hepatic coma and pre-coma;

- hypotension;

- pregnancy and lactation;

- hypersensitivity to torasemide and sulphonylureas;

- cardiac arrhythmias,

- simultaneous therapy with aminoglycosides or cephalosporins, or

- renal dysfunction due to drugs which cause renal damage.

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

Toremifene (Fareston)

Amiodarone, 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

Antiestrogens, coumarin anticoagulants ---> SmPC of [toremifene] of EMA

There is a known interaction between anti-estrogens and warfarin-type anticoagulants leading to a seriously increased bleeding time. Therefore, the concomitant should be avoided.

Antimalarial agents, toremifene [2] ---> SmPC of [2] of EMA

Astemizole, toremifene [2] ---> SmPC of [2] of EMA

Azole antifungals, toremifene [2] ---> SmPC of [2] of EMA

Theoretically the metabolism of toremifene is inhibited by drugs known to inhibit the CYP3A enzyme system which is reported to be responsible for its main metabolic pathways. Concomitant use should be carefully considered.

Bepridil, toremifene [2] ---> SmPC of [2] of EMA

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

Fareston should not be used during pregnancy

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

Enzyme inducers may increase the rate of toremifene metabolism thus lowering the steady-state concentration in serum. In such cases doubling of the daily dose may be necessary.

Cisapride, toremifene [2] ---> SmPC of [2] of EMA

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

Class IA antiarrhythmic agents, toremifene [2] ---> SmPC of [2] of EMA

Class III antiarrhythmic agents, toremifene [2] ---> SmPC of [2] of EMA

Coumarin anticoagulants, toremifene [2] ---> SmPC of [2] of EMA

There is a known interaction between anti-estrogens and warfarin-type anticoagulants leading to a seriously increased bleeding time. Therefore, the concomitant use of toremifene with such drugs should be avoided.

Diphemanil, toremifene [2] ---> SmPC of [2] of EMA

Disopyramide, toremifene [2] ---> SmPC of [2] of EMA

Dofetilide, toremifene [2] ---> SmPC of [2] of EMA

Enzyme inductors, toremifene [2] ---> SmPC of [2] of EMA

Enzyme inducers may increase the rate of toremifene metabolism thus lowering the steady-state concentration in serum. In such cases doubling of the daily dose may be necessary.

Erythromycin, toremifene [2] ---> SmPC of [2] of EMA

Fertility, toremifene [2] ---> SmPC of [2] of EMA

Toremifene is recommended for postmenopausal patients.

Halofantrine, toremifene [2] ---> SmPC of [2] of EMA

Haloperidol, toremifene [2] ---> SmPC of [2] of EMA

Hydroquinidine, toremifene [2] ---> SmPC of [2] of EMA

Hydroxyzine [1], toremifene ---> SmPC of [1] 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

Hypercalcemia, toremifene [2] ---> SmPC of [2] of EMA

Drugs which decrease renal calcium excretion, e.g. thiazide diuretics, may increase the risk of hypercalcaemia.

Ibutilide, toremifene [2] ---> SmPC of [2] of EMA

Itraconazol, toremifene [2] ---> SmPC of [2] of EMA

Ketoconazole, toremifene [2] ---> SmPC of [2] of EMA

Macrolide antibiotics, toremifene [2] ---> SmPC of [2] of EMA

Mequitazine, toremifene

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Mizolastine, toremifene [2] ---> SmPC of [2] of EMA

Moxifloxacin, toremifene [2] ---> SmPC of [2] of EMA

Nelfinavir, toremifene [2] ---> SmPC of [2] of EMA

Ospemifene [1], toremifene ---> SmPC of [1] of EMA

The safety of using ospemifene concomitantly with oestrogens or other SERMS has not been studied and its concurrent use is not recommended.

Pentamidine, toremifene [2] ---> SmPC of [2] of EMA

Phenobarbital, toremifene [2] ---> SmPC of [2] of EMA

Enzyme inducers may increase the rate of toremifene metabolism thus lowering the steady-state concentration in serum. In such cases doubling of the daily dose may be necessary.

Phenothiazines, toremifene [2] ---> SmPC of [2] of EMA

Phenytoin, toremifene [2] ---> SmPC of [2] of EMA

Enzyme inducers may increase the rate of toremifene metabolism thus lowering the steady-state concentration in serum. In such cases doubling of the daily dose may be necessary.

Pimozide, toremifene [2] ---> SmPC of [2] of EMA

Posaconazole, toremifene [2] ---> SmPC of [2] of EMA

Pregnancy, toremifene [2] ---> SmPC of [2] of EMA

Fareston should not be used during pregnancy

Protease inhibitors, toremifene [2] ---> SmPC of [2] of EMA

QT interval prolonging drugs, toremifene [2] ---> SmPC of [2] of EMA

Quinidine, toremifene [2] ---> SmPC of [2] of EMA

Rifampicin [1], toremifene ---> SmPC of [1] of eMC

Rifampicin is a potent inducer of certain cytochrome P-450 enzymes. Coadministration of rifampicin with drugs that are also metabolised through these cytochrome P-450 enzymes may accelerate the metabolism and reduce the activity of these other drugs.

Ritonavir, toremifene [2] ---> SmPC of [2] of EMA

Sertindole, toremifene [2] ---> SmPC of [2] of EMA

Sotalol, toremifene [2] ---> SmPC of [2] of EMA

Sparfloxacin, toremifene [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inhibitors, toremifene [2] ---> SmPC of [2] of EMA

Sugammadex [1], toremifene ---> SmPC of [1] of EMA

Clinicians should be aware that the recovery of the T4/T1 ratio to 0.9 could therefore be delayed in patients who have received toremifene on the same day of the operation.

Sultopride, toremifene [2] ---> SmPC of [2] of EMA

Terfenadine, toremifene [2] ---> SmPC of [2] of EMA

Thiazides, toremifene [2] ---> SmPC of [2] of EMA

Drugs which decrease renal calcium excretion, e.g. thiazide diuretics, may increase the risk of hypercalcaemia.

Toremifene [1], troleandomycin ---> SmPC of [1] of EMA

Toremifene [1], vincamine ---> SmPC of [1] of EMA

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

Toremifene, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with medicinal products known to also prolong the QTc interval and/or induce Torsades de pointes is either contraindicated or not recommended

CONTRAINDICATIONS of Toremifene (Fareston)

- Pre-existing endometrial hyperplasia and severe hepatic failure are contra-indications in long-term use of toremifene.

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

- Both in preclinical investigations and in humans, changes in cardiac electrophysiology have been observed following exposure to toremifene, in the form of QT prolongation. For reasons of drug safety, toremifene is therefore contraindicated in patients with:

- Congenital or documented acquired QT prolongation

- Electrolyte disturbances, particularly in uncorrected hypokalaemia

- Clinically relevant bradycardia

- Clinically relevant heart failure with reduced left-ventricular ejection fraction

- Previous history of symptomatic arrhythmias.

Toremifene should not be used concurrently with other drugs that prolong the QT interval

https://www.ema.europa.eu/en/documents/product-information/fareston-epar-product-information_en.pdf 30/07/2024

Toripalimab (Loqtorzi)

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

Toripalimab has minor influence on the ability to drive and use machines. In some patients, dizziness and fatigue have been reported following administration of toripalimab (see section 4.8).

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

If a woman chooses to be treated with toripalimab, she should be instructed not to breast-feed while receiving toripalimab and for at least 4 months after the last dose of toripalimab.

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

The use of systemic corticosteroids or immunosuppressants before starting toripalimab should be avoided because of their potential interference with the pharmacodynamic activity and efficacy of toripalimab.

Fertility, toripalimab [2] ---> SmPC of [2] of EMA

Studies to evaluate the effect of toripalimab on fertility have not been performed (see section 5.3).

Pregnancy, toripalimab [2] ---> SmPC of [2] of EMA

Toripalimab should not be used during pregnancy or in women of childbearing potential not using effective contraception unless the clinical benefit outweighs the potential risk.

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

Women of childbearing potential should use effective contraception during treatment with toripalimab and for at least 4 months after the last dose of toripalimab.

CONTRAINDICATIONS of Toripalimab (Loqtorzi)

- 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/loqtorzi-epar-product-information_en.pdf 24/09/2024

Trabectedin (Yondelis)

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

Fatigue and/or asthenia have been reported in patients receiving trabectedin. Patients who experience any of these adverse reactions during therapy must not drive or operate machines.

Alcohol, trabectedin [2] ---> SmPC of [2] of EMA

Alcohol consumption must be avoided during treatment with trabectedin due to the hepatotoxicity of the medicinal product

Aprepitant, trabectedin [2] ---> SmPC of [2] of EMA

Concomitant use of a strong CYP3A4 inhibitor with trabectedin may increase the plasma exposure of trabectedin. Concomitant use should be avoided. If the combination is needed, close monitoring of toxicities

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

Breast-feeding is contraindicated during treatment and 3 months thereafter

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

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

Preclinical data have demonstrated that trabectedin is a substrate to P-gp. Concomitant administration of inhibitors of P-gp may alter trabectedin distribution and/or elimination.

CYP3A4 inductors, trabectedin [2] ---> SmPC of [2] of EMA

The CYP3A4 induction may decrease the systemic exposure to trabectedin

CYP3A4 inhibitors, trabectedin [2] ---> SmPC of [2] of EMA

The CYP3A4 inhibition may increase the plasma concentrations of trabectedin. If the combination is needed, close monitoring of toxicities

Fertility, trabectedin [2] ---> SmPC of [2] of EMA

Trabectedin can have genotoxic effects. Advice on conservation of ovules or sperm should be sought prior to treatment because of the possibility of irreversible infertility due to therapy with Yondelis.

Fluconazole, trabectedin [2] ---> SmPC of [2] of EMA

Fosaprepitant, trabectedin [2] ---> SmPC of [2] of EMA

Hepatotoxic drugs, trabectedin [2] ---> SmPC of [2] of EMA

Caution should be taken if medicinal products associated with hepatotoxicity are administered concomitantly with trabectedin, since the risk of hepatotoxicity may be increased.

Ketoconazole, trabectedin [2] ---> SmPC of [2] of EMA

Men in fertile age, trabectedin [2] ---> SmPC of [2] of EMA

Men in fertile age must use effective contraception during treatment and 5 months after treatment (see section 4.4).

P-glycoprotein and CYP3A4 inhibitors, trabectedin

The P-glycoprotein and CYP3A4 inhibition may increase the plasma concentrations of trabectedin

Phenobarbital, trabectedin [2] ---> SmPC of [2] of EMA

Concomitant use of a strong CYP3A4 inductor with trabectedin may decrease the plasma exposure of trabectedin. Therefore, the concomitant use of trabectedin with strong CYP3A4 inducers should be avoided if possible

Phenytoin, trabectedin [2] ---> SmPC of [2] of EMA

Concomitant use of trabectedin with phenytoin may reduce phenytoin absorption leading to an exacerbation of convulsions. Combination of trabectedin with phenytoin is not recommended

Pregnancy, trabectedin [2] ---> SmPC of [2] of EMA

. If pregnancy occurs during treatment, the patient must be informed of the potential risk to the foetus (see section 5.3) and be monitored carefully.

Pregnancy, trabectedin [2] ---> SmPC of [2] of EMA

Based on its known mechanism of action, trabectedin may cause serious birth defects when administered during pregnancy. Trabectedin should not be used during pregnancy.

Rhabdomyolysis, trabectedin [2] ---> SmPC of [2] of EMA

Caution should be taken if medicinal products associated with rhabdomyolysis (e.g. statins), are administered concomitantly with trabectedin, since the risk of rhabdomyolysis may be increased

Rifampicin, trabectedin [2] ---> SmPC of [2] of EMA

Ritonavir, trabectedin [2] ---> SmPC of [2] of EMA

St. John's wort, trabectedin [2] ---> SmPC of [2] of EMA

Statins, trabectedin [2] ---> SmPC of [2] of EMA

Caution should be taken if medicinal products associated with rhabdomyolysis (e.g. statins), are administered concomitantly with trabectedin, since the risk of rhabdomyolysis may be increased

Strong CYP3A4 inductors, trabectedin [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inhibitors, trabectedin [2] ---> SmPC of [2] of EMA

Strong P-gp inhibitors, trabectedin [2] ---> SmPC of [2] of EMA

Preclinical data have demonstrated that trabectedin is a substrate to P-gp. Concomitant administration of inhibitors of P-gp may alter trabectedin distribution and/or elimination.

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

Combination of trabectedin with live attenuated vaccines is not recommended

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

Preclinical data have demonstrated that trabectedin is a substrate to P-gp. Concomitant administration of inhibitors of P-gp may alter trabectedin distribution and/or elimination.

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

Women of childbearing potential must use effective contraception during treatment and 3 months thereafter, and immediately inform the treating physician if a pregnancy occurs (see section 5.3).

Trabectedin [1], yellow fever vaccine ---> SmPC of [1] of EMA

Combination of trabectedin yellow fever vaccine is specifically contraindicated

CONTRAINDICATIONS of Trabectedin (Yondelis)

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

- Concurrent serious or uncontrolled infection

- Breast-feeding

- Combination with yellow fever vaccine

https://www.ema.europa.eu/en/documents/product-information/yondelis-epar-product-information_en.pdf 03/04/2025

Tralokinumab (Adtralza)

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

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

Infection, tralokinumab [2] ---> SmPC of [2] of EMA

Patients with pre-existing helminth infections should be treated before initiating treatment with tralokinumab.

Pregnancy, tralokinumab [2] ---> SmPC of [2] of EMA

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

Tralokinumab [1], vaccinations ---> SmPC of [1] of EMA

Live and live attenuated vaccines should not be given concurrently with tralokinumab as clinical safety and efficacy have not been established.

CONTRAINDICATIONS of Tralokinumab (Adtralza)

- 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/adtralza-epar-product-information_en.pdf 28/05/2025

Tramadol

Ability to drive, tramadol [2] ---> SmPC of [2] of eMC

Tramadol may cause drowsiness and this effect may be potentiated by alcohol and other CNS depressants. Ambulant patients should be warned not to drive or operate machinery if affected.

Abiraterone [1], tramadol ---> SmPC of [1] of EMA

Caution is advised when administering abiraterone with medicinal products activated by or metabolised by CYP2D6, particularly with medicinal products that have a narrow therapeutic index.

Acenocoumarol [1], tramadol ---> SmPC of [1] of eMC

The co-administration may enhance the anticoagulant effect of acenocoumarol and increase the bleeding risk

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

Concomitant administration of tramadol with other centrally acting drugs including alcohol may potentiate CNS depressant effects.

Amifampridine [1], tramadol ---> SmPC of [1] of EMA

The concomitant use of amifampridine and substances known to lower the epileptic threshold leads to an increased risk of seizures

Amiodarone, tramadol

Amiodarone may increase or decrease the effect of tramadol

Amitriptyline, tramadol [2] ---> SmPC of [2] of eMC

Tramadol can induce convulsions and increase the potential of other seizure threshold-lowering medicinal products to cause convulsions. Concomitant therapeutic use of tramadol and serotonergic drugs may cause serotonin toxicity.

Antidepressants with serotonergic effect, tramadol ---> SmPC of [vortioxetine] of EMA

Caution is advised when co-administrating medicines capable of lowering the seizure threshold.

Anxiolytics, tramadol [2] ---> SmPC of [2] of eMC

Concomitant administration of tramadol with other centrally acting drugs may potentiate CNS depressant effects.

Atomoxetine, tramadol

Seizures are a potential risk with atomoxetine. Caution is advised with concomitant use of medicinal drugs which are known to lower the seizure threshold

Baclofen, tramadol [2] ---> SmPC of [2] of eMC

Concomitant administration of tramadol with other centrally acting drugs may potentiate CNS depressant effects.

Barbiturates, tramadol [2] ---> SmPC of [2] of eMC

Concomitant administration of tramadol with other centrally acting drugs may potentiate CNS depressant effects.

Benzodiazepines, tramadol [2] ---> SmPC of [2] of eMC

Concomitant administration of tramadol with other centrally acting drugs may potentiate CNS depressant effects.

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

Tramadol should not be administered during breast feeding.

Buprenorphine, tramadol [2] ---> SmPC of [2] of eMC

Co-administration of tramadol with mixed agonist/antagonist drugs may reduce the analgesic effect of tramadol which is a pure agonist. A withdrawal syndrome may occur.

Bupropion, tramadol [2] ---> SmPC of [2] of eMC

Tramadol can induce convulsions and increase the potential of other seizure threshold-lowering medicinal products to cause convulsions.

Buspirone, tramadol

Caution should be exercised when buspirone is combined with serotoninergic drugs because there are reports about serotoninergic syndrome

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

Simultaneous administration of carbamazepine markedly decreases serum concentrations of tramadol to an extent that a decrease in analgesic effectiveness and shorter duration of action may occur.

