R

Rabeprazole

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

Alertness is impaired due to somnolence; it is recommended that driving and operating complex machinery be avoided.

Antacids, rabeprazole [2] ---> SmPC of [2] of eMC

In clinical trials, antacids were used concomitantly with the administration of rabeprazole and, in a specific drug-drug interaction study, no interaction with liquid antacids was observed.

Atazanavir, rabeprazole [2] ---> SmPC of [2] of eMC

Co-administration of atazanavir with rabeprazole is not recommended

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

Rabeprazole must not be used during breast feeding.

Clarithromycin, rabeprazole

The co-administration may increase the plasma levels of rabeprazole and of clarithromycin active metabolite

Darunavir/cobicistat [1], rabeprazole ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. REZOLSTA can be co-administered with proton pump inhibitors without dose adjustments.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], rabeprazole ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. Symtuza can be co-administered with proton pump inhibitors without dose adjustments.

Digoxin, rabeprazole

Increased bioavailability of digoxin

Dolutegravir/rilpivirine [1], rabeprazole ---> SmPC of [1] of EMA

Co-administration may significantly decrease rilpivirine plasma concentration. This may result in loss of therapeutic effect of Juluca. Co-administration of Juluca with proton pump inhibitors is contraindicated

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

Significant decreases in rilpivirine plasma concentrations are expected (reduced absorption, increase in gastric pH). Co-administration is contraindicated.

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

Co-administration of proton pump inhibitors has been observed to decrease the plasma concentrations of rilpivirine (due to an increase in gastric pH) which could potentially lead to loss of therapeutic effect. Concomitant use contraindicated

Itraconazol, rabeprazole [2] ---> SmPC of [2] of eMC

Acid secretion suppressors impair the absorption of itraconazole. It is recommended that itraconazole be administered with an acidic beverage (such as non-diet cola)

Ketoconazole, rabeprazole [2] ---> SmPC of [2] of eMC

Co-administration of rabeprazole sodium with ketoconazole may result in a significant decrease in antifungal plasma levels.

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

Proton pump inhibitor doses comparable to omeprazole 20 mg can be administered simultaneously with ledipasvir/sofosbuvir. Proton pump inhibitors should not be taken before ledipasvir/sofosbuvir.

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

Under fasting conditions, the coadministration of multiple doses of the proton pump inhibitor (PPI) rabeprazole with a single dose of 125 mg IBRANCE decreased palbociclib AUCinf and Cmax by 62% and 80%, respectively.

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

Rabeprazole is contraindicated during pregnancy.

Rabeprazole, rilpivirine [2] ---> SmPC of [2] of EMA

The increase of the gastric pH decreases the absorption, plasma level and therapeutic effect of rilpivirine. Rilpivirine must not be used with proton pump inhibitors

Rabeprazole, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required

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

If it is considered necessary to co-administer, then Epclusa should be administered with food and taken 4 hours before proton pump inhibitor at max doses comparable to omeprazole 20 mg.

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

Increase in gastric pH decreases velpatasvir solubility. Proton pump inhibitors may be administered with Vosevi at a dose that does not exceed doses comparable with omeprazole 20 mg.

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

CONTRAINDICATIONS of Rabeprazole

- Hypersensitivity to the active substance or to any of the excipients

- Pregnancy.

- Breast feeding.

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

Racecadotril

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

This medicinal product should not be administered to breastfeeding women.

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

Racecadotril should not be administered to pregnant women.

CONTRAINDICATIONS of Racecadotril

Hypersensitivity to the active substance or to any of the excipients.

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

Radium dichloride (Xofigo)

Abiraterone/niraparib [1], radium dichloride ---> SmPC of [1] of EMA

Treatment with Akeega plus prednisone or prednisolone in combination with Ra-223 treatment is contraindicated due to an increased risk of fractures and a trend for increased mortality among asymptomatic or mildly symptomatic prostate cancer patients

Breast-feeding, radium dichloride [2] ---> SmPC of [2] of EMA

Xofigo is not indicated in women. Xofigo is not to be used in women who are, or may be, pregnant or breast-feeding.

Calcium, radium dichloride [2] ---> SmPC of [2] of EMA

As interactions with calcium and phosphate cannot be excluded, pausing supplementation with these substances and/or Vitamin D should be considered some days before starting with Xofigo treatment.

Chemotherapy, radium dichloride [2] ---> SmPC of [2] of EMA

Concomitant chemotherapy with Xofigo may have additive effects on bone marrow suppression (see section 4.4). Safety and efficacy of concomitant chemotherapy with Xofigo have not been established.

Fertility, radium dichloride [2] ---> SmPC of [2] of EMA

Based on studies in animals, there is a potential risk that radiation from Xofigo may potentially have toxic effects on male gonads and spermatogenesis (see section 5.3). Male patients should seek advice on conservation of sperm prior to treatment.

Men, radium dichloride [2] ---> SmPC of [2] of EMA

Because of potential effects on spermatogenesis associated with radiation, men should be advised to use effective contraceptive methods during and up to 6 months after treatment with Xofigo.

Phosphates, radium dichloride [2] ---> SmPC of [2] of EMA

As interactions with calcium and phosphate cannot be excluded, pausing supplementation with these substances and/or Vitamin D should be considered some days before starting with Xofigo treatment.

Pregnancy, radium dichloride [2] ---> SmPC of [2] of EMA

Xofigo is not indicated in women. Xofigo is not to be used in women who are, or may be, pregnant or breast-feeding.

Radium dichloride [1], vitamin D ---> SmPC of [1] of EMA

As interactions with calcium and phosphate cannot be excluded, pausing supplementation with these substances and/or Vitamin D should be considered some days before starting with Xofigo treatment.

CONTRAINDICATIONS of Radium dichloride (Xofigo)

- Xofigo is contraindicated in combination with abiraterone acetate and prednisone/prednisolone (see section 4.4).

https://www.ema.europa.eu/en/documents/product-information/xofigo-epar-product-information_en.pdf 28/07/2025

Raloxifene (Evista)

Ampicillin, raloxifene [2] ---> SmPC of [2] of EMA

Peak concentrations of raloxifene are reduced with co-administration with ampicillin. However, since the overall extent of absorption and the elimination rate of raloxifene are not affected, raloxifene can be concurrently administered with ampicillin.

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

Concurrent administration of either calcium carbonate or aluminium and magnesium-hydroxide containing antacids do not affect the systemic exposure of raloxifene.

Antihistamines, raloxifene [2] ---> SmPC of [2] of EMA

No clinically relevant effects of the co-administration of the agents on raloxifene plasma concentrations were identified.

Benzodiazepines, raloxifene [2] ---> SmPC of [2] of EMA

No clinically relevant effects of the co-administration of the agents on raloxifene plasma concentrations were identified.

Bile-acid sequestrants, raloxifene [2] ---> SmPC of [2] of EMA

Raloxifene should not be co-administered with cholestyramine (or other anion exchange resins), which significantly reduces the absorption and enterohepatic cycling of raloxifene.

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

A risk to the newborns/infants cannot be excluded. Its clinical use, therefore, cannot be recommended in breast-feeding women. Evista may affect the development of the baby.

Cholestyramine, raloxifene [2] ---> SmPC of [2] of EMA

Raloxifene should not be co-administered with cholestyramine (or other anion exchange resins), which significantly reduces the absorption and enterohepatic cycling of raloxifene.

Clomiphene, raloxifene

Association not recommended

Coumarin anticoagulants, raloxifene [2] ---> SmPC of [2] of EMA

However, modest decreases in the prothrombin time have been observed, and if raloxifene is given concurrently with warfarin or other coumarin derivatives, the prothrombin time should be monitored.

Digoxin, raloxifene [2] ---> SmPC of [2] of EMA

Raloxifene does not affect the steady-state AUC of digoxin. The Cmax of digoxin increased by less than 5 %.

Famciclovir [1], raloxifene ---> SmPC of [1] of eMC

Raloxifene, strong aldehyde oxidase inhibitor, may prevent the transformation of famciclovir to penciclovir and decrease the efficacy of famciclovir

H2 antagonists, raloxifene [2] ---> SmPC of [2] of EMA

No clinically relevant effects of the co-administration of the agents on raloxifene plasma concentrations were identified.

Hormone-binding globulin, raloxifene [2] ---> SmPC of [2] of EMA

Raloxifene modestly increases hormone-binding globulin concentrations, including SHBG, TBG, and CBG, with corresponding increases in total hormone concentrations.

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

No clinically relevant effects of the co-administration of the agents on raloxifene plasma concentrations were identified.

Interactions, raloxifene [2] ---> SmPC of [2] of EMA

In vitro, raloxifene did not interact with the binding of warfarin, phenytoin, or tamoxifen.

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

Raloxifene has no effect on the pharmacokinetics of methylprednisolone given as a single dose.

Naproxen, raloxifene [2] ---> SmPC of [2] of EMA

No clinically relevant effects of the co-administration of the agents on raloxifene plasma concentrations were identified.

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

No clinically relevant effects of the co-administration of the agents on raloxifene plasma concentrations were identified.

Oral antibiotics, raloxifene [2] ---> SmPC of [2] of EMA

No clinically relevant effects of the co-administration of the agents on raloxifene plasma concentrations were identified.

Ospemifene [1], raloxifene ---> 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.

Paracetamol, raloxifene [2] ---> SmPC of [2] of EMA

No clinically relevant effects of the co-administration of the agents on raloxifene plasma concentrations were identified.

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

If this medicinal product is used mistakenly during pregnancy or the patient becomes pregnant while taking it, the patient should be informed of the potential hazard to the foetus (see section 5.3).

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

Evista is only for use in postmenopausal women. Evista must not be taken by women of child bearing potential. Raloxifene may cause foetal harm when administered to a pregnant woman.

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

However, modest decreases in the prothrombin time have been observed, and if raloxifene is given concurrently with warfarin or other coumarin derivatives, the prothrombin time should be monitored.

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.

CONTRAINDICATIONS of Raloxifene (Evista)

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

- Must not be used in women with child bearing potential

- Active or past history of venous thromboembolic events (VTE), including deep vein thrombosis, pulmonary embolism and retinal vein thrombosis.

- Hepatic impairment including cholestasis.

- Severe renal impairment.

- Unexplained uterine bleeding.

- Raloxifene should not be used in patients with signs or symptoms of endometrial cancer as safety in this patient group has not been adequately studied.

https://www.ema.europa.eu/en/documents/product-information/evista-epar-product-information_en.pdf 01/04/2025

Other trade names: Optruma, Raloxifene Teva, Raloxifeno: Aurobindo, Cinfa, Combix, Fair-Med, Kern Pharma, Mylan Pharmaceuticals, Ratiopharm, Sandoz, Stada, Tarbis, Tecnigen, VIR,

Raltegravir (Isentress)

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

Dizziness has been reported in some patients during treatment with regimens containing raltegravir. Dizziness may influence some patients' ability to drive and use machines (see section 4.8).

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

Co-administration of raltegravir with aluminium containing antacids is not recommended.

Aluminium, raltegravir [2] ---> SmPC of [2] of EMA

Co-administration of raltegravir with aluminium containing antacids is not recommended.

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

Aluminium and magnesium containing antacids reduce raltegravir plasma levels. Co-administration of raltegravir with aluminium and/or magnesium containing antacids is not recommended.

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

Atazanavir, inhibitor of UGT1A1, may increase the exposition of raltegravir. No dosage adjustment necessary.

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

Co-administration of raltegravir with medicinal products that are known to be potent UGT1A1 inhibitors (e.g., atazanavir) may increase plasma levels of raltegravir.

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

Concomitant use may increase AUC, Cmax and C12h. The mechanism is UGT1A1 inhibition by atazanavir. No dose adjustment is required for raltegravir if co-administered with EVOTAZ.

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

No dose adjustment required for raltegravir.

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

Since the clinical relevance of the boceprevir C8h decrease has not been established, increased clinical and laboratory monitoring for HCV suppression is recommended.

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

No dose adjustment required for raltegravir or boceprevir.

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

A risk to the newborns/infants cannot be excluded. It is recommended that women living with HIV do not breast-feed their infants in order to avoid transmission of HIV.

Calcium carbonate, raltegravir [2] ---> SmPC of [2] of EMA

Therefore, when raltegravir is co-administered with calcium carbonate containing antacids no dose adjustment is required.

Calcium carbonate, raltegravir ---> SmPC of [lamivudine/raltegravir] of EMA

Co-administration of raltegravir with a calcium carbonate antacid decreased raltegravir plasma levels; however, this interaction is not considered clinically meaningful.

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

Therefore, crizotinib may have the potential to increase plasma concentrations of coadministered medicinal products that are metabolised predominantly by UGT1A1 (e.g., raltegravir, irinotecan) or UGT2B7 (e.g., morphine, naloxone).

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

Based on these data, raltegravir is not expected to affect the pharmacokinetics of medicinal products that are substrates of these enzymes or P-glycoprotein.

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

No dose adjustment is required

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

At present the effect of raltegravir on darunavir plasma concentrations does not appear to be clinically relevant. Boosted PREZISTA and raltegravir can be used without dose adjustments.

Darunavir, raltegravir [2] ---> SmPC of [2] of EMA

The co-administration of raltegravir with darunavir resulted in a modest decrease in darunavir plasma concentrations. However, the effect of raltegravir on darunavir plasma concentrations does not appear to be clinically meaningful.

Darunavir/cobicistat [1], raltegravir ---> SmPC of [1] of EMA

At present the effect of raltegravir on darunavir plasma concentrations does not appear to be clinically relevant; REZOLSTA and raltegravir can be used without dose adjustments.

Darunavir/ritonavir, raltegravir ---> SmPC of [darunavir] of EMA

Some clinical studies suggest raltegravir may cause a modest decrease in darunavir plasma concentrations. Darunavir co-administered with low dose ritonavir and raltegravir can be used without dose adjustments.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, raltegravir ---> SmPC of [dasabuvir] of EMA

UGT1A1 inhibition by paritaprevir, ombitasvir and dasabuvir. No dose adjustment is necessary

Divalent cations, raltegravir ---> SmPC of [lamivudine/raltegravir] of EMA

Co-administration of lamivudine/raltegravir with antacids containing divalent metal cations may reduce raltegravir absorption by chelation, resulting in a decrease of raltegravir plasma levels.

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

No dose adjustment is required.

Drugs primarily metabolised by CYP3A4, raltegravir ---> SmPC of [lamivudine/raltegravir] of EMA

The results indicate that raltegravir is not an inducer or inhibitor of CYP3A4, and raltegravir is thus not anticipated to affect the pharmacokinetics of medicinal products which are CYP3A4 substrates.

Drugs primarily metabolised by UGT1A1, raltegravir [2] ---> SmPC of [2] of EMA

Given that raltegravir is metabolised primarily via UGT1A1, caution should be used when co-administering raltegravir with strong inducers of UGT1A1 (e.g., rifampicin). Rifampicin reduces plasma levels of raltegravir;

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

The induction of UGT1A1 may reduce plasma levels of raltegravir. No dosage adjustment necessary.

Efavirenz, raltegravir [2] ---> SmPC of [2] of EMA

Less potent inducers (e.g., efavirenz, nevirapine, etravirine, rifabutin, glucocorticoids, St. John's wort, pioglitazone) may be used with the recommended dose of raltegravir.

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

No dose adjustment is required.

Elimination, raltegravir [2] ---> SmPC of [2] of EMA

Based on in vitro and in vivo studies, raltegravir is eliminated mainly by metabolism via a UGT1A1-mediated glucuronidation pathway.

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

No clinically relevant drug-drug interaction is expected. No dose adjustment is required.

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

Tenofovir alafenamide exposure is not expected to be affected by maraviroc, nevirapine or raltegravir, nor is it expected to affect the metabolic and excretion pathways relevant to maraviroc, nevirapine or raltegravir.

Emtricitabine/tenofovir disoproxil, raltegravir [2] ---> SmPC of [2] of EMA

In addition, tenofovir disoproxil fumarate may increase plasma levels of raltegravir, however, the mechanism for this effect is unknown (see Table 1).

Emtricitabine/tenofovir disoproxil/sofosbuvir/velpatasvir, raltegravir ---> SmPC of [sofosbuvir/velpatasvir] of EM

No dose adjustment of Epclusa, raltegravir or emtricitabine/tenofovir disoproxil fumarate is required.

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

Concomitant agents that are substrates of UGT1A1 (e.g. raltegravir, atorvastatin, dolutegravir) may have increased exposure and should be therefore administered with caution.

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

No dosage adjustment required for raltegravir or hormonal contraceptives (estrogen and/or progesterone-based).

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

Etravirine and raltegravir can be used without dose adjustments.

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

Less potent inducers (e.g., efavirenz, nevirapine, etravirine, rifabutin, glucocorticoids, St. John's wort, pioglitazone) may be used with the recommended dose of raltegravir.

Famotidine, raltegravir [2] ---> SmPC of [2] of EMA

No dose adjustment required for raltegravir.

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

No effect on fertility was seen in male and female rats at doses up to 600 mg/kg/day which resulted in 3-fold exposure above the exposure at the recommended human dose.

Foods, raltegravir [2] ---> SmPC of [2] of EMA

Raltegravir may be administered with or without food. Food appears to increase pharmacokinetic variability relative to fasting.

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

Concomitant use is not recommended. Significant reductions in exposure and Cmin observed for both amprenavir and raltegravir (especially in fed conditions) may result in virological failure in patients.

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

No dose adjustment of either medicinal product is necessary.

Ganciclovir, raltegravir ---> SmPC of [valganciclovir] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Gastric pH increasing medication, raltegravir [2] ---> SmPC of [2] of EMA

Co-administration of raltegravir with other agents that increase gastric pH (e.g., omeprazole and famotidine) may increase the rate of raltegravir absorption and result in increased plasma levels of raltegravir (see Table 1).

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

Clinically significant increases in exposure were not observed for sensitive substrates of CYP3A (midazolam, felodipine) or UGT1A1 (raltegravir) when administered with Maviret. No dose adjustment is required.

Glucocorticoids, raltegravir [2] ---> SmPC of [2] of EMA

Less potent inducers (e.g., efavirenz, nevirapine, etravirine, rifabutin, glucocorticoids, St. John's wort, pioglitazone) may be used with the recommended dose of raltegravir.

H2 antagonists, raltegravir [2] ---> SmPC of [2] of EMA

The co-administration may increase the rate of raltegravir absorption. No dosage adjustment necessary.

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

No dosage adjustment required for raltegravir or hormonal contraceptives (estrogen and/or progesterone-based).

Indinavir, raltegravir [2] ---> SmPC of [2] of EMA

Less potent UGT1A1 inhibitors (e.g., indinavir, saquinavir) may also increase plasma levels of raltegravir, but to a lesser extent compared with atazanavir.

Iron salts, raltegravir [2] ---> SmPC of [2] of EMA

Given simultaneously iron salts are expected to reduce raltegravir plasma levels; taking iron salts at least two hours from the administration of raltegravir may allow to limit this effect.

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

Suitable alternatives that are not UGT substrates should be considered during treatment with Tibsovo. Patients should be monitored for loss of UGT substrate efficacy if use of such medicinal products cannot be avoided (see section 5.2).

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

No dose adjustment of Harvoni or raltegravir is required.

Less potent inducer, raltegravir [2] ---> SmPC of [2] of EMA

Less potent inducers (e.g., efavirenz, nevirapine, etravirine, rifabutin, glucocorticoids, St. John's wort, pioglitazone) may be used with the recommended dose of raltegravir.

Less potent inhibitor, raltegravir [2] ---> SmPC of [2] of EMA

Less potent UGT1A1 inhibitors (e.g., indinavir, saquinavir) may also increase plasma levels of raltegravir, but to a lesser extent compared with atazanavir.

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

No dosage adjustment necessary.

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

Co-administration of raltegravir with magnesium containing antacids is not recommended.

Magnesium, raltegravir [2] ---> SmPC of [2] of EMA

Co-administration of raltegravir with magnesium containing antacids is not recommended.

Maraviroc, raltegravir [2] ---> SmPC of [2] of EMA

No clinically significant interaction seen. No dosage adjustment necessary.

Methadone, raltegravir [2] ---> SmPC of [2] of EMA

No dose adjustment required for raltegravir or methadone.

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

No dosage adjustment required for raltegravir or midazolam. These results indicate that raltegravir is not an inducer/inhibitor of CYP3A4, and raltegravir is thus not anticipated to affect the PK of medicinal products which are CYP3A4 substrates.

Midazolam, raltegravir ---> SmPC of [lamivudine/raltegravir] of EMA

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

Raltegravir and nevirapine can be co-administered without dose adjustments

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

Coadministration of ritonavir and raltegravir results in a minor reduction in raltegravir levels

Norelgestromin, raltegravir [2] ---> SmPC of [2] of EMA

No dosage adjustment required for raltegravir or hormonal contraceptives (estrogen and/or progesterone-based).

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

UGT1A1 inhibition by paritaprevir, ombitasvir and dasabuvir. No dose adjustment is necessary

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

P-glycoprotein substrates, raltegravir [2] ---> SmPC of [2] of EMA

Based on these data, raltegravir is not expected to affect the pharmacokinetics of medicinal products that are substrates of these enzymes or P-glycoprotein.

Pharmacokinetics, raltegravir [2] ---> SmPC of [2] of EMA

In interaction studies, raltegravir did not have a clinically meaningful effect on the pharmacokinetics of etravirine, maraviroc, tenofovir disoproxil fumarate, hormonal contraceptives, methadone, midazolam or boceprevir.

Pharmacokinetics, raltegravir [2] ---> SmPC of [2] of EMA

Considerable inter-and intra-individual variability was observed in the pharmacokinetics of raltegravir.

Pharmacokinetics, raltegravir [2] ---> SmPC of [2] of EMA

Considerable inter-and intra-individual variability was observed in the pharmacokinetics of raltegravir.

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

The impact of other strong inducers of drug metabolizing enzymes, such as phenytoin and phenobarbital, on UGT1A1 is unknown.

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

The impact of other strong inducers of drug metabolizing enzymes, such as phenytoin and phenobarbital, on UGT1A1 is unknown.

Pioglitazone, raltegravir [2] ---> SmPC of [2] of EMA

Less potent inducers (e.g., efavirenz, nevirapine, etravirine, rifabutin, glucocorticoids, St. John's wort, pioglitazone) may be used with the recommended dose of raltegravir.

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

Raltegravir 400 mg twice daily can be used during pregnancy if clinically needed.

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

The co-administration may increase the rate of raltegravir absorption. No dosage adjustment necessary.

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

Less potent inducers (e.g., efavirenz, nevirapine, etravirine, rifabutin, glucocorticoids, St. John's wort, pioglitazone) may be used with the recommended dose of raltegravir.

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

Rifampicin reduces plasma levels of raltegravir. If co-administration with rifampicin is unavoidable, a doubling of the dose of raltegravir can be considered (see section 4.4).

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

Less potent UGT1A1 inhibitors (e.g., indinavir, saquinavir) may also increase plasma levels of raltegravir, but to a lesser extent compared with atazanavir.

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

Less potent inducers (e.g., efavirenz, nevirapine, etravirine, rifabutin, glucocorticoids, St. John's wort, pioglitazone) may be used with the recommended dose of raltegravir.

Raltegravir [1], strong UGT1A1 inductors ---> SmPC of [1] of EMA

Co-administration of raltegravir with medicinal products that are known to be potent UGT1A1 inhibitors (e.g., atazanavir) may increase plasma levels of raltegravir.

Raltegravir [1], strong UGT1A1 inhibitors ---> SmPC of [1] of EMA

The strong inhibition of UGT1A1 may increase plasma levels of raltegravir

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

Tenofovir may increase plasma levels of raltegravir. No dosage adjustment necessary.

Raltegravir [1], tipranavir/ritonavir ---> SmPC of [1] of EMA

No dose adjustment required for raltegravir.

Raltegravir [1], UGT1A1 inductors ---> SmPC of [1] of EMA

The induction of UGT1A1 may reduce plasma levels of raltegravir

Raltegravir [1], UGT1A1 inhibitors ---> SmPC of [1] of EMA

The inhibition of UGT1A1 may increase plasma levels of raltegravir

Raltegravir, rilpivirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required

Raltegravir, ritonavir [2] ---> SmPC of [2] of EMA

Co-administration of ritonavir and raltegravir results in a minor reduction in raltegravir levels

Raltegravir, simeprevir [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Raltegravir, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

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

No dose adjustment of sofosbuvir or tacrolimus is required when sofosbuvir and raltegravir are used concomitantly.

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

No dose adjustment of Vosevi, raltegravir or emtricitabine/tenofovir disoproxil fumarate is required.

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

Increased plasma levels of raltegravir. If co-administered, no dose adjustment is required.

Raltegravir, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No dose adjustment of Vemlidy or raltegravir is required.

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.

Raltegravir, valganciclovir [2] ---> SmPC of [2] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

CONTRAINDICATIONS of Raltegravir (Isentress)

- 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/isentress-epar-product-information_en.pdf 13/05/2024

Raltitrexed

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

Raltitrexed may cause malaise or asthenia following infusion and the ability to drive/use machinery could be impaired whilst such symptoms continue.

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

Raltitrexed should not be given to women who are breast feeding.

Calcium folinate, raltitrexed [2] ---> SmPC of [2] of eMC

Leucovorin (folinic acid), folic acid or vitamin preparations containing these agents must not be given immediately prior to or during administration of raltitrexed, since they may interfere with its action.

Folic acid, raltitrexed [2] ---> SmPC of [2] of eMC

Folinic acid, raltitrexed [2] ---> SmPC of [2] of eMC

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

Raltitrexed should not be used during pregnancy or in women who may become pregnant during treatment

Raltitrexed [1], tubular secretion ---> SmPC of [1] of eMC

Data suggest that active tubular secretion may contribute to the renal excretion of raltitrexed, indicating a potential interaction with other actively secreted drugs

CONTRAINDICATIONS of Raltitrexed

- 'Tomudex' should not be used in pregnant women, in women who may become pregnant during treatment or women who are breast feeding. Pregnancy should be excluded

before treatment with 'Tomudex' is commenced.

- 'Tomudex' is contraindicated in patients with severe renal impairment (creatinine clearance < 25 ml/min).

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

Ramipril

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

Some adverse effects (e.g. symptoms of a reduction in blood pressure such as dizziness) may impair the patient's ability to concentrate and react

ACE inhibitors, table salt ---> SmPC of [ramipril] of eMC

Increased dietary salt intake may attenuate the antihypertensive effect

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

Reduction of the antihypertensive effect of ramipril is to be anticipated. Furthermore, concomitant treatment of ACE inhibitors and NSAIDs may lead to an increased risk of worsening of renal function and to an increase in kalaemia.

AIIRA, ramipril

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)

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

Increased vasodilatation. The antihypertensive effect may increase.

Alfuzosin, ramipril [2] ---> SmPC of [2] of eMC

Potentiation of the risk of hypotension is to be anticipated. Caution is recommended

Aliskiren, ramipril [2] ---> SmPC of [2] of eMC

Dual blockade of the RAA system through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function

Allopurinol, ramipril [2] ---> SmPC of [2] of eMC

Increased likelihood of haematological reactions

Anaesthetics, ramipril [2] ---> SmPC of [2] of eMC

Potentiation of the risk of hypotension is to be anticipated. Caution is recommended

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

Potentiation of the risk of hypotension is to be anticipated. Caution is recommended

Baclofen, ramipril [2] ---> SmPC of [2] of eMC

Potentiation of the risk of hypotension is to be anticipated. Caution is recommended

Biguanides, ramipril [2] ---> SmPC of [2] of eMC

Hypoglycaemic reactions may occur. Blood glucose monitoring is recommended.

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

Ramipril is not recommended in the breast-feeding and alternative treatments with better established safety profiles during breast-feeding are preferable

Corticosteroids, ramipril [2] ---> SmPC of [2] of eMC

Increased likelihood of haematological reactions

Cyclosporine, ramipril [2] ---> SmPC of [2] of eMC

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

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

Increased likelihood of haematological reactions

Diuretics, ramipril [2] ---> SmPC of [2] of eMC

Potentiation of the risk of hypotension is to be anticipated. Caution is recommended

Dopamine, ramipril [2] ---> SmPC of [2] of eMC

The antihypertensive effect may be reduced: Blood pressure monitoring is recommended.

Doubutamine, ramipril [2] ---> SmPC of [2] of eMC

The antihypertensive effect may be reduced: Blood pressure monitoring is recommended.

Doxazosin, ramipril [2] ---> SmPC of [2] of eMC

Potentiation of the risk of hypotension is to be anticipated. Caution is recommended

Epinephrine, ramipril [2] ---> SmPC of [2] of eMC

The antihypertensive effect may be reduced: Blood pressure monitoring is recommended.

Heparin, ramipril [2] ---> SmPC of [2] of eMC

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

Hyperkalemia, ramipril [2] ---> SmPC of [2] of eMC

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

Immunosuppressives, ramipril [2] ---> SmPC of [2] of eMC

Increased likelihood of haematological reactions

Insulin glargine/lixisenatide [1], ramipril ---> SmPC of [1] of EMA

No dose adjustment for ramipril is required when co-administered with lixisenatide.

Insulin, ramipril [2] ---> SmPC of [2] of eMC

Hypoglycaemic reactions may occur. Blood glucose monitoring is recommended.

Isoproterenol, ramipril [2] ---> SmPC of [2] of eMC

The antihypertensive effect may be reduced: Blood pressure monitoring is recommended.

Lithium, ramipril [2] ---> SmPC of [2] of eMC

Excretion of lithium may be reduced by ACE inhibitors and therefore lithium toxicity may be increased. Lithium level must be monitored.

Lixisenatide [1], ramipril ---> SmPC of [1] of EMA

No dose adjustment for ramipril is required when co-administered with lixisenatide

NSAID, ramipril [2] ---> SmPC of [2] of eMC

Oral antidiabetics, ramipril [2] ---> SmPC of [2] of eMC

Hypoglycaemic reactions may occur. Blood glucose monitoring is recommended.

Organic nitrates, ramipril [2] ---> SmPC of [2] of eMC

Potentiation of the risk of hypotension is to be anticipated. Caution is recommended

Potassium, ramipril [2] ---> SmPC of [2] of eMC

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

Potassium-sparing diuretics, ramipril [2] ---> SmPC of [2] of eMC

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

Prazosin, ramipril [2] ---> SmPC of [2] of eMC

Potentiation of the risk of hypotension is to be anticipated. Caution is recommended

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

The use of ACE inhibitors is not recommended during the 1st trimester of pregnancy and are contraindicated during the 2nd and 3rd trimester of pregnancy.

Procainamide, ramipril [2] ---> SmPC of [2] of eMC

Increased likelihood of haematological reactions

Ramipril [1], sulfonylureas ---> SmPC of [1] of eMC

Hypoglycaemic reactions may occur. Blood glucose monitoring is recommended.