Centrally-acting antihypertensives, tramadol [2] ---> SmPC of [2] of eMC

Concomitant administration of tramadol with other centrally acting drugs may potentiate CNS depressant effects.

Cimetidine, tramadol [2] ---> SmPC of [2] of eMC

Simultaneous administration with cimetidine is associated with clinically insignificant changes in serum concentrations of tramadol.

Citalopram [1], tramadol ---> SmPC of [1] of eMC

Co-administration with serotonergic medicinal products may lead to enhancement of 5-HT associated effects. The combination is not recommended

Clomipramine, tramadol

Tramadol increases the risk of serotonin syndrome and seizures.

CNS depressants, tramadol [2] ---> SmPC of [2] of eMC

Concomitant administration of tramadol with other centrally acting drugs may potentiate CNS depressant effects.

Coumarin anticoagulants, tramadol [2] ---> SmPC of [2] of eMC

There have been isolated reports of interaction with coumarin anticoagulants resulting in an increased INR. Care should be taken if treatment with tramadol is started in patients taking anticoagulants.

CYP3A4 inductors, tramadol

The CYP3A4 induction may decrease plasma levels of tramadol

CYP3A4 inhibitors, tramadol

The CYP3A4 inhibition may increase plasma concentrations of tramadol

Dapoxetine [1], tramadol ---> 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

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/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

Duloxetine [1], tramadol ---> SmPC of [1] 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

Efavirenz, tramadol

May decrease the plasma levels of tramadol

Enzalutamide [1], tramadol ---> SmPC of [1] of EMA

Enzalutamide, enzymatic inductor, may increase the metabolism of tramadol and decrease its plasma levels and effect

Enzyme inductors, tramadol

The enzymatic inductor may decrease the plasma levels of tramadol. Co-administration is not recommended

Escitalopram [1], tramadol ---> SmPC of [1] of eMC

Co-administration of escitalopram with serotonergic medicinal products may lead to serotonin syndrome. Tramadol may lower the seizure threshold

Fluoxetine [1], tramadol ---> SmPC of [1] of eMC

Co-administration of fluoxetine with serotonergic drugs may increase the risk of serotonin syndrome.

Fluvoxamine [1], tramadol ---> SmPC of [1] of eMC

The serotonergic effects of fluvoxamine may be enhanced when used in combination with other serotonergic agents

Hypnotics, tramadol [2] ---> SmPC of [2] of eMC

Concomitant administration of tramadol with other centrally acting drugs may potentiate CNS depressant effects.

IMAOs, tramadol [2] ---> SmPC of [2] of eMC

Concomitant therapeutic use of tramadol and serotonergic drugs, such as MAO inhibitors, may cause serotonin toxicity. The combination of tramadol with MAO inhibitors or within 2 weeks of their withdrawal is contraindicated

Linezolid, tramadol [2] ---> SmPC of [2] of eMC

Loxapine [1], tramadol ---> SmPC of [1] of EMA

Caution is advised if loxapine is combined with other medicinal products known to lower the seizure threshold

Mefloquine [1], tramadol ---> SmPC of [1] of eMC

Concomitant administration of mefloquine and drugs known to lower the epileptogenic threshold may increase the risk of convulsions

Mianserin, tramadol

Enhancement of CNS depressant effect

Mirtazapine [1], tramadol ---> SmPC of [1] of eMC

Co-administration of mirtazapine with other serotonergic active substances may lead to an incidence of serotonin associated effects (serotonin syndrome). Caution should be advised

Moclobemide, tramadol

Co-administration is contraindicated

Nalbuphine, tramadol [2] ---> SmPC of [2] of eMC

Co-administration of tramadol with mixed agonist/antagonist drugs may reduce the analgesic effect of tramadol which is a pure agonist. A withdrawal syndrome may occur.

Naltrexone, tramadol

The use of tramadol mit naltrexone may decrease the analgetic effect

Naltrexone/bupropion [1], tramadol ---> SmPC of [1] of EMA

Caution should be used when prescribing naltrexone/bupropion to patients with predisposing factors that may increase the risk of seizure

Neuroleptics, tramadol [2] ---> SmPC of [2] of eMC

Concomitant administration of tramadol with other centrally acting drugs may potentiate CNS depressant effects.

Nevirapine, tramadol

Nevirapine may decrease the effect of tramadol by increasing tramadol metabolism and clearance

Ondansetron [1], tramadol ---> SmPC of [1] of eMC

Data from small studies indicate that ondansetron may reduce the analgesic effect of tramadol.

Opiate agonists, tramadol [2] ---> SmPC of [2] of eMC

Concomitant administration of tramadol with other centrally acting drugs may potentiate CNS depressant effects.

Opioid agonist/antagonists, tramadol [2] ---> SmPC of [2] of eMC

Co-administration of tramadol with mixed agonist/antagonist drugs may reduce the analgesic effect of tramadol which is a pure agonist. A withdrawal syndrome may occur.

Opioid analgesics, tramadol [2] ---> SmPC of [2] of eMC

Concomitant administration of tramadol with other centrally acting drugs may potentiate CNS depressant effects.

Paliperidone [1], tramadol ---> SmPC of [1] of EMA

Caution is advised if paliperidone is combined with other medicines known to lower the seizure threshold

Paroxetine [1], tramadol ---> SmPC of [1] of eMC

As with other SSRIs, co-administration with serotonergic drugs may lead to an incidence of 5-HT associated effects (serotonin syndrome)

Pentazocine, tramadol [2] ---> SmPC of [2] of eMC

Co-administration of tramadol with mixed agonist/antagonist drugs may reduce the analgesic effect of tramadol which is a pure agonist. A withdrawal syndrome may occur.

Perphenazine [1], tramadol ---> SmPC of [1] of eMC

Tramadol when given with perphenazine may increase the risk of convulsions.

Phenprocoumon, tramadol

Enhancement of phenprocoumon effect and increased bleeding risk with the concomitant administration of tramadol

Pregnancy, tramadol [2] ---> SmPC of [2] of eMC

There is inadequate evidence available on the safety of tramadol in human pregnancy, therefore tramadol should not be used in pregnant women.

Promazine [1], tramadol ---> SmPC of [1] of eMC

There is an increased risk of convulsions when promazine is coadministered with tramadol

Pyrimethamine, tramadol

Pyrimethamine may decrease the therapeutic effect of tramadol

Quinine, tramadol

Quinine may decrease the effect of tramadol by decreasing active metabolite production.

Regadenoson [1], tramadol ---> SmPC of [1] of EMA

Caution should be used when administering regadenoson to patients with a history of seizures or other risk factors for seizures, including the concomitant administration of medicinal products that lower seizure threshold

Sedating antihistamines, tramadol [2] ---> SmPC of [2] of eMC

Concomitant administration of tramadol with other centrally acting drugs may potentiate CNS depressant effects.

Sedative antidepressants, tramadol [2] ---> SmPC of [2] of eMC

Concomitant administration of tramadol with other centrally acting drugs may potentiate CNS depressant effects.

Sedatives, tramadol [2] ---> SmPC of [2] of eMC

Concomitant administration of tramadol with other centrally acting drugs may potentiate CNS depressant effects.

Seizure-threshold lowering drugs, tramadol [2] ---> SmPC of [2] of eMC

Tramadol can induce convulsions and increase the potential of other seizure threshold-lowering medicinal products to cause convulsions.

Serotonergic medicines, tramadol [2] ---> SmPC of [2] of eMC

Concomitant therapeutic use of tramadol and serotonergic drugs may cause serotonin toxicity.

Serotonin agonists, tramadol [2] ---> SmPC of [2] of eMC

Concomitant therapeutic use of tramadol and serotonergic drugs may cause serotonin toxicity.

Sertraline [1], tramadol ---> SmPC of [1] of EMA

Co-administration of sertraline with other drugs which enhance the effects of serotonergic neurotransmission should be undertaken with caution and avoided whenever possible due to the potential for a pharmacodynamic interaction

SNRIs, tramadol [2] ---> SmPC of [2] of eMC

SSRI, tramadol [2] ---> SmPC of [2] of eMC

St. John's wort, tramadol

St. John's wort, enzymatic inductor, may decrease the plasma concentrations of tramadol. St. John's Wort should be avoided

Stiripentol [1], tramadol ---> SmPC of [1] 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

Strong CYP2D6 inhibitors, tramadol

The strong CYP2D6 inhibition may increase the plasma concentrations of tramadol

Strong CYP3A4 inhibitors, tramadol

The strong CYP3A4 inhibition may increase the plasma concentrations of tramadol

Tetrahydrocannabinol, tramadol [2] ---> SmPC of [2] of eMC

Tramadol can induce convulsions and increase the potential of other seizure threshold-lowering medicinal products to cause convulsions.

Thalidomide, tramadol [2] ---> SmPC of [2] of eMC

Concomitant administration of tramadol with other centrally acting drugs may potentiate CNS depressant effects.

Tramadol [1], tricyclic antidepressant ---> SmPC of [1] of eMC

Tramadol [1], triptans ---> SmPC of [1] of eMC

Concomitant therapeutic use of tramadol and serotonergic drugs may cause serotonin toxicity.

Tramadol [1], warfarin ---> SmPC of [1] of eMC

Tramadol, tranylcypromine

Tranylcypromine should not be used concomitantly with tramadol. Life-threatening adverse reactions in the CNS or life-threatening effect of respiratory and circulatory function are possible

Tramadol, venlafaxine [2] ---> SmPC of [2] of eMC

Serotonin syndrome may occur with venlafaxine treatment, particularly with concomitant use of other agents that may affect the serotonergic neurotransmitter system

Tramadol, voriconazole

Dose reduction in oxycodone and other long-acting opiates metabolized by CYP3A4 (e.g., hydrocodone) should be considered. Frequent monitoring for opiate-associated adverse reactions may be necessary.

Tramadol, vortioxetine [2] ---> SmPC of [2] of EMA

Co-administration of medicinal products with serotonergic effect may lead to serotonin syndrome

CONTRAINDICATIONS of Tramadol

- Hypersensitivity to the active substance or to any of the excipients.

- Acute intoxication with alcohol, hypnotics, centrally acting analgesics, opioids or psychotropic drugs.

- Patients receiving monoamine oxidase inhibitors or within two weeks of their withdrawal

- Patients receiving buprenorphine, nalbuphine or pentazocine

- Severe hepatic impairment.

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

Trametinib (Mekinist)

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

The clinical status of the patient and the adverse reaction profile (fatigue, dizziness or eye problems) should be borne in mind when considering the patient's ability to perform tasks that require judgment, motor and cognitive skills.

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

Trametinib may result in transient inhibition of BCRP substrates (e.g., pitavastatin) in the gut, which may be minimised with staggered dosing (2 hours apart) of these agents and trametinib.

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

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

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

As it cannot be excluded that strong inhibition of hepatic P-gp may result in increased levels of trametinib, caution is advised when coadministering trametinib with medicinal products that are strong inhibitors of P-gp

Dabrafenib, trametinib [1] ---> SmPC of [2] 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, trametinib [2] ---> SmPC of [2] of EMA

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

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

In animals, no fertility studies have been performed, but adverse effects were seen on female reproductive organs (see section 5.3). Trametinib may impair fertility in humans.

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

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

Hormonal contraceptives, trametinib [2] ---> SmPC of [2] of EMA

Use with dabrafenib may render hormonal contraceptives less effective and therefore an alternative method of contraception, such as a barrier method, should be used when trametinib is used in combination with dabrafenib.

Hormonal contraceptives, trametinib [2] ---> SmPC of [2] of EMA

Based on clinical data, no loss of efficacy of hormonal contraceptives is expected when co-administered with trametinib monotherapy (see section 5.2).

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

Medications with a recognised risk of gastrointestinal perforation, trametinib [2] ---> SmPC of [2] of EMA

Colitis and gastrointestinal perforation, including fatal outcome, have been reported in patients taking trametinib as monotherapy and in combination with dabrafenib

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

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

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

Based on in vitro and in vivo data, trametinib is unlikely to significantly affect the pharmacokinetics of other medicinal products via interaction with CYP enzymes or transporters

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

Trametinib may result in transient inhibition of BCRP substrates (e.g., pitavastatin) in the gut, which may be minimised with staggered dosing (2 hours apart) of these agents and trametinib.

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

Trametinib should not be administered to pregnant women. If trametinib is used during pregnancy, or if the patient becomes pregnant while taking trametinib, the patient should be informed of the potential hazard to the foetus.

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

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

Strong P-gp inhibitors, trametinib [2] ---> SmPC of [2] of EMA

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

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

Female patients of reproductive potential must be advised to use effective methods of contraception during treatment with trametinib and for 16 weeks after stopping treatment.

CONTRAINDICATIONS of Trametinib (Mekinist)

- 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/mekinist-epar-product-information_en.pdf 07/03/2024

Other trade names: Spexotras

Trandolapril

Ability to drive, ACE inhibitors ---> SmPC of [trandolapril] of eMC

ACE inhibitors may affect the ability to drive or operate machinery, particularly at the start of treatment, when changing over from other medication or during concomitant use of alcohol.

Ability to drive, trandolapril [2] ---> SmPC of [2] of eMC

ACE inhibitors may affect the ability to drive or operate machinery, particularly at the start of treatment, when changing over from other medication or during concomitant use of alcohol.

Alcohol, trandolapril

Alcohol enhances the hypotensive effect

Allopurinol, trandolapril [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, trandolapril [2] ---> SmPC of [2] of eMC

Potassium-sparing diuretics or potassium supplements may increase the risk of hyperkalaemia, particularly in renal failure.

Antacids, trandolapril [2] ---> SmPC of [2] of eMC

Antacids may cause reduced bioavailability of ACE inhibitors.

Antiadrenergics, trandolapril [2] ---> SmPC of [2] of eMC

Adrenergic-blocking drugs should only be combined with trandolapril under careful supervision.

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

Combination of trandolapril with other antihypertensive agents may potentiate the antihypertensive response to trandolapril

Bendroflumethiazide, trandolapril

Trandolapril may attenuate the potassium loss caused by thiazide-type diuretic and may increase the hypotensive effect

Bicarbonate, trandolapril

Sodium bicarbonate may decrease the absorption of trandolapril.

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

Trandolapril is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.

Corticosteroids, trandolapril [2] ---> SmPC of [2] of eMC

Systemic corticosteroids may increase the risk of leucopoenia, if used concomitantly with ACE inhibitors.

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

Cytostatic agents may increase the risk of leucopoenia, if used concomitantly with ACE inhibitors.

Dextran sulphate, trandolapril

Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.

Diuretics, trandolapril [2] ---> SmPC of [2] of eMC

Combination of trandolapril with diuretics may potentiate the antihypertensive response to trandolapril

Ginseng, trandolapril

Ginseng may antagonize the antihypertensive effect of trandolapril.

Gold, trandolapril [2] ---> SmPC of [2] of eMC

Nitritoid reactions following injectable gold have been reported more frequently in patients receiving ACE inhibitor therapy.

Hyperkalemia, trandolapril

The combination may lead to hyperkalemia, particularly in renal failure. Co-administration is not recommended

Immunosuppressives, trandolapril [2] ---> SmPC of [2] of eMC

Immunosuppressive agents may increase the risk of leucopoenia, if used concomitantly with ACE inhibitors.

Insulin, trandolapril [2] ---> SmPC of [2] of eMC

Concomitant treatment with ACE inhibitors and antidiabetic agents may cause a pronounced hypoglycaemic effect with the risk of hypoglycaemia.

Lithium, trandolapril [2] ---> SmPC of [2] of eMC

Trandolapril may reduce the elimination of lithium and serum levels of lithium should be monitored.

Loop diuretics, trandolapril

Trandolapril may attenuate the potassium loss caused by loop diuretic and may increase the hypotensive effect

Narcotics, trandolapril

Increased hypotensive effect.

Neuroleptics, trandolapril [2] ---> SmPC of [2] of eMC

Combination of trandolapril with neuroleptic increases the risk of orthostatic hypotension.

NSAID, trandolapril [2] ---> SmPC of [2] of eMC

As with antihypertensives, NSAIDs may reduce the antihypertensive effects of trandolapril. An additive effect on serum potassium increase has been described when NSAIDs and ACE inhibitors have been used concomitantly, while renal function may be reduced.

Oral antidiabetics, trandolapril [2] ---> SmPC of [2] of eMC

Concomitant treatment with ACE inhibitors and antidiabetic agents may cause a pronounced hypoglycaemic effect with the risk of hypoglycaemia.