Ramipril [1], table salt ---> SmPC of [1] of eMC

Increased dietary salt intake may attenuate the antihypertensive effect

Ramipril [1], tamsulosin ---> SmPC of [1] of eMC

Potentiation of the risk of hypotension is to be anticipated. Caution is recommended

Ramipril [1], terazosine ---> SmPC of [1] of eMC

Potentiation of the risk of hypotension is to be anticipated. Caution is recommended

Ramipril [1], tricyclic antidepressant ---> SmPC of [1] of eMC

Potentiation of the risk of hypotension is to be anticipated. Caution is recommended

Ramipril [1], trimethoprim ---> SmPC of [1] of eMC

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

Ramipril [1], vasopressor sympathomimetics ---> SmPC of [1] of eMC

The antihypertensive effect may be reduced: Blood pressure monitoring is recommended.

Ramipril, sodium

Decreased hypotensive effect

Ramipril, tacrolimus

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

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.

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

Ramipril, vildagliptin ---> SmPC of [vildagliptin/metformin] of EMA

Drug-drug interaction studies in healthy subjects were conducted with amlodipine, ramipril, valsartan and simvastatin. No clinically relevant pharmacokinetic interactions were observed after co-administration with vildagliptin.

Ramipril, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

CONTRAINDICATIONS of Ramipril

- Hypersensitivity to the active substance, to any of the excipients or any other ACE (Angiotensin Converting Enzyme) inhibitors

- History of angioedema (hereditary, idiopathic or due to previous angioedema with ACE inhibitors or AIIRAs)

- Extracorporeal treatments leading to contact of blood with negatively charged surfaces

- Significant bilateral renal artery stenosis or renal artery stenosis in a single functioning kidney

- Second and third trimesters of pregnancy

- Ramipril must not be used in patients with hypotensive or haemodynamically unstable states.

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

Ramucirumab (Cyramza)

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

If patients experience symptoms affecting their ability to concentrate and react, it is recommended that they do not drive or use machines until the effect subsides.

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

Excretion in milk and oral absorption is expected to be low. As a risk to breast-fed newborns/infants cannot be excluded, breast-feeding should be discontinued during treatment with Cyramza and for at least 3 months after the last dose.

Docetaxel, ramucirumab [2] ---> SmPC of [2] of EMA

The pharmacokinetics of docetaxel or erlotinib were not affected when co-administered with ramucirumab.

Erlotinib, ramucirumab [2] ---> SmPC of [2] of EMA

The pharmacokinetics of docetaxel or erlotinib were not affected when co-administered with ramucirumab.

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

There are no data on the effect of ramucirumab on human fertility. Female fertility is likely to be compromised during treatment with ramucirumab based on studies in animals (see section 5.3).

Irinotecan, ramucirumab [2] ---> SmPC of [2] of EMA

The pharmacokinetics of irinotecan and its active metabolite, SN-38, were not affected when co-administered with ramucirumab.

Paclitaxel, ramucirumab [2] ---> SmPC of [2] of EMA

The pharmacokinetics of paclitaxel were not affected when co-administered with ramucirumab and the pharmacokinetics of ramucirumab were not affected when co-administered with paclitaxel.

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

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

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

Women of childbearing potential should use effective contraception during and up to 3 months after the last dose of ramucirumab treatment.

CONTRAINDICATIONS of Ramucirumab (Cyramza)

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

- For patients with NSCLC, ramucirumab is contraindicated where there is tumour cavitation or tumour involvement of major vessels (see section 4.4).

https://www.ema.europa.eu/en/documents/product-information/cyramza-epar-product-information_en.pdf 16/01/2026

Ranibizumab (Lucentis)

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

The treatment procedure may induce temporary visual disturbances, which may affect the ability to drive or use machines (see section 4.8).

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

As a precautionary measure, breast-feeding is not recommended during the use of Lucentis.

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

There are no data available on fertility.

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

Should not be used during pregnancy unless the expected benefit outweighs the potential risk to the foetus

Ranibizumab [1], thiazolidinedione ---> SmPC of [1] of EMA

The outcome with regard to visual acuity or central retinal subfield thickness (CSFT) in patients treated with Lucentis was not affected by concomitant treatment with thiazolidinediones.

Ranibizumab [1], VEGF inhibitors ---> SmPC of [1] of EMA

Lucentis should not be administered concurrently with other anti-VEGF medicinal products (systemic or ocular).

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

Women of childbearing potential should use effective contraception during treatment.

CONTRAINDICATIONS of Ranibizumab (Lucentis)

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

- Patients with active or suspected ocular or periocular infections.

- Patients with active severe intraocular inflammation.

https://www.ema.europa.eu/en/documents/product-information/lucentis-epar-product-information_en.pdf 17/12/2025

Other trade names: Byooviz, Ranivisio, Epruvy (previously Ranibizumab Midas), Ranibizumab Midas, Rimmyrah, Ximluci,

Ranitidine

Abacavir/lamivudine [1], ranitidine ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Abacavir/lamivudine/zidovudine [1], ranitidine ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Ability to drive, ranitidine

Headaches, dizziness, fatigue, restlessness and confusional states and hallucinations may occur

Acetylprocainamide, ranitidine

May reduce the excretion of acetylprocainamide

Alcohol, ranitidine

Increased alcohol effect

Almasilate, ranitidine

Decreased absorption of ranitidine

Aluminium hydroxide, ranitidine

The aluminium hydroxide may decrease the absorption of ranitidine. Separate administration by at least 2 hours

Aminophylline, ranitidine

Ranitidine reduces clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Antacids, ranitidine

Decreased ranitidine absorption. Take ranitidine 2 hours before antacid

Atenolol/nifedipine, ranitidine

Enhanced hypotensive effect

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

Ranitidine is excreted in human breast milk and women who are breast feeding will be advised to speak to their doctor

Calcium antagonists, ranitidine

Ranitidine can increase the calcium antagonist plasma level

Clarithromycin, ranitidine

The co-administration may increase the plasma levels of clarithromycin

Coumarin anticoagulants [1], ranitidine ---> SmPC of [1] of eMC

There have been reports of altered prothrombin time with coumarin anticoagulants. Due to the narrow therapeutic index, close monitoring of increased or decreased prothrombin time is recommended during concurrent treatment with ranitidine.

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

Care should be taken when using ciclosporin together with other active substances that exhibit nephrotoxic synergy

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

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

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

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

Darunavir/cobicistat [1], ranitidine ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. Darunavir/cobicistat can be co-administered with H2-receptor antagonists without dose adjustments.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], ranitidine ---> SmPC of [1] of EMA

Based on theoretical considerations, no mechanistic interaction is expected. Symtuza can be co-administered with H2-receptor antagonists without dose adjustments.

Darunavir/ritonavir, ranitidine ---> SmPC of [darunavir] of EMA

Darunavir co-administered with low dose ritonavir can be co-administered with H2-receptor antagonists without dose adjustments.

Delavirdine, ranitidine

Decrease in absorption of delavirdine

Didanosine, ranitidine

No dosage adjustment necessary.

Diltiazem [1], ranitidine ---> SmPC of [1] of eMC

Increase in plasma diltiazem concentrations. Patients currently receiving diltiazem therapy should be carefully monitored when initiating or discontinuing therapy with H2 antagonists. An adjustment in diltiazem daily dose may be necessary.

Dolutegravir/abacavir/lamivudine [1], ranitidine ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Dolutegravir/rilpivirine [1], ranitidine ---> SmPC of [1] of EMA

Only H2-receptor antagonists that can be dosed once daily should be used. H2-receptor antagonists should be taken well separated in time from the administration of Juluca (minimum 4 hours after or 12 hours before)

Eliglustat [1], ranitidine ---> SmPC of [1] of EMA

Caution should be used with weak CYP3A inhibitors in poor metabolisers.

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

Co-administration may cause significant decreases in rilpivirine plasma concentrations (reduced absorption, increase in gastric pH).

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

The increase of gastric pH decreases absorption, plasma level and effect of rilpivirine. The H2 antagonist should be administered at least 12 h before or 4 h after rilpivirine

Enoxacin, ranitidine

Decreased absorption of enoxacin. Separate administration at least 4 hours

Erlotinib [1], ranitidine ---> SmPC of [1] of EMA

Erlotinib is characterised by a decrease in solubility at pH above 5. Medicinal products that alter the pH of the upper Gastro-Intestinal (GI) tract may alter the solubility of erlotinib and hence its bioavailability.

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

Etravirine can be co-administered with H2-receptor antagonists without dose adjustments.

Fluvastatin [1], ranitidine ---> SmPC of [1] of eMC

Concomitant administration of fluvastatin with ranitidine results in an increase in the bioavailability of fluvastatin, which, however, is of no clinical relevance.

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

The increase in gastric pH decreases the fosamprenavir absorption. No dosage adjustment necessary

Glipizide, ranitidine

The co-administration may increase the plasma levels of glipizide and enhance its hypoglycemic effect

Ibandronic acid [1], ranitidine ---> SmPC of [1] of EMA

Intravenous ranitidine causes an increase in ibandronic acid bioavailability. No dosage adjustment is required when is administered with H2-antagonists

Ketoconazole, ranitidine

Decreased absorption of ketoconazole. Separate administration by at least 2 hours

Lamivudine/zidovudine [1], ranitidine ---> SmPC of [1] of EMA

No dosage adjustment necessary.

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

H2-receptor antagonists may be administered simultaneously with or staggered from ledipasvir/sofosbuvir at a dose that does not exceed doses comparable to famotidine 40 mg twice daily

Levofloxacin [1], ranitidine ---> SmPC of [1] of EMA

Clinical pharmacology studies have shown that the pharmacokinetics of levofloxacin were not affected to any clinically relevant extent when levofloxacin was administered together with ranitidine

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

No dosage adjustment necessary.

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

Dose adjustment of ranitidine may be required to obtain the desired clinical effect. Lumacaftor/ivacaftor may alter the exposure of ranitidine. Due to potential induction or inhibition of P-gp

Memantin [1], ranitidine ---> SmPC of [1] of EMA

Active substances that use the same renal cationic transport system as amantadine may possibly interact with memantine leading to a potential risk of increased plasma levels.

Midazolam [1], ranitidine ---> SmPC of [1] of EMA

Cimetidine, ranitidine and omeprazole have been shown to reduce the clearance of midazolam and other benzodiazepines and may potentiate their actions.

N-acetylprocainamide, ranitidine

May reduce the excretion of N-acetylprocainamide

Nebivolol [1], ranitidine ---> SmPC of [1] of eMC

Co-administration of ranitidine did not affect the pharmacokinetics of nebivolol.

Nitrendipine, ranitidine

The CYP3A4 inhibition may increase the plasma levels of nitrendipine

Oxetacaine, ranitidine

Decreased absorption of ranitidine

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

Co-administration of posaconazole with H2 receptor antagonists or with proton pump inhibitors should be avoided if possible.

Pramipexole, ranitidine

Decreased pramipexole clearance. Reduction of the pramipexole dose should be considered

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

Ranitidine should not be taken during pregnancy without consulting a doctor.

Procainamide, ranitidine

Reduced excretion of procainamide

Ranitidine, rilpivirine [2] ---> SmPC of [2] of EMA

The increase of gastric pH decreases absorption, plasma level and effect of rilpivirine. The H2 antagonist should be administered at least 12 h before or 4 h after rilpivirine

Ranitidine, risperidone [2] ---> SmPC of [2] of eMC

Ranitidine increased the bioavailability of risperidone, but only marginally that of the active antipsychotic fraction.

Ranitidine, ritonavir [2] ---> SmPC of [2] of EMA

Concurrent administration of omeprazole or ranitidine does not significantly modify ritonavir efficacy as a pharmacokinetic enhancer despite a slight change of exposure (about 6 - 18%).

Ranitidine, saquinavir [2] ---> SmPC of [2] of EMA

Increased saquinavir AUC. Increase not thought to be clinically relevant. No dose adjustment of saquinavir recommended.

Ranitidine, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required

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

Increase in gastric pH. H2-receptor antagonists may be administered simultaneously with or staggered from Epclusa at a dose that does not exceed doses comparable to famotidine 40 mg twice daily.

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

Increase in gastric pH decreases velpatasvir solubility. H2-receptor antagonists may be administered simultaneously with or staggered from Vosevi at a dose that does not exceed doses comparable with famotidine 40 mg twice daily.

Ranitidine, sucralfate

Concomitant administration of sucralfate may reduce the bioavailability of ranitidine. The bioavailability may be restored by separating the administration from sucralfate by 2 hours.

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.

Ranitidine, theophylline

Ranitidine reduces clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Ranitidine, tolbutamide [2] ---> SmPC of [2] of eMC

Increased hypoglycaemic effects have occurred or might be expected

Ranitidine, triazolam

Increased absorption of triazolam

Ranitidine, vandetanib [2] ---> SmPC of [2] of EMA

No change in dose of vandetanib is required when vandetanib is given with either ranitidine.

Ranitidine, vardenafil [2] ---> SmPC of [2] of EMA

The pharmacokinetics of vardenafil (20 mg) was not affected by co-administration with the H2-antagonist ranitidine

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

CONTRAINDICATIONS of Ranitidine

- Ranitidine is contraindicated for patients known to be hypersensitive to the drug or any of the ingredients

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

Ranolazine (Ranexa)

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

Ranexa may cause dizziness, blurred vision, diplopia, confusional state, coordination abnormal, hallucination (see section 4.8), which may affect the ability to drive and use machines.

Amitriptyline, ranolazine [2] ---> SmPC of [2] of EMA

There is a theoretical risk that concomitant treatment of ranolazine with other drugs known to prolong the QTc interval may give rise to a pharmacodynamic interaction and increase the possible risk of ventricular arrhythmias.

Astemizole, ranolazine [2] ---> SmPC of [2] of EMA

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

Ranolazine increased Cmax and AUC of atorvastatin. Dose limitation of atorvastatin and appropriate clinical monitoring may be considered when taking ranolazine.

Azithromycin, ranolazine

The simultaneous use is contraindicated.

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

Ranexa should not be used during breast-feeding.

Bupropion, ranolazine [2] ---> SmPC of [2] of EMA

The potential for inhibition of CYP2B6 has not been evaluated. Caution is advised during co-administration with CYP2B6 substrates

Cabozantinib [1], ranolazine ---> 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.

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

Rifampicin (600 mg once daily) decreases ranolazine steady-state concentrations by approximately 95%. Initiation of treatment with Ranexa should be avoided during administration of inducers of CYP3A4

Cerivastatin, ranolazine [2] ---> SmPC of [2] of EMA

Dose limitation of other statins, metabolised by CYP3A4, may be considered when taking ranolazine.

Clarithromycin, ranolazine [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

Class IA antiarrhythmic agents, ranolazine [2] ---> SmPC of [2] of EMA

Concomitant administration of class Ia antiarrhythmics with ranolazine is contraindicated

Class III antiarrhythmic agents, ranolazine [2] ---> SmPC of [2] of EMA

Concomitant administration of class III antiarrhythmics (other than amiodarone) with ranolazine is contraindicated

Cyclophosphamide, ranolazine [2] ---> SmPC of [2] of EMA

The potential for inhibition of CYP2B6 has not been evaluated. Caution is advised during co-administration with CYP2B6 substrates

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

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

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

The CYP3A4 induction may decrease the plasma levels of ranolazine. During the treatment with CYP3A4 inductors should not be initiated a therapy with ranolazine

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

Ranolazine is a moderate to potent inhibitor of P-gp and a mild inhibitor of CYP3A4, and may increase plasma concentrations of P-gp or CYP3A4 substrates. Tissue distribution of drugs which are transported by P-gp may be increased.

Darunavir/cobicistat [1], ranolazine ---> 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], ranolazine ---> SmPC of [1] of EMA

Co-administration is contraindicated due to the potential for serious and/or life-threatening adverse reactions

Darunavir/ritonavir, ranolazine ---> SmPC of [darunavir] of EMA

Co-administration of darunavir boosted with ritonavir, with active substances that are highly dependent on CYP3A for clearance and for which elevated plasma levels are associated with serious and/or life-threatening events is contraindicated

Digoxin, ranolazine [2] ---> SmPC of [2] of EMA

An increase in plasma digoxin concentrations by an average of 1.5-fold has been reported when Ranexa and digoxin are co-administered. Therefore, digoxin levels should be monitored following initiation and termination of Ranexa therapy.

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

Careful dose titration of ranolazine is recommended in patients treated with moderately potent CYP3A4 inhibitors. Down-titration of ranolazine may be required

Disopyramide, ranolazine [2] ---> SmPC of [2] of EMA

Dofetilide, ranolazine [2] ---> SmPC of [2] of EMA

Concomitant administration of class III antiarrhythmics (other than amiodarone) with ranolazine is contraindicated

Doxepin, ranolazine [2] ---> SmPC of [2] of EMA

Drugs metabolised by CYP2B6, ranolazine [2] ---> SmPC of [2] of EMA

The potential for inhibition of CYP2B6 has not been evaluated. Caution is advised during co-administration with CYP2B6 substrates

Drugs metabolised by CYP2D6, ranolazine [2] ---> SmPC of [2] of EMA

Ranolazine is partially metabolised by CYP2D6; therefore, inhibitors of this enzyme may increase plasma concentrations of ranolazine.

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

Ranolazine is a mild inhibitor of CYP3A4, and may increase plasma concentrations of CYP3A4 substrates.

Drugs primarily metabolised by CYP2B6, ranolazine [2] ---> SmPC of [2] of EMA

The potential for inhibition of CYP2B6 has not been evaluated. Caution is advised during co-administration with CYP2B6 substrates

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, ranolazine [2] ---> SmPC of [2] of EMA

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

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

Ranolazine is a mild inhibitor of CYP3A4, and may increase plasma concentrations of CYP3A4 substrates.

Efavirenz, ranolazine [2] ---> SmPC of [2] of EMA

The potential for inhibition of CYP2B6 has not been evaluated. Caution is advised during co-administration with CYP2B6 substrates

Eliglustat [1], ranolazine ---> SmPC of [1] of EMA

Caution should be used with weak CYP3A inhibitors in poor metabolisers.

Empagliflozin/metformin [1], ranolazine ---> SmPC of [1] of EMA

Co-administration of metformin with Inhibitors of OCT2 may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration.

Ertugliflozin/metformin [1], ranolazine ---> SmPC of [1] of EMA

Inhibitors of OCT2 may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration.

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

Careful dose titration of Ranexa is recommended in patients treated with diltiazem and other moderately potent CYP3A4 inhibitors (e.g. erythromycin, fluconazole). Down-titration of Ranexa may be required (see sections 4.2 and 4.4).

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

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

Flecainide, ranolazine [2] ---> SmPC of [2] of EMA

Therefore the exposure to metoprolol or other CYP2D6 substrates (e.g. propafenone and flecainide) may be increased during co-administration with Ranexa, and lower doses of these medicinal products may be required.

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

Grapefruit juice, ranolazine [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

Haloperidol, ranolazine

The CYP2D6 inhibition may increase the plasma concentrations of haloperidol

Imipramine, ranolazine [2] ---> SmPC of [2] of EMA

Irinotecan, ranolazine

Ranolazine, P-glycoprotein and CYP3A4 inhibitor, may increase the plasma concentrations of irinotecan

Itraconazol, ranolazine [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

Ketoconazole, ranolazine [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

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

Caution is advised if P-gp/BCRP inhibitors are added to letermovir combined with cyclosporine.

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

Due to CYP3A inhibition by lopinavir/ritonavir, concentrations of ranolazine are expected to increase. The concomitant administration of Kaletra and ranolazine is contraindicated (see section 4.3).

Lovastatine, ranolazine [2] ---> SmPC of [2] of EMA

Dose limitation of other statins, metabolised by CYP3A4 (e.g. lovastatin), may be considered when taking ranolazine.

Metformin, ranolazine [2] ---> SmPC of [2] of EMA

Plasma exposure of metformin (1000 mg twice daily) increased 1.4- and 1.8-fold in subjects with type 2 diabetes mellitus when coadministered with RANEXA 500 mg and 1000 mg twice daily respectively.

Metformin/saxagliptin/dapagliflozin [1], ranolazine ---> SmPC of [1] of EMA

Co-administration of metformin with inhibitors of OCT2 may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration;

Metoprolol, ranolazine [2] ---> SmPC of [2] of EMA

Miconazole, ranolazine

Oral miconazole is contraindicated with medicinal products that are metabolised by CYP3A4 and may prolong also the QT interval

Mizolastine, ranolazine [2] ---> SmPC of [2] of EMA

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

Nefazodone, ranolazine [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

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

Due to CYP3A inhibition by ritonavir, concentrations of ranolazine are expected to increase. The concomitant administration with ranolazine is contraindicated

Noxiptiline, ranolazine

The CYP2D6 inhibition may increase the plasma concentrations of noxiptiline

OCT2 substrates, ranolazine [2] ---> SmPC of [2] of EMA

Plasma exposure of metformin (1000 mg twice daily) increased 1.4- and 1.8-fold in subjects with type 2 diabetes mellitus when coadministered with RANEXA 500 mg and 1000 mg twice daily respectively.

Olanzapine, ranolazine

The CYP2D6 inhibition may increase the plasma concentrations of olanzapine

P-glycoprotein substrates, ranolazine [2] ---> SmPC of [2] of EMA

Ranolazine is a moderate to potent inhibitor of P-gp, and may increase plasma concentrations of P-gp substrates. Tissue distribution of drugs which are transported by P-gp may be increased.

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

Ranolazine is a substrate for P-gp. Inhibitors of P-gp (e.g. ciclosporin, verapamil) increase plasma levels of ranolazine. Careful dose titration of Ranexa is recommended in patients treated with P-gp inhibitors. Down-titration of Ranexa may be required

Paroxetine, ranolazine [2] ---> SmPC of [2] of EMA

Ranolazine is partially metabolised by CYP2D6; therefore, inhibitors of this enzyme may increase plasma concentrations of ranolazine. No dosage adjustment necessary.

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

Rifampicin (600 mg once daily) decreases ranolazine steady-state concentrations by approximately 95%. Initiation of treatment with Ranexa should be avoided during administration of inducers of CYP3A4

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

Rifampicin (600 mg once daily) decreases ranolazine steady-state concentrations by approximately 95%. Initiation of treatment with Ranexa should be avoided during administration of inducers of CYP3A4

Pimozide, ranolazine

The CYP2D6 inhibition may increase the plasma concentrations of pimozide and enhance the risk of QT-prolongation. The combination is contraindicated

Pindolol, ranolazine [2] ---> SmPC of [2] of EMA

Plasma exposure of metformin (1000 mg twice daily) increased 1.4- and 1.8-fold in subjects with type 2 diabetes mellitus when coadministered with RANEXA 500 mg and 1000 mg twice daily respectively.

Posaconazole, ranolazine [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

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

Ranexa should not be used during pregnancy unless clearly necessary.

Procainamide, ranolazine [2] ---> SmPC of [2] of EMA

Propafenone, ranolazine [2] ---> SmPC of [2] of EMA

Protease inhibitors, ranolazine [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

Protriptyline, ranolazine [2] ---> SmPC of [2] of EMA

Available data suggest that ranolazine is a mild inhibitor of CYP2D6. Therefore the exposure to CYP2D6 substrates may be increased during co-administration with ranolazine, and lower doses of these medicinal products may be required.

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

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

Ranolazine, P-glycoprotein and CYP3A4 inhibitor, may increase the plasma concentrations of quinidine. Increased risk of QT interval prolongation

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

Rifampicin (600 mg once daily) decreases ranolazine steady-state concentrations by approximately 95%. Initiation of treatment with Ranexa should be avoided during administration of inducers of CYP3A4

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

Simvastatin metabolism and clearance are highly dependent on CYP3A4. Ranolazine increased simvastatin plasma levels by about 2 fold. Cases of rhabdomyolysis have been observed in patients receiving ranolazine and simvastatin, in postmarketing experience.

Ranolazine [1], sirolimus ---> 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.

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

Concomitant administration of class III antiarrhythmics (other than amiodarone) with ranolazine is contraindicated

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

Rifampicin (600 mg once daily) decreases ranolazine steady-state concentrations by approximately 95%. Initiation of treatment with Ranexa should be avoided during administration of inducers of CYP3A4

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

Dose limitation of other statins, metabolised by CYP3A4 (e.g. lovastatin), may be considered when taking Ranexa.

Ranolazine [1], strong CYP2D6 inhibitors ---> SmPC of [1] of EMA

At the dose level 500 mg twice daily, co-administration of a potent inhibitor of CYP2D6 could result in an increase in ranolazine AUC of about 62%.

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

Rifampicin (600 mg once daily) decreases ranolazine steady-state concentrations by approximately 95%. Initiation of treatment with Ranexa should be avoided during administration of inducers of CYP3A4

Ranolazine [1], strong CYP3A4 inhibitors ---> SmPC of [1] 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

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

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.

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

Ranolazine [1], tissue distribution ---> SmPC of [1] of EMA

Tissue distribution of drugs which are transported by P-gp may be increased.

Ranolazine [1], tricyclic antidepressant ---> SmPC of [1] of EMA

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

Plasma exposure of metformin (1000 mg twice daily) increased 1.4- and 1.8-fold in subjects with type 2 diabetes mellitus when coadministered with RANEXA 500 mg and 1000 mg twice daily respectively.

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

Ranolazine, ritonavir [2] ---> SmPC of [2] of EMA

Increased plasma concentrations of ranolazine which may increase the potential for serious and/or life-threatening reactions

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).

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

Ranolazine, 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.

Ranolazine, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Concomitant use of medicinal products that interfere with common renal tubular transport systems involved in the renal elimination of metformin could increase systemic exposure to metformin.

Ranolazine, voriconazole [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

CONTRAINDICATIONS of Ranolazine (Ranexa)

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

- Severe renal impairment (creatinine clearance < 30 ml/min)

- Moderate or severe hepatic impairment

- Concomitant administration of potent CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, voriconazole, posaconazole, HIV protease inhibitors, clarithromycin, telithromycin, nefazodone)

- Concomitant administration of Class Ia (e.g. quinidine) or Class III (e.g. dofetilide, sotalol) antiarrhythmics other than amiodarone.

https://www.ema.europa.eu/en/documents/product-information/ranexa-epar-product-information_en.pdf 11/08/2022

Other trade names: Ranexa (previously Latixa),

Rasagiline (Azilect)

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

Patients should be cautioned about operating hazardous machines, including motor vehicles, until they are reasonably certain that rasagiline does not affect them adversely.

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

Caution should be exercised when rasagiline is administered to a breast-feeding mother

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

Co-administration of rasagiline and ciprofloxacin (an inhibitor of CYP1A2) increased the AUC of rasagiline by 83%.

CYP1A2 inductors, rasagiline [2] ---> SmPC of [2] of EMA

There is a risk that the plasma levels of rasagiline in smoking patients could be decreased, due to induction of the metabolising enzyme CYP1A2.

Dextromethorphan, rasagiline [2] ---> SmPC of [2] of EMA

In view of the MAO inhibitory activity of rasagiline, the concomitant administration of rasagiline and dextromethorphan is not recommended

Dopamine agonists, rasagiline [2] ---> SmPC of [2] of EMA

Rasagiline may cause daytime drowsiness, somnolence, and, occasionally, especially if used with other dopaminergic medicinal products -falling asleep during activities of daily living.

Dopaminergic drugs, rasagiline [2] ---> SmPC of [2] of EMA

Rasagiline may cause daytime drowsiness, somnolence, and, occasionally, especially if used with other dopaminergic medicinal products -falling asleep during activities of daily living.

Entacapone, rasagiline [2] ---> SmPC of [2] of EMA

Concomitant administration of rasagiline and entacapone increased rasagiline oral clearance by 28%.

Ephedrine, rasagiline [2] ---> SmPC of [2] of EMA

In view of the MAO inhibitory activity of rasagiline, co-administration of rasagiline and sympathomimetics such as those present in nasal and oral decongestants or cold medicinal products, containing ephedrine or pseudoephedrine, is not recommended

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

No human data on the effect of rasagiline on fertility are available. Non-clinical data indicate that rasagiline has no effect on fertility.

Fluoxetine, rasagiline [2] ---> SmPC of [2] of EMA

At least 5 weeks should elapse between discontinuation of fluoxetine and initiation of treatment with rasagiline. At least 14 days should elapse between discontinuation of rasagiline and initiation of treatment with fluoxetine or fluvoxamine.

Fluvoxamine, rasagiline [2] ---> SmPC of [2] of EMA

IMAOs, pethidine ---> SmPC of [rasagiline] of EMA

Serious adverse reactions have been reported with the concomitant use of pethidine and MAO inhibitors including another selective MAO-B inhibitor. The concomitant administration of rasagiline and pethidine is contraindicated

IMAOs, rasagiline [2] ---> SmPC of [2] of EMA

Rasagiline is contraindicated along with other MAO inhibitors (including medicinal and natural products without prescription e.g. St. John's Wort) as there may be a risk of non-selective MAO inhibition that may lead to hypertensive crises

Levodopa [1], rasagiline ---> SmPC of [1] of EMA

The use of selective MAO-B inhibitors (e.g. rasagiline, selegiline, and safinamide) with levodopa may be associated with orthostatic hypotension. Patients who are taking these medicinal products should be monitored closely.

Levodopa, rasagiline [2] ---> SmPC of [2] of EMA

Bei Parkinson-Patienten unter Rasagilin als Zusatztherapie zu einer chronischen Levodopa-Behandlung hatte die Levodopa-Behandlung keine klinisch bedeutsame Wirkung auf die Clearance von Rasagilin.

Levodopa/benserazide [1], rasagiline ---> SmPC of [1] of eMC

It should not be given in conjunction with, or within 2 weeks of withdrawal of, monoamine oxidase (MAO) inhibitors, except selective MAO-B inhibitors (e.g. selegiline) or selective MAO-A inhibitors (e.g. moclobemide)

Levodopa/carbidopa [1], rasagiline ---> SmPC of [1] of EMA

Numient can be taken concomitantly with the recommended dose of an MAO inhibitor, which is selective for MAO inhibitor type B such as selegiline and rasagiline.

Nasal decongestants, rasagiline [2] ---> SmPC of [2] of EMA

With MAO inhibitors there have been reports of interactions with the concomitant use of sympathomimetic m. In view of the MAO inhibitory activity of rasagiline, concomitant administration of rasagiline and sympathomimetics is not recommended

Nicotine, rasagiline [2] ---> SmPC of [2] of EMA

There is a risk that the plasma levels of rasagiline in smoking patients could be decreased, due to induction of the metabolising enzyme CYP1A2.

Non-selective monoamine reuptake inhibitor, rasagiline

Serious adverse reactions have been reported with the concomitant use

Opicapone [1], rasagiline ---> SmPC of [1] of EMA

Concomitant use of opicapone and MAO inhibitors for the treatment of Parkinson's disease, e.g. rasagiline (up to 1 mg/day) and selegiline (up to 10 mg/day in oral formulation or 1.25 mg/day in buccal absorption formulation), is permissible

Pethidine, rasagiline [2] ---> SmPC of [2] of EMA

Concomitant treatment of rasagiline with pethidine is contraindicated. At least 14 days must elapse between discontinuation of rasagiline and initiation of treatment with pethidine (risk of hypertensive crises)

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

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

Pseudoephedrine, rasagiline [2] ---> SmPC of [2] of EMA

Rasagiline [1], SSNRI ---> SmPC of [1] of EMA

Serious adverse reactions have been reported with the concomitant use of SSRIs, SNRIs, tricyclic/tetracyclic antidepressants and MAO inhibitors. Iin view of the MAO inhibitory activity of rasagiline, antidepressants should be administered with caution.

Rasagiline [1], SSRI ---> SmPC of [1] of EMA

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

Rasagiline [1], strong CYP1A2 inhibitors ---> SmPC of [1] of EMA

Thus, potent CYP1A2 inhibitors may alter rasagiline plasma levels and should be administered with caution.

Rasagiline [1], sympathomimetics ---> SmPC of [1] of EMA

Rasagiline [1], tetracyclic antidepressant ---> SmPC of [1] of EMA

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

Co-administration of rasagiline and theophylline (a substrate of CYP1A2) did not affect the pharmacokinetics of either product.

Rasagiline [1], tricyclic antidepressant ---> SmPC of [1] of EMA

Rasagiline [1], tyramine ---> SmPC of [1] of EMA

Rasagiline can be used safely without dietary tyramine restrictions.

Rasagiline, vortioxetine [2] ---> SmPC of [2] of EMA

The combination of vortioxetine with irreversible MAO-B inhibitors, such as selegiline or rasagiline should be administered with caution. Close monitoring for serotonin syndrome is necessary if used concomitantly (see section 4.4).

Rasagiline, zolmitriptan [2] ---> SmPC of [2] of eMC

The MAO inhibition may increase the serum concentration of zolmitriptan.

CONTRAINDICATIONS of Rasagiline (Azilect)

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

- Concomitant treatment with other monoamine oxidase (MAO) inhibitors (including medicinal and natural products without prescription e.g. St. John's Wort) or pethidine. At least 14 days must elapse between discontinuation of rasagiline and initiation of treatment with MAO inhibitors or pethidine.

- Severe hepatic impairment.

https://www.ema.europa.eu/en/documents/product-information/azilect-epar-product-information_en.pdf 18/08/2023

Other trade names: Rasagiline Mylan, Rasagiline ratiopharm,

Rasburicase (Fasturtec)

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

During treatment with Fasturtec, the advantage of breastfeeding should be weighted against the potential risk for the infant.

Enzyme, rasburicase [2] ---> SmPC of [2] of EMA

Rasburicase being an enzyme itself, it would be an unlikely candidate for drug-drug interactions.

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

There are no data regarding the effect of rasburicase on fertility.

Hemolysis, rasburicase [2] ---> SmPC of [2] of EMA

Haemolysis has been reported in patients receiving rasburicase. In such case, treatment should immediately and permanently be discontinued and appropriate measures initiated

Local anaesthetics, rasburicase ---> SmPC of [liposomal bupivacaine] of EMA

Patients that are administered local anaesthetics may be at increased risk of developing methaemoglobinamia when concurrently exposed to these oxidizing medicinal products

Methemoglobinemia, rasburicase [2] ---> SmPC of [2] of EMA

Methaemoglobinaemia has been reported in patients receiving rasburicase. Rasburicase should immediately and permanently be discontinued in patients having developed methaemoglobinaemia, and appropriate measures initiated

Nitrofurantoin, rasburicase

Organic nitrates, rasburicase

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

Because teratogenic effects of rasburicase cannot be ruled out, Fasturtec should only be used during pregnancy if strictly necessary.

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

Fasturtec is not recommended in women of childbearing potential not using contraception.

Rasburicase, sulphamides

CONTRAINDICATIONS of Rasburicase (Fasturtec)

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

- G6PD deficiency and other cellular metabolic disorders known to cause haemolytic anaemia.

- Hydrogen peroxide is a by-product of the conversion of uric acid to allantoin.

- In order to prevent possible haemolytic anaemia induced by hydrogen peroxide, rasburicase is contraindicated in patients with these disorders.

https://www.ema.europa.eu/en/documents/product-information/fasturtec-epar-product-information_en.pdf 12/08/2024

Ravulizumab (Ultomiris)

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

Since many medicinal products and immunoglobulins are secreted into human milk, breast-feeding should be discontinued during treatment with ravulizumab and up to 8 months after treatment.

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

Nonclinical reproductive toxicology studies conducted in mice with a murine surrogate molecule (BB5.1) identified no adverse effect on fertility of the treated females or males.

Immunoglobulins, ravulizumab [2] ---> SmPC of [2] of EMA

Chronic intravenous human immunoglobulin (IVIg) treatment may interfere with the endosomal neonatal Fc receptor (FcRn) recycling mechanism of monoclonal antibodies such as ravulizumab and thereby decrease serum ravulizumab concentrations.

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

In pregnant women the use of ravulizumab may be considered following an assessment of the risks and benefits.

Ravulizumab [1], rituximab ---> SmPC of [1] of EMA

Based on the potential inhibitory effect of ravulizumab on complement-dependent cytotoxicity of rituximab, ravulizumab may reduce the expected pharmacodynamic effects of rituximab.

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

Women of childbearing potential should use effective contraception methods during treatment and up to 8 months after treatment.

CONTRAINDICATIONS of Ravulizumab (Ultomiris)

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

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

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

https://www.ema.europa.eu/en/documents/product-information/ultomiris-epar-product-information_en.pdf 22/10/2025

Reboxetine

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

Any psychoactive drug can impair judgement or skills.

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

Reboxetine does not appear to potentiate the effect of alcohol on cognitive functions in healthy volunteers.

Amitriptyline, reboxetine

Concomitant use should be with caution.

Antidepressants, reboxetine [2] ---> SmPC of [2] of eMC

Concomitant use of reboxetine with other antidepressants (tricyclics, MAO inhibitors, SSRIs and lithium) has not been evaluated during clinical trials.

Azole antifungals, reboxetine [2] ---> SmPC of [2] of eMC

The CYP3A4 inhibition may increase the plasma levels of reboxetine (narrow therapeutic margin and primarily metabolised by the CYP3A4). Reboxetine should not be given together with drugs known to inhibit CYP3A4

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

Reboxetine is known to be excreted in breast milk. The use of reboxetine during breastfeeding can be considered if the potential benefits outweigh the risk for the child.

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

Low reboxetine serum levels have been reported with the concurrent administration of CYP3A4 inducers

CYP3A4 inductors, reboxetine [2] ---> SmPC of [2] of eMC

Low reboxetine serum levels have been reported with the concurrent administration of CYP3A4 inducers

CYP3A4 inhibitors, reboxetine [2] ---> SmPC of [2] of eMC

Ergot derivatives, reboxetine [2] ---> SmPC of [2] of eMC

Concomitant use of ergot derivatives and reboxetine might result in increased blood pressure.

Erythromycin, reboxetine [2] ---> SmPC of [2] of eMC

Fluoxetine, reboxetine [2] ---> SmPC of [2] of eMC

In an in vivo study performed in healthy volunteers, no clinically significant interaction between fluoxetine and reboxetine was observed. In patients, a different effect and safety profile upon combination of reboxetine and fluoxetine cannot be excluded

Fluvoxamine, reboxetine [2] ---> SmPC of [2] of eMC

Foods, reboxetine [2] ---> SmPC of [2] of eMC

Food intake delayed the absorption of reboxetine, but did not significantly influence the extent of absorption.

IMAOs, reboxetine [2] ---> SmPC of [2] of eMC

Concomitant use of MAO-inhibitors and reboxetine should be avoided in view of the potential risk (tyramine-like effect) based on their mechanisms of action.

Kaliuretic medicines, reboxetine [2] ---> SmPC of [2] of eMC

The possibility of hypokalaemia with concomitant use of potassium losing diuretics should be considered.

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

Not recommended because of reboxetine narrow's therapeutic margin.

Loop diuretics, reboxetine [2] ---> SmPC of [2] of eMC

The possibility of hypokalaemia with concomitant use of potassium losing diuretics should be considered.

Lorazepam, reboxetine [2] ---> SmPC of [2] of eMC

During their co-administration in healthy volunteers, mild to moderate drowsiness and short lasting orthostatic acceleration of heart rate have been observed.

Macrolide antibiotics, reboxetine [2] ---> SmPC of [2] of eMC

Miconazole, reboxetine

Oral miconazole is contraindicated with medicinal products that are metabolised by CYP3A4 and may prolong also the QT interval

Nefazodone, reboxetine [2] ---> SmPC of [2] of eMC

Phenobarbital, reboxetine [2] ---> SmPC of [2] of eMC

Low reboxetine serum levels have been reported with the concurrent administration of CYP3A4 inducers

Phenytoin, reboxetine [2] ---> SmPC of [2] of eMC

Low reboxetine serum levels have been reported with the concurrent administration of CYP3A4 inducers

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

Reboxetine should only be used in pregnancy if the potential benefits of treatment to the mother outweigh the possible risks to the developing foetus.

Reboxetine [1], rifampicin ---> SmPC of [1] of eMC

Low reboxetine serum levels have been reported with the concurrent administration of CYP3A4 inducers

Reboxetine [1], St. John's wort ---> SmPC of [1] of eMC

Low reboxetine serum levels have been reported with the concurrent administration of CYP3A4 inducers

Reboxetine [1], strong CYP3A4 inductors ---> SmPC of [1] of eMC

Low reboxetine serum levels have been reported with the concurrent administration of CYP3A4 inducers

Reboxetine [1], strong CYP3A4 inhibitors ---> SmPC of [1] of eMC

Reboxetine [1], thiazides ---> SmPC of [1] of eMC

The possibility of hypokalaemia with concomitant use of potassium losing diuretics should be considered.

CONTRAINDICATIONS of Reboxetine

- Known hypersensitivity to reboxetine or any of the components of the product.

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

Regadenoson (Rapiscan)

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

Regadenoson administration may result in adverse reactions such as dizziness, headache, and dyspnoea (see section 4.8) soon after administration.

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

In clinical studies, regadenoson was administered to patients taking other cardioactive medicinal products without apparent effects on the safety or efficacy profile of regadenoson.

Adenosine antagonists, regadenoson [2] ---> SmPC of [2] of EMA

The adenosine receptor antagonist may interfere with the vasodilation activity of regadenoson. Avoid consumption for at least 12 hours before regadenoson administration

Aminophylline, regadenoson [2] ---> SmPC of [2] of EMA

Aminophylline shorts the duration of the coronary blood flow response to regadenoson. Aminophylline is used to attenuate adverse reactions to regadenoson

ARB, regadenoson [2] ---> SmPC of [2] of EMA

In clinical studies, regadenoson was administered to patients taking other cardioactive medicinal products without apparent effects on the safety or efficacy profile of regadenoson.

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

In clinical studies, regadenoson was administered to patients taking other cardioactive medicinal products without apparent effects on the safety or efficacy profile of regadenoson.

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

If regadenoson is administered, the woman should not breast-feed for at least 10 hours (that is, at least 5 times the plasma elimination half-life) following regadenoson administration.

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

A decision should be made whether to discontinue breastfeeding or to abstain from regadenoson administration taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Bronchodilatators, regadenoson [2] ---> SmPC of [2] of EMA

Appropriate bronchodilator therapy and resuscitative measures should be available prior to regadenoson administration.

Caffeine, regadenoson [2] ---> SmPC of [2] of EMA

Methylxanthines are non-specific adenosine receptor antagonists and may interfere with the vasodilation activity of regadenoson.

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

In clinical studies, regadenoson was administered to patients taking other cardioactive medicinal products without apparent effects on the safety or efficacy profile of regadenoson.

Cardiac glycosides, regadenoson [2] ---> SmPC of [2] of EMA

In clinical studies, regadenoson was administered to patients taking other cardioactive medicinal products without apparent effects on the safety or efficacy profile of regadenoson.

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

Regadenoson does not inhibit the metabolism of substrates for CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 in human liver microsomes, indicating that it is unlikely to alter the PKs of medicinal products metabolised by these cytochrome P450 enzymes

Dipyridamole, regadenoson [2] ---> SmPC of [2] of EMA

Dipyridamole increases blood adenosine levels and the response to regadenoson may be altered when blood adenosine levels are increased. When possible, dipyridamole should be withheld for at least 2 days prior to regadenoson administration

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

Fertility studies with regadenoson have not been performed (see section 5.3).

Nitrates, regadenoson [2] ---> SmPC of [2] of EMA

In clinical studies, regadenoson was administered to patients taking other cardioactive medicinal products without apparent effects on the safety or efficacy profile of regadenoson.

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

Regadenoson should not be used during pregnancy unless clearly necessary.

Regadenoson [1], seizure-threshold lowering drugs ---> 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

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

Methylxanthines are non-specific adenosine receptor antagonists and may interfere with the vasodilation activity of regadenoson.

Regadenoson [1], tramadol ---> SmPC of [1] of EMA

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

However, given the proposed duration of use, the effects of the drug transporters are unlikely to be clinically relevant.

Regadenoson [1], xanthines ---> SmPC of [1] of EMA

Methylxanthines are non-specific adenosine receptor antagonists and may interfere with the vasodilation activity of regadenoson.

CONTRAINDICATIONS of Regadenoson (Rapiscan)

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

- Second or third degree atrioventricular (AV) block or sinus node dysfunction, unless these patients have a functioning artificial pacemaker.

- Unstable angina that has not been stabilised with medical therapy.

- Severe hypotension.

- Decompensated states of heart failure.

https://www.ema.europa.eu/en/documents/product-information/rapiscan-epar-product-information_en.pdf 03/09/2025

Regdanvimab (Regkirona)

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

Administration of regdanvimab while breast-feeding can be considered when clinically indicated.

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

Therefore, interactions with concomitant medicinal products that are renally excreted or that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are considered unlikely. Pharmacodynamic interactions No interaction studies have been performed

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

No fertility studies have been performed.

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

Regdanvimab should be used during pregnancy only if the expected benefit to the mother justifies the potential risk to the foetus.

CONTRAINDICATIONS of Regdanvimab (Regkirona)

- 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/regkirona-epar-product-information_en.pdf 24/04/2025 (withdraw)

Regorafenib (Stivarga)

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

If patients experience symptoms affecting their ability to concentrate and react during treatment with Stivarga, it is recommended that they do not drive or use machines until the effect subsides.

Antibiotics, regorafenib [2] ---> SmPC of [2] of EMA

The clinical significance of this neomycin interaction is unknown, but may result in a decreased efficacy of regorafenib. Pharmacokinetic interactions of other antibiotics have not been studied.

Anticoagulants, regorafenib [2] ---> SmPC of [2] of EMA

Blood counts and coagulation parameters should be monitored in patients treated with anticoagulants (e.g. warfarin and phenprocoumon) or other concomitant medicinal products that increase the risk of bleeding.

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

Co-administration of regorafenib may increase the plasma concentrations of other concomitant BCRP substrates (e.g. methotrexate, fluvastatin, atorvastatin).

BCRP inductors, regorafenib [2] ---> SmPC of [2] of EMA

Inhibitors and inducers of BCRP and P-glycoprotein may interfere with the exposure of M-2 and M-5. The clinical significance of these findings is unknown (see also section 5.2).

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

Inhibitors and inducers of BCRP and P-glycoprotein may interfere with the exposure of M-2 and M-5. The clinical significance of these findings is unknown (see also section 5.2).

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

Regorafenib, BCRP inhibitor, may increase the plasma levels of the BCRP substrate

Bile-acid sequestrants, regorafenib [2] ---> SmPC of [2] of EMA

Bile salt-sequestering agents may interact with regorafenib by forming insoluble complexes which may impact absorption (or reabsorption), thus resulting in potentially decreased exposure.

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

A risk to the breast-fed child cannot be excluded. Regorafenib could harm infant growth and development (see section 5.3). Breast-feeding must be discontinued during treatment with Stivarga.

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

Strong inducers of CYP3A4 should be avoided, or selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered.

Cholestagel, regorafenib [2] ---> SmPC of [2] of EMA

Bile salt-sequestering agents may interact with regorafenib by forming insoluble complexes which may impact absorption (or reabsorption), thus resulting in potentially decreased exposure.

Cholestyramine, regorafenib [2] ---> SmPC of [2] of EMA

Bile salt-sequestering agents may interact with regorafenib by forming insoluble complexes which may impact absorption (or reabsorption), thus resulting in potentially decreased exposure.

Clarithromycin, regorafenib [2] ---> SmPC of [2] 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.

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

Pharmacokinetic data indicate that regorafenib may be given concomitantly with substrates of CYP2C8, CYP2C9, CYP3A4, and CYP2C19 without a clinically meaningful drug interaction (see also section 4.4).

Diflunisal, regorafenib [2] ---> SmPC of [2] of EMA

Co-administration of a strong UGT1A9 inhibitor during regorafenib treatment should be avoided, as their influence on the steady-state exposure of regorafenib and its metabolites has not been studied.

Digoxin, regorafenib [2] ---> SmPC of [2] of EMA

Clinical data indicate that regorafenib has no effect on digoxin pharmacokinetics, therefore can be given concomitantly with p-glycoprotein substrates, such as digoxin, without a clinically meaningful drug interaction.

Drugs primarily metabolised by CYP2C19, regorafenib [2] ---> SmPC of [2] of EMA

Pharmacokinetic data indicate that regorafenib may be given concomitantly with substrates of CYP2C19 without a clinically meaningful drug interaction

Drugs primarily metabolised by CYP2C8, regorafenib [2] ---> SmPC of [2] of EMA

Pharmacokinetic data indicate that regorafenib may be given concomitantly with substrates of CYP2C8 without a clinically meaningful drug interaction

Drugs primarily metabolised by CYP2C9, regorafenib [2] ---> SmPC of [2] of EMA

Pharmacokinetic data indicate that regorafenib may be given concomitantly with substrates of CYP2C9 without a clinically meaningful drug interaction

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

Pharmacokinetic data indicate that regorafenib may be given concomitantly with substrates of CYP3A4 without a clinically meaningful drug interaction

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

There are no data on the effect of Stivarga on human fertility. Results from animal studies indicate that regorafenib can impair male and female fertility (see section 5.3).

Fluvastatin, regorafenib [2] ---> SmPC of [2] of EMA

Co-administration of regorafenib may increase the plasma concentrations of other concomitant BCRP substrates (e.g. methotrexate, fluvastatin, atorvastatin).

Foods, regorafenib [2] ---> SmPC of [2] of EMA

Stivarga should be taken at the same time each day. The tablets should be swallowed whole with water after a light meal that contains less than 30% fat.

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

Gastrointestinal perforation (including fatal outcome) and fistulae have been reported in patients treated with Stivarga. Discontinuation of Stivarga is recommended in patients developing gastrointestinal perforation or fistula.

Grapefruit juice, regorafenib [2] ---> SmPC of [2] 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.

Irinotecan, regorafenib [2] ---> SmPC of [2] of EMA

This indicates that co-administration of regorafenib may increase systemic exposure to UGT1A1 and UGT1A9 substrates.

Itraconazol, regorafenib [2] ---> SmPC of [2] 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.

Ketoconazole, regorafenib [2] ---> SmPC of [2] 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.

Mefenamic acid, regorafenib [2] ---> SmPC of [2] of EMA

Co-administration of a strong UGT1A9 inhibitor during regorafenib treatment should be avoided, as their influence on the steady-state exposure of regorafenib and its metabolites has not been studied.

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

Women of childbearing potential and men should ensure effective contraception during treatment and up to 8 weeks after completion of therapy.

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

Co-administration of regorafenib may increase the plasma concentrations of other concomitant BCRP substrates (e.g. methotrexate, fluvastatin, atorvastatin).

Neomycin, regorafenib [2] ---> SmPC of [2] of EMA

The clinical significance of this neomycin interaction is unknown, but may result in a decreased efficacy of regorafenib. Pharmacokinetic interactions of other antibiotics have not been studied.

Niflumic acid, regorafenib [2] ---> SmPC of [2] of EMA

Co-administration of a strong UGT1A9 inhibitor during regorafenib treatment should be avoided, as their influence on the steady-state exposure of regorafenib and its metabolites has not been studied.

P-glycoprotein substrates, regorafenib [2] ---> SmPC of [2] of EMA

P-gp inductors, regorafenib [2] ---> SmPC of [2] of EMA

Inhibitors and inducers of BCRP and P-glycoprotein may interfere with the exposure of M-2 and M-5. The clinical significance of these findings is unknown (see also section 5.2).

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

Inhibitors and inducers of BCRP and P-glycoprotein may interfere with the exposure of M-2 and M-5. The clinical significance of these findings is unknown (see also section 5.2).

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

Strong inducers of CYP3A4 should be avoided, or selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered.

Phenprocoumon, regorafenib [2] ---> SmPC of [2] of EMA

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

Strong inducers of CYP3A4 should be avoided, or selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered.

Posaconazole, regorafenib [2] ---> SmPC of [2] 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.

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

Stivarga should not be used during pregnancy unless clearly necessary and after careful consideration of the benefits for the mother and the risk to the foetus.

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

Strong inducers of CYP3A4 should be avoided, or selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered.

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

Administration of regorafenib (160 mg for 14 days) prior to administration of a single dose of rosuvastatin (5 mg), a BCRP substrate, resulted in a 3.8-fold increase in mean exposure (AUC) of rosuvastatin and a 4.6-fold increase in Cmax.

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

Strong inducers of CYP3A4 should be avoided, or selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered.

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

Strong inducers of CYP3A4 should be avoided, or selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered.

Regorafenib [1], strong CYP3A4 inhibitors ---> 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.

Regorafenib [1], strong UGT1A9 inhibitors ---> SmPC of [1] of EMA

Co-administration of a strong UGT1A9 inhibitor during regorafenib treatment should be avoided, as their influence on the steady-state exposure of regorafenib and its metabolites has not been studied.

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.

Regorafenib [1], UGT1A1 substrates ---> SmPC of [1] of EMA

This indicates that co-administration of regorafenib may increase systemic exposure to UGT1A1 and UGT1A9 substrates.

Regorafenib [1], UGT1A9 substrates ---> SmPC of [1] of EMA

This indicates that co-administration of regorafenib may increase systemic exposure to UGT1A1 and UGT1A9 substrates.

Regorafenib [1], voriconazole ---> 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.

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

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

Women of childbearing potential must be informed that regorafenib may cause foetal harm.

CONTRAINDICATIONS of Regorafenib (Stivarga)

- 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/stivarga-epar-product-information_en.pdf 02/07/2025

Relugolix (Orgovyx)

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

Fatigue and dizziness are very common (fatigue) and common (dizziness) adverse reactions that may influence the ability to drive and use machines.

Abiraterone, relugolix [2] ---> SmPC of [2] of EMA

No clinically meaningful interaction is expected and no dose adjustment of Orgovyx is required.

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

The concomitant use of Orgovyx with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes should be carefully evaluated (see section 4.4).

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

No clinically significant differences in the pharmacokinetics of relugolix were observed upon co-administration of relugolix with acid-reducing agents.

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

Co-administration of Orgovyx with rifampicin and other strong CYP3A4 and Pgp inducers is not recommended, as this may decrease the AUC and Cmax of relugolix and may therefore reduce the therapeutic effects of Orgovyx.

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

No dose modifications recommended for coadministration of relugolix and CYP3A4 inhibitors devoid of P-gp inhibition

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

Concomitant use of Orgovyx with erythromycin, azithromycin and other oral P-gp inhibitors is not recommended

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

No data are available regarding the presence of relugolix or its metabolites in human milk or its effect on the breast-fed infant. An effect on breast-feeding newborns/infants cannot be excluded.

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

Carvedilol, relugolix [2] ---> SmPC of [2] of EMA

Concomitant use of Orgovyx with erythromycin, azithromycin and other oral P-gp inhibitors is not recommended

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

Concomitant use of Orgovyx with erythromycin, azithromycin and other oral P-gp inhibitors is not recommended

Class IA antiarrhythmic agents, relugolix [2] ---> SmPC of [2] of EMA

The concomitant use of Orgovyx with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes should be carefully evaluated (see section 4.4).

Class III antiarrhythmic agents, relugolix [2] ---> SmPC of [2] of EMA

The concomitant use of Orgovyx with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes should be carefully evaluated (see section 4.4).

Contraception, relugolix [2] ---> SmPC of [2] of EMA

Based on findings in animals and mechanism of action, if a patient engages in sexual intercourse with a woman of childbearing potential, effective contraception during treatment and for 2 weeks after the last dose of Orgovyx must be used.

CYP3A4 substrates, relugolix [2] ---> SmPC of [2] of EMA

No dose adjustment of midazolam and other CYP3A substrates is required.

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

The increase in dabigatran exposure is not considered to be clinically meaningful. Therefore, clinically meaningful effects of a 120 mg dose of relugolix on other P-gp substrates are not expected.

Darolutamide, relugolix [2] ---> SmPC of [2] of EMA

Darolutamide is a weak inducer of CYP3A4. However the potential decrease in exposure is not expected to be clinically meaningful. No dose adjustment of Orgovyx is required.

Disopyramide, relugolix [2] ---> SmPC of [2] of EMA

The concomitant use of Orgovyx with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes should be carefully evaluated (see section 4.4).

Docetaxel, relugolix [2] ---> SmPC of [2] of EMA

No clinically meaningful interaction is expected and no dose adjustment of Orgovyx is required.

Dofetilide, relugolix [2] ---> SmPC of [2] of EMA

The concomitant use of Orgovyx with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes should be carefully evaluated (see section 4.4).

Dronedarone, relugolix [2] ---> SmPC of [2] of EMA

Concomitant use of Orgovyx with erythromycin, azithromycin and other oral P-gp inhibitors is not recommended

Efavirenz, relugolix [2] ---> SmPC of [2] of EMA

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

Therefore, no dose modifications are recommended for coadministration of relugolix and enzalutamide.

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

Concomitant use of Orgovyx with erythromycin, azithromycin and other oral P-gp inhibitors is not recommended

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

Based on findings in animals and mechanism of action, Orgovyx may impair fertility in males of reproductive potential (see section 5.3).

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

No dose modifications recommended for coadministration of relugolix and CYP3A4 inhibitors devoid of P-gp inhibition

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

Concomitant use of Orgovyx with erythromycin, azithromycin and other oral P-gp inhibitors is not recommended

Ibutilide, relugolix [2] ---> SmPC of [2] of EMA

The concomitant use of Orgovyx with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes should be carefully evaluated (see section 4.4).

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

Concomitant use of Orgovyx with erythromycin, azithromycin and other oral P-gp inhibitors is not recommended

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

Concomitant use of Orgovyx with erythromycin, azithromycin and other oral P-gp inhibitors is not recommended

Methadone, relugolix [2] ---> SmPC of [2] of EMA

The concomitant use of Orgovyx with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes should be carefully evaluated (see section 4.4).

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

No dose adjustment of midazolam and other CYP3A substrates is required.

Moxifloxacin, relugolix [2] ---> SmPC of [2] of EMA

The concomitant use of Orgovyx with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes should be carefully evaluated (see section 4.4).

Neuroleptics, relugolix [2] ---> SmPC of [2] of EMA

The concomitant use of Orgovyx with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes should be carefully evaluated (see section 4.4).

P-glycoprotein inductors and strong CYP3A4, relugolix [2] ---> SmPC of [2] of EMA

Co-administration of Orgovyx with combined P-gp and strong CYP3A inducers is not recommended. If co-administration is required, the Orgovyx dose should be increased (see section 4.2).

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

Concomitant use of Orgovyx with erythromycin, azithromycin and other oral P-gp inhibitors is not recommended

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

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

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

Studies in animals have shown that exposure to relugolix in early pregnancy may increase the risk of early pregnancy loss (see section 5.3). Based on the pharmacological effects, an adverse effect on pregnancy cannot be excluded.

Propafenone, relugolix [2] ---> SmPC of [2] of EMA

Concomitant use of Orgovyx with erythromycin, azithromycin and other oral P-gp inhibitors is not recommended

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

The concomitant use of Orgovyx with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes should be carefully evaluated (see section 4.4).

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

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

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

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

The decrease in exposure to rosuvastatin is not considered clinically meaningful; however, rosuvastatin may be titrated to achieve desired therapeutic effects.

Relugolix [1], sotalol ---> SmPC of [1] of EMA

The concomitant use of Orgovyx with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes should be carefully evaluated (see section 4.4).

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

Relugolix [1], tetracyclines ---> SmPC of [1] of EMA

Concomitant use of Orgovyx with erythromycin, azithromycin and other oral P-gp inhibitors is not recommended

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

Concomitant use of Orgovyx with erythromycin, azithromycin and other oral P-gp inhibitors is not recommended

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

No dose modifications recommended for coadministration of relugolix and CYP3A4 inhibitors devoid of P-gp inhibition

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

This medicinal product is not indicated in women of childbearing potential. It is not to be used in women who are, or may be, pregnant or breast-feeding (see section 4.1).

CONTRAINDICATIONS of Relugolix (Orgovyx)

- 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/orgovyx-epar-product-information_en.pdf 24/07/2024

Remdesivir (Veklury)

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

As the clinical experience is limited, a decision about breast-feeding during treatment should be made after a careful individual benefit-risk assessment.

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

No dose adjustment of remdesivir is required when it is co-administered with strong CYP3A4 and/or P-gp inducers.

Chloroquine, remdesivir [2] ---> SmPC of [2] of EMA

Due to antagonism observed in vitro, concomitant use of remdesivir with chloroquine phosphate or hydroxychloroquine sulphate is not recommended.

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

No interactions are expected when co-administering remdesivir with inhibitors of OATP1B1/1B3 and/or P-gp.

CYP1A2 substrates with narrow therapeutic index, remdesivir [2] ---> SmPC of [2] of EMA

Remdesivir induced CYPlA2 and potentially CYP3A in vitro. Co-administration of remdesivir with CYP1A2 or CYP3A4 substrates with narrow therapeutic index may lead to loss of their efficacy.

CYP3A4 substrates with narrow therapeutic index, remdesivir [2] ---> SmPC of [2] of EMA

Remdesivir induced CYPlA2 and potentially CYP3A in vitro. Co-administration of remdesivir with CYP1A2 or CYP3A4 substrates with narrow therapeutic index may lead to loss of their efficacy.

CYP3A4 substrates, remdesivir [2] ---> SmPC of [2] of EMA

No data is available, however it can be suggested that medicinal products that are substrates of CYP3A4 or substrates of OATP 1B1/1B3 should be administered at least 2 hours after remdesivir.

Dexamethasone, remdesivir [2] ---> SmPC of [2] of EMA

Dexamethasone is a substrate of CYP3A4 and although remdesivir inhibits CYP3A4, due to remdesivir's rapid clearance after I.V administration, remdesivir is unlikely to have a significant effect on dexamethasone exposure.

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

In male rats, there was no effect on mating or fertility with remdesivir treatment. In female rats, however, an impairment of fertility was observed (see section 5.3). The relevance for humans is unknown.

Hydroxychloroquine, remdesivir [2] ---> SmPC of [2] of EMA

Due to antagonism observed in vitro, concomitant use of remdesivir with chloroquine phosphate or hydroxychloroquine sulphate is not recommended.

OATP1B1 inhibitors, remdesivir [2] ---> SmPC of [2] of EMA

No interactions are expected when co-administering remdesivir with inhibitors of OATP1B1/1B3 and/or P-gp.

OATP1B3 inhibitors, remdesivir [2] ---> SmPC of [2] of EMA

No interactions are expected when co-administering remdesivir with inhibitors of OATP1B1/1B3 and/or P-gp.

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

No interactions are expected when co-administering remdesivir with inhibitors of OATP1B1/1B3 and/or P-gp.