Organic nitrates, trandolapril

Concomitant use of trandolapril with nitrates may result in further reduction of blood pressure

Potassium, trandolapril [2] ---> SmPC of [2] of eMC

Potassium-sparing diuretics or potassium supplements may increase the risk of hyperkalaemia, particularly in renal failure.

Potassium-sparing diuretics, trandolapril [2] ---> SmPC of [2] of eMC

Potassium-sparing diuretics or potassium supplements may increase the risk of hyperkalaemia, particularly in renal failure.

Pregnancy, trandolapril [2] ---> SmPC of [2] of eMC

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

Procainamide, trandolapril [2] ---> SmPC of [2] of eMC

Procainamide may increase the risk of leucopoenia, if used concomitantly with ACE inhibitors.

Sirolimus, trandolapril

Increased risk of angioedema.

Sodium, trandolapril

Decreased hypotensive effect

Spironolactone, trandolapril [2] ---> SmPC of [2] of eMC

Potassium-sparing diuretics or potassium supplements may increase the risk of hyperkalaemia, particularly in renal failure.

Sympathomimetics, trandolapril [2] ---> SmPC of [2] of eMC

The antihypertensive effects of ACE inhibitors may be reduced by sympathomimetics; patients should be carefully monitored.

Table salt, trandolapril

Decreased hypotensive effect

Thiazides, trandolapril

Trandolapril may attenuate the potassium loss caused by thiazide-type diuretic and may increase the hypotensive effect

Trandolapril [1], triamterene ---> SmPC of [1] of eMC

Potassium-sparing diuretics or potassium supplements may increase the risk of hyperkalaemia, particularly in renal failure.

Trandolapril [1], tricyclic antidepressant ---> SmPC of [1] of eMC

Combination of trandolapril with tricyclic antidepressant increases the risk of orthostatic hypotension.

Trandolapril, vasodilators

Concomitant use of trandolapril with vasodilatators may result in further reduction of blood pressure

CONTRAINDICATIONS of Trandolapril

- Known hypersensitivity to trandolapril.

- History of angioedema associated with administration of an ACE inhibitor.

- Hereditary/idiopathic angioneurotic oedema.

- Second and third trimester of pregnancy

- Lactation.

- Use in children.

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

Trandolapril/verapamil

Ability to drive, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

There are no data available, but an effect cannot be ruled out, since the undesirable effects such as dizziness and fatigue can occur.

ACE inhibitors, antacids ---> SmPC of [trandolapril/verapamil] of eMC

Antacids induce decreased bioavailability of ACE inhibitors.

Acetylsalicylic acid, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

The concomitant use of acetylsalicylic acid can increase the side effect profile of acetylsalicylic acid (may increase the risk of bleeding).

Alcohol, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Alcohol enhances the hypotensive effect

Allopurinol, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Concomitant administration of allopurinol with ACE inhibitors may lead to an increased risk for leukopenia

Almotriptan, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of almotriptan thus increasing risk of toxicity

Amiloride, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Potassium sparing diuretics may lead to significant increases in serum potassium, particularly in the presence of renal function impairment.

Anaesthetics, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Trandolapril/verapamil may enhance the hypotensive effects of certain anaesthetic medicinal products.

Antacids, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Antacids induce decreased bioavailability of ACE inhibitors.

Antiarrhythmics, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

The concurrent use of verapamil and cardiodepressives, i.e., medicinal products that inhibit cardiac impulse generation and conduction, may produce undesirable additive effects

Antihypertensives, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Antihypertensive medicinal products increase the hypotensive effect of trandolapril/verapamil

Atorvastatin, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Increase in serum exposure (and the myopathy and rhabdomyolysis risk) has been reported for simvastatin when concomitantly administered with verapamil. The dose of simvastatin (and other statins also metabolised by CYP3A4) should be adapted accordingly.

Betablockers, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

The combination of verapamil with beta-blockers may provide a strong AV-conduction disturbance, which in some cases may lead to severe bradycardia: serious cardiodepression may also arise.

Breast-feeding, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

It is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.

Buspirone, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of buspirone thus increasing risk of toxicity

Carbamazepine, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of carbamazepine thus increasing risk of toxicity

Cardiodepressants, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

The concurrent use of verapamil and cardiodepressives, i.e., medicinal products that inhibit cardiac impulse generation and conduction, may produce undesirable additive effects

Cardiodepressants, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

The concurrent use of verapamil and cardiodepressives, i.e., medicinal products that inhibit cardiac impulse generation and conduction, may produce undesirable additive effects

Cimetidine, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil concentrations may be increased by cimetidine

Cimetidine, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

Verapamil concentrations may be increased by cimetidine

Clarithromycin, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil concentrations may be increased by clarithromycin

Colchicine, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

When verapamil and colchicine are administered together, inhibition of P-gp and/or CYP3A by verapamil may lead to increased exposure to colchicine. Combined use is not recommended.

Corticosteroids, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Concomitant administration of systemic corticosteroids with ACE inhibitors may lead to an increased risk for leukopenia

Cyclosporine, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of ciclosporin thus increasing risk of toxicity

Cytostatics, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Concomitant administration of cytostatics with ACE inhibitors may lead to an increased risk for leukopenia

Dantrolene, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

The simultaneous use of verapamil with dantrolene is not recommended.

Dantrolene, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

The simultaneous use of verapamil with dantrolene is not recommended.

Digitoxin, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of digitoxin thus increasing risk of toxicity

Digitoxin, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

Verapamil may increase the plasma concentrations of digitoxin thus increasing risk of toxicity

Digoxin, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of digoxine thus increasing risk of toxicity

Diuretics, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Patients on diuretics and especially those who are volume-and / or salt depleted may experience an excessive reduction of blood pressure after initiation of therapy with an ACE inhibitor.

Doxorubicine, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of doxorubicine thus increasing risk of toxicity

Doxorubicine, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

Verapamil may increase the plasma concentrations of doxorubicine thus increasing risk of toxicity

Drugs primarily metabolised by CYP3A4, trandolapril/verapamil

Verapamil, CYP3A4 inhibitor, may increase the plasma concentrations of the medicinal product mainly metabolized by CYP3A4

Erythromycin, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil concentrations may be increased by erythromycin

Everolimus, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of everolimus thus increasing risk of toxicity

Glibenclamide, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of glibenclamide thus increasing risk of toxicity

Glibenclamide, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

Verapamil may increase the plasma concentrations of glibenclamide thus increasing risk of toxicity

Gold, trandolapril/verapamil

Nitritoid reactions following injectable gold have been reported more frequently in patients receiving ACE inhibitor therapy.

Grapefruit juice, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil concentrations may be increased by grapefruit juice

Halogenated anaesthetics, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

The concurrent use of verapamil and cardiodepressives, i.e., medicinal products that inhibit cardiac impulse generation and conduction, may produce undesirable additive effects

Hyperkalemia, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Potassium supplements or potassium sparing diuretics are generally not recommended, since they may lead to significant increases in plasma potassium.

Imipramine, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of imipramine thus increasing risk of toxicity

Immunosuppressives, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Concomitant administration of immunosuppressive medicinal products with ACE inhibitors may lead to an increased risk for leukopenia

Insulin, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Increased reduction of blood glucose

Lithium, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

There have been reports of both an increase and a reduction in the effects of lithium used concurrently with verapamil. The concomitant administration of ACE inhibitors with lithium may reduce the excretion of lithium.

Lovastatine, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Metoprolol, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of metoprolol thus increasing risk of toxicity

Midazolam, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of midazolam thus increasing risk of toxicity

Muscle relaxants, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

The effect of muscle relaxants (such as neuromuscular blockers) may be enhanced.

Narcotics, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Postural hypotension may occur.

Neuroleptics, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

As with all antihypertensives, there is an elevated risk of orthostatic hypotension when combining antihypertensives with major tranquillisers

NSAID, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

The administration of NSAIDs may reduce the antihypertensive effect of an ACE inhibitor. It has been described that NSAIDs and ACE inhibitors exert an additive effect on the increase in serum potassium, whereas renal function may decrease.

Oral antidiabetics, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Increased reduction of blood glucose

Phenobarbital, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil concentrations may be reduced by phenobarbital

Phenytoin, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil concentrations may be reduced by phenytoin

Potassium, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Potassium supplements, or potassium containing salt substitutes may lead to significant increases in serum potassium, particularly in the presence of renal function impairment.

Potassium-sparing diuretics, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Potassium sparing diuretics may lead to significant increases in serum potassium, particularly in the presence of renal function impairment.

Prazosin, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of prazosin thus increasing risk of toxicity

Prazosin, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

Verapamil may increase the plasma concentrations of prazosin thus increasing risk of toxicity

Pregnancy, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

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

Procainamide, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Concomitant administration of procainamide with ACE inhibitors may lead to an increased risk for leukopenia

Propranolol, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of propranolol thus increasing risk of toxicity

Quinidine, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of quinidine thus increasing risk of toxicity

Quinidine, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

Verapamil may increase the plasma concentrations of quinidine thus increasing risk of toxicity

Rifampicin, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil concentrations may be reduced by rifampicin

Simvastatine, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Sirolimus, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of sirolimus thus increasing risk of toxicity

Spironolactone, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Potassium sparing diuretics may lead to significant increases in serum potassium, particularly in the presence of renal function impairment.

St. John's wort, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil concentrations may be reduced by St. John's wort

St. John's wort, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

Verapamil concentrations may be reduced by St. John's wort

Statins metabolised by CYP3A4, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Statins metabolised by CYP3A4, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

Strong CYP3A4 inductors, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Inducers of CYP3A4 have caused lowering of plasma levels of verapamil. Patients should be monitored for drug interactions.

Strong CYP3A4 inhibitors, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Clinically significant interactions have been reported with inhibitors of CYP3A4 causing elevation of plasma levels of verapamil. Patients should be monitored for drug interactions.

Sulfinpyrazone, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil concentrations may be reduced by sulfinpyrazone

Sympathomimetics, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Sympathomimetics may reduce the antihypertensive effects of ACE inhibitors

Tacrolimus, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of tacrolimus thus increasing risk of toxicity

Telithromycin, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil concentrations may be increased by telithromycin

Terazosine, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of terazosin thus increasing risk of toxicity

Terazosine, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

Verapamil may increase the plasma concentrations of terazosin thus increasing risk of toxicity

Theophylline, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of theophylline thus increasing risk of toxicity

Trandolapril/verapamil [1], triamterene ---> SmPC of [1] of eMC

Potassium sparing diuretics may lead to significant increases in serum potassium, particularly in the presence of renal function impairment.

CONTRAINDICATIONS of Trandolapril/verapamil

- Hypersensitivity to trandolapril or any other ACE inhibitor and/or verapamil or to any of the excipients

- History of angioneurotic oedema associated with previous ACE inhibitor therapy

- Hereditary/idiopathic angioneurotic oedema

- Cardiogenic shock

- Recent myocardial infarction with complications

- Second- or third-degree AV block without a functioning pacemaker

- SA block

- Sick sinus syndrome in patients without a functioning pacemaker

- Congestive heart failure

- Atrial flutter/fibrillation in association with an accessory pathway (e.g. WPW-syndrome)

- Severe renal impairment (creatinine clearance < 30 mL/min)

- Dialysis

- Liver cirrhosis with ascites

- Aortic or mitral stenosis, obstructive hypertrophic cardiomyopathy

- Primary aldosteronism

- 2nd and 3rd trimester of pregnancy

- Use in children and adolescents (<18 years)

- Is contraindicated in patients concomitantly treated with i.v. â-adrenoreceptor antagonists (exception: intensive care)

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

Tranexamic acid

Agents which affect haemostasis, tranexamic acid

The co-administration may weaken the antifibrinolytic effect of tranexamic acid

Breast-feeding, tranexamic acid [2] ---> SmPC of [2] of eMC

Tranexamic acid passes into breast milk to a concentration of approximately one hundredth of the concentration in the maternal blood. An antifibrinolytic effect in the infant is unlikely.

Estrogens, tranexamic acid

There is a potential risk of thrombus formation with estrogens

Pregnancy, tranexamic acid [2] ---> SmPC of [2] of eMC

Tranexamic acid crosses the placenta. The usual caution with use of drugs in pregnancy should be observed.

Streptokinase [1], tranexamic acid ---> SmPC of [1] of eMC

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Streptokinase/streptodornase, tranexamic acid

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Thrombolytics, tranexamic acid [2] ---> SmPC of [2] of eMC

Tranexamic acid will counteract the thrombolytic effect of fibrinolytic preparations.

Ticagrelor [1], tranexamic acid ---> SmPC of [1] of EMA

Antifibrinolytic therapy and/or recombinant factor VIIa may increase haemostasis. Ticagrelor may be resumed after the cause of bleeding has been identified and controlled.

Tranexamic acid [1], tretinoin ---> SmPC of [1] of eMC

There is a risk of thrombosis (both venous and arterial) which may involve any organ system, during the first month of treatment. Therefore, caution should be exercised when treating patients with the combination of tretinoin and anti-fibrinolytic agents

Tranexamic acid, urokinase

Effect inhibition of urokinase

CONTRAINDICATIONS of Tranexamic acid

- Hypersensitivity to tranexamic acid or any of the other ingredients.

- Active thromboembolic disease.

- History of venous or arterial thrombosis.

- Fibrinolytic conditions following consumption coagulopathy.

- Severe renal impairment (risk of accumulation).

- History of convulsions.

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

Trastuzumab (Herceptin)

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

Patients experiencing infusion-related symptoms should be advised not to drive and use machines until symptoms abate.

Anastrozole, trastuzumab [2] ---> SmPC of [2] of EMA

The administration of concomitant anastrozole did not appear to influence the pharmacokinetics of trastuzumab.

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.

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

As human IgG1 is secreted into human milk, and the potential for harm to the infant is unknown, women should not breast-feed during trastuzumab therapy and for 7 months after the last dose.

Capecitabine, trastuzumab [2] ---> SmPC of [2] of EMA

However, capecitabine itself showed higher concentrations and a longer half-life when combined with Herceptin.

Carboplatin, trastuzumab [2] ---> SmPC of [2] of EMA

Pharmacokinetic data from Study H4613g/GO01305 in patients with metastatic or locally advanced inoperable HER2-positive cancer suggested that trastuzumab had no impact on the PK of carboplatin

Carmustine, trastuzumab

Trastuzumab may increase the risk of neutropenia and anemia.

Cisplatin, trastuzumab [2] ---> SmPC of [2] of EMA

The data also suggested that the pharmacokinetics of cisplatin were not affected by concurrent use of capecitabine or by concurrent use of capecitabine plus Herceptin.

Cyclophosphamide, trastuzumab

The co-administration may increase the cardiotoxicity

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

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

Estramustine, trastuzumab

Trastuzumab may increase the risk of neutropenia and anemia.

Fertility, trastuzumab [2] ---> SmPC of [2] of EMA

There is no fertility data available.

Hydrocortisone, trastuzumab

Trastuzumab may increase the risk of neutropenia and anemia.

Hydroxychloroquine, trastuzumab

Concomitant use of hydroxychloroquine y trastuzumab may increase the risk of neutropenia

Idarubicin [1], trastuzumab ---> SmPC of [1] of eMC

Trastuzumab may increase the cardiotoxicity of anthracycline. Physicians should avoid anthracycline-based therapy for up to 24 weeks after stopping trastuzumab

Lapatinib [1], trastuzumab ---> SmPC of [1] of EMA

Concomitant administration of Tyverb with capecitabine, letrozole or trastuzumab did not meaningfully alter the pharmacokinetics of these medicinal products (or the metabolites of capecitabine) or lapatinib.

Mercaptopurine, trastuzumab

Trastuzumab may increase the risk of neutropenia and anemia

Mitoxantrone, trastuzumab ---> SmPC of [idarubicin] of eMC

Trastuzumab may increase the cardiotoxicity of anthracycline. Physicians should avoid anthracycline-based therapy for up to 24 weeks after stopping trastuzumab

Mycophenolate mofetil, trastuzumab

May increase the risk of neutropenia and anemia.

Mycophenolate, trastuzumab

May increase the risk of neutropenia and anemia.

Oxaliplatin, trastuzumab

Trastuzumab may increase the risk of neutropenia and anemia.

Paclitaxel, trastuzumab [2] ---> SmPC of [2] of EMA

Pharmacokinetic data suggested that exposure to paclitaxel and doxorubicin (and their major metabolites 6-? hydroxylpaclitaxel, POH, and doxorubicinol, DOL) was not altered in the presence of trastuzumab

Pertuzumab [1], trastuzumab ---> SmPC of [1] of EMA

No pharmacokinetic (PK) interactions were observed and no evidence of a drug-drug interaction has been shown between pertuzumab and trastuzumab

Pixantrone, trastuzumab ---> SmPC of [idarubicin] of eMC

Trastuzumab may increase the cardiotoxicity of anthracycline. Physicians should avoid anthracycline-based therapy for up to 24 weeks after stopping trastuzumab

Pregnancy, trastuzumab [2] ---> SmPC of [2] of EMA

As animal reproduction studies are not always predictive of human response, Herceptin should be avoided during pregnancy unless the potential benefit for the mother outweighs the potential risk to the foetus.