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

Remdesivir should not be used during first trimester in pregnancy unless the clinical condition of the woman requires treatment with it. Use in the second and third trimester of pregnancy may be considered.

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

No dose adjustment of remdesivir is required when it is co-administered with strong CYP3A4 and/or P-gp inducers.

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

No interactions are expected when co-administering remdesivir with strong CYP3A4 inducers or CYP3A4 inhibitors.

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

Use of effective contraception during treatment should be considered in women of child-bearing potential.

Remdesivir, sotrovimab [2] ---> SmPC of [2] of EMA

In vitro pharmacodynamic studies showed no antagonism between sotrovimab and remdesivir or bamlanivimab.

CONTRAINDICATIONS of Remdesivir (Veklury)

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/veklury-epar-product-information_en.pdf 27/06/2024

Remifentanil

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

If an early discharge is envisaged after application of remifentanil, following treatment using anaesthetic agents, patients should be advised not to drive or operate machinery

Benzodiazepines, remifentanil [2] ---> SmPC of [2] of eMC

As with other opioids remifentanil decreases the amounts or doses of benzodiazepines required for anaesthesia

Betablockers, remifentanil [2] ---> SmPC of [2] of eMC

The cardiovascular effects of remifentanil (hypotension and bradycardia), may exacerbate in patients receiving concomitant cardiac depressant drugs

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

Caution should be exercised and nursing mothers should be advised to discontinue breast-feeding for 24 hours following administration of remifentanil.

Calcium antagonists, remifentanil [2] ---> SmPC of [2] of eMC

The cardiovascular effects of remifentanil (hypotension and bradycardia), may exacerbate in patients receiving concomitant cardiac depressant drugs

CNS depressants, remifentanil [2] ---> SmPC of [2] of eMC

If doses of concomitantly administered CNS depressant medicinal products are not reduced patients may experience an increased incidence of adverse effects associated with these agents.

Halogenated anaesthetics, remifentanil [2] ---> SmPC of [2] of eMC

As with other opioids remifentanil decreases the amounts or doses of inhaled and IV anaesthetics required for anaesthesia

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

Remifentanil should not be used during pregnancy unless clearly necessary.

Remifentanil, succinylcholine

Remifentanil may prolong the neuromuscular blocking effects of suxamethonium

Remifentanil, suxamethonium

Remifentanil may prolong the neuromuscular blocking effects of suxamethonium

CONTRAINDICATIONS of Remifentanil

- As glycine is present in the formulation, Remifentanil 1 mg Powder for Concentrate for Solution for Injection or Infusion is contraindicated for epidural and intrathecal use

- Remifentanil is contra-indicated in patients with known hypersensitivity to remifentanil and other fentanyl analogues or any other component of the preparation

- Remifentanil is contra-indicated for use as the sole agent for induction of anaesthesia.

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

Remimazolam (Byfavo)

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

Remimazolam has a major influence on the ability to drive and use machines. Prior to receiving remimazolam, the patient should be warned not to drive a vehicle or operate a machine until completely recovered.

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

Alcohol intake should be avoided for 24 hours before remimazolam administration since it may markedly enhance the sedative effect of remimazolam

Barbiturates, remimazolam [2] ---> SmPC of [2] of EMA

The co-administration of remimazolam with opioids and CNS depressants, including alcohol, is likely to result in enhanced sedation and cardiorespiratory depression.

Benzodiazepines, remimazolam [2] ---> SmPC of [2] of EMA

The co-administration of remimazolam with opioids and CNS depressants, including alcohol, is likely to result in enhanced sedation and cardiorespiratory depression.

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

The administration of remimazolam to breastfeeding mothers should be avoided. If there is a need to administer remimazolam, then discontinuation of breastfeeding for 24 hours after administration is advised.

Centrally acting antihypertensive, remimazolam [2] ---> SmPC of [2] of EMA

The co-administration of remimazolam with opioids and CNS depressants, including alcohol, is likely to result in enhanced sedation and cardiorespiratory depression.

CNS depressants, remimazolam [2] ---> SmPC of [2] of EMA

The co-administration of remimazolam with opioids and CNS depressants, including alcohol, is likely to result in enhanced sedation and cardiorespiratory depression.

Etomidate, remimazolam [2] ---> SmPC of [2] of EMA

The co-administration of remimazolam with opioids and CNS depressants, including alcohol, is likely to result in enhanced sedation and cardiorespiratory depression.

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

There are no human data on the effects of remimazolam on fertility. In animal studies there was no effect on mating or fertility with remimazolam treatment

Ketamine, remimazolam [2] ---> SmPC of [2] of EMA

The co-administration of remimazolam with opioids and CNS depressants, including alcohol, is likely to result in enhanced sedation and cardiorespiratory depression.

Opiates, remimazolam [2] ---> SmPC of [2] of EMA

Concomitant use of remimazolam and opioids may result in profound sedation and respiratory depression. Patients should be monitored for respiratory depression and depth of sedation

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

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Byfavo during pregnancy.

Propofol, remimazolam [2] ---> SmPC of [2] of EMA

The co-administration of remimazolam with opioids and CNS depressants, including alcohol, is likely to result in enhanced sedation and cardiorespiratory depression.

Remimazolam [1], sedative antidepressants ---> SmPC of [1] of EMA

The co-administration of remimazolam with opioids and CNS depressants, including alcohol, is likely to result in enhanced sedation and cardiorespiratory depression.

CONTRAINDICATIONS of Remimazolam (Byfavo)

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

- Unstable myasthenia gravis.

https://www.ema.europa.eu/en/documents/product-information/byfavo-epar-product-information_en.pdf 28/11/2025

Repaglinide (Enyglid)

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

Patients should be advised to take precautions to avoid hypoglycaemia whilst driving.

Abiraterone [1], repaglinide ---> SmPC of [1] of EMA

No clinically meaningful increases in exposure are expected when abiraterone is combined with drugs that are predominantly eliminated by CYP2C8

Abiraterone/niraparib [1], repaglinide ---> SmPC of [1] of EMA

Patients should be monitored for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with Akeega because of the abiraterone acetate component.

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

Angiotensin converting enzyme (ACE)-inhibitors may enhance and/or prolong the hypoglycaemic effect of repaglinide.

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

Alcohol may enhance and/or prolong the hypoglycaemic effect of repaglinide

Anabolic steroids, repaglinide [2] ---> SmPC of [2] of EMA

Anabolic steroids may enhance and/or prolong the hypoglycaemic effect of repaglinide.

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

Other antidiabetics may enhance and/or prolong the hypoglycaemic effect of repaglinide

Apalutamide [1], repaglinide ---> SmPC of [1] of EMA

When substrates of P-gp, BCRP or OATP1B1 are co-administered with Erleada, evaluation for loss of efficacy of the substrate should be performed and dose adjustment of the substrate may be required to maintain optimal plasma concentrations.

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

Barbiturates may reduce the hypoglycaemic effect of repaglinide

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

Beta-blocking medicinal products may mask the symptoms of hypoglycaemia.

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

Repaglinide should not be used in breast-feeding women.

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

In vitro an inhibition of OATP1B1/3 transporters by bulevirtide was observed, albeit only at a concentration ≥ 0.5 然. As a precautionary measure, close clinical monitoring is warranted when OATP1B1/3 substrates are co-administered.

Cabazitaxel [1], repaglinide ---> SmPC of [1] of EMA

The risk of interaction with OATP1B1 substrates is possible, notably during the infusion duration (1 hour) and up to 20 minutes after the end of the infusion.

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

Rifampicin, a potent inducer of CYP3A4, but also CYP2C8, acts both as an inducer and inhibitor of the metabolism of repaglinide. It cannot be excluded that other inducers may have a similar effect.

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

Co-administration of cimetidine, nifedipine, oestrogen, or simvastatin with repaglinide, all CYP3A4 substrates, did not significantly alter the pharmacokinetic parameters of repaglinide.

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

Clarithromycin may enhance and/or prolong the hypoglycaemic effect of repaglinide.

Clopidogrel [1], repaglinide ---> SmPC of [1] of EMA

Due to the risk of increased plasma concentrations, concomitant administration of clopidogrel and drugs primarily cleared by CYP2C8 metabolism (e.g., repaglinide, paclitaxel) should be undertaken with caution

Clopidogrel/acetylsalicylic acid [1], repaglinide ---> SmPC of [1] of EMA

Colchicine, repaglinide

The CYP3A4 and CYP2C8 inhibition/induction may increase/decrease the plasma concentrations of repaglinide. Special care should be taken

Colesevelam [1], repaglinide ---> SmPC of [1] of EMA

Co-administration of colesevelam and repaglinide caused a 19% reduction in the Cmax of repaglinide. No interaction was observed when colesevelam was administered 1 hour after repaglinide.

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

Corticosteroids may reduce the hypoglycaemic effect of repaglinide

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

Ciclosporin may enhance and/or prolong the hypoglycaemic effect of repaglinide. The concomitant use of ciclosporin with repaglinide should be avoided.

CYP2C8 inductors, repaglinide [2] ---> SmPC of [2] of EMA

In vitro data indicate that repaglinide is metabolised predominantly by CYP2C8, but also by CYP3A4. Metabolism, and by that clearance of repaglinide, may be altered by substances which influence these cytochrome P-450 enzymes via induction.

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

CYP3A4 and CYP2C8 inhibitors, repaglinide [2] ---> SmPC of [2] of EMA

Special care should be taken when both inhibitors of CYP2C8 and 3A4 are coadministered simultaneously with repaglinide.

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

Danazol may reduce the hypoglycaemic effect of repaglinide

Darunavir/ritonavir, repaglinide ---> SmPC of [darunavir] of EMA

Co-administration of darunavir and ritonavir and medicinal products primarily metabolised by CYP2C8 may result in decreased systemic exposure to such medicinal products, which could decrease or shorten their therapeutic effect.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, repaglinide ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of OATP1B1 inhibition by paritaprevir. Caution should be used and dose decrease maybe needed for repaglinide when administered with Viekirax with or without dasabuvir.

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

Concomitant administration of deferasirox, a moderate inhibitor of CYP2C8 and CYP3A4, with repaglinide, a CYP2C8 substrate, increased repaglinide AUC and Cmax. The concomitant use of deferasirox with repaglinide should be avoided.

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

Repaglinide had no clinically relevant effect on the pharmacokinetic properties of digoxin, theophylline or warfarin at steady state, when administered to healthy volunteers.

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

Caution is advised when sensitive oral OATP1B1 substrates (e.g. atorvastatin, pravastatin, rosuvastatin repaglinide, bosentan) are co-administered with entrectinib, due to the risk of increased absorption.

Enzyme inductors, repaglinide [2] ---> SmPC of [2] of EMA

Rifampicin, a potent inducer of CYP3A4, but also CYP2C8, acts both as an inducer and inhibitor of the metabolism of repaglinide. It cannot be excluded that other inducers may have a similar effect.

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

Co-administration of cimetidine, nifedipine, oestrogen, or simvastatin with repaglinide, all CYP3A4 substrates, did not significantly alter the pharmacokinetic parameters of repaglinide.

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

Embryotoxicity, abnormal limb development in rat foetuses and new born pups, was observed in female rats exposed to high doses in the last stage of pregnancy and during the lactation period. Repaglinide was detected in the milk of animals.

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

Repaglinide should be taken before main meals (i.e. preprandially). Doses are usually taken within 15 minutes of the meal but time may vary from immediately preceding the meal to as long as 30 minutes before the meal

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

Gemfibrozil may enhance and/or prolong the hypoglycaemic effect of repaglinide. The concomitant use of gemfibrozil and repaglinide is contraindicated

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

Monoamine oxidase inhibitors (MAOI) may enhance and/or prolong the hypoglycaemic effect of repaglinide.

Irbesartan/hydrochlorothiazide [1], repaglinide ---> SmPC of [1] of EMA

Dose adjustment of antidiabetic treatment such as repaglinide may be required (see section 4.4).

Isavuconazole [1], repaglinide ---> SmPC of [1] of EMA

No CRESEMBA dose adjustment necessary. Repaglinide: no dose adjustment required.

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

Co-administration of 100 mg itraconazole, an inhibitor of CYP3A4, has also been studied in healthy volunteers, and increased the AUC by 1.4-fold. No significant effect on the glucose level in healthy volunteers was observed.

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

Coadministration may increase exposures of substrates of these transporters, such as statins, glyburide, nateglinide and repaglinide. When used concomitantly with substrates of OATP1B1 or OATP1B3, caution and appropriate monitoring should be used.

Ivosidenib [1], repaglinide ---> 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).

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

Co-administration of 200 mg ketoconazole increased the repaglinide (AUC and Cmax) by 1.2-fold with profiles of blood glucose concentrations altered by less than 8% when administered concomitantly (a single dose of 4 mg repaglinide).

Lapatinib [1], repaglinide ---> SmPC of [1] of EMA

Lapatinib inhibits CYP2C8 in vitro at clinically relevant concentrations. Co-administration of lapatinib with medicinal products with narrow therapeutic windows that are substrates of CYP2C8 should be avoided

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

In vitro studies indicate that larotrectinib may induce PXR regulated enzymes (e.g. CYP2C family and UGT). Co-administration of larotrectinib with CYP2C8, CYP2C9 or CYP2C19 substrates may decrease their exposure.

Lefamulin [1], repaglinide ---> SmPC of [1] of EMA

Inhibition of CYP3A4, CYP2C8. Co-administration with lefamulin may lead to higher exposures of repaglinide and is contraindicated

Leflunomide [1], repaglinide ---> SmPC of [1] of EMA

Monitoring patients with concomitant use of medicinal products metabolised by CYP2C8, such as repaglinide, paclitaxel, pioglitazone or rosiglitazone, is recommended as they may have higher exposure.

Lesinurad [1], repaglinide ---> SmPC of [1] of EMA

Based on interaction studies in healthy subjects or gout patients, Zurampic does not have clinically significant interactions with NSAIDs (naproxen and indomethacin), colchicine, repaglinide, tolbutamide, febuxostat or allopurinol.

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

Letermovir may increase or decrease the plasma concentrations of repaglinide. (The net effect is not known). Concomitant use is not recommended.

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

A higher dose of repaglinide may be required to obtain the desired clinical effect. Lumacaftor/ivacaftor may decrease the exposure of repaglinide, which may reduce its efficacy. Due to induction of CYP3A/2C8 by lumacaftor

Medicinal products that are mainly secreted by the bile, repaglinide [2] ---> SmPC of [2] of EMA

When repaglinide is used together with other medicinal products that are mainly secreted by the bile, like repaglinide, any potential interaction should be considered.

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

Mitapivat may induce UGT1A1, CYP2B6, CYP2C8, CYP2C9 and CYP2C19 and may decrease systemic exposure to substrates of these enzymes (e.g. irinotecan [UGT1A1]; bupropion [CYP2B6]; omeprazole [CYP2C19]; repaglinide [CYP2C8]; warfarin [CYP2C9]).

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

Co-administration of cimetidine, nifedipine, oestrogen, or simvastatin with repaglinide, all CYP3A4 substrates, did not significantly alter the pharmacokinetic parameters of repaglinide.

Non-selective betablockers, repaglinide [2] ---> SmPC of [2] of EMA

Non selective beta blocking substances may enhance and/or prolong the hypoglycaemic effect of repaglinide.

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

NSAIDs may enhance and/or prolong the hypoglycaemic effect of repaglinide.

OATP1B1 inhibitors, repaglinide [2] ---> SmPC of [2] of EMA

Repaglinide appears to be a substrate for active hepatic uptake (organic anion transporting protein OATP1B1). Substances that inhibit OATP1B1 may likewise have the potential to increase plasma concentrations of repaglinide

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

Octreotide may enhance and/or prolong the hypoglycaemic effect of repaglinide

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

Olaparib is an inhibitor of OATP1B1. It cannot be excluded that olaparib may increase the exposure to substrates of OATP1B1

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

OATP1B1 inhibition by paritaprevir. Caution should be used and dose decrease maybe needed for repaglinide when administered with Viekirax with or without dasabuvir.

Opicapone [1], repaglinide ---> SmPC of [1] of EMA

Opicapone is a weak inhibitor of CYP2C8. Thus, particular consideration should be given to medicinal products metabolised by CYP2C8 and their co-administration must be avoided.

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

Oral contraceptives may reduce the hypoglycaemic effect of repaglinide

Padeliporfin [1], repaglinide ---> SmPC of [1] of EMA

The use of medicinal products that are substrates of OATP1B1 or OATP1B3 for which concentration-dependent serious adverse events have been observed should be avoided on the day of TOOKAD infusion and for at least 24 hours after administration.

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

Repaglinide had no clinically relevant effect on the pharmacokinetic properties of digoxin, theophylline or warfarin at steady state, when administered to healthy volunteers.

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

Rifampicin, a potent inducer of CYP3A4, but also CYP2C8, acts both as an inducer and inhibitor of the metabolism of repaglinide. It cannot be excluded that other inducers may have a similar effect.

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

Rifampicin, a potent inducer of CYP3A4, but also CYP2C8, acts both as an inducer and inhibitor of the metabolism of repaglinide. It cannot be excluded that other inducers may have a similar effect.

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

Pirtobrutinib is a moderate inhibitor of CYP2C8. Pirtobrutinib increased the AUC and Cmax of repaglinide (a substrate of CYP2C8) by 130 % and 98 %, respectively.

Pitolisant [1], repaglinide ---> SmPC of [1] of EMA

With other CYP3A4, CYP2B6 (e.g. efavirenz, bupropion), CYP2C (e.g. repaglinide, phenytoin, warfarin), P-gp (e.g. dabigatran, digoxin) and UGT (e.g. morphine, paracetamol, irinotecan) substrates, caution should be made

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

Although a risk to inhibition of pixantrone towards CYP2C8 could not be ascertained, caution should be observed when co-administering substances that are primarily metabolised via CYP2C8

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

Repaglinide should be avoided during pregnancy.

Proteolytic enzymes enriched in bromelain [1], repaglinide ---> 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

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

Rifampicin, a potent inducer of CYP3A4, but also CYP2C8, acts both as an inducer and inhibitor of the metabolism of repaglinide. Concomitant use of rifampicin and repaglinide might therefore induce a need for repaglinide dose adjustment

Repaglinide [1], salicylates ---> SmPC of [1] of EMA

Salicylates may enhance and/or prolong the hypoglycaemic effect of repaglinide.

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

Co-administration of cimetidine, nifedipine, oestrogen, or simvastatin with repaglinide, all CYP3A4 substrates, did not significantly alter the pharmacokinetic parameters of repaglinide.

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

Rifampicin, a potent inducer of CYP3A4, but also CYP2C8, acts both as an inducer and inhibitor of the metabolism of repaglinide. It cannot be excluded that other inducers may have a similar effect.

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

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

Repaglinide [1], sympathomimetics ---> SmPC of [1] of EMA

Sympathomimetics may reduce the hypoglycaemic effect of repaglinide

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

Repaglinide had no clinically relevant effect on the pharmacokinetic properties of digoxin, theophylline or warfarin at steady state, when administered to healthy volunteers.

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

Thiazides may reduce the hypoglycaemic effect of repaglinide

Repaglinide [1], thyroid hormones ---> SmPC of [1] of EMA

Thyroid hormones may reduce the hypoglycaemic effect of repaglinide

Repaglinide [1], trimethoprim ---> SmPC of [1] of EMA

Trimethoprim may enhance and/or prolong the hypoglycaemic effect of repaglinide. The concomitant use of trimethoprim with repaglinide should be avoided.

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

Repaglinide had no clinically relevant effect on the pharmacokinetic properties of digoxin, theophylline or warfarin at steady state, when administered to healthy volunteers.

Repaglinide, ripretinib [2] ---> SmPC of [2] of EMA

In vitro studies suggested ripretinib may inhibit CYP2C8. QINLOCK is to be used with caution in combination with substrates of CYP2C8 (e.g. repaglinide, paclitaxel), as co-administration may lead to increased exposure of CYP2C8 substrates.

Repaglinide, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib increased the Cmax and AUC of repaglinide (a substrate of CYP2C8) by approximately 91% and 188% respectively. Therefore, coadministration with sensitive CYP2C8 substrates should be avoided.

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.

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

Telaprevir, OATP inhibitor, may increase the repaglinide plasma levels. Caution is warranted and clinical monitoring is recommended.

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.

Repaglinide, 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.

Repaglinide, vismodegib [2] ---> SmPC of [2] of EMA

In vitro, vismodegib is an inhibitor of OATP1B1. It cannot be excluded that vismodegib may increase the exposure to substrates of OATP1B1. In particular, caution should be exercised if vismodegib is administered in combination with any statin.

CONTRAINDICATIONS of Repaglinide (Enyglid)

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

- Diabetes mellitus type 1, C-peptide negative.

- Diabetic ketoacidosis, with or without coma.

- Severe hepatic function disorder.

- Concomitant use of gemfibrozil

https://www.ema.europa.eu/en/documents/product-information/enyglid-epar-product-information_en.pdf 05/02/2025

Other trade names: NovoNorm, Prandin, Repaglinida: Accord, Actavis, Alter, Apotex, Aurobindo, Cinfa, Combix, Edigen, Goibela, Kern Pharma, Krka, Mylan, Normon, Pensa, Ratiopharm, Sandoz, Stada, Tarbis, Teva,

Repotrectinib (Augtyro)

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

AUGTYRO has moderate influence on the ability to drive and use machines. Patients should be advised of potential CNS effects and vision disorders with AUGTYRO as these effects may influence the ability to drive and use machines.

Alfentanyl, repotrectinib [2] ---> SmPC of [2] of EMA

Caution is advised when CYP3A4 substrates are co-administered with repotrectinib, due to risk of therapeutic failure.

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

Coadministration of AUGTYRO with strong or moderate CYP3A4 or P-gp inducers decreases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

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

Co-administration of AUGTYRO with sensitive substrates of P-gp, BCRP, OATP1B1, MATE1 or MATE2-K may increase their exposure. The clinical relevance is unknown.

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

It is unknown whether repotrectinib or its metabolites are excreted in human milk. A risk to the suckling child cannot be excluded. Breast-feeding should be discontinued during treatment with AUGTYRO and for 10 days after the final dose.

Bupropion, repotrectinib [2] ---> SmPC of [2] of EMA

In vitro studies indicate that repotrectinib is a CYP2B6 inducer. Co-administration of AUGTYRO with sensitive substrates of CYP2B6 substrates (including but not limited to bupropion, efavirenz) may decrease their exposure.

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

Coadministration of AUGTYRO with strong or moderate CYP3A4 or P-gp inducers decreases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

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

Caution is advised when CYP3A4 substrates are co-administered with repotrectinib, due to risk of therapeutic failure.

CYP2C19 substrates, repotrectinib [2] ---> SmPC of [2] of EMA

Co-administration of AUGTYRO with CYP2C8, CYP2C9 or CYP2C19 substrates (including but not limited to repaglinide, warfarin, tolbutamide or omeprazole) may alter their exposure.

CYP2C8 substrates, repotrectinib [2] ---> SmPC of [2] of EMA

Co-administration of AUGTYRO with CYP2C8, CYP2C9 or CYP2C19 substrates (including but not limited to repaglinide, warfarin, tolbutamide or omeprazole) may alter their exposure.

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

Co-administration of AUGTYRO with CYP2C8, CYP2C9 or CYP2C19 substrates (including but not limited to repaglinide, warfarin, tolbutamide or omeprazole) may alter their exposure.

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

Co-administration of AUGTYRO with sensitive substrates of P-gp, BCRP, OATP1B1, MATE1 or MATE2-K may increase their exposure. The clinical relevance is unknown.

Digoxin, repotrectinib [2] ---> SmPC of [2] of EMA

Co-administration of AUGTYRO with sensitive substrates of P-gp, BCRP, OATP1B1, MATE1 or MATE2-K may increase their exposure. The clinical relevance is unknown.

Drugs primarily metabolised by CYP2B6, repotrectinib [2] ---> SmPC of [2] of EMA

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

Caution is advised when CYP3A4 substrates are co-administered with repotrectinib, due to risk of therapeutic failure.

Edoxaban, repotrectinib [2] ---> SmPC of [2] of EMA

Co-administration of AUGTYRO with sensitive substrates of P-gp, BCRP, OATP1B1, MATE1 or MATE2-K may increase their exposure. The clinical relevance is unknown.

Efavirenz, repotrectinib [2] ---> SmPC of [2] of EMA

Erdafitinib [1], repotrectinib ---> SmPC of [1] of EMA

If Balversa is co-administered with a moderate CYP3A4 inducer the dose should be cautiously increased by 1 to 2 mg and adjusted gradually every two to three weeks based on clinical monitoring for adverse reactions, not to exceed 9 mg.

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

Caution is advised when CYP3A4 substrates are co-administered with repotrectinib, due to risk of therapeutic failure.

Felodipine, repotrectinib [2] ---> SmPC of [2] of EMA

Co-administration of AUGTYRO with strong or moderate CYP3A4 or P-gp inhibitors increases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

Fentanyl, repotrectinib [2] ---> SmPC of [2] of EMA

Caution is advised when CYP3A4 substrates are co-administered with repotrectinib, due to risk of therapeutic failure.

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

No fertility studies have been conducted with repotrectinib (see section 5.3). The effect of repotrectinib on male and female fertility is unknown.

Fexofenadine, repotrectinib [2] ---> SmPC of [2] of EMA

Co-administration of AUGTYRO with sensitive substrates of P-gp, BCRP, OATP1B1, MATE1 or MATE2-K may increase their exposure. The clinical relevance is unknown.

Fluvoxamine, repotrectinib [2] ---> SmPC of [2] of EMA

Co-administration of AUGTYRO with strong or moderate CYP3A4 or P-gp inhibitors increases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

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

Co-administration of AUGTYRO with strong or moderate CYP3A4 or P-gp inhibitors increases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

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

Repotrectinib is a moderate CYP3A4 inducer, which can decrease progestin or oestrogen exposure to an extent that could reduce the effectiveness of systemically acting hormonal contraceptives including oral contraceptives.

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

Co-administration of AUGTYRO with strong or moderate CYP3A4 or P-gp inhibitors increases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

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

Co-administration of AUGTYRO with strong or moderate CYP3A4 or P-gp inhibitors increases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

Lovastatine, repotrectinib [2] ---> SmPC of [2] of EMA

Caution is advised when CYP3A4 substrates are co-administered with repotrectinib, due to risk of therapeutic failure.

MATE1 substrates, repotrectinib [2] ---> SmPC of [2] of EMA

Co-administration of AUGTYRO with sensitive substrates of P-gp, BCRP, OATP1B1, MATE1 or MATE2-K may increase their exposure. The clinical relevance is unknown.

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

Male patients with female partners of childbearing potential must use condoms during treatment and for 4 months following the final dose of AUGTYRO.

Metformin, repotrectinib [2] ---> SmPC of [2] of EMA

Co-administration of AUGTYRO with sensitive substrates of P-gp, BCRP, OATP1B1, MATE1 or MATE2-K may increase their exposure. The clinical relevance is unknown.

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

Co-administration of AUGTYRO with sensitive substrates of P-gp, BCRP, OATP1B1, MATE1 or MATE2-K may increase their exposure. The clinical relevance is unknown.

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

Caution is advised when CYP3A4 substrates are co-administered with repotrectinib, due to risk of therapeutic failure.

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

Co-administration of AUGTYRO with strong or moderate CYP3A4 or P-gp inhibitors increases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

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

Co-administration of AUGTYRO with strong or moderate CYP3A4 or P-gp inhibitors increases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

OATP1B1 substrates, repotrectinib [2] ---> SmPC of [2] of EMA

Co-administration of AUGTYRO with sensitive substrates of P-gp, BCRP, OATP1B1, MATE1 or MATE2-K may increase their exposure. The clinical relevance is unknown.

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

Co-administration of AUGTYRO with CYP2C8, CYP2C9 or CYP2C19 substrates (including but not limited to repaglinide, warfarin, tolbutamide or omeprazole) may alter their exposure.

P-glycoprotein substrates, repotrectinib [2] ---> SmPC of [2] of EMA

Co-administration of AUGTYRO with sensitive substrates of P-gp, BCRP, OATP1B1, MATE1 or MATE2-K may increase their exposure. The clinical relevance is unknown.

P-gp inductors, repotrectinib [2] ---> SmPC of [2] of EMA

Coadministration of AUGTYRO with strong or moderate CYP3A4 or P-gp inducers decreases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

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

Co-administration of AUGTYRO with strong or moderate CYP3A4 or P-gp inhibitors increases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

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

Coadministration of AUGTYRO with strong or moderate CYP3A4 or P-gp inducers decreases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

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

Co-administration of AUGTYRO with strong or moderate CYP3A4 or P-gp inhibitors increases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

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

AUGTYRO should not be used unless clinical condition of the woman requires treatment with AUGTYRO. Women of childbearing potential have to use highly effective contraception (see sections 4.4 and 5.3).

Repaglinide, repotrectinib [2] ---> SmPC of [2] of EMA

Co-administration of AUGTYRO with CYP2C8, CYP2C9 or CYP2C19 substrates (including but not limited to repaglinide, warfarin, tolbutamide or omeprazole) may alter their exposure.

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

Coadministration of AUGTYRO with strong or moderate CYP3A4 or P-gp inducers decreases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

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

Co-administration of AUGTYRO with strong or moderate CYP3A4 or P-gp inhibitors increases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

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

Coadministration of AUGTYRO with strong or moderate CYP3A4 or P-gp inducers decreases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

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

Co-administration of AUGTYRO with sensitive substrates of P-gp, BCRP, OATP1B1, MATE1 or MATE2-K may increase their exposure. The clinical relevance is unknown.

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

Co-administration of AUGTYRO with strong or moderate CYP3A4 or P-gp inhibitors increases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

Repotrectinib [1], Seville orange ---> SmPC of [1] of EMA

Co-administration of AUGTYRO with strong or moderate CYP3A4 or P-gp inhibitors increases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

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

Caution is advised when CYP3A4 substrates are co-administered with repotrectinib, due to risk of therapeutic failure.

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

Caution is advised when CYP3A4 substrates are co-administered with repotrectinib, due to risk of therapeutic failure.

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

Coadministration of AUGTYRO with strong or moderate CYP3A4 or P-gp inducers decreases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

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

Co-administration of AUGTYRO with sensitive substrates of P-gp, BCRP, OATP1B1, MATE1 or MATE2-K may increase their exposure. The clinical relevance is unknown.

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

Coadministration of AUGTYRO with strong or moderate CYP3A4 or P-gp inducers decreases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

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

Co-administration of AUGTYRO with strong or moderate CYP3A4 or P-gp inhibitors increases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

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

Co-administration of AUGTYRO with sensitive substrates of P-gp, BCRP, OATP1B1, MATE1 or MATE2-K may increase their exposure. The clinical relevance is unknown.

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

Caution is advised when CYP3A4 substrates are co-administered with repotrectinib, due to risk of therapeutic failure.

Repotrectinib [1], tolbutamide ---> SmPC of [1] of EMA

Co-administration of AUGTYRO with CYP2C8, CYP2C9 or CYP2C19 substrates (including but not limited to repaglinide, warfarin, tolbutamide or omeprazole) may alter their exposure.