Tacrolimus, trastuzumab

Trastuzumab may increase the risk of neutropenia and anemia

Thiotepa, trastuzumab

Trastuzumab may increase the risk of neutropenia and anemia

Topotecan, trastuzumab

Trastuzumab may increase the risk of neutropenia and anemia.

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

Women of childbearing potential should be advised to use effective contraception during treatment with Herceptin and for 7 months after treatment has concluded (see section 5.2).

CONTRAINDICATIONS of Trastuzumab (Herceptin)

- Hypersensitivity to trastuzumab, murine proteins, or to any of the excipients listed in section 6.1

- Severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.

https://www.ema.europa.eu/en/documents/product-information/herceptin-epar-product-information_en.pdf 21/08/2024

Other trade names: Enhertu, Herwenda, Herzuma, Kanjinti, Ogivri, Ontruzant, Trazimera, Zercepac,

Trastuzumab emtansine (Kadcyla)

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

Patients experiencing infusion-related reactions (flushing, chills, pyrexia, dyspnoea, hypotension, wheezing, bronchospasm, and tachycardia) should be advised not to drive and use machines until symptoms abate.

Atazanavir, trastuzumab emtansine [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inhibitors with trastuzumab emtansine should be avoided due to the potential for an increase in DM1 exposure and toxicity.

Breast-feeding, trastuzumab emtansine [2] ---> SmPC of [2] of EMA

Women should discontinue breast-feeding prior to initiating. Women may begin breast-feeding 7 months after concluding treatment

Clarithromycin, trastuzumab emtansine [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inhibitors with trastuzumab emtansine should be avoided due to the potential for an increase in DM1 exposure and toxicity.

Fertility, trastuzumab emtansine [2] ---> SmPC of [2] of EMA

No reproductive and developmental toxicology studies have been conducted with trastuzumab emtansine.

Indinavir, trastuzumab emtansine [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inhibitors with trastuzumab emtansine should be avoided due to the potential for an increase in DM1 exposure and toxicity.

Itraconazol, trastuzumab emtansine [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inhibitors with trastuzumab emtansine should be avoided due to the potential for an increase in DM1 exposure and toxicity.

Ketoconazole, trastuzumab emtansine [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inhibitors with trastuzumab emtansine should be avoided due to the potential for an increase in DM1 exposure and toxicity.

Men, trastuzumab emtansine [2] ---> SmPC of [2] of EMA

Male patients or their female partners should also use effective contraception.

Nefazodone, trastuzumab emtansine [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inhibitors with trastuzumab emtansine should be avoided due to the potential for an increase in DM1 exposure and toxicity.

Nelfinavir, trastuzumab emtansine [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inhibitors with trastuzumab emtansine should be avoided due to the potential for an increase in DM1 exposure and toxicity.

Pregnancy, trastuzumab emtansine [2] ---> SmPC of [2] of EMA

Women who become pregnant must immediately contact their doctor. If a pregnant woman is treated with trastuzumab emtansine, close monitoring by a multidisciplinary team is recommended.

Pregnancy, trastuzumab emtansine [2] ---> SmPC of [2] of EMA

Administration of trastuzumab emtansine to pregnant women is not recommended and women should be informed of the possibility of harm to the foetus before they become pregnant

Ritonavir, trastuzumab emtansine [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inhibitors with trastuzumab emtansine should be avoided due to the potential for an increase in DM1 exposure and toxicity.

Saquinavir, trastuzumab emtansine [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inhibitors with trastuzumab emtansine should be avoided due to the potential for an increase in DM1 exposure and toxicity.

Strong CYP3A4 inhibitors, trastuzumab emtansine [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inhibitors with trastuzumab emtansine should be avoided due to the potential for an increase in DM1 exposure and toxicity.

Telithromycin, trastuzumab emtansine [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inhibitors with trastuzumab emtansine should be avoided due to the potential for an increase in DM1 exposure and toxicity.

Trastuzumab emtansine [1], voriconazole ---> SmPC of [1] of EMA

Concomitant use of strong CYP3A4 inhibitors with trastuzumab emtansine should be avoided due to the potential for an increase in DM1 exposure and toxicity.

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

Women of childbearing potential should use effective contraception while receiving trastuzumab emtansine and for 7 months following the last dose of trastuzumab emtansine.

CONTRAINDICATIONS of Trastuzumab emtansine (Kadcyla)

- 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/kadcyla-epar-product-information_en.pdf 22/03/2023

Travoprost (Travatan)

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

However as with any eye drop, temporary blurred vision or other visual disturbances may affect the ability to drive or use machines. If blurred vision occurs at instillation, the patient must wait until the vision clears before driving or using machines.

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

It is unknown whether travoprost from the eye drops is excreted in human breast milk. Animal studies have shown excretion of travoprost and metabolites in breast milk. The use of TRAVATAN by breast-feeding mothers is not recommended.

Fertility, travoprost [2] ---> SmPC of [2] of EMA

There are no data on the effects of TRAVATAN on human fertility. Animal studies showed no effect of travoprost on fertility at doses more than 250 times the maximum recommended human ocular dose.

Pregnancy, travoprost [2] ---> SmPC of [2] of EMA

Travoprost has harmful pharmacological effects on pregnancy and/or the fetus/new-born child. TRAVATAN should not be used during pregnancy unless clearly necessary.

CONTRAINDICATIONS of Travoprost (Travatan)

- 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/travatan-epar-product-information_en.pdf 07/06/2022

Other trade names: Fredomat, Izba, Provastor,

Travoprost/timolol (DuoTrav)

Ability to drive, travoprost/timolol [2] ---> SmPC of [2] of EMA

As with any eye drop, temporary blurred vision or other visual disturbances may occur.

Adrenaline, travoprost/timolol [2] ---> SmPC of [2] of EMA

Mydriasis resulting from concomitant use of ophthalmic beta-blockers and adrenaline has been reported occasionally.

Amiodarone, travoprost/timolol [2] ---> SmPC of [2] of EMA

The potential exists for additive effects and production of hypotension and/or marked bradycardia.

Antiarrhythmics, travoprost/timolol [2] ---> SmPC of [2] of EMA

The potential exists for additive effects and production of hypotension and/or marked bradycardia.

Betablockers, clonidine ---> SmPC of [travoprost/timolol] of EMA

The hypertensive reaction to sudden withdrawal of clonidine can be potentiated when taking beta blockers.

Betablockers, travoprost/timolol [2] ---> SmPC of [2] of EMA

The potential exists for additive effects and production of hypotension and/or marked bradycardia.

Breast-feeding, travoprost/timolol [2] ---> SmPC of [2] of EMA

The use of DuoTrav by breast-feeding women is not recommended.

Calcium antagonists, travoprost/timolol [2] ---> SmPC of [2] of EMA

The potential exists for additive effects and production of hypotension and/or marked bradycardia.

Digital glycosides, travoprost/timolol [2] ---> SmPC of [2] of EMA

The potential exists for additive effects and production of hypotension and/or marked bradycardia.

Fertility, travoprost/timolol [2] ---> SmPC of [2] of EMA

Animal studies showed no effect of travoprost on fertility at doses up to 75 times the maximum recommended human ocular dose, whereas no relevant effect of timolol was noted at this dose level.

Fluoxetine, timolol ---> SmPC of [travoprost/timolol] of EMA

Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors and timolol.

Fluoxetine, travoprost/timolol [2] ---> SmPC of [2] of EMA

Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors and timolol.

Guanethidine, travoprost/timolol [2] ---> SmPC of [2] of EMA

The potential exists for additive effects and production of hypotension and/or marked bradycardia.

Insulin, travoprost/timolol [2] ---> SmPC of [2] of EMA

The beta-blocker may increase the hypoglycaemic effect of insulin. Blockade of beta-adrenoreceptors may mask the symptoms of hypoglycaemia

Oral antidiabetics, travoprost/timolol [2] ---> SmPC of [2] of EMA

The beta-blocker may increase the hypoglycaemic effect of antidiabetic agent. Blockade of beta-adrenoreceptors may mask the symptoms of hypoglycaemia

Parasympathomimetics, travoprost/timolol [2] ---> SmPC of [2] of EMA

The potential exists for additive effects and production of hypotension and/or marked bradycardia.

Paroxetine, timolol ---> SmPC of [travoprost/timolol] of EMA

Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors and timolol.

Paroxetine, travoprost/timolol [2] ---> SmPC of [2] of EMA

Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors and timolol.

Pregnancy, travoprost/timolol [2] ---> SmPC of [2] of EMA

Travoprost has harmful pharmacological effects on pregnancy and/or the foetus/newborn child. DuoTrav should not be used during pregnancy unless clearly necessary.

Quinidine, timolol ---> SmPC of [travoprost/timolol] of EMA

Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors and timolol.

Quinidine, travoprost/timolol [2] ---> SmPC of [2] of EMA

Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors and timolol.

Strong CYP2D6 inhibitors, travoprost/timolol [2] ---> SmPC of [2] of EMA

Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors and timolol.

Travoprost/timolol [1], women of childbearing potential ---> SmPC of [1] of EMA

DuoTrav must not be used in women of child-bearing age/potential unless adequate contraceptive measures are in place (see section 5.3).

CONTRAINDICATIONS of Travoprost/timolol (DuoTrav)

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

- Hypersensitivity to other beta-blockers.

- Reactive airway disease including bronchial asthma, or a history of bronchial asthma, severe chronic obstructive pulmonary disease.

- Sinus bradycardia, sick sinus syndrome, including sino-atrial block, second or third degree atrioventricular block not controlled with pace-maker. Overt cardiac failure, cardiogenic shock.

- Severe allergic rhinitis and corneal dystrophies.

https://www.ema.europa.eu/en/documents/product-information/duotrav-epar-product-information_en.pdf 07/01/2025

Trazodone

Ability to drive, trazodone [2] ---> SmPC of [2] of eMC

Patients should be cautioned against the risks of driving or operating machinery until they are sure they are not affected by drowsiness, sedation, dizziness, confusional states, or blurred vision.

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

Trazodone intensifies the sedative effects of alcohol. Alcohol should be avoided during trazodone therapy.

Analgesics, trazodone

The co-administration may enhance the CNS depressant effect

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

The sedative effects of antihistaminic drugs may be intensified; dosage reduction is recommended in such instance.

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

Hypotension, including orthostatic hypotension and syncope, has been reported to occur in patients receiving trazodone. Co-administration of hypotensor therapy with trazodone may require a reduction in the dose of the hypotensor drug

Antimalarial agents, trazodone [2] ---> SmPC of [2] of eMC

Concomitant use of trazodone with drugs known to prolong the QT interval may increase the risk of ventricular arrhythmias, including torsade de pointes. Caution should be used when these drugs are coadministered with trazodone.

Anxiolytics, trazodone [2] ---> SmPC of [2] of eMC

The sedative effects of anxiolytics may be intensified; dosage reduction is recommended in such instance.

Astemizole, trazodone [2] ---> SmPC of [2] of eMC

Atazanavir/cobicistat [1], trazodone ---> SmPC of [1] of EMA

Plasma concentrations of trazodone may be increased when co-administered with EVOTAZ. The mechanism is CYP3A4 inhibition by atazanavir and cobicistat. If trazodone is co-administered with EVOTAZ, the combination should be used with caution.

Barbiturates, tetracyclic antidepressant ---> SmPC of [trazodone] of eMC

The metabolism of antidepressants is accelerated due to hepatic effects by barbiturates

Barbiturates, trazodone [2] ---> SmPC of [2] of eMC

The metabolism of antidepressants is accelerated due to hepatic effects by barbiturates

Barbiturates, tricyclic antidepressant ---> SmPC of [trazodone] of eMC

The metabolism of antidepressants is accelerated due to hepatic effects by barbiturates

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

Due to the paucity of data, a decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy

Buspirone [1], trazodone ---> SmPC of [1] of eMC

Concomitant administration of buspirone and trazodone showed a 3-6 fold increase of ALT in some patients.

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

Carbamazepine reduced plasma concentrations of trazodone when coadministered.

Chlorpromazine, trazodone [2] ---> SmPC of [2] of eMC

Severe orthostatic hypotension has been observed in case of concomitant use of trazodone und phenothiazines

Cimetidine, trazodone [2] ---> SmPC of [2] of eMC

The metabolism of antidepressants is inhibited by cimetidine.

Class IA antiarrhythmic agents, trazodone [2] ---> SmPC of [2] of eMC

Class III antiarrhythmic agents, trazodone [2] ---> SmPC of [2] of eMC

Clonidine, trazodone [2] ---> SmPC of [2] of eMC

Studies in laboratory animals suggest that trazodone may inhibit most of the acute actions of clonidine.

CNS depressants, trazodone

The co-administration may enhance the CNS depressant effect

Cobicistat [1], trazodone ---> SmPC of [1] of EMA

Plasma concentrations of trazodone may be increased when co-administered with cobicistat.

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/emtricitabine/tenofovir alafenamide [1], trazodone ---> SmPC of [1] 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.

Digoxin, trazodone [2] ---> SmPC of [2] of eMC

Concurrent use with trazodone may result in elevated serum levels of digoxin

Duloxetine [1], trazodone ---> SmPC of [1] of EMA

Efavirenz, trazodone

The inhibition and induction of CYP3A4 may alter trazodone efficacy and toxicity

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [1], trazodone ---> SmPC of [1] of EMA

Concentrations of antidepressant agents may be increased when co-administered with cobicistat. Careful dose titration of the antidepressant and monitoring for antidepressant response is recommended.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], trazodone ---> SmPC of [1] of EMA

Plasma concentrations of trazodone may be increased when co-administered with cobicistat.

Erythromycin, trazodone [2] ---> SmPC of [2] of eMC

It is likely that potent CYP3A4 inhibitors may lead to substantial increases in trazodone plasma concentrations. The co-administration of trazodone and potent CYP3A4 inhibitors should be avoided where possible.

Fluoxetine, trazodone [2] ---> SmPC of [2] of eMC

Rare cases have been reported of elevated trazodone plasma levels and adverse effects when trazodone had been combined with fluoxetine, a CYP1A2/2D6 inhibitor. A pharmacodynamic interaction (serotonine syndrome) could not be excluded.

Fluphenazine, trazodone [2] ---> SmPC of [2] of eMC

Severe orthostatic hypotension has been observed in case of concomitant use of trazodone und phenothiazines

Halofantrine, trazodone [2] ---> SmPC of [2] of eMC

Halogenated anaesthetics, trazodone [2] ---> SmPC of [2] of eMC

Trazodone may enhance the effects of volatile anaesthetics, and caution should be exercised in such instances.

Haloperidol, trazodone [2] ---> SmPC of [2] of eMC

Hypnotics, trazodone [2] ---> SmPC of [2] of eMC

The sedative effects of hypnotic drugs may be intensified; dosage reduction is recommended in such instance.

Idelalisib [1], trazodone ---> SmPC of [1] of EMA

The co-administration of idelalisib with trazodone may increase the serum concentrations of trazodone. Careful dose titration of the antidepressant and monitoring for antidepressant response is recommended.

IMAOs, trazodone [2] ---> SmPC of [2] of eMC

Use of trazodone with MAOIs, or within 2 weeks of stopping treatment with these compounds is not recommended. The giving of MAOIs within 1 week of stopping trazodone is also not recommended.

Indinavir, trazodone [2] ---> SmPC of [2] of eMC

Indinavir/ritonavir, trazodone ---> SmPC of [indinavir] of EMA

An increase in the incidence in trazodone-related adverse events was noted when coadministered with ritonavir. The combination of trazodone with indinavir/ritonavir should be used with caution

Itraconazol, trazodone [2] ---> SmPC of [2] of eMC

Ketoconazole, trazodone [2] ---> SmPC of [2] of eMC

Lapatinib, trazodone

The CYP3A4 inhibition may increase the exposition to trazodone

Levodopa, trazodone [2] ---> SmPC of [2] of eMC

Trazodone has been well tolerated in depressed parkinsonian patients receiving therapy with levodopa. Antidepressants can accelerate the metabolism of levodopa.

Levomepromazine, trazodone [2] ---> SmPC of [2] of eMC

Severe orthostatic hypotension has been observed in case of concomitant use of trazodone und phenothiazines

Lopinavir/ritonavir [1], trazodone ---> SmPC of [1] of EMA

Adverse events of nausea, dizziness, hypotension and syncope were observed following co-administration of trazodone and ritonavir. It is unknown whether the combination of lopinavir/ritonavir causes a similar increase in trazodone exposure.