Repotrectinib [1], UGT substrates ---> SmPC of [1] of EMA

Co-administration of AUGTYRO with CYP2C8, CYP2C9 or CYP2C19 substrates (including but not limited to repaglinide, warfarin, tolbutamide or omeprazole) may alter their exposure.

Repotrectinib [1], valsartan ---> SmPC of [1] of EMA

Co-administration of AUGTYRO with sensitive substrates of P-gp, BCRP, OATP1B1, MATE1 or MATE2-K may increase their exposure. The clinical relevance is unknown.

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

Co-administration of AUGTYRO with strong or moderate CYP3A4 or P-gp inhibitors increases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

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

Co-administration of AUGTYRO with strong or moderate CYP3A4 or P-gp inhibitors increases repotrectinib plasma concentrations and should thus be avoided (see section 4.4).

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

Co-administration of AUGTYRO with CYP2C8, CYP2C9 or CYP2C19 substrates (including but not limited to repaglinide, warfarin, tolbutamide or omeprazole) may alter their exposure.

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

Female patients of childbearing potential should have medically supervised pregnancy testing prior to initiating AUGTYRO therapy.

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

Female patients of childbearing potential must use highly effective contraception during treatment with AUGTYRO and for at least 2 months following the final dose.

CONTRAINDICATIONS of Repotrectinib (Augtyro)

- 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/augtyro-epar-product-information_en.pdf 28/01/2025

Reslizumab (Cinqaero)

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

In humans, during the first few days after birth antibodies may be transferred to the newborns through milk. In this short period, a risk to the suckling child cannot be excluded. Afterwards, CINQAERO could be used during breast-feeding if appropriate.

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

There are no fertility data in humans. Available non-clinical data do not suggest an effect on fertility.

Immunosuppressant medicinal products, reslizumab [2] ---> SmPC of [2] of EMA

Reslizumab has not been studied in patients concurrently taking immunosuppressant medicinal products other than oral corticosteroids (OCS); therefore, the safety and efficacy profile of reslizumab in these patients is unknown.

Pharmacological interactions, reslizumab [2] ---> SmPC of [2] of EMA

In vitro data indicate that IL-5 and reslizumab are unlikely to affect CYP1A2, 3A4 or 2B6 activity. Based on the characteristics of reslizumab, drug-drug interactions are not expected.

Population pharmacokinetic analysis, reslizumab [2] ---> SmPC of [2] of EMA

Results of population pharmacokinetic analysis confirm that concomitant use of either leukotriene antagonists or systemic corticosteroids does not affect the pharmacokinetics of reslizumab

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

As a precautionary measure, it is preferable to avoid the use of CINQAERO during pregnancy. Reslizumab has a long half-life. This should be taken into consideration.

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

No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving reslizumab or the response to new immunisations in patients receiving reslizumab.

CONTRAINDICATIONS of Reslizumab (Cinqaero)

- 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/cinqaero-epar-product-information_en.pdf 26/05/2023

Respiratory syncytial virus vaccine (Arexvy)

Ability to drive, respiratory syncytial virus vaccine [2] ---> SmPC of [2] of EMA

Arexvy has a minor influence on the ability to drive and use machines. Some of the effects mentioned under section 4.8 "Undesirable effects" (e.g. fatigue) may temporarily affect the ability to drive or use machines.

Breast-feeding, respiratory syncytial virus vaccine [2] ---> SmPC of [2] of EMA

There are no data on the excretion of Arexvy in human or animal milk. Arexvy is not recommended in breast-feeding/lactating women.

Fertility, respiratory syncytial virus vaccine [2] ---> SmPC of [2] of EMA

Animal studies with Arexvy or with an investigational unadjuvanted RSVPreF3 vaccine do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

Influenza vaccine, respiratory syncytial virus vaccine [2] ---> SmPC of [2] of EMA

Arexvy may be administered concomitantly with seasonal influenza vaccine (quadrivalent, standard dose, unadjuvanted, inactivated).

Pregnancy, respiratory syncytial virus vaccine [2] ---> SmPC of [2] of EMA

Arexvy is not recommended during pregnancy.

Respiratory syncytial virus vaccine [1], vaccinations ---> SmPC of [1] of EMA

If Arexvy is to be given at the same time as another injectable vaccine, the vaccines should always be administered at different injection sites.

CONTRAINDICATIONS of Respiratory syncytial virus vaccine (Arexvy)

- 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/arexvy-epar-product-information_en.pdf 23/03/2026

Other trade names: Abrysvo

Retapamulin (Altargo)

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

A decision must be made to either discontinue breast-feeding or to discontinue/abstain from therapy

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

The strong CYP3A4 inhibition may increase the plasma concentrations of retapamulin. Caution is advised

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

Retapamulin ointment should only be used in pregnancy when topical antibacterial therapy is clearly indicated and the use of retapamulin is considered to be preferable

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

The strong CYP3A4 inhibition may increase the plasma concentrations of retapamulin. Caution is advised

CONTRAINDICATIONS of Retapamulin (Altargo)

- 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/altargo-epar-product-information_en.pdf 15/03/2019

Reteplase (Rapilysin)

Abciximab, reteplase [2] ---> SmPC of [2] of EMA

Heparin, vitamin K antagonists and medicinal product that alter platelet function (such as acetylsalicylic acid, dipyridamole and abciximab) may increase the risk of bleeding if administered prior to, during or after reteplase therapy.

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

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

It is not known whether reteplase is excreted into breast milk. Breast milk should be discarded within the first 24 hours after thrombolytic therapy.

Clopidogrel, reteplase [2] ---> SmPC of [2] of EMA

Caution should be employed when used reteplase with other medicinal products affecting haemostasis

Dipyridamole, reteplase [2] ---> SmPC of [2] of EMA

Enoxaparin sodium [1], reteplase ---> 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.

GP IIb/IIIa inhibitors, reteplase [2] ---> SmPC of [2] of EMA

Caution should be employed when used reteplase with other medicinal products affecting haemostasis

Heparin, reteplase [2] ---> SmPC of [2] of EMA

Heparinoids, reteplase [2] ---> SmPC of [2] of EMA

Caution should be employed when used reteplase with other medicinal products affecting haemostasis

Low molecular weight heparins, reteplase [2] ---> SmPC of [2] of EMA

Caution should be employed when used reteplase with other medicinal products affecting haemostasis

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

Caution should be employed when used reteplase with other medicinal products affecting haemostasis

Platelet aggregation inhibitors, reteplase [2] ---> SmPC of [2] of EMA

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

Except in life-threatening situations, Rapilysin should not be used in pregnant women.

Reteplase [1], ticlopidine ---> SmPC of [1] of EMA

Caution should be employed when used reteplase with other medicinal products affecting haemostasis

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

CONTRAINDICATIONS of Reteplase (Rapilysin)

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

Because thrombolytic therapy increases the risk of bleeding, reteplase is contra-indicated in the following situations:

- known haemorrhagic diathesis.

- patients with current concomitant therapy with oral anticoagulants (e.g. warfarin sodium)

- intracranial neoplasm, arteriovenous malformation or aneurysm

- neoplasm with increased bleeding risk

- history of cerebrovascular accident

- recent (< 10 days) prolonged and vigorous external heart massage

- severe uncontrolled hypertension

- active peptic ulceration

- portal hypertension (oesophageal varices)

- severe liver or renal dysfunction

- acute pancreatitis, pericarditis, bacterial endocarditis

- within 3 months of severe bleeding, major trauma or major surgery (e.g. coronary artery bypass graft, intracranial or intraspinal surgery or trauma), obstetrical delivery, organ biopsy, previous puncture of non-compressible vessels.

https://www.ema.europa.eu/en/documents/product-information/rapilysin-epar-product-information_en.pdf 01/06/2023

Retifanlimab (Zynyz)

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

Because of potential adverse reactions such as fatigue (see section 4.8), patients should be advised to use caution when driving or operating machinery until they are certain that retifanlimab does not adversely affect them.

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

For this specific period, a decision should be made whether to discontinue/abstain from retifanlimab therapy, taking into account the benefit of breast-feeding to the child and the benefit of therapy to the woman.

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

However, systemic corticosteroids or other immunosuppressants can be used after starting retifanlimab to treat immune-related adverse reactions (see sections 4.2 and 4.4).

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

The use of systemic corticosteroids or immunosuppressants before starting retifanlimab, except for physiological doses of systemic corticosteroids (≤ 10 mg/day prednisone or equivalent), should be avoided

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

Retifanlimab is not expected to be a victim or perpetrator of drug-drug interactions involving drug transporters or CYP enzymes.

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

No clinical data are available on the possible effects of retifanlimab on fertility. Animal reproduction studies to evaluate the effect of retifanlimab on fertility have not been conducted.

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

Interactions, retifanlimab [2] ---> SmPC of [2] of EMA

No formal pharmacokinetic drug interaction studies have been conducted with retifanlimab. Since retifanlimab is cleared from the circulation through catabolism, no metabolic drug-drug interactions are expected.

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

ZYNYZ is not recommended during pregnancy and in women of childbearing potential not using effective contraception (see section 5.3).

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

Women of childbearing potential should use effective contraception during treatment with retifanlimab and for at least 4 months after the last dose of retifanlimab.

CONTRAINDICATIONS of Retifanlimab (Zynyz)

- 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/zynyz-epar-product-information_en.pdf 02/05/2024

Retigabine (Trobalt)

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

Adverse reactions such as dizziness, somnolence, diplopia and blurred vision were reported in controlled clinical studies, particularly during titration

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

Co-administration of ethanol (1.0 g/kg) with retigabine (200 mg) resulted in an increase in visual blurring in healthy volunteers. It is recommended that patients are advised about the possible effects on vision if they take Trobalt with alcohol.

Anaesthetics, retigabine [2] ---> SmPC of [2] of EMA

Trobalt may increase the duration of anaesthesia induced by some anaesthetics (for example thiopental sodium)

Antiepileptics, retigabine [2] ---> SmPC of [2] of EMA

In vitro data indicated a low potential for interaction of retigabine with other antiepileptic drugs

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

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

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

Based on these pooled data, retigabine did not cause clinically significant effects on the plasma trough concentrations of this antiepileptic medicinal product and it had no clinically significant effects on retigabine pharmacokinetics

Clobazam, retigabine [2] ---> SmPC of [2] of EMA

Based on these pooled data, retigabine did not cause clinically significant effects on the plasma trough concentrations of this antiepileptic medicinal product

Clonazepam, retigabine [2] ---> SmPC of [2] of EMA

Based on these pooled data, retigabine did not cause clinically significant effects on the plasma trough concentrations of this antiepileptic medicinal product

Digoxin, retigabine [2] ---> SmPC of [2] of EMA

There was no meaningful change in digoxin Cmax. No dose adjustment of digoxin is needed.

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

The effect of retigabine on human fertility has not been established.

Gabapentin, retigabine [2] ---> SmPC of [2] of EMA

Based on these pooled data, retigabine did not cause clinically significant effects on the plasma trough concentrations of this antiepileptic medicinal product

Lamotrigine, retigabine [2] ---> SmPC of [2] 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

Levetiracetam, retigabine [2] ---> SmPC of [2] of EMA

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

No clinically significant effect of retigabine there was on the pharmacokinetics of the estrogen (ethinyl estradiol)/progestogen (norethindrone) nor low dose combination oral contraceptive on the pharmacokinetics of retigabine.

Oxcarbazepine, retigabine [2] ---> SmPC of [2] of EMA

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

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

Pregabalin, retigabine [2] ---> SmPC of [2] of EMA

Based on these pooled data, retigabine did not cause clinically significant effects on the plasma trough concentrations of pregabalin

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

In women being treated for epilepsy, sudden discontinuation of antiepileptic medicine therapy should be avoided as this may lead to breakthrough seizures that could have serious consequences for the woman and the unborn child.

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

Trobalt is not recommended during pregnancy and in women of childbearing age, not using contraception

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

Caution should be taken when Trobalt is prescribed with medicinal products known to increase QT interval and in patients with known prolonged QT interval, congestive cardiac failure, ventricular hypertrophy, hypokalaemia or hypomagnesaemia

Retigabine [1], thiopental ---> SmPC of [1] of EMA

Trobalt may increase the duration of anaesthesia induced by some anaesthetics (for example thiopental sodium; see section 5.1).

Retigabine [1], topiramate ---> SmPC of [1] of EMA

Retigabine [1], valproate ---> SmPC of [1] of EMA

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

Specialist advice should be given to women who are of childbearing potential. The need for treatment with antiepileptic medicinal products should be reviewed when a woman is planning to become pregnant.

Retigabine [1], zonisamide ---> 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

CONTRAINDICATIONS of Retigabine (Trobalt)

- 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/trobalt-epar-product-information_en.pdf 19/11/2018

Rezafungin (Rezzayo)

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

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

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

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

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

The need for dose adjustments is considered unlikely for medicinal products that are substrates for the CYP2C8, CYP3A4, CYP1A2, and CYP2B6 enzymes and P-gp, BCRP, OATP, OCT1, OCT2, MATE1, and MATE2 transporter proteins, when administered with rezafungin.

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

No data on the effect of rezafungin on human fertility are available. Rezafungin did not affect fertility in female rats or reproductive performance in male rats, despite reversible testicular effects in male rats (see section 5.3).

Ibrutinib, rezafungin [2] ---> SmPC of [2] of EMA

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

Medicinal products, rezafungin [2] ---> SmPC of [2] of EMA

The need for dose adjustments of rezafungin is considered unlikely when rezafungin is co-administered with other medicinal products.

Mycophenolate mofetil, rezafungin [2] ---> SmPC of [2] of EMA

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

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

Rezafungin is not recommended to be used during pregnancy and in women of childbearing potential not using contraception unless the benefit outweighs the potential risk to the foetus.

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.

Rezafungin [1], venetoclax ---> 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.

CONTRAINDICATIONS of Rezafungin (Rezzayo)

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

- Hypersensitivity to other medicinal products of the echinocandin class.

https://www.ema.europa.eu/en/documents/product-information/rezzayo-epar-product-information_en.pdf 18/06/2025

Ribavirin (Rebetol) (withdraw)

Abacavir [1], ribavirin ---> SmPC of [1] of EMA

As abacavir and ribavirin share the same phosphorylation pathways, a possible intracellular interaction between these drugs has been postulated, which could lead to a reduction in intracellular phosphorylated metabolites of ribavirin

Abacavir/lamivudine [1], ribavirin ---> SmPC of [1] of EMA

As abacavir and ribavirin share the same phosphorylation pathways, a possible intracellular interaction between these medicinal products has been postulated, which could lead to a reduction in intracellular phosphorylated metabolites of ribavirin

Abacavir/lamivudine/zidovudine [1], ribavirin ---> SmPC of [1] of EMA

Ribavirin inhibits phosphorylation of zidovudine, which may increase the HIV plasma viraemia. Concomitant use is not recommended due to an increased risk of anaemia

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

Patients who develop fatigue, somnolence, or confusion during treatment must be cautioned to avoid driving or operating machinery.

Aluminium, ribavirin [2] ---> SmPC of [2] of EMA

The bioavailability of ribavirin 600 mg was decreased by co-administration with an antacid containing magnesium aluminium and simethicone. This interaction is not considered to be clinically relevant.

Azathioprine, peginterferon/ribavirin ---> SmPC of [ribavirin] of EMA

Pancytopenia and bone marrow suppression have been reported in the literature to occur within 3 to 7 weeks after the administration of a peginterferon and ribavirin concomitantly with azathioprine.

Azathioprine, pegylated interferon alfa/ribavirin ---> SmPC of [ribavirin] of EMA

The use of pegylated alpha interferons and ribavirin concomitantly with azathioprine should be avoided.

Azathioprine, ribavirin [2] ---> SmPC of [2] of EMA

Rebetol, by having an inhibitory effect on inosine monophosphate dehydrogenase, may interfere with azathioprine metabolism possibly leading to an accumulation of 6-MTIMP, which has been associated with myelotoxicity in patients treated with azathioprine

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

It is not known whether Rebetol is excreted in human milk. Because of the potential for adverse reactions in breast-fed infants, breast-feeding must be discontinued prior to initiation of treatment.

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

Rebetol does not inhibit cytochrome P450 enzymes. There is no evidence from toxicity studies that Rebetol induces liver enzymes. Therefore, there is a minimal potential for P450 enzyme-based interactions.

Didanosine [1], ribavirin/stavudine ---> SmPC of [1] of eMC

Fatal hepatic failure, as well as peripheral neuropathy, pancreatitis and symptomatic hyperlactatemia/lactic acidosis have been reported in patients receiving didanosine and ribavirin with or without stavudine. Co-administration is not recommended

Didanosine, ribavirin [2] ---> SmPC of [2] of EMA

Pharmacologically, Rebetol increases phosphorylated metabolites of purine nucleosides in vitro. This activity could potentiate the risk of lactic acidosis induced by purine nucleoside analogs (e.g. didanosine or abacavir).

Dolutegravir/abacavir/lamivudine [1], ribavirin/abacavir ---> SmPC of [1] of EMA

Both drugs are guanosine analogues, and there is a potential to reduce intracellular phosphorylated metabolites. Caution should be exercised when both drugs are co-administered

Dolutegravir/lamivudine [1], ribavirin ---> SmPC of [1] of EMA

No dose adjustment is necessary.

Dolutegravir/rilpivirine [1], ribavirin ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], ribavirin ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], ribavirin ---> SmPC of [1] of EMA

No dose adjustment is required.

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

No clinically relevant drug-drug interaction is expected. No dose adjustment is required.

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

No dose adjustment of ribavirin is required.

Epoetin alfa [1], ribavirin ---> SmPC of [1] of EMA

The combination of epoetin alfa with interferon and ribavirin has led to a loss of effect and development of a condition called pure red cell aplasia (PRCA), a severe form of anaemia, in rare cases.

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

Based on the renal elimination pathway of ribavirin, no drug interactions are expected

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

Significant teratogenic and/or embryocidal potential have been demonstrated for Rebetol in all animal species in which adequate studies have been conducted, occurring at doses as low as one twentieth of the recommended human dose (see section 5.3).

Foods, ribavirin [2] ---> SmPC of [2] of EMA

The oral bioavailability was increased by coadministration of a high fat meal.

Half-life, ribavirin [2] ---> SmPC of [2] of EMA

Any potential for interactions may persist for up to two months (five half-lives for Rebetol) after cessation of Rebetol therapy due to the long half-life (see section 5.2).

Interferon alfa-2b, ribavirin [2] ---> SmPC of [2] of EMA

No pharmacokinetic interactions were noted between Rebetol and peginterferon alfa-2b or interferon alfa-2b in a multiple-dose pharmacokinetic study.

Interferon alfa-2b/ribavirin, nucleoside and nucleotide reverse transcriptase inhibitors ---> SmPC of [ribavirin]

Caution should be taken in HIV-positive subjects co-infected with HCV who receive nucleoside reverse transcriptase inhibitor (NRTI) treatment (especially ddI and d4T) and associated interferon alfa-2b/ribavirin treatment.

Magnesium, ribavirin [2] ---> SmPC of [2] of EMA

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

Male patients or their female partners of childbearing age must be advised to use an effective contraceptive during treatment with Rebetol and for six months after treatment.

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

Routine monthly pregnancy tests must be performed during this time. Men whose partners are pregnant must be instructed to use a condom to minimise delivery of Rebetol to the partner.

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

Extreme care must be taken to avoid pregnancy in partners of male patients taking Rebetol (see sections 4.3, 4.4 and 5.3). Rebetol accumulates intracellularly and is cleared from the body very slowly.

Nevirapine [1], ribavirin ---> SmPC of [1] of EMA

Ribavirin and nevirapine can be co-administered without dose adjustments

Peginterferon alfa-2a [1], ribavirin ---> SmPC of [1] of EMA

The use of peginterferon alfa-2a and ribavirin concomitantly with azathioprine should be avoided.

Peginterferon alfa-2b, ribavirin [2] ---> SmPC of [2] of EMA

No pharmacokinetic interactions were noted between Rebetol and peginterferon alfa-2b or interferon alfa-2b in a multiple-dose pharmacokinetic study.

Peginterferon alfa-2b, ribavirin [2] ---> SmPC of [2] of EMA

Initiation of peginterferon alfa-2b is contraindicated in HCV/HIV patients with cirrhosis and a Child-Pugh score ≥ 6.

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

The use of Rebetol is contraindicated during pregnancy. Rebetol has been shown in preclinical studies to be teratogenic and genotoxic

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

There is no evidence that Rebetol interacts with non-nucleoside reverse transcriptase inhibitors or protease inhibitors.

Ribavirin [1], simeticone ---> SmPC of [1] of EMA

Ribavirin [1], teratogenic risk ---> SmPC of [1] of EMA

If pregnancy does occur during treatment or within nine months from stopping treatment, the patient must be advised of the significant teratogenic risk of Rebetol to the foetus (see section 4.4).

Ribavirin [1], women ---> SmPC of [1] of EMA

Rebetol must not be used by females who are pregnant. Extreme care must be taken to avoid pregnancy in female patients. Rebetol therapy must not be initiated until a report of a negative pregnancy test has been obtained immediately prior to initiation of

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

Females of childbearing potential must use an effective contraceptive during treatment and for nine months after treatment has been concluded; routine monthly pregnancy tests must be performed during this time.

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

The exacerbation of anaemia due to Rebetol has been reported when zidovudine is part of the regimen used to treat HIV. The concomitant use of Rebetol with zidovudine is not recommended due to an increased risk of anaemia.

Ribavirin, rilpivirine [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required.

Ribavirin, stavudine [2] ---> SmPC of [2] of EMA

In vitro studies indicate that the activation of stavudine is inhibited by doxorubicin and ribavirin therefore, coadministration of stavudine with either doxorubicin or ribavirin should be undertaken with caution.

Ribavirin, zalcitabine

Ribavirin may increase the hepatotoxicity of zalcitabine.

CONTRAINDICATIONS of Ribavirin (Rebetol) (withdraw) - Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Pregnancy (see sections 4.4, 4.6 and 5.3). In females of childbearing potential, Rebetol must not be initiated until a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy.

- Breast-feeding.

- History of severe pre-existing cardiac disease, including unstable or uncontrolled cardiac disease, in the previous six months (see section 4.4).

- Haemoglobinopathies (e.g., thalassemia, sickle-cell anaemia).

Please refer to the corresponding SmPC of medicinal products used in combination with Rebetol for contraindications specific to these products.

https://www.ema.europa.eu/en/documents/product-information/rebetol-epar-product-information_en.pdf 07/11/2023

Other trade names: Copegus, Cotronak, Ribavirina Aurobindo, Ribavirin BioPartners, Ribavirin Mylan (previously Ribavirin Three Rivers), Ribavirina Normon, Ribavirina Sandoz, Ribavirin Teva, Ribavirin Teva Pharma B.V.,

Ribociclib (Kisqali)

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

Kisqali may have minor influence on the ability to drive and use machines. Patients should be advised to be cautious when driving or using machines in case they experience fatigue, dizziness or vertigo during treatment with Kisqali (see section 4.8).

Alfentanyl, ribociclib [2] ---> SmPC of [2] 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

Alfuzosin, ribociclib [2] ---> SmPC of [2] of EMA

Concomitant administration of ribociclib at the 600 mg dose this CYP3A4 substrates should be avoided

Alpelisib [1], ribociclib ---> SmPC of [1] of EMA

Caution is recommended when Piqray is used in combination with CYP3A4 substrates that also possess an additional time-dependent inhibition and induction potential on CYP3A4 that affects their own metabolism (e.g. rifampicin, ribociclib, encorafenib).

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

Coadministration of ribociclib at the 600 mg dose this CYP3A4 substrates should be avoided. Co-administration of Kisqali with medicines with a known potential to prolong the QT interval such as anti-arrhythmic medicinal products should be avoided

Anastrozole, ribociclib [2] ---> SmPC of [2] of EMA

Data from a clinical study in patients with breast cancer indicated no clinically relevant drug interaction between ribociclib and anastrozole following co-administration of these medicinal products.

Antiarrhythmics, ribociclib [2] ---> SmPC of [2] of EMA

Co-administration of Kisqali with medicinal products with a known potential to prolong the QT interval such as anti-arrhythmic medicinal products and other medicinal products that are known to prolong the QT interval should be avoided

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

BCRP substrates with narrow therapeutic range, ribociclib [2] ---> SmPC of [2] of EMA

Caution and monitoring for toxicity are advised during concomitant treatment with sensitive substrates of these transporters which exhibit a narrow therapeutic index

Bepridil, ribociclib [2] ---> SmPC of [2] of EMA

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

Ribociclib and its metabolites readily passed into the milk of lactating rats. Patients receiving Kisqali should not breast-feed for at least 21 days after the last dose.

BSEP substrates with small therapeutic index, ribociclib [2] ---> SmPC of [2] of EMA

Caution and monitoring for toxicity are advised during concomitant treatment with sensitive substrates of these transporters which exhibit a narrow therapeutic index

Caffeine, ribociclib [2] ---> SmPC of [2] of EMA

At the clinically relevant dose of 600 mg, simulations using PBPK models predicted only weak inhibitory effects of ribociclib on CYP1A2 substrates (<2-fold increase in AUC).

Capivasertib [1], ribociclib ---> 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, ribociclib [2] ---> SmPC of [2] of EMA

The concomitant use of strong CYP3A4 inducers may therefore lead to decreased exposure and consequently a risk for lack of efficacy. The concomitant use of strong CYP3A4 inducers should be avoided

Chloroquine, ribociclib [2] ---> SmPC of [2] of EMA

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

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

Concomitant administration of ribociclib at the 600 mg dose this CYP3A4 substrates should be avoided

Clarithromycin, ribociclib [2] ---> SmPC of [2] 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.

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

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

No dose adjustments of ribociclib are required at initiation of treatment with mild or moderate CYP3A4 inhibitors. However, monitoring of ribociclib-related AEs is recommended.

Digoxin, ribociclib [2] ---> SmPC of [2] of EMA

Caution and monitoring for toxicity are advised during concomitant treatment with sensitive substrates of this transporter which exhibit a narrow therapeutic index

Dihydroergotamine, ribociclib [2] ---> SmPC of [2] of EMA

Concomitant administration of ribociclib at the 600 mg dose this CYP3A4 substrates should be avoided

Disopyramide, ribociclib [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP1A2, ribociclib [2] ---> SmPC of [2] of EMA

At the clinically relevant dose of 600 mg, simulations using PBPK models predicted only weak inhibitory effects of ribociclib on CYP1A2 substrates (<2-fold increase in AUC).

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, ribociclib [2] ---> SmPC of [2] of EMA

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

Ribociclib is a moderate to strong CYP3A4 inhibitor and may interact with medicinal substrates that are metabolised via CYP3A4, which can lead to increased serum concentrations of the concomitantly used medicinal product.

Efavirenz, ribociclib [2] ---> SmPC of [2] of EMA

The concomitant use of moderate CYP3A4 inducers may lead to decreased exposure and consequently a risk for impaired efficacy, in particular in patients treated with ribociclib at 400 mg or 200 mg once daily.

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

Concomitant administration of ribociclib at the 600 mg dose this CYP3A4 substrates should be avoided

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

No dose adjustments of ribociclib are required at initiation of treatment with mild or moderate CYP3A4 inhibitors. However, monitoring of ribociclib-related AEs is recommended.

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

Fentanyl, ribociclib [2] ---> SmPC of [2] of EMA

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

There are no clinical data available regarding effects of ribociclib on fertility. Based on animal studies, ribociclib may impair fertility in males of reproductive potential (see section 5.3).

Fulvestrant, ribociclib [2] ---> SmPC of [2] of EMA

Data from a clinical study in patients with breast cancer indicated no clinically relevant effects of fulvestrant on ribociclib exposure following co-administration of these medicinal products.

Gastric pH increasing medication, ribociclib [2] ---> SmPC of [2] of EMA

Ribociclib exhibits high solubility at or below pH 4.5 and in bio-relevant media (at pH 5.0 and 6.5). However, altered ribociclib absorption was not observed in population pharmacokinetic and non-compartmental pharmacokinetic analyses.

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

Patients should be instructed to avoid pomegranates or pomegranate juice and grapefruit or grapefruit juice. These are known to inhibit cytochrome CYP3A4 enzymes and may increase the exposure to ribociclib.

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

Halofantrine, ribociclib [2] ---> SmPC of [2] of EMA

Haloperidol, ribociclib [2] ---> SmPC of [2] of EMA

Indinavir, ribociclib [2] ---> SmPC of [2] 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.

Itraconazol, ribociclib [2] ---> SmPC of [2] 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.

Ketoconazole, ribociclib [2] ---> SmPC of [2] 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.

Letrozol, ribociclib [2] ---> SmPC of [2] of EMA

Data from a clinical study in patients with breast cancer and population pharmacokinetic analysis indicated no drug interaction between ribociclib and letrozole following co-administration of these medicinal products.

Levofloxacin, ribociclib [2] ---> SmPC of [2] of EMA

Lopinavir, ribociclib [2] ---> SmPC of [2] 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.

Lovastatine, ribociclib [2] ---> SmPC of [2] of EMA

Concomitant administration of ribociclib at the 600 mg dose this CYP3A4 substrates should be avoided

MATE1 substrates with small therapeutic index, ribociclib [2] ---> SmPC of [2] of EMA

Caution and monitoring for toxicity are advised during concomitant treatment with sensitive substrates of these transporters which exhibit a narrow therapeutic index

Metformin, ribociclib [2] ---> SmPC of [2] of EMA

Caution and monitoring for toxicity are advised during concomitant treatment with sensitive substrates of this transporter which exhibit a narrow therapeutic index

Methadone, ribociclib [2] ---> SmPC of [2] of EMA

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

Concomitant administration of ribociclib at the 600 mg dose this CYP3A4 substrates should be avoided

Moderate CYP3A4 inductors, ribociclib [2] ---> SmPC of [2] of EMA

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

No dose adjustments of ribociclib are required at initiation of treatment with mild or moderate CYP3A4 inhibitors. However, monitoring of ribociclib-related AEs is recommended.

Moxifloxacin, ribociclib [2] ---> SmPC of [2] of EMA

Nefazodone, ribociclib [2] ---> SmPC of [2] 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.

Nelfinavir, ribociclib [2] ---> SmPC of [2] 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.

OATP1B1 substrates with small therapeutic index, ribociclib [2] ---> SmPC of [2] of EMA

Caution and monitoring for toxicity are advised during concomitant treatment with sensitive substrates of these transporters which exhibit a narrow therapeutic index

OATP1B3 substrates with small therapeutic index, ribociclib [2] ---> SmPC of [2] of EMA

Caution and monitoring for toxicity are advised during concomitant treatment with sensitive substrates of these transporters which exhibit a narrow therapeutic index

OCT1 substrates with small therapeutic index, ribociclib [2] ---> SmPC of [2] of EMA

Caution and monitoring for toxicity are advised during concomitant treatment with sensitive substrates of these transporters which exhibit a narrow therapeutic index

OCT2 substrates with small therapeutic index, ribociclib [2] ---> SmPC of [2] of EMA

Caution and monitoring for toxicity are advised during concomitant treatment with sensitive substrates of these transporters which exhibit a narrow therapeutic index

Ondansetron, ribociclib [2] ---> SmPC of [2] of EMA

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

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

P-glycoprotein substrates with small therapeutic index, ribociclib [2] ---> SmPC of [2] of EMA

Caution and monitoring for toxicity are advised during concomitant treatment with sensitive substrates of these transporters which exhibit a narrow therapeutic index

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

The concomitant use of strong CYP3A4 inducers may therefore lead to decreased exposure and consequently a risk for lack of efficacy. The concomitant use of strong CYP3A4 inducers should be avoided

Pimozide, ribociclib [2] ---> SmPC of [2] of EMA

Pitavastatin, ribociclib [2] ---> SmPC of [2] of EMA

Caution and monitoring for toxicity are advised during concomitant treatment with sensitive substrates of this transporter which exhibit a narrow therapeutic index

Pomegranate juice, ribociclib [2] ---> SmPC of [2] of EMA

Pomegranate, ribociclib [2] ---> SmPC of [2] of EMA

Posaconazole, ribociclib [2] ---> SmPC of [2] 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.