Mephenytoin, trazodone

Increased hydantoin plasma levels

Mizolastine, trazodone [2] ---> SmPC of [2] of eMC

Moxifloxacin, trazodone [2] ---> SmPC of [2] of eMC

Muscle relaxants, trazodone [2] ---> SmPC of [2] of eMC

Trazodone may enhance the effects of muscle relaxants, and caution should be exercised in such instances.

Nefazodone, trazodone [2] ---> SmPC of [2] of eMC

Nelfinavir [1], trazodone ---> SmPC of [1] of EMA

Concomitant use of trazodone and nelfinavir may increase plasma concentrations of trazodone and a lower dose of trazodone should be considered.

Neuroleptics, trazodone [2] ---> SmPC of [2] of eMC

The sedative effects of antipsychotic drugs may be intensified; dosage reduction is recommended in such instance.

Ombitasvir/paritaprevir/ritonavir [1], trazodone ---> SmPC of [1] of EMA

CYP3A4 substrates may require dose adjustment and/or clinical monitoring

Oral contraceptives, tetracyclic antidepressant ---> SmPC of [trazodone] of eMC

The metabolism of antidepressants is accelerated due to hepatic effects by oral contraceptives

Oral contraceptives, trazodone [2] ---> SmPC of [2] of eMC

The metabolism of antidepressants is accelerated due to hepatic effects by oral contraceptives

Oral contraceptives, tricyclic antidepressant ---> SmPC of [trazodone] of eMC

The metabolism of antidepressants is accelerated due to hepatic effects by oral contraceptives

Pentamidine, trazodone [2] ---> SmPC of [2] of eMC

Perphenazine, trazodone [2] ---> SmPC of [2] of eMC

Severe orthostatic hypotension has been observed in case of concomitant use of trazodone und phenothiazines

Phenothiazines, trazodone [2] ---> SmPC of [2] of eMC

Severe orthostatic hypotension has been observed in case of concomitant use of trazodone und phenothiazines

Phenytoin, tetracyclic antidepressant ---> SmPC of [trazodone] of eMC

The metabolism of antidepressants is accelerated due to hepatic effects by phenytoin

Phenytoin, trazodone [2] ---> SmPC of [2] of eMC

The metabolism of antidepressants is accelerated due to hepatic effects by phenytoin. Concurrent use with trazodone may result in elevated serum levels of phenytoin

Phenytoin, tricyclic antidepressant ---> SmPC of [trazodone] of eMC

The metabolism of antidepressants is accelerated due to hepatic effects by phenytoin

Pimozide, trazodone [2] ---> SmPC of [2] of eMC

Pregnancy, trazodone [2] ---> SmPC of [2] of eMC

Caution should be exercised when prescribing to pregnant women.

QT interval prolonging drugs, trazodone [2] ---> SmPC of [2] of eMC

Ritonavir [1], trazodone ---> SmPC of [1] of EMA

An increase in the incidence in trazodone-related adverse reactions was noted when co-administered with ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer.

Ritonavir-boosted protease inhibitors, trazodone ---> SmPC of [ritonavir] of EMA

An increase in the incidence in trazodone-related adverse reactions was noted when co-administered with ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer.

Saquinavir/ritonavir, trazodone ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Serotonergic medicines, trazodone [2] ---> SmPC of [2] of eMC

Interactions in terms of serotonine syndrome/malignant neuroleptic syndrome have been described in case of concomitant use of trazodone and other serotonergically acting substances

SNRIs, trazodone [2] ---> SmPC of [2] of eMC

Interactions in terms of serotonine syndrome/malignant neuroleptic syndrome have been described in case of concomitant use of trazodone and other serotonergically acting substances

Sparfloxacin, trazodone [2] ---> SmPC of [2] of eMC

SSRI, trazodone [2] ---> SmPC of [2] of eMC

Interactions in terms of serotonine syndrome/malignant neuroleptic syndrome have been described in case of concomitant use of trazodone and other serotonergically acting substances

St. John's wort [1], trazodone ---> SmPC of [1] of eMC

Undesirable effects may be more frequent when trazodone is administered together with preparations containing Hypericum perforatum (St John's wort).

Strong CYP3A4 inhibitors, trazodone [2] ---> SmPC of [2] of eMC

Telaprevir [1], trazodone ---> SmPC of [1] of EMA

Telaprevir, CYP3A4 inhibitor, may increase the plasma levels of trazodone. Caution is recommended

Tipranavir/ritonavir, trazodone ---> SmPC of [tipranavir] of EMA

Increased plasma concentrations of trazodone. The combination should be used with caution and a lower dose of trazodone should be considered.

Trazodone [1], tricyclic antidepressant ---> SmPC of [1] of eMC

Interactions in terms of serotonine syndrome/malignant neuroleptic syndrome have been described in case of concomitant use of trazodone and other serotonergically acting substances

Trazodone [1], triptans ---> SmPC of [1] of eMC

Interactions in terms of serotonine syndrome/malignant neuroleptic syndrome have been described in case of concomitant use of trazodone and other serotonergically acting substances

Trazodone [1], warfarin ---> SmPC of [1] of eMC

There have been reports of changes in prothrombin time in patients concomitantly receiving trazodone and warfarin.

CONTRAINDICATIONS of Trazodone

- Known sensitivity to trazodone and any of the excipients.

- Alcohol intoxication and intoxication with hypnotics.

- Acute myocardial infarction.

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

Tremelimumab (Imjudo)

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

Because of the potential for adverse reactions from tremelimumab in breast-fed infants, breastfeeding women are advised not to breast-feed during treatment and for at least 3 months after the last dose.

Carboplatin, tremelimumab [2] ---> SmPC of [2] of EMA

POSEIDON study showed no clinically meaningful PK interactions between tremelimumab, durvalumab, nab-paclitaxel, gemcitabine, pemetrexed, carboplatin or cisplatin in the concomitant treatment.

Cisplatin, tremelimumab [2] ---> SmPC of [2] of EMA

POSEIDON study showed no clinically meaningful PK interactions between tremelimumab, durvalumab, nab-paclitaxel, gemcitabine, pemetrexed, carboplatin or cisplatin in the concomitant treatment.

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

However, systemic corticosteroids or other immunosuppressants can be used after starting tremelimumab to treat immune-related adverse reactions (see section 4.4).

Fertility, tremelimumab [2] ---> SmPC of [2] of EMA

Mononuclear cell infiltration in prostate and uterus was observed in repeat-dose toxicity studies (see Section 5.3). The clinical relevance of these findings for fertility is unknown.

Gemcitabine, tremelimumab [2] ---> SmPC of [2] of EMA

POSEIDON study showed no clinically meaningful PK interactions between tremelimumab, durvalumab, nab-paclitaxel, gemcitabine, pemetrexed, carboplatin or cisplatin in the concomitant treatment.

Immunosuppressives, tremelimumab [2] ---> SmPC of [2] of EMA

However, systemic corticosteroids or other immunosuppressants can be used after starting tremelimumab to treat immune-related adverse reactions (see section 4.4).

Pemetrexed, tremelimumab [2] ---> SmPC of [2] of EMA

POSEIDON study showed no clinically meaningful PK interactions between tremelimumab, durvalumab, nab-paclitaxel, gemcitabine, pemetrexed, carboplatin or cisplatin in the concomitant treatment.

Pregnancy, tremelimumab [2] ---> SmPC of [2] of EMA

Tremelimumab 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.

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

Women of childbearing potential should use effective contraception during treatment with tremelimumab and for at least 3 months after the last dose of tremelimumab.

CONTRAINDICATIONS of Tremelimumab (Imjudo)

- 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/imjudo-epar-product-information_en.pdf 14/08/2025

Other trade names: AstraZeneca,

Treosulfan (Trecondi)

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

Treosulfan has moderate influence on the ability to drive and use machines. It is likely that certain adverse reactions of treosulfan like nausea, vomiting or dizziness could affect these functions.

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

It is unknown whether treosulfan is excreted in human milk. Breast-feeding should be discontinued during treatment with treosulfan.

Chemotherapy [1], treosulfan ---> SmPC of [1] of EMA

No interaction of treosulfan was observed in high-dose chemotherapy.

Chloroquine, treosulfan [2] ---> SmPC of [2] of eMC

In one patient the effect of ibuprofen/chloroquine was reduced with concomitant administration of treosulfan.

CYP2C19 substrates with narrow therapeutic index, treosulfan [2] ---> SmPC of [2] of EMA

Medicinal products with a narrow therapeutic index (e.g. digoxin) that are substrates for CYP3A4, CYP2C19 or P-gp should not be given during treatment with treosulfan.

Digoxin, treosulfan [2] ---> SmPC of [2] of EMA

Medicinal products with a narrow therapeutic index (e.g. digoxin) that are substrates for CYP3A4, CYP2C19 or P-gp should not be given during treatment with treosulfan.

Drugs metabolised by CYP3A4, treosulfan [2] ---> SmPC of [2] of EMA

Detailed in vitro studies did not completely exclude potential interactions between high plasma concentrations of treosulfan and CYP3A4, CYP2C19, or P-glycoprotein (P-gp) substrates.

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, treosulfan [2] ---> SmPC of [2] of EMA

Medicinal products with a narrow therapeutic index (e.g. digoxin) that are substrates for CYP3A4, CYP2C19 or P-gp should not be given during treatment with treosulfan.

Fertility, treosulfan [2] ---> SmPC of [2] of EMA

Treosulfan might impair fertility in men and women. Men should seek advice on cryo-conservation of sperm prior to treatment because of the possibility of irreversible infertility.

Fludarabine, treosulfan [2] ---> SmPC of [2] of EMA

The effect of treosulfan on the pharmacokinetics of fludarabine is not known.

Ibuprofen, treosulfan [2] ---> SmPC of [2] of eMC

In one patient the effect of ibuprofen/chloroquine was reduced with concomitant administration of treosulfan.

P-glycoprotein substrates with small therapeutic index, treosulfan [2] ---> SmPC of [2] of EMA

Medicinal products with a narrow therapeutic index (e.g. digoxin) that are substrates for CYP3A4, CYP2C19 or P-gp should not be given during treatment with treosulfan.

Pregnancy, treosulfan [2] ---> SmPC of [2] of EMA

Treosulfan is contraindicated during pregnancy

Thiotepa [1], treosulfan ---> SmPC of [1] of EMA

Treosulfan [1], vaccinations ---> SmPC of [1] of EMA

Concomitant use of live attenuated vaccines is not recommended.

CONTRAINDICATIONS of Treosulfan (Trecondi)

- Hypersensitivity to the active substance

- Active non-controlled infectious disease

- Severe concomitant cardiac, lung, liver, and renal impairment

- Fanconi anaemia and other DNA breakage repair disorders

- Pregnancy (see section 4.6)

- Administration of live vaccine

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

Treprostinil (Trepulmix)

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

Treprostinil has minor influence on the ability to drive and use machines at the initiation of treatment or dose adjustments. They may be accompanied by undesirable effects such as symptomatic systemic hypotension or dizziness

Anticoagulants, treprostinil [2] ---> SmPC of [2] of EMA

Treprostinil may inhibit platelet function. Concomitant administration of treprostinil with platelet aggregation inhibitors, including NSAIDs, nitric oxide donors or anticoagulants may increase the risk of bleeding.

Antihypertensives, treprostinil [2] ---> SmPC of [2] of EMA

Concomitant administration of treprostinil with diuretics, antihypertensive agents or other vasodilators increases the risk of systemic hypotension.

Bosentan, treprostinil [2] ---> SmPC of [2] of EMA

In a pharmacokinetic study in humans, in which bosentan (250 mg/day) and treprostinil diolamine (oral dose of 2 mg/day) were administered concomitantly, no pharmacokinetic interaction between treprostinil and bosentan was observed.

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

It is not known whether treprostinil is excreted in human milk. Breastfeeding women taking treprostinil should be advised to discontinue breastfeeding.

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

Other CYP2C8 inducers (e.g. phenytoin, carbamazepine, phenobarbital and St. John's Wort) may lead to reduced exposure to treprostinil.

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.

Dipyridamole, treprostinil

The co-administration may increase the risk of bleeding. Additive hypotensive effect.

Diuretics, treprostinil [2] ---> SmPC of [2] of EMA

Concomitant administration of treprostinil with diuretics, antihypertensive agents or other vasodilators increases the risk of systemic hypotension.

Furosemide, treprostinil

Decreased treprostinil clearance

Gemfibrozil, treprostinil [2] ---> SmPC of [2] of EMA

Concomitant administration of cytochrome P450 (CYP2C8) enzyme inhibitors (as gemfibrozil) may lead to increased exposure (both Cmax and AUC) to treprostinil.

Nitric oxide donors, treprostinil [2] ---> SmPC of [2] of EMA

NSAID, treprostinil [2] ---> SmPC of [2] of EMA

Phenobarbital, treprostinil [2] ---> SmPC of [2] of EMA

Other CYP2C8 inducers (e.g. phenytoin, carbamazepine, phenobarbital and St. John's Wort) may lead to reduced exposure to treprostinil.

Phenytoin, treprostinil [2] ---> SmPC of [2] of EMA

Other CYP2C8 inducers (e.g. phenytoin, carbamazepine, phenobarbital and St. John's Wort) may lead to reduced exposure to treprostinil.

Platelet aggregation inhibitors, treprostinil [2] ---> SmPC of [2] of EMA

Treprostinil may inhibit platelet function.

Pregnancy, treprostinil [2] ---> SmPC of [2] of EMA

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

Rifampicin, treprostinil [2] ---> SmPC of [2] of EMA

Concomitant administration of CYP2C8 enzyme inducers (for example rifampicin) may result in a decreased exposure to treprostinil. At a reduced exposure, it is likely to have decreased clinical efficacy.

Sildenafil, treprostinil [2] ---> SmPC of [2] of EMA

In a pharmacokinetic study in humans, in which sildenafil (60mg/day) and treprostinil diolamine (oral dose of 2 mg/day) were administered concomitantly, no pharmacokinetic interaction between treprostinil and sildenafil was observed.

St. John's wort, treprostinil [2] ---> SmPC of [2] of EMA

Other CYP2C8 inducers (e.g. phenytoin, carbamazepine, phenobarbital and St. John's Wort) may lead to reduced exposure to treprostinil.

Strong CYP2B6 inductors, treprostinil [2] ---> SmPC of [2] of EMA

Strong CYP2C8 inhibitors, treprostinil [2] ---> SmPC of [2] of EMA

Concomitant administration of cytochrome P450 (CYP2C8) enzyme inhibitors (as gemfibrozil) may lead to increased exposure (both Cmax and AUC) to treprostinil.

Tissue-type plasminogen activator, treprostinil

Treprostinil may reduce the thrombolytic efficacy of tissue plasminogen activator (t-PA) by increasing hepatic clearance of t-PA

Treprostinil [1], trimethoprim ---> SmPC of [1] of EMA

Treprostinil [1], vasodilators ---> SmPC of [1] of EMA

Concomitant administration of treprostinil with diuretics, antihypertensive agents or other vasodilators increases the risk of systemic hypotension.

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

Contraception is recommended during treprostinil treatment.

CONTRAINDICATIONS of Treprostinil (Trepulmix)

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

- Pulmonary veno-occlusive disease.

- Severe decompensated left heart failure.

- Severe hepatic impairment (Child-Pugh Class C).

- Active gastrointestinal ulcer, intracranial haemorrhage, gastrointestinal injury or other

- Active gastrointestinal ulcer, intracranial haemorrhage, gastrointestinal injury or other gastrointestinal bleeding.

- Congenital or acquired valvular defects with clinically relevant myocardial dysfunction not related to pulmonary hypertension.

- Severe coronary heart disease or unstable angina

- Myocardial infarction within the last six months

- Severe arrhythmias

- Cerebrovascular events (e.g. transient ischaemic attack, stroke) within the last three months.

- Co-administration with other prostanoids

https://www.ema.europa.eu/en/documents/product-information/trepulmix-epar-product-information_en.pdf 31/07/2025

Tretinoin

Acitretin [1], tretinoin ---> SmPC of [1] of eMC

Risk of hypervitaminosis A. The combination is contraindicated

Aminocaproic acid [1], tretinoin ---> SmPC of [1] of eMC

Antifibrinolytics, tretinoin [2] ---> SmPC of [2] of eMC

Aprotinin, tretinoin [2] ---> SmPC of [2] of eMC

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

Nursing must be discontinued if therapy with tretinoin is initiated.