Pravastatine, ribociclib [2] ---> SmPC of [2] of EMA

Caution and monitoring for toxicity are advised during concomitant treatment with sensitive substrates of this transporter which exhibit a narrow therapeutic index

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

Pregnancy status should be verified prior to starting treatment with Kisqali. Kisqali is not recommended during pregnancy and in women of childbearing potential not using contraception.

Procainamide, ribociclib [2] ---> SmPC of [2] of EMA

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

The use of Kisqali with medicinal products known to prolong QTc interval and/or strong CYP3A4 inhibitors should be avoided as this may lead to clinically meaningful prolongation of the QTcF interval

Quetiapine, ribociclib [2] ---> SmPC of [2] of EMA

Concomitant administration of ribociclib at the 600 mg dose this CYP3A4 substrates should be avoided

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

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

The concomitant use of strong CYP3A4 inducers may therefore lead to decreased exposure and consequently a risk for lack of efficacy. The concomitant use of strong CYP3A4 inducers should be avoided

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

Caution and monitoring for toxicity are advised during concomitant treatment with sensitive substrates of this transporter which exhibit a narrow therapeutic index

Ribociclib [1], saquinavir ---> 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.

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

Concomitant administration of ribociclib at the 600 mg dose this CYP3A4 substrates should be avoided

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

Concomitant administration of ribociclib at the 600 mg dose this CYP3A4 substrates should be avoided

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

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

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

The concomitant use of strong CYP3A4 inducers may therefore lead to decreased exposure and consequently a risk for lack of efficacy. The concomitant use of strong CYP3A4 inducers should be avoided

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

The concomitant use of strong CYP3A4 inducers may therefore lead to decreased exposure and consequently a risk for lack of efficacy. The concomitant use of strong CYP3A4 inducers should be avoided

Ribociclib [1], strong CYP3A4 inhibitors ---> 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.

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

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

Data from a clinical study in patients with breast cancer indicated that tamoxifen exposure was increased approximately 2-fold following co-administration of ribociclib and tamoxifen. Kisqali is not recommended to be used in combination with tamoxifen

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.

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.

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

Concomitant administration of ribociclib at the 600 mg dose this CYP3A4 substrates should be avoided

Ribociclib [1], UGT1A1 substrates with narrow therapeutic index ---> SmPC of [1] of EMA

Caution and monitoring for toxicity are advised during concomitant treatment with sensitive substrates of these transporters which exhibit a narrow therapeutic index

Ribociclib [1], verapamil ---> 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.

Ribociclib [1], voriconazole ---> 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.

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

Women of childbearing potential who are receiving Kisqali should use effective contraception (e.g. double-barrier contraception) during therapy and for at least 21 days after stopping treatment with Kisqali.

Ribociclib, ritonavir [2] ---> SmPC of [2] 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.

CONTRAINDICATIONS of Ribociclib (Kisqali)

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

https://www.ema.europa.eu/en/documents/product-information/kisqali-epar-product-information_en.pdf 21/08/2024

Rifabutin

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

Strong inducers of CYP3A4 (decreased mean plasma AUCinf of abiraterone) during treatment are to be avoided, unless there is no therapeutic alternative.

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

Appropriate monitoring is recommended for patients taking concomitant strong CYP3A inducers (including, but not limited to, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampicin and St. John's Wort (Hypericum perforatum)).

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

Co-administration of amprenavir with rifabutin resulted in a 193 %increase in rifabutin AUC and an increase of rifabutin-related adverse events.

Analgesics, rifabutin [2] ---> SmPC of [2] of eMC

Rifabutin has been shown to induce the enzymes of the cytochrome P450 3A subfamily and therefore may affect the pharmacokinetic behaviour of drugs metabolised by the enzymes belonging to this subfamily.

Antacids, rifabutin

Antacids should be taken 3 hours after taking rifabutin in order to avoid interactions

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

Antiepileptics, rifabutin

Rifabutin has a similar structure as rifampicin. Concomitant use of rifabutin and anticonvulsants may decrease anticonvulsant effects

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

Concomitant administration of aripiprazole and inducers of CYP3A4 may be expected to reduce the geometric means of Cmax and AUC for aripiprazole. The concomitant use of CYP3A4 inducers with aripiprazole should be avoided

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

CYP3A4 inhibition by atazanavir and cobicistat may increase rifabutin exposition. Co-administration of EVOTAZ and rifabutin is not recommended.

Atazanavir/ritonavir, rifabutin ---> SmPC of [atazanavir] of EMA

Increased monitoring for rifabutin-associated adverse reactions including neutropenia and uveitis is warranted due to an expected increase in exposure to rifabutin.

Atovaquone [1], rifabutin ---> SmPC of [1] of eMC

Concomitant administration of rifampicin or rifabutin is not recommended as it is known to reduce plasma concentrations of atovaquone

Atovaquone/proguanil [1], rifabutin ---> SmPC of [1] of eMC

Concomitant administration of rifampicin or rifabutin is not recommended as it is known to reduce plasma concentrations of atovaquone

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

Co-administration of axitinib with strong CYP3A4/5 inducers may decrease axitinib plasma concentrations. Selection of concomitant medicinal products with no or minimal CYP3A4/5 induction potential is recommended.

Azithromycin [1], rifabutin ---> SmPC of [1] of eMC

Coadministration of azithromycin and rifabutin did not affect the serum concentrations of either drug. Neutropenia was observed in subjects receiving concomitant treatment of azithromycin and rifabutin.

Barbiturates, rifabutin

Rifabutin has a similar structure as rifampicin. Concomitant use of rifabutin and barbiturates may decrease the barbiturate effects

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

Bedaquiline exposure may be reduced during co-administration with inducers of CYP3A4. Co-administration of bedaquiline and moderate or strong CYP3A4 inducers used systemically should be avoided.

Betablockers, rifabutin

Rifabutin has a similar structure as rifampicin. Concomitant use of rifabutin and betablockers may decrease betablocker effects

Bictegravir/emtricitabine/tenofovir alafenamide [1], rifabutin ---> SmPC of [1] of EMA

Co-administration is not recommended due to the expected decrease of tenofovir alafenamide.

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

The concomitant use of bosutinib with strong CYP3A inductors should be avoided, as a decrease in bosutinib plasma levels will occur.

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

Due to lack of data in pregnant women, as a precautionary measure, rifabutin should not be administered to breast-feeding women

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

The concomitant use of strong CYP3A inducers with Alunbrig should be avoided

Brotizolam, rifabutin

The strong CYP3A4 induction may decrease the plasma concentrations of brotizolam

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

Repeated administration of rifampin, a strong CYP3A inducer, resulted in an increase in cabazitaxel clearance. Therefore concomitant administration of strong CYP3A inducers should be avoided as a decrease of plasma concentrations of cabazitaxel may occur

Cardiac glycosides, rifabutin [2] ---> SmPC of [2] of eMC

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

Co-administration of ceritinib with strong CYP3A inducers decreases ceritinib plasma concentrations. Concomitant use of strong CYP3A inducers should be avoided.

Chloramphenicol, rifabutin

Rifabutin has a similar structure as rifampicin. Concomitant use of rifabutin and chloramphenicol may decrease chloramphenicol effects

Cimetidine, rifabutin

The co-administration of rifabutin with enzymatic inhibitors, e.g. cimetidine, may increase the bioavailability of rifabutin. A reduction of the doses may be required

Clarithromycin [1], rifabutin ---> SmPC of [1] of eMC

Concomitant administration of rifabutin and clarithromycin resulted in an increase in rifabutin, and decrease in clarithromycin serum levels together with an increased risk of uveitis.

Clofibrate, rifabutin

Rifabutin has a similar structure as rifampicin. Concomitant use of rifabutin and clofibrate may decrease clofibrate effects

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

Co-administration of rifabutin, a potent CYP3A inducer, may significantly decrease cobicistat plasma concentrations. The combination is not recommended

Conjugated oestrogens/bazedoxifene [1], rifabutin ---> SmPC of [1] of EMA

The metabolism of oestrogens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes

Corticosteroids, rifabutin [2] ---> SmPC of [2] of eMC

Cotrimoxazole, rifabutin [2] ---> SmPC of [2] of eMC

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

Coadministration of crizotinib with strong CYP3A inducers may decrease crizotinib plasma concentrations. The concurrent use of strong CYP3A inducers should be avoided

Cyclosporine, rifabutin [2] ---> SmPC of [2] of eMC

Cyproterone/ethinylestradiol [1], rifabutin ---> 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.

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

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

Dapsone, rifabutin [2] ---> SmPC of [2] of eMC

Darunavir/cobicistat [1], rifabutin ---> SmPC of [1] of EMA

Based on theoretical considerations rifabutin (CYP3A induction) is expected to decrease darunavir and/or cobicistat plasma concentrations. Co-administration of darunavir/cobicistat with rifabutin is not recommended.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], rifabutin ---> SmPC of [1] of EMA

Based on theoretical considerations these antimycobacterials are expected to decrease darunavir and/or cobicistat and/or tenofovir alafenamide plasma concentrations. CYP3A and/or P-gp induction

Darunavir/ritonavir, rifabutin ---> SmPC of [darunavir] of EMA

Rifabutin, inducer and substrate of CYP3A, may increase the darunavir exposition

Desogestrel [1], rifabutin ---> SmPC of [1] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones

Diazepam, rifabutin

Rifabutin has a similar structure as rifampicin. Concomitant use of rifabutin and diazepam may decrease the diazepam effects

Didanosine, rifabutin

No dosage adjustment necessary.

Digitoxin, rifabutin

The strong CYP3A4 induction may decrease the plasma concentrations of digitoxin

Disopyramide, rifabutin

Rifabutin has a similar structure as rifampicin. Concomitant use of rifabutin and disopyramide may decrease disopyramide effects

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

The induction of UGT1A1 and CYP3A may decrease the dolutegravir plasma levels. No dosage adjustment necessary.

Dolutegravir/abacavir/lamivudine [1], rifabutin ---> SmPC of [1] of EMA

The induction of UGT1A1 and CYP3A may decrease the dolutegravir plasma levels. No dosage adjustment necessary.

Drugs primarily metabolised by CYP3A4, rifabutin [2] ---> SmPC of [2] of eMC

Dydrogesterone/estradiol [1], rifabutin ---> 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

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

The CYP3A4 induction by efavirenz decreases the plasma concentrations of rifabutin

Efavirenz/emtricitabine/tenofovir disoproxil [1], rifabutin ---> SmPC of [1] of EMA

The CYP3A4 induction may decrease the rifabutin exposition

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

Concomitant administration of a strong CYP3A4 inducer resulted in a decrease in eliglustat exposure. Use of a strong CYP3A inducer with eliglustat is not recommended in poor, intermediate and extensive metabolisers.

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

Co-administration of elvitegravir and rifabutin is not recommended.

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

Co-administration of rifabutin, a potent CYP3A inducer, may significantly decrease cobicistat and elvitegravir plasma concentrations, which may result in loss of therapeutic effect and development of resistance.

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

Co-administration of rifabutin, a potent CYP3A inducer, may significantly decrease cobicistat and elvitegravir plasma concentrations. The combination is not recommended

Elvitegravir/ritonavir, rifabutin ---> SmPC of [elvitegravir] of EMA

Co-administration of elvitegravir and rifabutin is not recommended.

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

Co-administration is likely to cause significant decreases in the plasma concentrations of tenofovir alafenamide (induction of P-gp). Co-administration is contraindicated.

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

Co-administration is likely to cause significant decreases in rilpivirine plasma concentrations (induction of CYP3A enzymes).

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

Medicinal products that induce P-gp activity (e.g., rifampicin, rifabutin, carbamazepine, phenobarbital) are expected to decrease the absorption of tenofovir alafenamide, resulting in decreased plasma concentration of tenofovir alafenamide

Enzyme inhibitors, rifabutin

The co-administration of rifabutin with enzymatic inhibitors, e.g. cimetidine, may increase the bioavailability of rifabutin. A reduction of the doses may be required

Estradiol valerate/norgestrel [1], rifabutin ---> 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

Estradiol [1], rifabutin ---> SmPC of [1] of eMC

The metabolism of estrogens and progestagens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes

Estradiol/norethisterone [1], rifabutin ---> SmPC of [1] of eMC

The metabolism of oestrogens and progestogens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes

Estrogens, rifabutin ---> SmPC of [estradiol] of eMC

The metabolism of estrogens and progestagens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes

Ethambutol, rifabutin [2] ---> SmPC of [2] of eMC

No significant interaction may be expected with ethambutol, theophylline, sulphonamides, pyrazinamide and zalcitabine

Ethinyl estradiol, rifabutin ---> 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, rifabutin

Interactions can occur with drugs that induce hepatic enzymes which can result in increased clearance of sex hormones

Ethinylestradiol/desogestrel [1], rifabutin ---> SmPC of [1] of eMC

Interactions can occur with drugs that induce microsomal enzymes, which can result in increased clearance of sex hormones

Ethinylestradiol/gestodene [1], rifabutin ---> 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], rifabutin ---> 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.

Etravirine with a boosted PI, rifabutin ---> SmPC of [etravirine] of EMA

The combination of etravirine with a boosted PI and rifabutin should be used with caution due to the risk of decrease in etravirine exposure and the risk of increase in rifabutin and 25-O-desacetyl-rifabutin exposures.

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

Based on historical data, a decrease in etravirine exposure may be expected whereas an increase in rifabutin exposure and especially in 25-O-desacetyl-rifabutin may be expected.

Fluconazole [1], rifabutin ---> SmPC of [1] of eMC

Fluconazole increases serum concentrations of rifabutin, leading to increase in the AUC of rifabutin up to 80%. There have been reports of uveitis in patients to whom fluconazole and rifabutin were coadministered.

Fludrocortisone [1], rifabutin ---> SmPC of [1] of eMC

Increased metabolic clearance of fludrocortisone. Patients should be carefully observed for possible diminished effect of steroid, and the dosage should be adjusted accordingly.

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

The increase of 25-O-desacetylrifabutin (active metabolite) (mixed CYP3A4 induction/inhibition) could potentially lead to an increase of rifabutin related adverse events, notably uveitis. A reduction in the rifabutin dosage by at least 75% is recommended

Gestagens, rifabutin ---> SmPC of [estradiol] of eMC

The metabolism of estrogens and progestagens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes

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

There was a significant decrease in the rate and extent of guanfacine exposure when co-administered with rifampin, a CYP3A4 inducer. Other CYP3A4 inducers may have a comparable effect

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

Potent CYP 3A4 inducers can enhance the metabolic clearance of cortisol, decrease terminal half-life and thus reduce circulating levels and increase fluctuations of cortisol (due to shorter terminal half-life).

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

The co-administration of idelalisib with rifabutin may increase the serum concentrations of rifabutin. Increased monitoring for rifabutin-associated adverse reactions including neutropenia and uveitis is recommended.

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

Dose reduction of rifabutin and dose increase of Crixivan has not been confirmed in clinical studies. Therefore coadministration is not recommended. If rifabutin treatment is required, alternative agents for treating HIV infection should be sought.

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

The CYP3A4 inhibition/induction may increase/decrease the plasma concentrations of rifabutin/indinavir.

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

Co-administration of CRESEMBA with potent/moderate CYP3A4/5 inducers is contraindicated, since these medicinal products can significantly decrease plasma concentrations of isavuconazole

Isoniazid, rifabutin [2] ---> SmPC of [2] of eMC

Clinical studies have shown that rifabutin does not affect the pharmacokinetics of isoniazid

Itraconazol [1], rifabutin ---> SmPC of [1] of eMC

Coadministration of itraconazole with potent enzyme inducers of CYP3A4 may decrease the bioavailability of itraconazole and hydroxy-itraconazole to such an extent that efficacy may be largely reduced.

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

Co-administration of ivacaftor with rifampicin, a strong CYP3A inducer, decreased ivacaftor exposure (AUC) and M1 exposure. Co-administration with strong CYP3A inducers is not recommended

Ixabepilone, rifabutin

The strong CYP3A4 induction may reduce plasma concentrations of ixabepilone

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

Ketoconazole HRA is mainly metabolised by cytochrome CYP3A4. Enzyme-inducing drugs may significantly reduce the bioavailability of ketoconazole. Use of Ketoconazole HRA with potent enzyme inducers is not recommended.

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

Lapatinib is predominantly metabolised by CYP3A. The CYP3A4 induction decreases the exposition to lapatinib. Co-administration of lapatinib with known inducers of CYP3A4 should be avoided.

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

Medicinal products that are potent P-gp inducers may significantly decrease ledipasvir and sofosbuvir plasma concentrations leading to reduced therapeutic effect of ledipasvir/sofosbuvir and thus are contraindicated with Harvoni

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

Co-treatment with moderate and strong inducers may give rise to subtherapeutic letermovir exposure

Levonorgestrel [1], rifabutin ---> SmPC of [1] of eMC

The metabolism of levonorgestrel is enhanced by concomitant use of liver enzyme inducers.

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

Lopinavir/ritonavir, CYP3A4 inhibitors, may increase the exposition of rifabutin

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

A higher dose of rifabutin may be required to obtain the desired clinical effect. Lumacaftor/ivacaftor may decrease the exposure of rifabutin, which may reduce its efficacy.

Medroxyprogesterone, rifabutin ---> SmPC of [estradiol] of eMC

The metabolism of progestogens may be increased by concomitant administration of compounds known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes.

Methadone, rifabutin [2] ---> SmPC of [2] of eMC

Methylprednisolone, rifabutin

The strong CYP3A4 induction may decrease the plasma concentrations of glucocorticoid

Mexiletine, rifabutin

Rifabutin has a similar structure as rifampicin. Concomitant use of rifabutin and mexiletine may decrease mexiletine effects

Miconazole, rifabutin

Miconazole, strong CYP3A4 inhibitor, may increase the plasma levels of rifabutin. Caution is recommended

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

Mitotane has been shown to have an inductive effect on cytochrome P450 enzymes. Therefore, the plasma concentrations of the substances metabolised via cytochrome P450 may be modified.

Narcotics, rifabutin [2] ---> SmPC of [2] of eMC

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

Increased AUC values of rifabutin and decreased AUC values of nelfinavir

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

Rifabutin and nevirapine can be co-administered without dose adjustments. However, due to the high interpatient variability some patients may experience large increases in rifabutin exposure and may be at higher risk for rifabutin toxicity.

Norelgestromin/ethinylestradiol [1], rifabutin ---> SmPC of [1] of EMA

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

Norethisterone acetate, rifabutin

Reduced contraceptive efficacy with hepatic enzyme-inducing drugs

Norethisterone enantate [1], rifabutin ---> SmPC of [1] of eMC

Reduced contraceptive efficacy with hepatic enzyme-inducing drugs

Norgestimate, rifabutin

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

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

The magnitude of the effect of moderate to strong inducers (e.g. efavirenz, rifabutin) on olaparib exposure is not established, therefore the co-administration of olaparib with these drugs is also not recommended.

Oral antidiabetics, rifabutin [2] ---> SmPC of [2] of eMC

Oral contraceptives, rifabutin [2] ---> SmPC of [2] of eMC

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

Rifampicin, strong CYP3A/CYP2C9 enzyme inducer, decreased the ospemifene AUC by 58%. Therefore, co-administration of ospemifene with strong enzyme inducers would be expected to decrease the exposure of ospemifene, which may decrease the clinical effect.

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

Strong inducers may reduce the efficacy of panobinostat, therefore the concomitant use of strong CYP3A4 inducers should be avoided.

Para-aminosalicylic acid, rifabutin [2] ---> SmPC of [2] of eMC

As p-aminosalicylic acid has been shown to impede GI absorption of rifamycins it is recommended that when it and rifabutin are both to be administered they be given with an interval of 8-12 hours.

Para-aminosalicylic acid, rifamicyn ---> SmPC of [rifabutin] of eMC

As p-aminosalicylic acid has been shown to impede GI absorption of rifamycins it is recommended that when it and rifabutin are both to be administered they be given with an interval of 8-12 hours.

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

The possible induction of CYP3A4 and P-glycoprotein may decrease the plasma concentrations of pazopanib. The combination should be avoided

Phenytoin, rifabutin [2] ---> SmPC of [2] of eMC

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

Coadministration of ponatinib with strong CYP3A4 inducers (decreases in ponatinib exposure are possible) should be avoided, and alternatives to the CYP3A4 inducer should be sought, unless the benefit outweighs the possible risk of ponatinib underexposure

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

Rifabutin can decrease the plasma levels of posaconazole. Posaconazole may increase plasma levels of rifabutin. Concomitant use should be avoided

Prednisone [1], rifabutin ---> SmPC of [1] of eMC

The efficacy of glucocorticoids is reduced.

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

Due to lack of data in pregnant women, as a precautionary measure, rifabutin should not be administered to pregnant women

Progestagens, rifabutin

Rifabutin has a similar structure as rifampicin. Concomitant use of rifabutin and progestagens may decrease progestagen effects

Pyrazinamide, rifabutin [2] ---> SmPC of [2] of eMC

No significant interaction may be expected with ethambutol, theophylline, sulphonamides, pyrazinamide and zalcitabine

Quinidine, rifabutin [2] ---> SmPC of [2] of eMC

Rifabutin [1], sulfonylureas ---> SmPC of [1] of eMC

Rifabutin [1], sulphonamides ---> SmPC of [1] of eMC

No significant interaction may be expected with ethambutol, theophylline, sulphonamides, pyrazinamide and zalcitabine

Rifabutin [1], theophylline ---> SmPC of [1] of eMC

No significant interaction may be expected with ethambutol, theophylline, sulphonamides, pyrazinamide and zalcitabine

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

Throughout co-administration of rilpivirine with rifabutin, the rilpivirine dose should be increased from 25 mg once daily to 50 mg once daily. When rifabutin co-administration is stopped, the rilpivirine dose should be decreased to 25 mg once daily.

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

Due to the large increase in rifabutin AUC, the concomitant use of rifabutin with ritonavir dosed as an antiretroviral agent is contraindicated

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

The effect of moderate inducers (e.g. efavirenz, rifabutin) is not established; therefore, the use of rolapitant in patients already given a moderate inducer is not recommended

Rifabutin, roxithromycin

Roxithromycin may increase the plasma levels of rifabutin

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

The strong CYP3A4 induction may reduce the AUC of ruxolitinib. It is possible that an increase of the ruxolitinib dose is needed with strong CYP3A4 inductors

Rifabutin, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Possible increase in exposure to rifabutin. Monitoring of neutropenia and liver enzyme levels is recommended

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

It is not recommended to co-administer simeprevir with rifabutin (CYP3A4 enzyme induction) as co-administration may result in loss of therapeutic effect of simeprevir.

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

Inductors of CYP3A4 increase the metabolism of sirolimus and decrease sirolimus levels. Co-administration of sirolimus with strong inductors of CYP3A4 is not recommended

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

Medicinal products that are potent P-gp inducers in the intestine may significantly decrease sofosbuvir plasma concentration leading to reduced therapeutic effect of Sovaldi and thus are contraindicated with Sovaldi

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

Medicinal products that are potent P-glycoprotein or potent cytochrome P450 inducers are contraindicated with Epclusa. Co-administration will significantly decrease sofosbuvir or velpatasvir plasma levels and could result in loss of efficacy of Epclusa

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

Medicinal products that are strong inducers of P-gp or strong inducers of CYP2B6, CYP2C8, or CYP3A4 may decrease plasma levels of sofosbuvir, velpatasvir and/or voxilaprevir. The use of such medicinal products with Vosevi is contraindicated

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

Sonidegib undergoes metabolism primarily by CYP3A4, and concomitant administration of strong inducers of CYP3A4 can decrease sonidegib concentrations significantly. Concomitant use of strong CYP3A inducers should be avoided

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

Concomitant use of substances known to induce CYP3A4 may affect the metabolism of tacrolimus and thereby decrease tacrolimus blood levels.

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.

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

The strong CYP3A4 induction may decrease exposure of the active moieties, temsirolimus and its metabolite, sirolimus. Concomitant treatment of temsirolimus with agents that have CYP3A4/5 induction potential should be avoided

Rifabutin, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Co-administration of Vemlidy with inducers of P-glycoprotein (P-gp) may decrease tenofovir alafenamide plasma concentrations and is not recommended.

Rifabutin, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Tezacaftor exposures can be expected to decrease significantly during co-administration with strong CYP3A inducers; therefore, co-administration with strong CYP3A inducers is not recommended.

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

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

Administration of the potent CYP3A4 inducers markedly decreased Cmax and AUC of ulipristal acetate and its active metabolite. Concomitant use of ulipristal acetate and potent CYP3A4 inducers is not recommended

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

Concomitant administration of vemurafenib and potent inducers of CYP3A4 may lead to suboptimal exposure to vemurafenib and should be avoided.

Rifabutin, verapamil

Rifabutin has a similar structure as rifampicin. Concomitant use of rifabutin and verapamil may decrease verapamil effects

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

Rifabutin, strong CYP3A4 inductor, may decrease the plasma levels of voriconazole. Concomitant use should be avoided

CONTRAINDICATIONS of Rifabutin

- Hypersensitivity or history of hypersensitivity to the active substance, other rifamycins (e.g. rifampicin) or to any of the excipients

- Due to insufficient clinical experience in pregnant and breast-feeding women and in children, Mycobutin should not be used in these patients.

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

Rifampicin

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

Potent enzymatic inducers such as rifampicin, phenobarbital and phenytoin may via their action on UDP-glucuronyltransferases slightly decrease the plasma concentrations of abacavir.

Abacavir/lamivudine [1], rifampicin ---> SmPC of [1] of EMA

Potential to slightly decrease abacavir plasma concentrations through UGT induction. Insufficient data to recommend dosage adjustment.

Abacavir/lamivudine/zidovudine [1], rifampicin ---> SmPC of [1] of EMA

Potential to slightly decrease abacavir plasma concentrations through and decreased AUC of zidovudine (both by UGT induction)

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

Concomitant use of strong CYP3A4 inducers should be avoided due to the risk of decreased efficacy of abemaciclib.

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

No studies on the effects on the ability to drive and use machines have been performed.

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

Strong inducers of CYP3A4 (decreased mean plasma AUCinf of abiraterone) during treatment are to be avoided, unless there is no therapeutic alternative.

Acenocoumarol [1], rifampicin ---> SmPC of [1] of eMC

The co-administration may decrease the anticoagulant effect

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

Strong P-gp inducers may decrease exposure to afatinib

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

Rifampicin an inducer of all three cytochromes (1A2, 2C9 and 2C19) involved in the metabolism of agomelatine may decrease the bioavailability of agomelatine.

Ajmaline, rifampicin

Co-administration of ajmaline with enzymatic inductors decreases significant the plasma concentrations of ajmaline

Alcohol, rifampicin

The alcohol intake increases the incidence of rifampicin-induced hepatotoxicity and the metabolism of rifampicin

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

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

Inducers of P-gp might decrease the bioavailability of aliskiren. Caution required with concomitant use

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

The concomitant use of CYP3A4 inducers may give a lower plasma concentration of amlodipine. Amlodipine should be used with caution together with CYP3A4 inducers.

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

The concomitant use of CYP3A4 inducers (e.g. rifampicin, Hypericum perforatum) may give a lower plasma concentration of amlodipine.

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

Inducers of P-gp might decrease the bioavailability of aliskiren. Caution required with concomitant use

Alogliptin/pioglitazone [1], rifampicin ---> SmPC of [1] of EMA

The CYP2C8 induction may decrease the plasma concentrations of pioglitazone. Close monitoring of glycaemic control should be considered

Alprazolam, rifampicin

The strong CYP3A4 induction may decrease the plasma levels of alprazolam

Alprenolol, rifampicin

Rifampicin, enzymatic inductor, may increase the metabolism of alprenolol and decrease its plasma levels and effect

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

Transient increase in exposition to ambrisentan. Patients on ambrisentan therapy should be closely monitored when starting treatment with rifampicin

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

The concomitant use of amifampridine with medicinal products known to cause QT prolongation is contraindicated as this combination may lead to an enhanced risk of ventricular tachycardia, notably torsade de pointes

Aminophylline [1], rifampicin ---> SmPC of [1] of eMC

Rifampicin may decrease plasma theophylline concentrations

Amitriptyline, rifampicin [2] ---> SmPC of [2] 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.

Amlodipine, rifampicin ---> SmPC of [amlodipine/valsartan] of EMA

The concomitant use of CYP3A4 inducers may give a lower plasma concentration of amlodipine. Amlodipine should be used with caution together with CYP3A4 inducers.

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

The concomitant use of CYP3A4 inducers may give a lower plasma concentration of amlodipine. The OATP1B1 inhibition by rifampicin may increase the plasma concentrations of valsartan

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

The concomitant use of CYP3A4 inducers may give a lower plasma concentration of amlodipine. Amlodipine should be used with caution together with CYP3A4 inducers.

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

It is expected that the CYP3A4 induction by rifampicin reduces amprenavir AUC. The decrease in amprenavir AUC can result in virological failure and resistance development.

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

It is expected that the CYP3A4 induction by rifampicin reduces amprenavir AUC. The decrease in amprenavir AUC can result in virological failure and resistance development. Combination with concomitant low-dose ritonavir is contraindicated

Antacids, rifampicin

The antacid decreases the absorption of rifampicin. Rifampicin should be given at least 1 hour before the ingestion of antacids

Anticholinergics, rifampicin

The anticholinergic agent decreases the absorption of rifampicin. Rifampicin should be given at least 1 hour before the anticholinergic agent

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

The concomitant use of apixaban with strong CYP3A4 and P-gp inducers may lead to reduced apixaban plasma concentrations. No dose adjustment for apixaban (almost always) is required during concomitant therapy with such agents

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

Co-administration of strong CYP3A4 enzyme inducer rifampicin resulted in a reduction of systemic exposure of apremilast. Therefore, the use of strong CYP3A4 enzyme inducers with apremilast is not recommended.

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

Concomitant administration of aprepitant with active substances that strongly induce CYP3A4 activity should be avoided as the combination results in reductions of the plasma concentrations of aprepitant that may result in decreased efficacy of aprepitant

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

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

Caution should be exercised when ataluren is co-administered with medicinal products that are inducers of UGT1A9 (e.g. rifampicin).