CYP2C8 inductors [1], tretinoin ---> SmPC of [1] of eMC

As tretinoin is metabolised by the hepatic P450 system, there is the potential for alteration of pharmacokinetics parameters in patients administered concomitant medications that are also inducers or inhibitors of this system.

CYP2C8 inhibitors [1], tretinoin ---> SmPC of [1] of eMC

Drugs metabolised by CYP2C8, tretinoin

Tretinoin, CYP2C8 inhibitor, may increase the plasma concentrations of the medicinal products metabolized by CYP2C8

Drugs primarily metabolised by CYP2C8, tretinoin

Tretinoin, CYP2C8 inhibitor, may increase the plasma concentrations of the medicinal products principally metabolized by CYP2C8

Enzyme inductors, tretinoin

Enzyme inhibitors, tretinoin

Gestagens, tretinoin

Tretinoin decreases the contraceptive effect of gestagen. The co-administration is contraindicated

Lapatinib, tretinoin

The CYP2C8 inhibition may increase the exposition to oral tretinoin

Phenothiazines, tretinoin

Concomitant use of tretinoin crème with photosensitizers should be avoided

Pregnancy, tretinoin [2] ---> SmPC of [2] of eMC

Its use is contraindicated in pregnant women and women who might become pregnant and within one month after cessation of treatment, unless the benefit of tretinoin treatment outweighs the risk of foetal abnormalities

Quinolones, tretinoin

Concomitant use of tretinoin crème with photosensitizers should be avoided

Retinol [1], tretinoin ---> SmPC of [1] of eMC

As with other retinoids, tretinoin must not be administered in combination with vitamin A because symptoms of hypervitaminosis A could be aggravated

Strong CYP2C8 inductors [1], tretinoin ---> SmPC of [1] of eMC

Strong CYP2C8 inhibitors [1], tretinoin ---> SmPC of [1] of eMC

Sulphonamides, tretinoin

Concomitant use of tretinoin crème with photosensitizers should be avoided

Sun, tretinoin

The effects of UV light are enhanced by retinoid therapy. Therefore patients should avoid excessive exposure to sunlight and the unsupervised use of sun lamps.

Tetracyclines, tretinoin

Concomitant use of tretinoin crème with photosensitizers should be avoided

Thiazides, tretinoin

Concomitant use of tretinoin crème with photosensitizers should be avoided

Tranexamic acid [1], tretinoin ---> SmPC of [1] of eMC

CONTRAINDICATIONS of Tretinoin

- Known allergy to tretinoin, retinoids or to any of the excipients

- Pregnancy

- Breast-feeding

- Tetracyclines

- Vitamin A

- Vesanoid contains soya-bean oil, therefore Vesanoid is contraindicated in patients allergic to soya or peanut.

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

Triamcinolone acetonide

ACE inhibitors, triamcinolone acetonide

Increased risk of changes in blood counts

Amiodarone, triamcinolone acetonide

Concomitant use of triamcinolone with class III antiarrhythmics is not recommended

Amphotericin, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Patients should be observed for hypokalaemia.

Anticholinergics, triamcinolone acetonide

Additional increase in the intraocular pressure

Anticholinesterase, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Effects of anticholinesterase agent may be antagonized.

Antihypertensives, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Corticosteroids antagonise the effects of antihypertensives and diuretics. The hypokalaemic effect of diuretics, including acetazolamide, is enhanced.

Atropine, triamcinolone acetonide

Additional increase in the intraocular pressure

Barbiturates, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Hepatic enzyme inducers may increase the metabolic clearance of triamcinolone

Bepridil, triamcinolone acetonide

Concomitant use of triamcinolone with class III antiarrhythmics is not recommended

Breast-feeding, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Corticosteroids may pass into breast milk. Infants of mothers taking high doses of systemic corticosteroids for prolonged periods may have a degree of adrenal suppression.

Carbamazepine, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Hepatic enzyme inducers may increase the metabolic clearance of triamcinolone

Chloroquine, triamcinolone acetonide

Increased risk of myopathies and cardiomyopathies

Class IA antiarrhythmic agents, triamcinolone acetonide

Concomitant use of triamcinolone with class I antiarrhythmics is not recommended

Class III antiarrhythmic agents, triamcinolone acetonide

Concomitant use of triamcinolone with class III antiarrhythmics is not recommended

Corticosteroids, cyclosporine ---> SmPC of [triamcinolone acetonide] of eMC

Monitor for evidence of increased toxicity of cyclosporine when the two are used concurrently.

Corticosteroids, insulin ---> SmPC of [triamcinolone acetonide] of eMC

Corticosteroids may increase blood glucose; diabetic control should be monitored, especially when corticosteroids are initiated, discontinued, or changed in dosage.

Corticosteroids, oral anticoagulants ---> SmPC of [triamcinolone acetonide] of eMC

Corticosteroids may potentiate or decrease anticoagulant action. Patients receiving oral anticoagulants and corticosteroids should therefore be closely monitored.

Corticosteroids, oral antidiabetics ---> SmPC of [triamcinolone acetonide] of eMC

Corticosteroids may increase blood glucose; diabetic control should be monitored, especially when corticosteroids are initiated, discontinued, or changed in dosage.

Cyclosporine, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Monitor for evidence of increased toxicity of cyclosporine when the two are used concurrently.

Digital glycosides, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Co-administration of triamcinolone and digitalis glycosides may enhance the possibility of digitalis toxicity.

Disopyramide, triamcinolone acetonide

Concomitant use of triamcinolone with class I antiarrhythmics is not recommended

Electrolyte imbalance, triamcinolone acetonide

Concomitant use of triamcinolone acetonide with medicinal products that cause electrolyte imbalance is not recommended

Enzyme inductors, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Hepatic enzyme inducers may increase the metabolic clearance of triamcinolone

Estrogens, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Oestrogens, including oral contraceptives may increase corticosteroid half-life and concentration and decrease clearance

Growth hormone, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

The growth-promoting effect may be inhibited.

Hydroxychloroquine, triamcinolone acetonide

Increased risk of myopathies and cardiomyopathies

Hypokalemia, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Patients should be observed for hypokalaemia.

Insulin, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Corticosteroids may increase blood glucose; diabetic control should be monitored, especially when corticosteroids are initiated, discontinued, or changed in dosage.

Isoniazid, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Isoniazid serum concentrations may be decreased.

Ketoconazole, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Corticosteroid clearance may be decreased, resulting in increased effects.

Loop diuretics, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Patients should be observed for hypokalaemia.

Mefloquine, triamcinolone acetonide

Increased risk of myopathies and cardiomyopathies

Muscle relaxants (non-depolarizing), triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Corticosteroids may decrease or enhance the neuromuscular blocking action.

NSAID, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Corticosteroids may increase the incidence and/or severity of GI bleeding and ulceration associated with NSAIDs.

Oral anticoagulants, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Corticosteroids may potentiate or decrease anticoagulant action. Patients receiving oral anticoagulants and corticosteroids should therefore be closely monitored.

Oral antidiabetics, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Corticosteroids may increase blood glucose; diabetic control should be monitored, especially when corticosteroids are initiated, discontinued, or changed in dosage.

Oral contraceptives, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Oestrogens, including oral contraceptives may increase corticosteroid half-life and concentration and decrease clearance

Praziquantel, triamcinolone acetonide

The co-administration may decrease the plasma levels of praziquantel

Pregnancy, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

As with all drugs, corticosteroids should only be prescribed when the benefits to the mother and child outweigh the risks.

Procainamide, triamcinolone acetonide

Concomitant use of triamcinolone with class I antiarrhythmics is not recommended

Quinidine, triamcinolone acetonide

Concomitant use of triamcinolone with class I antiarrhythmics is not recommended

Rifampicin, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Hepatic enzyme inducers may increase the metabolic clearance of triamcinolone

Salicylates, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Corticosteroids can reduce serum salicylate levels and therefore decrease their effectiveness.

Sotalol, triamcinolone acetonide

Concomitant use of triamcinolone with class III antiarrhythmics is not recommended

Thiazides, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Patients should be observed for hypokalaemia.

Thyroyd therapy, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Metabolic clearance of adrenocorticoids is decreased in hypothyroid patients and increased in hyperthyroid patients. Changes in thyroid status of the patient may necessitate adjustment in adrenocorticoid dosage.

Triamcinolone acetonide [1], vaccinations ---> SmPC of [1] of eMC

Neurological complications and lack of antibody response may occur when patients taking corticosteroids are vaccinated.

CONTRAINDICATIONS of Triamcinolone acetonide

- Hypersensitivity to any of the ingredients.

- Systemic infections unless specific anti-infective therapy is employed.

- Administration by intravenous, intrathecal epidural, or intraocular injection.

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

Triazolam

Ability to drive, triazolam

Drowsiness or dizziness may occur

Alcohol, triazolam

Alcohol intake should be avoided during treatment with triazolam because alcohol may potentiate the triazolam action in an unpredictable fashion.

Amiodarone [1], triazolam ---> SmPC of [1] of eMC

Amiodarone, CYP3A4 inhibitor, may increase the plasma concentrations of triazolam

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

Amprenavir must not be administered concurrently with medicinal products with narrow therapeutic windows that are substrates of cytochrome P450 3A4 (CYP3A4) (oral triazolam).

Anaesthetics, triazolam

Increased CNS depressant effect with the co-administration of triazolam and anesthetics may occur

Antidepressants, triazolam

Increased CNS depressant effect with the co-administration of triazolam and antidepressants may occur

Antiepileptics, triazolam

Increased CNS depressant effect with the co-administration of triazolam and antiepileptics may occur

Anxiolytics, triazolam

Increased CNS depressant effect with the co-administration of triazolam and anxiolytic drugs may occur

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

The potential effects of increased plasma concentrations of midazolam or other benzodiazepines metabolised via CYP3A4 (alprazolam, triazolam) should be considered when co-administering these medicinal products with EMEND (125 mg/80 mg).

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

Atazanavir is metabolised in the liver through CYP3A4. It inhibits CYP3A4. Therefore, REYATAZ is contraindicated with medicinal products that are substrates of CYP3A4 and have a narrow therapeutic index

Atazanavir/cobicistat [1], triazolam ---> SmPC of [1] of EMA

Azole antifungals, triazolam

The strong CYP3A4 inhibition may increase the plasma concentrations of triazolam. Concomitant use of triazolam with this azole antifungal is not recommended

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

Co-administration of oral midazolam and oral triazolam with Victrelis is contraindicated

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

Victrelis, with peginterferon alfa and ribavirin, is contraindicated in coadministration with medicines that are highly dependent on CYP3A4/5 for clearance, and for which elevated plasma levels are associated with serious and/or life-threatening events

Breast-feeding, triazolam

Benzodiazepine passes into the breast milk. Contraindicated

Carbamazepine, triazolam

Carbamazepine causes induction of CYP3A4. The effect of triazolam coadministered with carbamazepine is significantly reduced

Cimetidine, triazolam

It is recommended caution and, if necessary, a dose reduction should be considered when using triazolam with cimetidine

Clarithromycin, triazolam [2] ---> SmPC of [2] of eMC

Concomitant use of triazolam and clarithromycin may increase the plasma levels of triazolam. The co-administration should be avoided

CNS depressants, triazolam

Benzodiazepins have an additive effect, when are combined with other CNS depressants. Triazolam should be used with caution when it is combined with CNS depressants

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

Co-administration of cobicistat with medicinal products which are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated

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

No dose adjustment is required

Darunavir/cobicistat [1], triazolam ---> 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/ritonavir, triazolam ---> SmPC of [darunavir] of EMA

Dasabuvir with ombitasvir/paritaprevir/ritonavir, triazolam ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EMA

Diltiazem [1], triazolam ---> SmPC of [1] of eMC

Diltiazem significantly increases plasma concentrations of triazolam and prolongs its half-life.

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

The combination is contraindicated since inhibition of metabolism by efavirenz (CYP3A4 inhibitor) may lead to serious, life-threatening events

Efavirenz/emtricitabine/tenofovir disoproxil [1], triazolam ---> SmPC of [1] of EMA

The combination is contraindicated since inhibition of metabolism by efavirenz (CYP3A4 inhibitor) may lead to serious, life-threatening events

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [1], triazolam ---> SmPC of [1] of EMA

Co-administration of Genvoya and some medicinal products that are primarily metabolised by CYP3A may increase plasma concentrations of these products, which are associated with the potential for serious/life-threatening adverse reactions. Contraindicated

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], triazolam ---> SmPC of [1] of EMA

Association contraindicated with MP that are highly dependent on CYP3A for clearance, and for which elevated levels are associated with serious and/or life-threatening events

Erythromycin, triazolam [2] ---> SmPC of [2] of eMC

It is recommended caution and, if necessary, a dose reduction should be considered when using triazolam with macrolide antibiotics

Fluconazole [1], triazolam ---> SmPC of [1] of eMC

Potentiated and prolonged effects of triazolam have been observed at concomitant treatment with fluconazole.

Fluvoxamine [1], triazolam ---> SmPC of [1] 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.

Fosamprenavir/ritonavir, triazolam ---> SmPC of [fosamprenavir] of EMA

Fosamprenavir/ritonavir, CYP3A4 inhibitors, increase the plasma concentrations of triazolam. They should not be co-administered with orally administered triazolam

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

The potential effects of increased plasma concentrations of midazolam or other benzodiazepines metabolised via CYP3A4 should be considered when co-administering these medicinal products with fosaprepitant.

Grapefruit juice, triazolam

Concomitant intake with grapefruit juice has increases the bioavailibility of triazolam

Hypnotics, triazolam

Increased CNS depressant effect with the co-administration of triazolam and hypnotic drugs may occur

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

The co-administration of idelalisib with triazolam may increase the serum concentrations of triazolam. Idelalisib should not be co-administered with triazolam

Imatinib, triazolam

Imatinib may increase plasma levels of triazolam due to inhibition of CYP3A4. It is recommended caution with the concomitant use

Indinavir [1], triazolam ---> SmPC of [1] 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.

Indinavir/ritonavir, triazolam ---> SmPC of [indinavir] of EMA

Interferon, triazolam

Caution should be used when administering interferon with medicines mainly metabolised by hepatic cytochrome P450 and have a narrow therapeutic window

Isoniazid, triazolam

Caution is advised when combining triazolam with isoniazid

Itraconazol [1], triazolam ---> SmPC of [1] of eMC

The strong CYP3A4 inhibition increases the plasma concentrations of triazolam. The co-administration with oral triazolam is contraindicated

Ivacaftor [1], triazolam ---> SmPC of [1] 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.

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

Contraindicated due to the risk of potentially prolonged or increased sedation and respiratory depression.

Lopinavir/ritonavir [1], triazolam ---> SmPC of [1] of EMA

Lopinavir/ritonavir should not be co-administered with medicinal products that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life threatening events.

Lumacaftor/ivacaftor [1], triazolam ---> SmPC of [1] of EMA

Concomitant use of lumacaftor/ivacaftor with these benzodiazepines is not recommended. Lumacaftor/ivacaftor will decrease the exposures of midazolam or triazolam, which will reduce their efficacy.

Macrolide antibiotics, triazolam

It is recommended caution and, if necessary, a dose reduction should be considered when using triazolam with macrolide antibiotics

Miconazole [1], triazolam ---> SmPC of [1] of eMC

Miconazole, strong CYP3A4 inhibitor, is contraindicated with medicines that are mainly metabolised by CYP3A4 and also have small therapeutic index

Modafinil [1], triazolam ---> SmPC of [1] of eMC

Modafinil, CYP3A4 inductor, may decrease the plasma concentrations of triazolam

Muscle relaxants, triazolam

The co-administration of triazolam and muscle relaxants may enhance the muscle relaxant effect

Narcotic analgesics, triazolam

Increased CNS depressant effect with the co-administration of triazolam and narcotic analgesics may occur. Enhancement of the euphoria may also occur, leading to an increase in psychological dependence

Nefazodone, triazolam

The strong CYP3A4 inhibition may increase the plasma concentrations of triazolam. Concomitant use of triazolam with nefazodone is contraindicated

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

Co-administration of nelfinavir with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4 is contraindicated.

Netupitant/palonosetron [1], triazolam ---> SmPC of [1] of EMA

The potential effects of increased plasma concentrations of benzodiazepines metabolized via CYP3A4 should be considered when coadministering these active substances with netupitant/palonosetron.