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

Rifampicin is a strong CYP3A4 inducer and has been shown to cause a 72% decrease in atazanavir AUC which can result in virological failure and resistance development. The combination is contraindicated

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

Coadministration (contraindicated) of EVOTAZ with strong inducers of CYP3A may result in decreased plasma concentrations of atazanavir and/or cobicistat, leading to loss of therapeutic effect and possible development of resistance to atazanavir.

Atenolol, rifampicin

Rifampicin, enzymatic inductor, may increase the metabolism of atenolol and decrease its plasma levels and effect

Atenolol/nifedipine [1], rifampicin ---> SmPC of [1] of eMC

Upon co-administration of nifedipine with rifampicin, the bioavailability of nifedipine is distinctly reduced and thus its efficacy weakened. The use of atenolol/nifedipine in combination with rifampicin is therefore contraindicated.

Atorvastatin [1], rifampicin ---> SmPC of [1] of eMC

Concomitant administration of atorvastatin with inducers of cytochrome P450 3A can lead to variable reductions in plasma concentrations of atorvastatin.

Atovaquone [1], rifampicin ---> SmPC of [1] of eMC

When the two drugs were taken concomitantly, decreased concentrations of atovaquone and increased concentrations of rifampicin were observed.

Atovaquone/proguanil [1], rifampicin ---> SmPC of [1] of eMC

Concomitant administration of rifampicin is not recommended as it is known to reduce plasma concentrations of atovaquone

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

The potential effect of CYP inducers, especially inducers of CYP3A4 on the pharmacokinetics and efficacy of avanafil has not been evaluated. The concomitant use of avanafil and a CYP inducer is not recommended as it may decrease the efficacy of avanafil.

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

Azathioprine, rifampicin

Rifampicin, enzymatic inductor, may increase the metabolism of azathioprine and decrease its plasma levels and effect. Risk of transplant rejection

Azole antifungals, rifampicin [2] ---> SmPC of [2] of eMC

Barbiturates, rifampicin [2] ---> SmPC of [2] of eMC

Barnidipine, rifampicin

The enzymatic inductor may decrease the plasma levels of barnidipine. Caution is recommended

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

The metabolism of bazedoxifene may be increased by concomitant use of substances known to induce UGTs potentially leading to decreased systemic concentrations of bazedoxifene.

BCG intravesical [1], rifampicin ---> SmPC of [1] of eMC

The treatment with anti-tuberculosis drugs is contraindicated

Beclometasone [1], rifampicin ---> SmPC of [1] of eMC

Rifampicin enhances the corticosteroid metabolism and its therapeutic effects may be reduced. Therefore it may be necessary to adjust the dose of corticosteroid accordingly

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

Bedaquiline exposure may be reduced during co-administration with inducers of CYP3A4. Co-administration of bedaquiline and moderate or strong CYP3A4 inducers used systemically should be avoided.

Benperidol [1], rifampicin ---> SmPC of [1] of eMC

Rifampicin may theoretically enhance the metabolic breakdown of neuroleptics, necessitating an increased dose.

Benzodiazepines, rifampicin [2] ---> SmPC of [2] of eMC

Betablockers, rifampicin [2] ---> SmPC of [2] of eMC

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

On the basis of the oxidative metabolism of bexarotene by cytochrome P450 3A4 (CYP3A4). Co-administration with CYP3A4 inducers may theoretically cause a reduction in plasma bexarotene concentrations.

Bictegravir/emtricitabine/tenofovir alafenamide [1], rifampicin ---> SmPC of [1] of EMA

Co-administration of rifampicin may decrease tenofovir alafenamide plasma concentrations. Co-administration is contraindicated due to the effect of rifampicin on the bictegravir component of Biktarvy.

Bilastine [1], rifampicin ---> SmPC of [1] of eMC

Medicinal products that are substrates or inhibitors of OATP1A2 may likewise have the potential to decrease bioavailability of bilastine (OATP1A2 substrate).

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

UGT1A1 inducers (such as rifampicin and phenobarbital) and inhibitors (such as indinavir, atazanavir, sorafenib) should be co-administered with caution.

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

Inducers of CYP1A2 enzymes (such as carbamazepine and rifampicin) may decrease binimetinib exposure, which could result in a decrease of efficacy.

Bisoprolol [1], rifampicin ---> SmPC of [1] of eMC

Slight reduction of the half-life of bisoprolol possible due to the induction of hepatic drug-metabolising enzymes. Normally no dosage adjustment is necessary.

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

The concomitant use of boceprevir with rifampicin may significantly reduce the plasma exposure of boceprevir. No data are available, therefore, the combination of boceprevir with these medicines is not-recommended

Boosted protease-inhibitors, rifampicin ---> SmPC of [etravirine] of EMA

Rifampicin is contraindicated in combination with boosted PIs.

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

The concomitant use of bortezomib with strong CYP3A4 inducers is not recommended, as efficacy may be reduced.

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

The strong CYP2C9 and CYP3A4 induction decreases the plasma concentrations of bosentan. The combination is not recommended

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

The concomitant use of bosutinib with strong CYP3A inductors should be avoided, as a decrease in bosutinib plasma levels will occur.

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

Rifampicin is excreted in breast milk, patients receiving rifampicin should not breast feed unless in the physician's judgement the potential benefit to the patient outweighs the potential risk to the infant.

Brentuximab vedotin [1], rifampicin ---> SmPC of [1] of EMA

Co-administration of brentuximab vedotin with rifampicin, a strong CYP3A4 inducer, did not alter the plasma exposure to brentuximab vedotin. Coadministration of rifampicin appeared to reduce plasma concentrations of MMAE metabolites that could be assayed

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

If brexpiprazole is used concomitantly with strong CYP3A4 inducers (e.g. rifampicin), the total daily dose requirement of brexpiprazole is increased by approximately a factor of three times the recommended daily dose

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

The concomitant use of strong CYP3A inducers with Alunbrig should be avoided

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

In healthy subjects, coadministration with the strong enzyme inducer rifampicin (600 mg/day for 5 days), decreased brivaracetam area under the plasma concentration curve (AUC) by 45 %.

Bromperidol, rifampicin

The co-administration may decrease the plasma levels of bromperidol

Brotizolam, rifampicin

The strong CYP3A4 induction may decrease the plasma concentrations of brotizolam

Budesonide [1], rifampicin ---> SmPC of [1] of eMC

Concomitant treatment of budesonide with CYP3A4 inducers may reduce budesonide exposure, which may require a dose increase.

Bunazosin, rifampicin

Rifampicin, enzymatic inductor, may increase the metabolism of bunazosin and decrease its plasma levels and effect

Buprenorphine [1], rifampicin ---> SmPC of [1] of eMC

The interaction between buprenorphine and CYP3A4 inducers has not been investigated. It is recommended that patients that are treated with buprenorphine are monitored closely if enzyme inducers are given concomitantly.

Buprenorphine/naloxone [1], rifampicin ---> SmPC of [1] of EMA

Concomitant use of CYP3A4 inducers with buprenorphine may decrease buprenorphine plasma concentrations, potentially resulting in sub-optimal treatment of opioid dependence with buprenorphine.

Buspirone [1], rifampicin ---> SmPC of [1] of eMC

When used buspirone in combination with a potent inducer of CYP3A4, an adjustment of the dosage of buspirone may be necessary to maintain buspirone's anxiolytic effect.

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

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

Co-administration of cabozantinib with strong CYP3A4 inductors (decreased plasma cabozantinib exposure (AUC) should be approached with caution.

Calcium antagonists, rifampicin [2] ---> SmPC of [2] of eMC

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

Enzyme inducers may give rise to decreased exposure of canagliflozin. These decreases in exposure to canagliflozin may decrease efficacy.

Canagliflozin/metformin [1], rifampicin ---> SmPC of [1] of EMA

Enzyme inducers may give rise to decreased exposure of canagliflozin. These decreases in exposure to canagliflozin may decrease efficacy.

Carbamazepine [1], rifampicin ---> SmPC of [1] of eMC

The carbamazepine plasma levels may be decreased.

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

Co-administration of cariprazine with strong and moderate inducers of CYP3A4 may result in a significant decrease in total cariprazine exposure, therefore the co-administration of cariprazine and strong or moderate CYP3A4 inducers is contraindicated

Carvedilol [1], rifampicin ---> SmPC of [1] of eMC

Rifampicin, enzymatic inductor, may increase the metabolism of carvedilol and decrease its plasma levels and effect

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

Concomitant use of caspofungin with the enzym inducer may result in a decrease in caspofungin AUC.

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

Concomitant use of inducers of celecoxib with CYP2C9 may reduce plasma concentrations of celecoxib.

Celiprolol, rifampicin

Rifampicin, enzymatic inductor, may increase the metabolism of celiprolol and decrease its plasma levels and effect

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

Co-administration of ceritinib with strong CYP3A inducers decreases ceritinib plasma concentrations. Concomitant use of strong CYP3A inducers should be avoided.

Chloramphenicol, rifampicin [2] ---> SmPC of [2] of eMC

Chlordiazepoxide [1], rifampicin ---> SmPC of [1] of eMC

Inducers (e.g. rifampicin) may increase clearance of benzodiazepines

Chlormadinone, rifampicin

The co-administration increases the metabolism and decreases the plasma levels of gestagen

Chlorprothixene, rifampicin

Rifampicin, enzymatic inductor, may decrease the plasma levels of co-administered chlorprothixene

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

The effect of CYP3A4 and CYP2C19 inducers on cilostazol pharmacokinetics has not been evaluated. The antiplatelet effect may theoretically be altered

Cimetidine, rifampicin

Rifampicin, enzymatic inductor, may increase the metabolism of cimetidine and decrease its plasma levels and effect

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

Cinacalcet is metabolised in part by the enzyme CYP3A4. Co-administration of a strong inductor of CYP3A4 may decrease cinacalcet levels. Dose adjustment of cinacalcet may be required

Clarithromycin [1], rifampicin ---> SmPC of [1] of eMC

Drugs that are inducers of CYP3A may induce the metabolism of clarithromycin. This may result in sub-therapeutic levels of clarithromycin leading to reduced efficacy.

Clofibrate, rifampicin [2] ---> SmPC of [2] of eMC

Clomipramine [1], rifampicin ---> SmPC of [1] of eMC

Rifampicin (CYP3A a. CYP2C inducer) may decrease clomipramine levels as co-administration of drugs known to induce cytochrome P450 enzymes, principally CYP3A4, CYP2C19 may accelerate the metabolism and decrease the efficacy of clomipramine

Clonazepam [1], rifampicin ---> SmPC of [1] of eMC

Known inducers of hepatic enzymes, e.g. rifampicin, may increase the clearance of benzodiazepines.

Clopidogrel, rifampicin

The strong CYP3A4 induction may increase plasma concentrations of the active metabolite and the effect of clopidogrel. The co-administration should be discouraged

Cloprednol, rifampicin

The strong CYP3A4 induction may decrease the plasma concentrations of cloprednol

Clozapine [1], rifampicin ---> SmPC of [1] of eMC

Concomitant administration of clozapine with substances known to induce cytochrome P450 enzymes may decrease the plasma levels of clozapine, leading to reduced efficacy.

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

Co-administration of cobicistat with medicinal products that are strong inducers of CYP3A may result in decreased plasma concentrations of cobicistat. Coadministration is contraindicated

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

Concomitant use of moderate and strong CYP3A inducers should be avoided. Given that cobimetinib concentrations are likely to be significantly reduced when co-administered with moderate to strong CYP3A inducers, patient's efficacy may be compromised.

Conjugated oestrogens/bazedoxifene [1], rifampicin ---> SmPC of [1] of EMA

The metabolism of oestrogens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes

Corticosteroids, rifampicin [2] ---> SmPC of [2] of eMC

Cotrimoxazole [1], rifampicin ---> SmPC of [1] of eMC

Concomitant use of cotrimoxazole and rifampicin can result in increased rifampicin serum levels and reduced plasma half-life of trimethoprim.

Coumarin anticoagulants, rifampicin

Rifampicin, enzymatic inductor, may increase the metabolism of coumarine and decrease its plasma levels and effect

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

Coadministration of crizotinib with strong CYP3A inducers may decrease crizotinib plasma concentrations. The concurrent use of strong CYP3A inducers should be avoided

Cyclophosphamide, rifampicin

The CYP3A4 induction may increase the toxicity of cyclophosphamide (prodrug)

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

Rifampicin induces ciclosporin intestinal and liver metabolism. Ciclosporin doses may need to be increased 3- to 5-fold during co-administration.

Cyproterone [1], rifampicin ---> SmPC of [1] of eMC

Inducers of CYP3A4 may reduce the levels of cyproterone acetate.

Cyproterone/ethinylestradiol [1], rifampicin ---> 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.

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

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

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

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

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

Dabrafenib is a substrate for the metabolising enzymes CYP3A4. Medicines that are strong inductors of CYP3A4 are therefore likely to decrease dabrafenib concentrations. Avoid coadministration of dabrafenib with potent inducers of CYP3A4.

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

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

Dapsone, rifampicin [2] ---> SmPC of [2] of eMC

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

Substances that are inducers of CYP3A4 are likely to decrease the plasma concentrations of darifenacin.

Darunavir/cobicistat, rifampicin ---> SmPC of [darunavir] of EMA

Darunavir and cobicistat are metabolised by CYP3A, and co-administration with CYP3A inducers may result in subtherapeutic plasma exposure to darunavir. Co-administration of darunavir/cobicistat with strong inducers of CYP3A is contraindicated

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], rifampicin ---> SmPC of [1] of EMA

Co-administration is contraindicated due to the potential for loss of therapeutic effect

Darunavir/ritonavir, rifampicin ---> SmPC of [darunavir] of EMA

Concomitant use of darunavir/ritonavir with strong CYP3A4 inductors may decrease plasma concentrations of darunavir and ritonavir. Concomitant use of darunavir/ritonavir with strong CYP3A4 inductors is contraindicated

Dasabuvir with ombitasvir/paritaprevir/ritonavir, rifampicin ---> SmPC of [dasabuvir] of EMA

CYP3A4/CYP2C8 induction by rifampicin may decrease the plasma concentrations of dasabuvir, ombitasvir and paritaprevir. Concomitant use is contraindicated

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

Co-administration (contraindicated) of dasabuvir with medicinal products that are strong or moderate enzyme inducers is expected to decrease dasabuvir plasma concentrations and reduce its therapeutic effect

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

The administration of dasatinib with a strong CYP3A4 inductor may increase metabolism and decrease dasatinib plasma concentrations. Therefore, concomitant use of potent CYP3A4 inducers with dasatinib is not recommended.

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

The concomitant use of deferasirox with potent UGT inducers may result in a decrease in deferasirox efficacy.

Deflazacort [1], rifampicin ---> SmPC of [1] of eMC

Deflazacort is metabolised in the liver. It is recommended to increase the maintenance dose of deflazacort if drugs which are liver enzyme inducers are co-administered

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

Taking medicinal products that are strong inducers of CYP3A4 (e.g. carbamazepine) with delamanid is contraindicated

Desogestrel [1], rifampicin ---> SmPC of [1] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones

Dexibuprofen, rifampicin

The CYP2C9 induction may decrease the dexibuprofen effect

Dextromethorphan/quinidine [1], rifampicin ---> SmPC of [1] of EMA

Potent CYP3A4 inducers may accelerate the metabolism of quinidine, resulting in lower plasma concentrations and hence decreased inhibition of CYP2D6. This may lead to decreased efficacy of dextromethorphan/quinidine.

Diazepam, rifampicin [2] ---> SmPC of [2] of eMC

The enzymatic inductor may increase clearance of benzodiazepines

Diclofenac, rifampicin

Rifampicin, enzymatic inductor, may increase the metabolism of diclofenac and decrease its plasma levels and effect

Dienogest, rifampicin

The enzymatic induction may decrease the plasma levels of dienogest

Digital glycosides, rifampicin [2] ---> SmPC of [2] of eMC

Digitoxin, rifampicin

The strong CYP3A4 induction may decrease the plasma concentrations of digitoxin

Digoxin [1], rifampicin ---> SmPC of [1] of eMC

Serum levels of digoxin may be reduced by concomitant administration of rifampicin

Dihydropyridines, rifampicin ---> SmPC of [nicardipine] of eMC

Rifampicin, strong CYP3A4 inductor, may decrease the plasma levels of dihydropyridine.

Diltiazem [1], rifampicin ---> SmPC of [1] of eMC

Risk of decrease of diltiazem plasma levels after initiating therapy with rifampicin

Disopyramide [1], rifampicin ---> SmPC of [1] of eMC

Inducers of CYP3A may reduce disopyramide and increase MN-disopyramide serum levels. Since the magnitude of such potential effects is not foreseeable, such drug combinations are not recommended.

Disulfiram [1], rifampicin ---> SmPC of [1] of eMC

Disulfiram inhibits the oxidation and renal excretion of rifampicin.

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

The induction of UGT1A1 and CYP3A may decrease the dolutegravir plasma levels. In the presence of integrase class resistance this combination should be avoided

Dolutegravir/abacavir/lamivudine [1], rifampicin ---> SmPC of [1] of EMA

The induction of UGT1A1 and CYP3A may decrease the dolutegravir plasma levels. The co-administration of rifampicin with dolutegravir/abacavir/lamivudine is not recommended.

Dolutegravir/rilpivirine [1], rifampicin ---> SmPC of [1] of EMA

Co-administration may cause significant decreases in rilpivirine plasma concentrations. This may result in loss of therapeutic effect of Juluca. Co-administration of Juluca with rifampicin is contraindicated

Donepezil [1], rifampicin ---> SmPC of [1] of eMC

The enzymatic induction may decrease the plasma levels of donepezil

Doxorubicine [1], rifampicin ---> SmPC of [1] of eMC

Concomitant administration of doxorubicin with inducers of CYP450 might decrease plasma concentrations of doxorubicin and reduce efficacy.

Doxycycline [1], rifampicin ---> SmPC of [1] of eMC

Drugs that induce hepatic enzymes such as rifampicin may accelerate the decomposition of doxycycline

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

Rifampicin decreased dronedarone exposure. Therefore, co-administration of rifampicin and other potent CYP3A4 inducers is not recommended as they decrease dronedarone exposure.

Dydrogesterone, rifampicin ---> SmPC of [dydrogesterone/estradiol] 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

Dydrogesterone/estradiol [1], rifampicin ---> 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

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

Co-administration of edoxaban with the P-gp inducer rifampicin led to a decrease in mean edoxaban AUC and a shortened half-life, with possible decreases in its pharmacodynamic effects.

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

The CYP3A4 and CYP2B6 induction by rifampicin decreases the plasma concentrations of efavirenz

Efavirenz/emtricitabine/tenofovir disoproxil [1], rifampicin ---> SmPC of [1] of EMA

The CYP3A4 and CYP2B6 induction may decrease the plasma concentrations of efavirenz. No dose adjustment of rifampicin is recommended when given with Atripla

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

OATP1B inhibition and CYP3A induction. Co-administration is contraindicated.

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

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

Medicinal products that induce multiple enzymes have the potential to decrease eltrombopag concentrations.

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

Co-administration of elvitegravir with medicines that are strong inducers of CYP3A is contraindicated as the expected decrease in elvitegravir plasma levels can lead to loss of therapeutic effect and possible development of resistance to elvitegravir

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

Co-administration of Genvoya and some medicinal products that induce CYP3A may result in significantly decreased cobicistat and elvitegravir plasma concentrations, which may result in loss of therapeutic effect and development of resistance.

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

The contraindicated coadministration of Stribild and rifampicin (CYP3A inducer) may result in significantly decreased cobicistat and elvitegravir plasma concentrations, which may result in loss of therapeutic effect and development of resistance

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

Inhibition of OATP1B1/1B3 transporters by co-administration with rifampicin resulted in a 75% increase in Cmax and a 35% increase in AUC of empagliflozin. These changes were not considered to be clinically meaningful.

Empagliflozin/linagliptin [1], rifampicin ---> SmPC of [1] of EMA

Co-administration of rifampicin decreased linagliptin exposure by 40 %, suggesting that the efficacy of linagliptin may be reduced when administered in combination with a strong P-glycoprotein (P-gp) or cytochrome P450 (CYP) isozyme CYP3A4 inducer

Empagliflozin/metformin [1], rifampicin ---> SmPC of [1] of EMA

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

Co-administration is likely to cause significant decreases in the plasma concentrations of tenofovir alafenamide (induction of P-gp). Co-administration is contraindicated.

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

Eviplera must not be used in combination with rifampicin as co-administration is likely to cause significant decreases in rilpivirine plasma concentrations (induction of CYP3A enzymes). This may result in loss of therapeutic effect of Eviplera.

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

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

No dose adjustment is required.

Enalapril, rifampicin [2] ---> SmPC of [2] of eMC

The co-administration decreases the plasma levels of enalaprilat, active metabolite of enalapril

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

A reduction in encorafenib exposure is likely and may result in compromised efficacy. Alternative agents with no or minimal CYP3A induction potential should be considered.

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

Co-administration of ritonavir (potent CYP3A4 inhibitor) or saquinavir in combination with a booster dose of ritonavir or rifampicin (potent CYP3A4 inducer) did not result in clinically significant changes of the pharmacokinetics of enfuvirtide.

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

Following oral administration of the moderate CYP2C8 and strong CYP3A4 inducer rifampin (600 mg once daily) to healthy male subjects, the AUC of enzalutamide plus the active metabolite decreased by 37% while Cmax remained unchanged.

Enzyme inductors, rifampicin

The use of rifampicin with medicinal products that also are metabolized by the enzymes of the cytochrom-P450 may accelerate and reduce the activity of these medicinal products

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

Due to the risk of decreased eplerenone efficacy, the concomitant use of strong CYP3A4 inducers with eplerenone is not recommended

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

No drug-drug interactions are expected with CYP3A4 inhibitors and inducers. Eribulin exposure (AUC and Cmax) was unaffected by ketoconazole, a CYP3A4 and P glycoprotein (Pgp) inhibitor, and rifampicin, a CYP3A4 inducer.

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

Erlotinib is metabolised in the liver by the hepatic cytochromes in humans, primarily CYP3A4 and to a lesser extent by CYP1A2. Potent inducers of CYP3A4 activity increase erlotinib metabolism and significantly decrease erlotinib plasma concentrations.

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

Multiple-dose administration of rifampin (a UGT and CYP inducer) decreases ertugliflozin AUC and Cmax by 39% and 15%, respectively. This decrease in exposure is not considered clinically relevant and therefore, no dose adjustment is recommended.

Ertugliflozin/metformin [1], rifampicin ---> SmPC of [1] of EMA

Erythromycin, rifampicin

The CYP3A4 induction may increase the metabolism of erythromycin and decrease its plasma concentrations and effect

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

Medicinal products known to induce CYP2C19 or CYP3A4 or both (such as rifampicin and St. John's wort (Hypericum perforatum)) may lead to decreased esomeprazole serum levels by increasing the esomeprazole metabolism.

Estradiol valerate/norgestrel [1], rifampicin ---> 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

Estradiol [1], rifampicin ---> SmPC of [1] of eMC

The metabolism of estrogens and progestagens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes

Estradiol/norethisterone [1], rifampicin ---> SmPC of [1] of eMC

The metabolism of oestrogens and progestogens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes

Estrogens, rifampicin ---> SmPC of [estradiol] of eMC

The metabolism of estrogens and progestagens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes

Ethinyl estradiol, rifampicin ---> SmPC of [ethinylestradiol/desogestrel] of eMC

Interactions can occur with drugs that induce microsomal enzymes, which can result in increased clearance of sex hormones

Ethinylestradiol/chlormadinone, rifampicin

Interactions can occur with drugs that induce hepatic enzymes which can result in increased clearance of sex hormones

Ethinylestradiol/desogestrel [1], rifampicin ---> 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], rifampicin ---> 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], rifampicin ---> 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], rifampicin ---> 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], rifampicin ---> SmPC of [1] of eMC

Etonogestrel [1], rifampicin ---> 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

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

Rifampicin, enzymatic inductor, may increase the metabolism of etoricoxib and decrease its plasma levels

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

Rifampicin is expected to decrease plasma concentrations of etravirine. Combination not recommended.

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

Decreased exposure of everolimus expected. Avoid the use of concomitant potent CYP3A4 inducers.

Exemestane [1], rifampicin ---> SmPC of [1] of eMC

The co-administration of drugs known to induce CYP3A4 may reduce the efficacy of exemestane.

Ezetimibe/atorvastatin [1], rifampicin ---> SmPC of [1] of eMC

Concomitant administration of atorvastatin with inducers of cytochrome P450 3A4 (e.g., efavirenz, rifampicin, St. John's Wort) can lead to variable reductions in plasma concentrations of atorvastatin.

Ezetimibe/simvastatine [1], rifampicin ---> SmPC of [1] of eMC

Because rifampicin is a potent CYP3A4 inducer, patients undertaking long-term rifampicin therapy (e.g. treatment of tuberculosis) may experience loss of efficacy of simvastatin.

Felodipine, rifampicin ---> SmPC of [felodipine/metoprolol] of eMC

The enzymatic induction may decrease the plasma levels of felodipine

Felodipine/metoprolol, rifampicin

It has been shown that CYP3A4 inductors decrease the plasma concentrations of felodipine. The concomitant use with strong CYP3A4 inductors should be avoided. Rifampicin, enzymatic inductor, may increase the metabolism of metoprolol

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

The CYP3A4 induction may decrease the plasma levels of felodipine. The co-administration of felodipine with CYP3A4 inductors should be avoided

Fenofibrate/simvastatin [1], rifampicin ---> SmPC of [1] of EMA

Because rifampicin is a potent CYP 3A4 inducer that interferes with simvastatin metabolism, patients undertaking long-term rifampicin therapy may experience loss of efficacy of simvastatin.

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

Induction of CYP3A4 may lead to subtherapeutic plasma levels. Concomitant use (of fesoterodine) with CYP3A4 inducers is not recommended

Fexofenadine, rifampicin

Rifampicin, enzymatic inductor, may increase the metabolism of fexofenadine and decrease its plasma levels and effect

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

Co-administration of fingolimod with strong CYP3A4 enzyme inducers may reduce the AUC of fingolimod and its metabolite. The co-administration should be used with caution.

Fluconazole [1], rifampicin ---> SmPC of [1] of eMC

Concomitant administration of fluconazole and rifampicin resulted in a 25% decrease in the AUC and 20% shorter half-life of fluconazole. In patients receiving concomitant rifampicin, an increase in the fluconazole dose should be considered

Fludrocortisone [1], rifampicin ---> SmPC of [1] of eMC

Increased metabolic clearance of fludrocortisone. Patients should be carefully observed for possible diminished effect of steroid, and the dosage should be adjusted accordingly.

Fluocortolone, rifampicin

The strong CYP3A4 induction may decrease the plasma concentrations of fluocortolone

Flurazepam [1], rifampicin ---> SmPC of [1] of eMC

Known inducers of hepatic enzymes, eg rifampicin, may increase the clearance of benzodiazepines.

Fluvastatin [1], rifampicin ---> SmPC of [1] of eMC

Administration of fluvastatin to healthy volunteers pre-treated with rifampicin resulted in a reduction of the bioavailability of fluvastatin by about 50%.

Foods, rifampicin

Rifampicin preferably be taken at least 30 minutes before a meal or 2 hours after a meal to ensure rapid and complete absorption.

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

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

Concomitant administration of fosaprepitant with active substances that strongly induce CYP3A4 activity should be avoided as the combination could result in reductions of the plasma concentrations of aprepitant

Fosphenytoin [1], rifampicin ---> SmPC of [1] of eMC

CYP2C9/2C19 induction may decrease plasma phenytoin concentrations. Blood levels and/or effects of rifampicin may be altered by phenytoin

Gadoxetate, rifampicin

Block of hepatic uptake of gadoxetic acid and decreased hepatic contrast

Gadoxetic acid, rifampicin

Block of hepatic uptake of gadoxetic acid and decreased hepatic contrast

Gallopamil, rifampicin

The enzymatic inductor increased the metabolism and decreases the plasma levels of phenylalkylamine

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

Substances that are inducers of CYP3A4 activity may increase metabolism and decrease gefitinib plasma concentrations and thereby reduce the efficacy of gefitinib. Concomitant medicinal products that induce CYP3A4 should be avoided.

Gestagens, rifampicin ---> SmPC of [estradiol] of eMC

The metabolism of estrogens and progestagens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes

Gestrinone, rifampicin [2] ---> SmPC of [2] of eMC

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

Medicinal products that are strong P-gp and CYP3A inducers could significantly decrease glecaprevir or pibrentasvir plasma levels and may lead to reduced therapeutic effect of Maviret or loss of virologic response. Co-administration is contraindicated

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

The co-administration may weaken the hypoglycemic effect

Gliclazide, rifampicin

Rifampicin, enzymatic inductor, may increase the metabolism of gliclazide and decrease its plasma levels and effect

Glimepiride [1], rifampicin ---> SmPC of [1] of eMC

Glimepiride is metabolized by cytochrome P450 2C9 (CYP2C9). Its metabolism is known to be influenced by concomitant administration of CYP2C9 inducers (e.g. rifampicin). Weakening of the blood-glucose-lowering effect and possible hyperglycaemia

Gliquidone, rifampicin

Hyperglycemic reactions may occur as expression of weakening effect of gliquidone with gliquidone is co-administered with rifampicin

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

There was a significant decrease in the rate and extent of guanfacine exposure when co-administered with rifampin, a CYP3A4 inducer. Other CYP3A4 inducers may have a comparable effect

Haloperidol [1], rifampicin ---> SmPC of [1] of eMC

When prolonged treatment with enzyme-inducing drugs is added to haloperidol therapy, this results in a significant reduction of haloperidol plasma levels.

Halothane, rifampicin [2] ---> SmPC of [2] of eMC

When rifampicin is given concomitantly with halothane, the potential for hepatotoxicity is increased. The concomitant use of rifampicin and halothane should be avoided.

Hemp extract, rifampicin

The co-administration may decrease the Cmax and THC and CBD.

Hexobarbital, rifampicin

Rifampicin, enzymatic inductor, may increase the metabolism of hexobarbital and decrease its plasma levels and effect

Hydantoins, rifampicin

Rifampicin, enzymatic inductor, may increase the metabolism of hydantoin and decrease its plasma levels and effect

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

Hydroquinidine, rifampicin

Concurrent administration of hydroquinidine with enzyme-inducing drugs may reduce the plasma concentrations of hydroquinidine.

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

Ibrutinib is primarily metabolised by cytochrome P450 enzyme 3A4. Administration with inducers of CYP3A4 can decrease ibrutinib plasma concentrations. Avoid concomitant use of strong CYP3A4 inducers

Ibuprofen, rifampicin

The CYP2C9 induction may decrease the ibuprofen effect

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

Co-administration of idelalisib with moderate or strong CYP3A inducers should be avoided as this may result in decreased efficacy

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

Substances that are inducers of CYP3A4 activity may significantly reduce exposure to imatinib, potentially increasing the risk of therapeutic failure. Concomitant use of strong CYP3A4 inducers and imatinib should be avoided.

Imidapril [1], rifampicin ---> SmPC of [1] of eMC

The administration of rifampicin reduced the plasma level of imidaprilat, the active metabolite of imidapril. The antihypertensive effect of imidapril might therefore be reduced.