Neuroleptics, triazolam

Increased CNS depressant effect with the co-administration of triazolam and antipsychotic (neuroleptic) drugs may occur

Ombitasvir/paritaprevir/ritonavir [1], triazolam ---> SmPC of [1] of EMA

Oral contraceptives, triazolam

Oral contraceptives may increase plasma levels of triazolam due to inhibition of CYP3A4. It is recommended caution with the concomitant use

Paroxetine, triazolam

Caution is advised when combining triazolam with paroxetine

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

Concomitant use of posaconazole with any benzodiazepine that is metabolised by CYP3A4 increases plasma concentrations of the benzodiazepine. Due to the risk of prolonged sedation it is recommended that dose adjustments should be considered

Pregnancy, triazolam

The benzodiazepine crosses the placental barrier. Contraindicated

Protease inhibitors, triazolam [2] ---> SmPC of [2] of eMC

Decreased clearance of triazolam. The co-administration is contraindicated

Ranitidine, triazolam

Increased absorption of triazolam

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

Concomitant administration of ribociclib at the 600 mg dose this CYP3A4 substrates should be avoided

Rifampicin, triazolam

Rifampicin causes induction of CYP3A4. The effect of triazolam coadministered with rifampicin is significantly reduced

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

Increased plasma concentrations of triazolam, increasing the risk of extreme sedation and respiratory depression and is therefore contraindicated

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

Concomitant use of saquinavir with triazolam is contraindicated due to the potential for prolonged or increased sedation, respiratory depression

Saquinavir/ritonavir, triazolam ---> SmPC of [saquinavir] of EMA

Increased triazolam plasma concentrations. Triazolam is contraindicated in combination with saquinavir/ritonavir, due to the risk of potentially prolonged or increased sedation and respiratory depression

Sedating antihistamines, triazolam

Increased CNS depressant effect with the co-administration of triazolam and sedative antihistaminics may occur

Sedatives, triazolam

Increased CNS depressant effect with the co-administration of triazolam and sedative drugs may occur

Sertraline, triazolam

Caution is advised when combining triazolam with sertraline

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

Intestinal CYP3A4 enzyme inhibition. Caution is warranted when this medicinal product with narrow therapeutic index is co-administered with OLYSIO via the oral route.

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

Increased plasma benzodiazepine levels may occur via decreased hepatic metabolism leading to excessive sedation. Caution should be exercised

Strong CYP3A4 inductors, triazolam

The CYP3A4 induction may decrease plasma concentrations of triazolam

Strong CYP3A4 inhibitors, triazolam

The strong CYP3A4 inhibition may increase the plasma concentrations of triazolam

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

Association contraindicated with oral triazolam. Its elevated levels are associated with prolonged or increased sedation or respiratory depression

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

The CYP3A4 inhibition by telithromycin may increase the plasma levels of triazolam.

Tipranavir/ritonavir, triazolam ---> SmPC of [tipranavir] of EMA

Triazolam, troleandomycin

It is recommended caution and, if necessary, a dose reduction should be considered when using triazolam with macrolide antibiotics

Triazolam, verapamil

Caution is advised when combining triazolam with verapamil

Triazolam, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to increase the plasma concentrations of benzodiazepines that are metabolised by CYP3A4 and lead to a prolonged sedative effect.

Trientine (Cuprior)

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

Although there is no evidence that calcium or magnesium antacids alter the efficacy of trientine, it is good practice to separate their administration.

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

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

Fertility, trientine [2] ---> SmPC of [2] of EMA

It is unknown whether trientine has an effect on human fertility.

Foods, trientine [2] ---> SmPC of [2] of EMA

It is important that Cuprior is given on an empty stomach, at least one hour before meals or two hours after meals and at least one hour apart from any other medicinal product, food, or milk

Iron, trientine [2] ---> SmPC of [2] of EMA

Since iron and trientine may inhibit absorption of each other, iron supplements should be taken after at least two hours have elapsed from the administration of trientine.

Pregnancy, trientine [2] ---> SmPC of [2] of EMA

Cuprior should only be used in pregnancy after careful consideration of the benefits compared with the risks of treatment in the individual patient.

Trientine [1], zinc ---> SmPC of [1] of EMA

The combination of trientine with zinc is not recommended.

Trientine, zinc acetate

Complexion of zinc by the chelator. The administration of both should be separated by at least 1 hour

CONTRAINDICATIONS of Trientine (Cuprior)

- 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/cuprior-epar-product-information_en.pdf 26/03/2024

Other trade names: Cufence,

Trifluoperazine

Ability to drive, trifluoperazine [2] ---> SmPC of [2] of eMC

Trifluoperazine may cause side effects including drowsiness, dizziness and visual disturbances

Alcohol, trifluoperazine

Alcohol enhances the sedative effect of neuroleptics. Alcohol intake should be avoided during the treatment

Amiodarone [1], trifluoperazine ---> 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, trifluoperazine

Co-administration is not recommended

Anaesthetics, trifluoperazine [2] ---> SmPC of [2] of eMC

Potentiation may occur if antipsychotic drugs are combined with CNS depressants

Antacids, trifluoperazine ---> SmPC of [alimemazine] of eMC

Antacids can reduce the absorption of phenothiazines.

Antiadrenergics, trifluoperazine

Trifluoperazine may reverse the hypotensive effect of antiadrenergic agent

Anticholinergics, trifluoperazine [2] ---> SmPC of [2] of eMC

The anticholinergic effect of neuroleptics may be enhanced by other anticholinergic drugs.

Antidepressants, trifluoperazine [2] ---> SmPC of [2] of eMC

Potentiation may occur if antipsychotic drugs are combined with CNS depressants

Antiepileptics, trifluoperazine

Phenothiazines may decrease the seizure threshold

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

Breast feeding should only be allowed at the discretion of the physician.

Carteolol, trifluoperazine

The co-administration increases the risk of heart rhythm disorders, particularly torsades de pointes

Cholinergic agents, trifluoperazine

The co-administration may decrease the absorption of trifluoperazine

Clonidine, trifluoperazine [2] ---> SmPC of [2] of eMC

The anti-hypertensive action of guanethidine and related compounds may be reduced by phenothiazine derivatives

CNS depressants, trifluoperazine [2] ---> SmPC of [2] of eMC

Potentiation may occur if antipsychotic drugs are combined with CNS depressants

Coffee, trifluoperazine

The co-administration may decrease the absorption of trifluoperazine

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.

Electrolyte imbalance, trifluoperazine [2] ---> SmPC of [2] of eMC

Phenothiazines increase the risk of ventricular arrhythmias when given with drugs causing electrolyte imbalances.

Guanethidine, phenothiazines ---> SmPC of [trifluoperazine] of eMC

The anti-hypertensive action of guanethidine may be reduced by phenothiazine derivatives

Guanethidine, trifluoperazine [2] ---> SmPC of [2] of eMC

The anti-hypertensive action of guanethidine may be reduced by phenothiazine derivatives

Hydrochlorothiazide, trifluoperazine ---> 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

Hydroquinidine, trifluoperazine

Concomitant use is not recommended due to increased risk of heart rhythm disorders (torsades de pointes)

Hypnotics, trifluoperazine [2] ---> SmPC of [2] of eMC

Potentiation may occur if antipsychotic drugs are combined with CNS depressants

Indapamide [1], trifluoperazine ---> SmPC of [1] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Losartan/hydrochlorothiazide [1], trifluoperazine ---> SmPC of [1] of eMC

Periodic monitoring of serum potassium and ECG is recommended when losartan/hydrochlorothiazide is administered with torsades de pointes-inducing medicinal products

Oral anticoagulants, trifluoperazine [2] ---> SmPC of [2] of eMC

Trifluoperazine may diminish the effect of oral anticoagulants.

Parasympathomimetics, trifluoperazine

The co-administration may decrease the absorption of trifluoperazine

Pregnancy, trifluoperazine [2] ---> SmPC of [2] of eMC

Drug treatment should be avoided in pregnancy unless essential, especially during the first trimester.

QT interval prolonging drugs, trifluoperazine [2] ---> SmPC of [2] of eMC

Phenothiazines increase the risk of ventricular arrhythmias when given with drugs which prolong the QT interval

Quinidine, trifluoperazine

The phenothiazine may enhance the cardiodepressant effect of quinidine

Sedatives, trifluoperazine [2] ---> SmPC of [2] of eMC

Potentiation may occur if antipsychotic drugs are combined with CNS depressants

Sotalol [1], trifluoperazine ---> SmPC of [1] of eMC

Sympatholytic drug, trifluoperazine

Trifluoperazine may reverse the hypotensive effect of antiadrenergic agent

Sympathomimetics, trifluoperazine

Trifluoperazine may antagonize the effect of sympathomimetic agent

Tea, trifluoperazine

The co-administration may decrease the absorption of trifluoperazine

Telmisartan/hydrochlorothiazide [1], trifluoperazine ---> SmPC of [1] of EMA

Thiazides, trifluoperazine

The co-administration of phenothiazines with diuretic thiazides may cause severe hypotension.

Tiapride, trifluoperazine

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

Trifluoperazine, xipamide

The combination increases the risk of ventricular arrhythmias, particularly torsades de pointes (favored by hypokaliemia). It is recommended a special caution

CONTRAINDICATIONS of Trifluoperazine

- Do not use 'Stelazine' in comatose patients, particularly is associated with other central nervous system depressants.

- Do not use 'Stelazine' in those patients with existing blood dyscrasias or known liver damage, or in those hypersensitive to trifluoperazine, related compounds, or any of the excipients.

- Patients with uncontrolled cardiac decompensation should not be given 'Stelazine'.

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

Trifluridine/tipiracil (Lonsurf)

Ability to drive, trifluridine/tipiracil [2] ---> SmPC of [2] of EMA

Lonsurf has minor influence on the ability to drive and use machines. Fatigue, dizziness or malaise may occur during treatment

Breast-feeding, trifluridine/tipiracil [2] ---> SmPC of [2] of EMA

A risk to the suckling child cannot be excluded. Breast-feeding should be discontinued during treatment with Lonsurf.

Cytochrome P450, trifluridine/tipiracil [2] ---> SmPC of [2] of EMA

In vitro studies indicated that trifluridine, tipiracil hydrochloride and 5-[trifluoromethyl] uracil (FTY) did not inhibit/induce the activity of human cytochrome P450 (CYP) isoforms.

Fertility, trifluridine/tipiracil [2] ---> SmPC of [2] of EMA

Patients who wish to conceive a child should be advised to seek reproductive counselling and cryo-conservation of either the ovum or sperm prior to starting Lonsurf treatment.

Foods, trifluridine/tipiracil [2] ---> SmPC of [2] of EMA

Lonsurf is for oral use. The tablets must be taken with a glass of water within 1 hour after completion of the morning and evening meals.

Hormonal contraceptives, trifluridine/tipiracil [2] ---> SmPC of [2] of EMA

It is unknown whether Lonsurf may reduce the effectiveness of hormonal contraceptives. Therefore, women using hormonal contraceptive must also use a barrier contraceptive method.

Human thymidine kinase substrates, trifluridine/tipiracil [2] ---> SmPC of [2] of EMA

Caution is required when using medicinal products that are human thymidine kinase substrates, e.g., zidovudine.

MATE1 inhibitors, trifluridine/tipiracil [2] ---> SmPC of [2] of EMA

Tipiracil hydrochloride was a substrate for OCT2 and MATE1, therefore, the concentration might be increased when Lonsurf is administered concomitantly with inhibitors of OCT2 or MATE1.

Men, trifluridine/tipiracil [2] ---> SmPC of [2] of EMA

Men with a partner of child-bearing potential must use effective contraception during treatment and for up to 6 months after discontinuation of treatment.

OCT2 inhibitors, trifluridine/tipiracil [2] ---> SmPC of [2] of EMA

Tipiracil hydrochloride was a substrate for OCT2 and MATE1, therefore, the concentration might be increased when Lonsurf is administered concomitantly with inhibitors of OCT2 or MATE1.

Pregnancy, trifluridine/tipiracil [2] ---> SmPC of [2] of EMA

Lonsurf should not be used during pregnancy unless the clinical condition of the woman requires treatment with Lonsurf.

QT interval prolonging drugs, trifluridine/tipiracil [2] ---> SmPC of [2] of EMA

Lonsurf had no clinically relevant effect on QT/QTc prolongation compared with placebo in an open label study in patients with advanced solid tumours.

Trifluridine/tipiracil [1], women of childbearing potential ---> SmPC of [1] of EMA

Therefore, women of child-bearing potential must use highly effective contraceptive measures while taking Lonsurf and for 6 months after stopping treatment.

Trifluridine/tipiracil [1], zidovudine ---> SmPC of [1] of EMA

Caution is required when using medicinal products that are human thymidine kinase substrates, e.g., zidovudine.

CONTRAINDICATIONS of Trifluridine/tipiracil (Lonsurf)

- 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/lonsurf-epar-product-information_en.pdf 11/09/2023

Triflusal

Anticoagulants, triflusal

Triflusal enhances the effect of anticoagulant agent

Breast-feeding, triflusal

It is necessary to consider possible risks and potential advantages before administering this drug to breastfeeding patients.

Glipizide, triflusal

Triflusal enhances the effect of sulfonylurea

Glisentide, triflusal

The metabolite of triflusal, 2-hydroxy-4-trifluoro-methyl-benzoic acid, impairs the serum protein binding of glisentide and increases the plasma levels of glisentide.

Heparin, triflusal

Triflusal enhances the effect of anticoagulant agent

NSAID, triflusal

The metabolite of triflusal, 2-hydroxy-4-trifluoro-methyl-benzoic acid, impairs the serum protein binding of NSAID and increases the plasma levels of NSAIDs.

Pregnancy, triflusal

It is necessary to consider possible risks and potential advantages before administering this drug to pregnant patients.

Sulfonylureas, triflusal

Triflusal enhances the effect of sulfonylurea

Triflusal, warfarin

The metabolite of triflusal, 2-hydroxy-4-trifluoro-methyl-benzoic acid, impairs the serum protein binding of warfarin and increases the plasma levels of warfarin.

Trimetazidine

Ability to drive, trimetazidine

Dizziness and somnolence may occur

Breast-feeding, trimetazidine

The lactation is not recommended

Pregnancy, trimetazidine

It use should be avoided during the pregnancy

Trimipramine

Ability to drive, trimipramine [2] ---> SmPC of [2] of eMC

Trimipramine may initially impair alertness. Patients should be warned of the possible hazard when driving or operating machinery.

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

Tricyclic antidepressants potentiate the central nervous depressant action of alcohol.

Amiodarone, trimipramine

Additive QT-prolongation may occur, increasing the risk of serious ventricular arrhythmias. The co-administration should be used with caution

Amphetamine, trimipramine

The co-administration may cause hypertensive crisis

Anorexics, trimipramine

The co-administration may cause hypertensive crisis

Anticholinergics, trimipramine

The co-administration of trimipramine with other anticholinergic drugs may enhance the central and peripheral effects (particularly delirium)

Antidepressants, trimipramine

The co-administration may enhance the parasympatholytic effect of trimipramine

Antiepileptics, trimipramine

Risk of generalized convulsive seizures

Antihypertensives, trimipramine

Concomitant use of trimipramine and antihypertensive (except clonidine and related compounds) can increase the risk of orthostatic hypotension

Antimalarial agents, trimipramine

Additive QT-prolongation may occur, increasing the risk of serious ventricular arrhythmias. The co-administration should be used with caution

Anxiolytics, trimipramine [2] ---> SmPC of [2] of eMC

The co-administration of trimipramine with other CNS depressants may increase the CNS depressant effect.

Baclofen, trimipramine

Concomitant use increases muscle hypotonia

Barbiturates, trimipramine [2] ---> SmPC of [2] of eMC

The co-administration of trimipramine with other CNS depressants may increase the CNS depressant effect. Barbiturates may increase the rate of metabolism.

Betanidine, trimipramine

The combination may potentiate the effect of tricyclic antidepressant. The antidepressant may decrease/abolish the central hypotensive effect. Combination should be avoided

Black tea, trimipramine

Decreased absorption and plasma levels of trimipramine

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

Trimipramine is contraindicated during lactation.

Cabergoline, trimipramine

Increased risk of serotonin syndrome.

Carbamazepine, trimipramine

Risk of generalized convulsive seizures

Centrally-acting antihypertensives, trimipramine

The co-administration of trimipramine with other CNS depressants may increase the CNS depressant effect.

Cimetidine, trimipramine

The metabolism of antidepressants is inhibited by cimetidine.

Citalopram, trimipramine

The previous or concomitant treatment of SSRIs with trimipramine may increase the plasma levels of both antidepressants by substrate competition

Class IA antiarrhythmic agents, trimipramine

Additive QT-prolongation may occur, increasing the risk of serious ventricular arrhythmias. The co-administration should be used with caution

Class III antiarrhythmic agents, trimipramine

Additive QT-prolongation may occur, increasing the risk of serious ventricular arrhythmias. The co-administration should be used with caution

Clonidine, trimipramine

Trimipramine may decrease the antihypertensive effect of clonidine.

CNS depressants, trimipramine [2] ---> SmPC of [2] of eMC

The co-administration of trimipramine with other CNS depressants may increase the CNS depressant effect.

Coffee, trimipramine

Possible decrease of trimipramine effect

CYP2D6 inhibitors, trimipramine

The CYP2D6 inhibition may increase plasma concentrations of trimipramine, which has a narrow therapeutic index

Epinephrine, trimipramine [2] ---> SmPC of [2] of eMC

Trimipramine should not be given with sympathomimetic agents

Fluoxetine, trimipramine

The previous or concomitant treatment of SSRIs with trimipramine may increase the plasma levels of both antidepressants by substrate competition

Fluvoxamine, trimipramine

The previous or concomitant treatment of SSRIs with trimipramine may increase the plasma levels of both antidepressants by substrate competition

Fruit juice, trimipramine

Possible decrease of trimipramine effect

Guanethidine, trimipramine [2] ---> SmPC of [2] of eMC

Trimipramine may decrease the antihypertensive effect of guanethidine

Hypnotics, trimipramine [2] ---> SmPC of [2] of eMC

The co-administration of trimipramine with other CNS depressants may increase the CNS depressant effect.

Hypokalemia, trimipramine

Increased hypokalaemic effects

IMAOs, trimipramine [2] ---> SmPC of [2] of eMC

Trimipramine should not be given concurrently with, or within 2 weeks of cessation of, therapy with monoamine oxidase inhibitors.

Interferon, trimipramine

Caution should be used when administering interferon with medicines mainly metabolised by hepatic cytochrome P450 and have a narrow therapeutic window

Isoprenaline, trimipramine [2] ---> SmPC of [2] of eMC

Trimipramine should not be given with sympathomimetic agents

Methyldopa, trimipramine

The combination may potentiate the effect of tricyclic antidepressant. The antidepressant may decrease/abolish the central hypotensive effect. Combination should be avoided

Morphinan derivatives, trimipramine [2] ---> SmPC of [2] of eMC

The co-administration of trimipramine with other CNS depressants may increase the CNS depressant effect.

Neuroleptics, trimipramine

Additive QT-prolongation may occur, increasing the risk of serious ventricular arrhythmias. The co-administration should be used with caution

Noradrenaline, trimipramine [2] ---> SmPC of [2] of eMC

Trimipramine should not be given with sympathomimetic agents

Norepinephrine, trimipramine [2] ---> SmPC of [2] of eMC

Trimipramine should not be given with sympathomimetic agents

Paroxetine, trimipramine

The previous or concomitant treatment of SSRIs with trimipramine may increase the plasma levels of both antidepressants by substrate competition

Phenelzine [1], trimipramine ---> SmPC of [1] of eMC

Phenelzine should not be administered at the same time as, or within 14 days of, treatment with trimipramine

Phenylephrine, trimipramine [2] ---> SmPC of [2] of eMC

Trimipramine should not be given with sympathomimetic agents

Phenylpropanolamine, trimipramine [2] ---> SmPC of [2] of eMC

Trimipramine should not be given with sympathomimetic agents

Phenytoin, trimipramine

Increased elimination of trimipramine

Pregnancy, trimipramine [2] ---> SmPC of [2] of eMC

Do not use in pregnancy especially during the first and last trimesters unless there are compelling reasons.

QT interval prolonging drugs, trimipramine

Additive QT-prolongation may occur, increasing the risk of serious ventricular arrhythmias. The co-administration should be used with caution

Quinidine, trimipramine

Additive QT-prolongation may occur, increasing the risk of serious ventricular arrhythmias. The co-administration should be used with caution

Reserpine, trimipramine

The combination may potentiate the effect of tricyclic antidepressant. The antidepressant may decrease/abolish the central hypotensive effect. Combination should be avoided

Sedating antihistamines, trimipramine [2] ---> SmPC of [2] of eMC

The co-administration of trimipramine with other CNS depressants may increase the CNS depressant effect.

Sedatives, trimipramine [2] ---> SmPC of [2] of eMC

The co-administration of trimipramine with other CNS depressants may increase the CNS depressant effect.

SSRI, trimipramine

The previous or concomitant treatment of SSRIs with trimipramine may increase the plasma levels of both antidepressants by substrate competition

Strong CYP2D6 inhibitors, trimipramine

The strong CYP2D6 inhibition may increase plasma concentrations of trimipramine

Sunitinib, trimipramine

The additive QT-prolonging may increase the risk of severe ventricular arrhythmias. The co-administration should be avoided

Sympathomimetics, trimipramine [2] ---> SmPC of [2] of eMC

Trimipramine should not be given with sympathomimetic agents

Tiapride, trimipramine

Enhancement of CNS depressant effect

CONTRAINDICATIONS of Trimipramine

- Recent myocardial infarction

- Any degree of heart block or other cardiac arrhythmias

- Mania

- Severe liver disease

- During breast feeding

- Hypersensitivity to trimipramine maleate or to any of the excipients

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

Triptorelin

Ability to drive, triptorelin [2] ---> SmPC of [2] of eMC

The ability to drive and use machines may be impaired should the patient experience dizziness, somnolence and visual disturbances (being possible undesirable effects of treatment), or resulting from the underlying disease.

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

Triptorelin is not recommended for use during lactation.

Clebopride, 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.

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.

Estrogens, triptorelin

When triptorelin is co-administered with drugs affecting pituitary secretion of gonadotropins, caution should be exercised and it is recommended that the patient's hormonal status be supervised.

Gestagens, triptorelin

When triptorelin is co-administered with drugs affecting pituitary secretion of gonadotropins, caution should be exercised and it is recommended that the patient's hormonal status be supervised.

Metoclopramide, 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.

Neuroleptics, 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.

Pregnancy, triptorelin [2] ---> SmPC of [2] of eMC

Triptorelin should not be used during pregnancy since concurrent use of GnRH agonists is associated with a theoretical risk of abortion or foetal abnormality.

Prolactin levels raise, 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.

Risperidone, 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.

Sertraline, 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.

Triptorelin [1], verapamil ---> SmPC of [1] 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 Triptorelin

- Hypersensitivity to GnRH, its analogues or any other component of the medicinal product

- Pregnancy and lactation

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

Tropisetron

Ability to drive, tropisetron

Dizziness and tiredness may occur

Alcohol, tropisetron

It is recommended to avoid alcohol use during treatment

Breast-feeding, tropisetron

Tropisetron should not be used during breastfeeding

Carbamazepine, tropisetron

The enzymatic inductor may increase the metabolism of tropisetron and decrease its plasma levels

Enzyme inductors, tropisetron

The enzymatic inductor may increase the metabolism of tropisetron and decrease its plasma levels

Panobinostat [1], tropisetron ---> SmPC of [1] 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.

Phenobarbital, tropisetron

The enzymatic inductor may increase the metabolism of tropisetron and decrease its plasma levels

Pregnancy, tropisetron

Tropisetron should not be administered to pregnant women.

QT interval prolonging drugs, tropisetron

Caution is warranted for concomitant use of tropisetron with QTc interval prolonging medicines

Rifampicin, tropisetron

The enzymatic inductor may increase the metabolism of tropisetron and decrease its plasma levels

Trospium

Ability to drive, trospium [2] ---> SmPC of [2] of eMC

Principally, disorders of accommodation can lower the ability to actively participate in road traffic and to use machines.

Amantadine, trospium [2] ---> SmPC of [2] of eMC

Potentiation of the effect of drugs with anticholinergic action

Anticholinergics, trospium [2] ---> SmPC of [2] of eMC

Potentiation of the effect of drugs with anticholinergic action

Beta-adrenergic agonists, trospium [2] ---> SmPC of [2] of eMC

Enhancement of the tachycardic action of beta-sympathomimetics

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

Caution should be exercised when prescribing to breastfeeding women.

Cholestyramine, trospium [2] ---> SmPC of [2] of eMC

An inhibition of the absorption of trospium chloride cannot be excluded. Therefore the simultaneous administration of these drugs with trospium chloride is not recommended.

Colestipol, trospium [2] ---> SmPC of [2] of eMC

An inhibition of the absorption of trospium chloride cannot be excluded. Therefore the simultaneous administration of these drugs with trospium chloride is not recommended.

Guar, trospium [2] ---> SmPC of [2] of eMC

An inhibition of the absorption of trospium chloride cannot be excluded. Therefore the simultaneous administration of these drugs with trospium chloride is not recommended.

Metoclopramide, trospium [2] ---> SmPC of [2] of eMC

Decrease in efficacy of pro-kinetic agents

Pregnancy, trospium [2] ---> SmPC of [2] of eMC

Caution should be exercised when prescribing to pregnant women.

Prokinetics, trospium [2] ---> SmPC of [2] of eMC

Decrease in efficacy of pro-kinetic agents

Tricyclic antidepressant, trospium [2] ---> SmPC of [2] of eMC

Potentiation of the effect of drugs with anticholinergic action

CONTRAINDICATIONS of Trospium

- Trospium chloride is contraindicated in patients with urinary retention, severe gastro-intestinal condition (including toxic megacolon), myasthenia gravis, narrow-angle glaucoma, and tachyarrhythmia.

- Trospium chloride is also contraindicated in patients who have demonstrated hypersensitivity to the active substance or to any of the excipients.

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

Troxerutin

Breast-feeding, troxerutin

Contraindicated

Pregnancy, troxerutin

If troxerutin is to be administered during pregnancy, the benefits and potential risks must be weighed.

Tucatinib (Tukysa)

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

The clinical status of the patient should be considered when assessing the patient's ability to perform tasks that require judgment, motor, or cognitive skills.

Alfentanyl, 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.

Avanafil, 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.

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

Breast-feeding should be discontinued during treatment with TUKYSA. Breast-feeding may be resumed 1 week after treatment.

Buspirone, 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.

Capivasertib [1], tucatinib ---> SmPC of [1] of EMA

Co-administration of TRUQAP with strong CYP3A4 inhibitors increases capivasertib concentration, which may increase the risk of TRUQAP toxicity. Co-administration with strong CYP3A4 inhibitors should be avoided

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

Co-administration of tucatinib with strong CYP3A or moderate CYP2C8 inducers such as rifampicin, phenytoin, St. John's wort, or carbamazepine should be avoided as this may result in decreased activity of tucatinib

CYP2C8 inductors, tucatinib [2] ---> SmPC of [2] of EMA

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

Concomitant use of tucatinib with a P-gp substrate may increase the plasma concentrations of the P-gp substrate, which may increase the toxicity associated with the P-gp substrate.

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.

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.

Digoxin, tucatinib [2] ---> SmPC of [2] of EMA

Concomitant use of tucatinib with a P-gp substrate may increase the plasma concentrations of the P-gp substrate, which may increase the toxicity associated with the P-gp substrate.

Drugs primarily metabolised by CYP2C8, tucatinib [2] ---> SmPC of [2] of EMA

A clinical drug interaction study found that co-administration of tucatinib with repaglinide (a CYP2C8 substrate) resulted in an increase in repaglinide concentrations. No dose adjustment is required.

Drugs primarily metabolised by CYP2C9, tucatinib [2] ---> SmPC of [2] of EMA

Based on clinical drug interaction studies conducted with tucatinib, no drug interactions were observed when tucatinib is combined with tolbutamide (a sensitive CYP2C9 substrate). No dose adjustment is required.

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, tucatinib [2] ---> SmPC of [2] of EMA

Concomitant use of tucatinib with CYP3A substrates, when minimal concentration changes may lead to serious or life-threatening toxicities, should be avoided.

Drugs primarily metabolised by CYP3A4, 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.

Ebastine, 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.

Everolimus, 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.

Fertility, tucatinib [2] ---> SmPC of [2] of EMA

Based on findings from animal studies, tucatinib may impair fertility in females of reproductive potential

Gemfibrozil, tucatinib [2] ---> SmPC of [2] of EMA

Co-administration of tucatinib with strong CYP2C8 inhibitors such as gemfibrozil should be avoided as this may result in increased risk of tucatinib toxicity

Ibrutinib, 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.

Itraconazol, tucatinib [2] ---> SmPC of [2] of EMA

A clinical drug interaction study found that co-administration of a single dose of 300 mg tucatinib with itraconazole (a strong CYP3A inhibitor) resulted in an increase in tucatinib concentrations. No dose adjustment is required.

Lomitapide, 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.

Lovastatine, 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.

MATE1 substrates, tucatinib [2] ---> SmPC of [2] of EMA

A clinical drug interaction study found that co-administration of tucatinib with metformin (a MATE1/2-K substrate) resulted in an increase in metformin concentrations. No dose adjustment is required.

Men, tucatinib [2] ---> SmPC of [2] of EMA

Male patients with female partners of childbearing potential should also be advised to use effective contraception during and up to at least 1 week after treatment (see section 4.4).

Metformin, tucatinib [2] ---> SmPC of [2] of EMA

A clinical drug interaction study found that co-administration of tucatinib with metformin (a MATE1/2-K substrate) resulted in an increase in metformin concentrations. No dose adjustment is required.

Midazolam, 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.

Moderate CYP2C8 inductors, tucatinib [2] ---> SmPC of [2] of EMA

Naloxegol, 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.

Omeprazole, tucatinib [2] ---> SmPC of [2] of EMA

Based on clinical drug interaction studies conducted with tucatinib, no drug interactions were observed when tucatinib is combined with omeprazole (a proton pump inhibitor).

P-glycoprotein substrates, tucatinib [2] ---> SmPC of [2] of EMA

Concomitant use of tucatinib with a P-gp substrate may increase the plasma concentrations of the P-gp substrate, which may increase the toxicity associated with the P-gp substrate.

Phenytoin, tucatinib [2] ---> SmPC of [2] of EMA

Pregnancy, tucatinib [2] ---> SmPC of [2] of EMA

TUKYSA should not be used during pregnancy unless the clinical condition of the woman requires treatment with tucatinib. If the patient becomes pregnant during treatment, the potential hazard to the foetus/newborn child must be explained to the patient.

Proton pump inhibitors, tucatinib [2] ---> SmPC of [2] of EMA

Based on clinical drug interaction studies conducted with tucatinib, no drug interactions were observed when tucatinib is combined with omeprazole (a proton pump inhibitor).

Repaglinide, tucatinib [2] ---> SmPC of [2] of EMA

Rifampicin, tucatinib [2] ---> SmPC of [2] of EMA

Saquinavir, 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.

Simvastatine, 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.

Sirolimus, 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.

St. John's wort, tucatinib [2] ---> SmPC of [2] of EMA

Strong CYP2C8 inhibitors, tucatinib [2] ---> SmPC of [2] of EMA

Co-administration of tucatinib with strong CYP2C8 inhibitors such as gemfibrozil should be avoided as this may result in increased risk of tucatinib toxicity

Strong CYP3A4 inductors, tucatinib [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inhibitors, tucatinib [2] ---> SmPC of [2] of EMA

Tacrolimus, 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.

Tipranavir, 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.

Tolbutamide, tucatinib [2] ---> SmPC of [2] of EMA

Triazolam, 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.

Tucatinib [1], vardenafil ---> SmPC of [1] 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.

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

Women of childbearing potential should be advised to avoid becoming pregnant and to use effective contraception during and up to at least 1 week after treatment.

CONTRAINDICATIONS of Tucatinib (Tukysa)

- 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/tukysa-epar-product-information_en.pdf 13/08/2024

Turoctocog alfa (NovoEight)

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

Experience regarding the use of factor VIII during pregnancy and breastfeeding is not available. Therefore, factor VIII should be used during pregnancy and lactation only if clearly indicated.

Pregnancy, turoctocog alfa [2] ---> SmPC of [2] of EMA

Experience regarding the use of factor VIII during pregnancy and breastfeeding is not available. Therefore, factor VIII should be used during pregnancy and lactation only if clearly indicated.

CONTRAINDICATIONS of Turoctocog alfa (NovoEight)

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

- Known allergic reaction to hamster protein.

https://www.ema.europa.eu/en/documents/product-information/novoeight-epar-product-information_en.pdf 19/05/2021

Turoctocog alfa pegol (Esperoct)

Breast-feeding, turoctocog alfa pegol [2] ---> SmPC of [2] of EMA Factor VIII should be used during pregnancy and lactation only if clearly indicated.

Medicinal products, turoctocog alfa pegol [2] ---> SmPC of [2] of EMA No interactions of human coagulation factor VIII (rDNA) with other medicinal products have been reported.

Pregnancy, turoctocog alfa pegol [2] ---> SmPC of [2] of EMA Factor VIII should be used during pregnancy and lactation only if clearly indicated.

CONTRAINDICATIONS of Turoctocog alfa pegol (Esperoct)

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

- Known allergic reaction to hamster protein.

https://www.ema.europa.eu/en/documents/product-information/esperoct-epar-product-information_en.pdf 04/07/2024

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