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

Rifampicin, CYP3A4 inductor, may decrease the plasma concentrations of indinavir. The concomitant use is contraindicated

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

Rifampicin, CYP3A4 inductor, may decrease the plasma concentrations of indinavir. The concomitant use is contraindicated

Indocyanine green, rifampicin

Extinction enhancement

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

The effects of CYP2C9 inducers such as rifampicin on the pharmacokinetic of irbesartan have not been evaluated.

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

Co-administration of ONIVYDE with inducers of CYP3A4 may reduce systemic exposure of ONIVYDE.

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

Co-administration of CRESEMBA with potent/moderate CYP3A4/5 inducers is contraindicated, since these medicinal products can significantly decrease plasma concentrations of isavuconazole

Isoniazid [1], rifampicin ---> SmPC of [1] of eMC

When rifampicin is given concomitantly with isoniazid, the potential for hepatotoxicity is increased. Patients receiving both rifampicin and isoniazid should be monitored closely for hepatotoxicity.

Isradipine [1], rifampicin ---> SmPC of [1] of eMC

Concurrent administration of isradipine with rifampicin greatly reduces the plasma concentrations of isradipine. Concomitant administration of isradipine with enzyme-inducing drugs should be avoided.

Itraconazol [1], rifampicin ---> SmPC of [1] of eMC

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

Ivabradine is metabolised by CYP3A4 only. CYP3A4 inducers may decrease ivabradine exposure and activity. The concomitant use of CYP3A4 inducing medicinal products may require an adjustment of the dose of ivabradine.

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

Co-administration of ivacaftor with rifampicin, a strong CYP3A inducer, decreased ivacaftor exposure (AUC) and M1 exposure. Co-administration with strong CYP3A inducers is not recommended

Ixabepilone, rifampicin

The strong CYP3A4 induction may reduce plasma concentrations of ixabepilone

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

Co-administration of ixazomib with rifampicin decreased ixazomib Cmax by 54% and AUC by 74%. Therefore, co-administration of strong CYP3A inducers with ixazomib is not recommended

Kebuzone, rifampicin

Decreased effect of kebuzone

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

Lacidipine [1], rifampicin ---> SmPC of [1] of eMC

Lacidipine is known to be metabolised by cytochrome CYP3A4 and, therefore, significant inhibitors and inducers of CYP3A4 administered concurrently may interact with the metabolism and elimination of lacidipine.

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

The enzymatic induction may decrease plasma concentrations of lacosamide. Starting or ending treatment with enzyme inducers should be done with caution

Lamivudine/raltegravir [1], rifampicin ---> SmPC of [1] of EMA

The induction of UGT1A1 may decrease raltegravir exposition. Concomitant use is not recommended

Lamivudine/zidovudine [1], rifampicin ---> SmPC of [1] of EMA

The UGT induction may decrease AUC of zidovudine. Insufficient data to recommend dosage adjustment.

Lamotrigine [1], rifampicin ---> SmPC of [1] of eMC

Rifampicin increased lamotrigine clearance and decreased lamotrigine half-life due to induction of the hepatic enzymes responsible for glucuronidation.

Lansoprazole [1], rifampicin ---> SmPC of [1] of eMC

Enzyme inducers affecting CYP2C19 and CYP3A4 can markedly reduce the plasma concentrations of lansoprazole.

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

Lapatinib is predominantly metabolised by CYP3A. The CYP3A4 induction decreases the exposition to lapatinib. Co-administration of lapatinib with known inducers of CYP3A4 should be avoided.

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

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

A771726 peak levels were increased by approximately 40%, whereas the AUC was not significantly changed.

Lercanidipine [1], rifampicin ---> SmPC of [1] of eMC

Co-administration of lercanidipine with CYP3A4 inducers should be approached with caution since the antihypertensive effect may be reduced and blood pressure should be monitored more frequently than usual.

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

Rifampin, an inhibitor of OATPs and an inducer of CYP2C9, decreased lesinurad exposure and slightly reduced the amount of lesinurad excreted unchanged in urine with no clinically relevant effect.

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

Co-treatment with moderate and strong inducers may give rise to subtherapeutic letermovir exposure

Levobupivacaine, rifampicin

The strong CYP3A4 induction may reduce plasma concentrations of levobupivacaine

Levomethadone, rifampicin

The enzymatic induction may decrease the plasma levels of levomethadone and abstinence syndrome may occur

Levonorgestrel [1], rifampicin ---> SmPC of [1] of eMC

The metabolism of levonorgestrel is enhanced by concomitant use of liver enzyme inducers.

Levonorgestrel/ethinylestradiol [1], rifampicin ---> 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.

Levothyroxine [1], rifampicin ---> SmPC of [1] of eMC

Metabolism of levothyroxine (thyroxine) accelerated by rifampicin. (may increase requirements for levothyroxine (thyroxine) in hypothyroidism)

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

Multiple co-administration of 5 mg linagliptin with rifampicin, a potent inductor of P-glycoprotein and CYP3A4, resulted in a 39.6% and 43.8% decreased linagliptin steady-state AUC and Cmax, respectively, and about 30% decreased DPP-4 inhibition at troug

Linagliptin/metformin [1], rifampicin ---> SmPC of [1] of EMA

The full efficacy of linagliptin in combination with strong P-gp inducers might not be achieved, particularly if these are administered long-term.

Linezolid [1], rifampicin ---> SmPC of [1] of eMC

Rifampicin decreased the linezolid Cmax and AUC by a mean 21% [90%CI,15,27 ] and a mean 32% [90%CI,27,37 ], respectively. The mechanism of this interaction and its clinical significance are unknown.

Liothyronine, rifampicin

The enzymatic induction may decrease the plasma levels and the effect of liothyronine.

Lofepramine [1], rifampicin ---> SmPC of [1] of eMC

There is a possibility of plasma concentrations of some tricyclics being reduced by rifampicin.

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

Medicines that induce CYP3A4 would be expected to increase the rate and extent of metabolism of lomitapide. Consequently, this would reduce the effect of lomitapide. Any impact on efficacy is likely to be variable.

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

Co-administration of Kaletra with rifampicin is not recommended. Rifampicin in combination with Kaletra causes large decreases in lopinavir concentrations which may in turn significantly decrease the lopinavir therapeutic effect.

Lorazepam [1], rifampicin ---> SmPC of [1] of eMC

Inducers may increase clearance of benzodiazepines

Lorcainide, rifampicin

Rifampicin, enzymatic inductor, may increase the metabolism of lorcainide and decrease its plasma levels and effect

Losartan [1], rifampicin ---> SmPC of [1] of eMC

It was found that concomitant treatment of losartan with rifampicin (inducer of metabolism enzymes) gave a 40% reduction in plasma concentration of the active metabolite of losartan.

Losartan/hydrochlorothiazide [1], rifampicin ---> SmPC of [1] of eMC

Rifampicin has been reported to reduce levels of active metabolite.

Lovastatine, rifampicin [2] ---> SmPC of [2] of eMC

Rifampicin is a potent inducer of certain cytochrome P450 enzymes. Coadministration of rifampicin with drugs that are metabolised through cytochrome P450 enzymes may accelerate the metabolism and reduce the activity of these other drugs.

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

Concomitant use of lumacaftor/ivacaftor with these anti-mycobacterial is not recommended. The exposure of ivacaftor will be decreased, which may reduce the efficacy of lumacaftor/ivacaftor.

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

Lurasidone and its active metabolite ID-14283 are primarily metabolised by CYP3A4. Lurasidone is contraindicated with strong CYP3A4 inductors

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

In the presence of strong CYP3A4 inducers reduced efficacy of macitentan could occur. The combination of macitentan with strong CYP3A4 inducers should be avoided

Manidipine, rifampicin

Manidipine should not be administered with CYP3A4 inductors

Maprotiline, rifampicin

The enzymatic induction may increase the formation of desmethyl maprotiline and decrease the effect of maprotiline. Dose adjustment may be necessary

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

Maraviroc is a substrate of cytochrome P450 CYP3A4. Co-administration of maraviroc with medicinal products that induce CYP3A4 may decrease maraviroc concentrations and reduce its therapeutic effects.

Medroxyprogesterone [1], rifampicin ---> SmPC of [1] of eMC

The metabolism of progestogens may be increased by concomitant administration of compounds known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes.

Mefloquine [1], rifampicin ---> SmPC of [1] of eMC

Inductors of the isoenzyme CYP3A4 may modify the pharmacokinetics/metabolism of mefloquine, leading to an decrease in mefloquine plasma concentration.

Megestrol, rifampicin

Accelerated metabolism of rifampicin

Melagatran, rifampicin

The induction of P-glycoprotein may decrease the exposure to melagatran

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

CYP1A2 inducers such as carbamazepine and rifampicin may give rise to reduced plasma concentrations of melatonin.

Meprobamate [1], rifampicin ---> SmPC of [1] of eMC

Like barbiturates, meprobamate can cause induction of liver enzymes, so that the availability and blood levels of drugs given concurrently that are metabolised in the liver may be affected.

Mesalazine, rifampicin

Possible attenuation of the tuberculostatic effect

Mestranol, rifampicin

Rifampicin, enzymatic inductor, may increase the metabolism of mestranol and decrease its plasma levels and effect

Metabolized by cytochrome P450, rifampicin [2] ---> SmPC of [2] of eMC

Methadone [1], rifampicin ---> SmPC of [1] of eMC

The hepatic enzyme-inducing drugs may lower plasma methadone levels and produce symptoms of withdrawal in methadone dependent patients.

Methylergometrine, rifampicin

Strong CYP3A4 inhibitors may weaken the pharmacological effect of methylergometrine

Methylprednisolone, rifampicin

The strong CYP3A4 induction may decrease the plasma concentrations of glucocorticoid

Metildigoxin, rifampicin

Decreased plasma levels of metildigoxin

Metoprolol, rifampicin

Rifampicin, enzymatic inductor, may increase the metabolism of metoprolol and decrease its plasma levels and effect

Metronidazole, rifampicin

Rifampicin, enzymatic inductor, may increase the metabolism of metronidazole and decrease its plasma levels and effect

Mexiletine, rifampicin [2] ---> SmPC of [2] of eMC

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

Rifampicin (7 days of 600 mg once daily) decreased the plasma concentrations of intravenous midazolam by about 60%. The terminal half-life decreased by about 50-60%.

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

Concomitant use of Rydapt with strong inducers of CYP3A4 (e.g. carbamazepine, rifampicin, enzalutamide, phenytoin, St. John's Wort [Hypericum perforatum]) is contraindicated

Mifepristone [1], rifampicin ---> SmPC of [1] of eMC

CYP3A4 inductors may induce mifepristone metabolism (lowering serum levels of mifepristone).

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

Substances that are inducers of CYP3A decrease the plasma concentrations of mirabegron. No dose adjustment is needed for mirabegron when administered with therapeutic doses of rifampicin or other CYP3A inducers.

Mirtazapine [1], rifampicin ---> SmPC of [1] of eMC

The strong CYP3A4 induction may decrease the plasma concentrations of mirtazapine

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

Mitotane has been shown to have an inductive effect on cytochrome P450 enzymes. Therefore, the plasma concentrations of the substances metabolised via cytochrome P450 may be modified.

Montelukast [1], rifampicin ---> SmPC of [1] of eMC

Decreased montelukast AUC when is coadministered with strong inducers of CYP3A4

Morphine [1], rifampicin ---> SmPC of [1] of eMC

Plasma concentrations of morphine sulphate may be reduced by rifampicin.

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

In patients not also taking ciclosporin, concomitant administration of mycophenolate mofetil and rifampicin resulted in a decrease in MPA exposure (AUC 0-12 h) of 18% to 70%.

Mycophenolate, rifampicin ---> SmPC of [mycophenolate mofetil] of EMA

In patients not also taking ciclosporin, concomitant administration of mycophenolate mofetil and rifampicin resulted in a decrease in MPA exposure (AUC 0-12 h) of 18% to 70%.

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

Concomitant administration with a UGT inducer may potentially lead to subtherapeutic nalmefene plasma concentrations.

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

Drugs known to induce CYP2C19 and CYP3A4 may lead to decreased esomeprazole serum levels by increasing the esomeprazole metabolism.

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

Rifampin may reduce the hypoglycaemic effect of nateglinide

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

Potent inducers of CYP3A4 (e.g., rifampicin, phenobarbital and carbamazepine) may reduce nelfinavir plasma concentrations and their coadministration is contraindicated

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

Co-administration with this medical product that is strong inducer of the CYP3A4/Pgp isoform of cytochrome P450 is contraindicated

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

Netupitant is mainly metabolized by CYP3A4; therefore, co-administration with medicinal products that induce CYP3A4 may decrease netupitant plasma concentrations. Consequently, concomitant administration with strong CYP3A4 inducers should be avoided.

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

It is not recommended to co-administer rifampicin and nevirapine

Nicardipine [1], rifampicin ---> SmPC of [1] of eMC

Nicardipine is metabolized by cytochrome P450 3A4. Concomitant administration of nicardipine with inductors of cytochrome P450 3A4 may alter the plasma levels of nicardipine.

Nifedipine [1], rifampicin ---> SmPC of [1] of eMC

Nifedipine should not be administered concomitantly with rifampicin, as effective plasma levels of nifedipine may not be achieved as a result of enzyme induction.

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

The concomitant administration of other medicinal products that induce CYP3A4 is likely to reduce exposure to nilotinib to a clinically relevant extent. Concomitant use should be avoided

Nilvadipine, rifampicin

The enzymatic induction may decrease the plasma levels of nilvadipine

Nimodipine [1], rifampicin ---> SmPC of [1] of eMC

The concomitant use of oral nimodipine and rifampicin is contraindicated. The efficacy of nimodipine could be reduced if rifampicin is administered concomitantly.

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

Potent P-gp inducers may decrease exposure to nintedanib. Co-administration with nintedanib should be carefully considered.

Nisoldipine, rifampicin

Rifampicin, strong CYP3A4 inductor, may decrease the plasma levels of nisoldipine. The co-administration is contraindicated.

Nitrazepam [1], rifampicin ---> SmPC of [1] of eMC

Known inducers of hepatic enzymes may increase the clearance of benzodiazepines.

Nitrendipine, rifampicin

Rifampicin, strong CYP3A4 inductor, may decrease the plasma levels of nitrendipine. The co-administration is contraindicated.

Nomegestrol, rifampicin

The enzymatic inductor may increase the metabolism of nomegestrol and decrease its plasma levels

Nomegestrol/estradiol [1], rifampicin ---> 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], rifampicin ---> SmPC of [1] of EMA

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

Norethisterone acetate, rifampicin

Reduced contraceptive efficacy with hepatic enzyme-inducing drugs

Norethisterone enantate [1], rifampicin ---> SmPC of [1] of eMC

Reduced contraceptive efficacy with hepatic enzyme-inducing drugs

Norethisterone, rifampicin

Rifampicin, enzymatic inductor, may increase the metabolism of norethisterone and decrease its plasma levels and effect

Norgestimate, rifampicin

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, rifampicin

The enzymatic induction may accelerate the metabolism of steroid hormones and decrease their plasma levels and effect.

Nortriptyline, rifampicin [2] ---> SmPC of [2] of eMC

OATP1B1 substrates, rifampicin

La inhibition of OATP1B1 may increase the plasma levels of OATP1B1 substrates. The co-administration should be undertaken with caution

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

Known strong inducers of CYP3A4/5 are not recommended with olaparib, as it is possible that the efficacy of olaparib could be substantially reduced

Olmesartan medoxomil/amlodipine [1], rifampicin ---> SmPC of [1] of eMC

The concomitant use of amlodipine and CYP3A4 inducers may give a lower plasma concentration of amlodipine. Amlodipine should be used with caution together with CYP3A4 inducers.

Olsalazine, rifampicin

The tuberculostatic effect of rifampicin may be decreased

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

Coadministration of Viekirax with/without dasabuvir with drugs that are strong or moderate enzyme inducers is expected to decrease ombitasvir, paritaprevir, and ritonavir plasma levels and reduce their therapeutic effect. Concomitant use contraindicated

Omeprazole, rifampicin

Principle actives known to induce CYP2C19 and CYP3A4 may increase the omeprazole metabolism and decrease its plasma levels

Ondansetron [1], rifampicin ---> SmPC of [1] of eMC

In patients treated with potent inducers of CYP3A4, the oral clearance of ondansetron was increased and ondansetron blood concentrations were decreased.

Opiates, rifampicin [2] ---> SmPC of [2] of eMC

Oral antidiabetics, rifampicin [2] ---> SmPC of [2] of eMC

Oral contraceptives, rifampicin [2] ---> SmPC of [2] of eMC

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

It is recommended that concomitant use of strong CYP3A inducers (e.g. Phenytoin, rifampicin and carbamazepine) with TAGRISSO should be avoided.

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

Oxazepam [1], rifampicin ---> SmPC of [1] of eMC

Rifampicin may increase the metabolism of oxazepam

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

The metabolism of paclitaxel is catalysed, in part, by cytochrome P450 isoenzymes CYP2C8 and CYP3A4. Therefore, caution should be exercised when administering paclitaxel concomitantly with medicines known to induce either CYP2C8 or CYP3A4.

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

Coadministration of CYP3A inducers may lead to decreased palbociclib exposure and consequently a risk for lack of efficacy. Therefore, concomitant use of palbociclib with strong CYP3A4 inducers should be avoided.

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

Rifampicin, inducer of P-gp, may increase in renal clearance of paliperidone

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

Strong inducers may reduce the efficacy of panobinostat, therefore the concomitant use of strong CYP3A4 inducers should be avoided.

Para-aminosalicylic acid, rifampicin [2] ---> SmPC of [2] of eMC

If p-aminosalicylic acid and rifampicin are both included in the treatment regimen, they should be given not less than eight hours apart to ensure satisfactory blood levels.

Paracetamol, rifampicin

The enzymatic inductor may decrease the plasma levels of paracetamol and increase its hepatotoxicity. Caution is recommended

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

The metabolism of valdecoxib may increase when co-administered with enzyme inducers

Paroxetine [1], rifampicin ---> SmPC of [1] of eMC

No initial dosage adjustment is considered necessary when the drug is to be co-administered with known drug metabolising enzyme inducers

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

Concomitant treatment with inducers of CYP3A4 should be avoided due to risk of decreased exposure to pazopanib

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

Rifampicin, enzymatic inductor, may increase the metabolism of antiepileptic agent and decrease its plasma levels and effect

Perazine, rifampicin

The enzymatic inductor may increase the metabolism of perazine and decrease its plasma levels

Phenazone, rifampicin

The enzymatic induction may increase the metabolism of phenazone and decrease its plasma levels

Phenindione [1], rifampicin ---> SmPC of [1] of eMC

Rifampicin antagonises the effect of phenindione

Phenobarbital, rifampicin [2] ---> SmPC of [2] of eMC

Phenprocoumon, rifampicin

Weakening of phenprocoumon effect with the use concomitant or prior of rifampicin

Phenylalkylamines, rifampicin

The enzymatic inductor increased the metabolism and decreases the plasma levels of phenylalkylamine

Phenylbutazone, rifampicin

The co-administration may decrease the effect of phenylbutazone

Phenytoin, rifampicin [2] ---> SmPC of [2] of eMC

Phytomenadione, rifampicin

Possible bleeding in newborn due to vitamin K deficiency

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

Co-administration of pioglitazone with rifampicin (an inducer of cytochrome P450 2C8) is reported to result in a 54% decrease in AUC of pioglitazone.

Pioglitazone/glimepiride [1], rifampicin ---> SmPC of [1] of EMA

Co-administration of pioglitazone with rifampicin (an inducer of CYP2C8) is reported to result in a 54% decrease in AUC of pioglitazone. The pioglitazone dose may need to be increased when rifampicin is concomitantly administered.

Pioglitazone/metformin [1], rifampicin ---> SmPC of [1] of EMA

Piperaquine/artenimol [1], rifampicin ---> SmPC of [1] of EMA

Enzyme inducing medicinal products are likely to lead to reduced piperaquine plasma concentrations. The concentration of DHA may also be reduced. Concomitant treatment with such medicinal products is not recommended.

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

Co-administration of medicinal products that act as potent inducers of both CYP1A2 and the other CYP isoenzymes involved in the metabolism of pirfenidone (e.g. rifampicin) may result in significant lowering of pirfenidone plasma levels.

Pitavastatin, rifampicin

The co-administration may increase the AUC of pravastatine.

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

Co-administration of pitolisant with potent CYP3A4 inducers (e.g. rifampicin, phenobarbital, carbamazepine, phenytoin) should be done with caution.

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

Caution should be taken when pixantrone is continuously co-administered with efflux transport inducers, as pixantrone excretion might be increased with a consequent decrease of systemic exposure.

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

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

Posaconazole concentrations may be significantly lowered in combination; therefore, concomitant use with posaconazole should be avoided unless the benefit to the patient outweighs the risk

Prajmalium, rifampicin

The enzymatic inductor decreases significant the plasma concentrations of prajmaline

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

CYP3A inductors are not anticipated to have a significant effect on the pharmacokinetics of the prasugrel active metabolite.

Praziquantel, rifampicin [2] ---> SmPC of [2] of eMC

Prednisolone [1], rifampicin ---> SmPC of [1] of eMC

Rifampicin enhances the corticosteroid metabolism and its therapeutic effects may be reduced. Therefore it may be necessary to adjust the dose of prednisolone accordingly

Prednisone [1], rifampicin ---> SmPC of [1] of eMC

The efficacy of glucocorticoids is reduced.

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

Rifampicin should be used in pregnant women or in women of child bearing potential only if the potential benefit justifies the potential risk to the foetus.

Primidone, rifampicin

The co-administration may decrease the primidone effect

Probenecide, rifampicin

The co-administration may delay the elimination of rifampicin and increase its plasma levels, effects and adverse reactions

Progesterone, rifampicin

The strong CYP3A4 induction may decrease the levels of progesterone

Propafenone [1], rifampicin ---> SmPC of [1] of eMC

There has been a report of the lowering of propafenone levels by rifampicin, via the hepatic mixed oxidase system. This reduction may lead to breakthrough arrhythmias.

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

Blood levels of propranolol may be decreased by co-administration of enzyme inducers

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

Co-administration of protease inhibitors with rifampicin substantially decreases protease inhibitor concentrations.

Prothionamide, rifampicin

The co-administration of hepatotoxic medicinal products increase the probability of hepatotoxic effects

Pyrazinamide, rifampicin

Pyrazinamide may decrease the plasma levels of rifampicin.

Quetiapine [1], rifampicin ---> SmPC of [1] of eMC

Rifampicin, enzymatic inductor, may increase the metabolism of quetiapine and decrease its plasma levels and effect

Quinidine, rifampicin [2] ---> SmPC of [2] of eMC

Quinine, rifampicin [2] ---> SmPC of [2] of eMC

Quinolones, rifampicin [2] ---> SmPC of [2] of eMC

Radiologic contrasts, rifampicin [2] ---> SmPC of [2] of eMC

Rifampicin may impair biliary excretion of contrast media used for visualization of the gallbladder, due to competition for biliary excretion.

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

Rifampicin, strong inducer of UGT1A1, reduces plasma levels of raltegravir. Caution is recommended

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

The CYP3A4 induction may decrease the plasma levels of ranolazine. During the treatment with CYP3A4 inductors should not be initiated a therapy with ranolazine

Reboxetine [1], rifampicin ---> SmPC of [1] of eMC

Low reboxetine serum levels have been reported with the concurrent administration of CYP3A4 inducers

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

The strong CYP3A4 inductor may increase metabolism of regorafenib. The combination of regorafenib with strong CYP3A4 inductors should be avoided

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

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

The concomitant use of strong CYP3A4 inducers may therefore lead to decreased exposure and consequently a risk for lack of efficacy. The concomitant use of strong CYP3A4 inducers should be avoided

Rifampicin [1], serotonin antagonists ---> SmPC of [1] of eMC

Rifampicin [1], statins metabolised by CYP3A4 ---> SmPC of [1] of eMC

Rifampicin [1], sulfonylureas ---> SmPC of [1] of eMC

Rifampicin [1], thiazolidinediones ---> SmPC of [1] of eMC

Rifampicin [1], thiopental ---> SmPC of [1] of eMC

Rifampicin [1], thyroid hormones ---> SmPC of [1] of eMC

Rifampicin has enzyme induction properties that can enhance the metabolism of endogenous substrates including adrenal hormones, thyroid hormones and vitamin D.

Rifampicin [1], tocainide ---> SmPC of [1] of eMC

Rifampicin [1], toremifene ---> SmPC of [1] of eMC

Rifampicin [1], tricyclic antidepressant ---> SmPC of [1] of eMC

Rifampicin [1], vitamin D ---> SmPC of [1] of eMC

Rifampicin has enzyme induction properties that can enhance the metabolism of endogenous substrates including adrenal hormones, thyroid hormones and vitamin D.

Rifampicin [1], warfarin ---> SmPC of [1] of eMC

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

The CYP3A4 induction by rifampicin may decrease the plasma concentrations and the therapeutic effect of rilpivirine. The co-administration is contraindicated

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

In vitro studies suggest that CYP1A2 is the principal isozyme involved in the initial oxidative metabolism of riluzole. Inducers of CYP1A2 could increase the rate of riluzole elimination.

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

It is expected that concomitant administration of potent CYP3A4 inducers may reduce the plasma concentration of rimonabant and may result in loss of efficacy.

Rifampicin, risperidone [2] ---> SmPC of [2] of eMC

The CYP3A4 and P-glycoprotein induction may decrease the plasma levels of the active antipsychotic fraction of risperidone

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

The inducing effect of rifampicin (next to that of ritonavir itself) is small and may have no clinical relevant effect on ritonavir levels

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

The strong CYP3A4 induction may decrease the plasma concentrations of rivaroxaban. Concomitant administration of strong CYP3A4 inducers should be avoided unless the patient is closely observed for signs and symptoms of thrombosis.

Rifampicin, rofecoxib

Rifampicin decreases the plasma levels of rofecoxib

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

The use of strong cytochrome P450 enzyme inducers may reduce the therapeutic efficacy of roflumilast. Thus, roflumilast treatment is not recommended in patients receiving strong cytochrome P450 enzyme inducers.

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

Concomitant administration of rifampicin, a strong enzyme inducer significantly decreased the systemic exposure to rolapitant and to its active metabolite.

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

Varuby in patients who require chronic administration of strong inducers (e.g. rifampicin, carbamazepine, enzalutamide, phenytoin) is not recommended

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

Co-administration of rosiglitazone with rifampicin (an inducer of CYP2C8) resulted in a 66 % decrease in rosiglitazone plasma concentrations.

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

The strong CYP3A4 induction may reduce the AUC of ruxolitinib. It is possible that an increase of the ruxolitinib dose is needed with strong CYP3A4 inductors

Rifampicin, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

Co-administration of Entresto with inhibitors of OATP1B1, OATP1B3, OAT3 (e.g. rifampicin, ciclosporin), OAT1 (e.g. tenofovir, cidofovir) or MRP2 (e.g. ritonavir) may increase the systemic exposure of LBQ657 or valsartan.

Rifampicin, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Rifampicin is contraindicated in combination with Invirase/ritonavir. Risk of severe hepatocellular toxicity

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

The strong CYP3A4 induction may decrease the plasma concentrations of saxagliptin. Glycemic control should be carefully assessed

Rifampicin, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Using CYP3A4 inducers may reduce the glycaemic lowering effect of Qtern. Glycaemic control should be assessed when it is used concomitantly with a potent CYP3A4/5 inducer

Rifampicin, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Concomitant administration of saxagliptin with the potent CYP3A4/5 inducer rifampicin, reduced Cmax and AUC of saxagliptin by 53% and 76%, respectively.

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

In the presence of 600 mg rifampicin, once a day, an inducer of CYP2C8, the exposure to the active metabolite was reduced by half. Dose adjustment of selexipag may be required with concomitant administration of inducers of CYP2C8.

Rifampicin, sertindole

The metabolism of sertindole may be significantly enhanced by agents known to induce CYP isozymes, which can decrease the plasma concentrations of sertindole

Rifampicin, sibutramine [2] ---> SmPC of [2] of eMC

Rifampicin, phenytoin, carbamazepine, phenobarbital and dexamethasone are CYP3A4 enzyme inducers and may accelerate sibutramine metabolism, although this has not been studied experimentally.

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

Concomitant administration of strong CYP3A4 inducers, such as rifampin, is expected to cause greater decreases in plasma concentrations of sildenafil.

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

Silodosin is metabolised extensively, mainly via CYP3A4, alcohol dehydrogenase and UGT2B7. Substances that inhibit or induce these enzymes may affect the plasma concentrations of silodosin and its active metabolite.

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

It is not recommended to co-administer simeprevir with rifampicin (CYP3A4 enzyme induction) as co-administration may result in loss of therapeutic effect of simeprevir.

Rifampicin, simvastatine ---> SmPC of [fenofibrate/simvastatin] of EMA

Because rifampicin is a potent CYP 3A4 inducer that interferes with simvastatin metabolism, patients undertaking long-term rifampicin therapy may experience loss of efficacy of simvastatin.

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

Inductors of CYP3A4 increase the metabolism of sirolimus and decrease sirolimus levels. Co-administration of sirolimus with strong inductors of CYP3A4 is not recommended

Rifampicin, sodium valproate [2] ---> SmPC of [2] of eMC

Rifampicin may decrease the valproic acid blood levels resulting in a lack of therapeutic effect. Therefore, valproate dosage adjustment may be necessary when it is co-administered with rifampicin.

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

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

Induction of P-gp and CYPs. Epclusa is contraindicated with rifampicin, a potent P-gp and CYP inducer

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

Rifampicin, solifenacin [2] ---> SmPC of [2] of eMC

Since solifenacin is metabolised by CYP3A4, pharmacokinetic interactions are possible with CYP3A4 inducers

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

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

Inducers of CYP3A4 activity and/or glucuronidation may increase metabolism of sorafenib and thus decrease sorafenib concentrations.

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

Administration of sunitinib with potent CYP3A4 inducers may decrease sunitinib concentrations. Combination with CYP3A4 inducers should therefore be avoided

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

Concomitant use of substances known to induce CYP3A4 may affect the metabolism of tacrolimus and thereby decrease tacrolimus blood levels.

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

The CYP3A4 induction may decrease the plasma concentrations of tadalafil

Rifampicin, talinolol

Concomitant use of a P-gp inductor decreases the bioavailability of talinolol

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.

Rifampicin, 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.

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

Rifampicin, tegafur

The enzymatic inductor increases the release of 5-fluorouracil of tegafur

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

Concomitant administration of telaprevir is contraindicated with active substances that strongly induce CYP3A and thus may lead to lower exposure and loss of efficacy of telaprevir

Rifampicin, 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.

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

The concomitant use of CYP3A4 inducers may lead to a lower plasma concentration of amlodipine.

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

Rifampicin, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Co-administration of Vemlidy with inducers of P-glycoprotein (P-gp) may decrease tenofovir alafenamide plasma concentrations and is not recommended.

Rifampicin, terbinafine [2] ---> SmPC of [2] of eMC

Rifampicin increases the clearance of terbinafine and may decrease the effect or plasma concentration of terbinafine

Rifampicin, 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.

Rifampicin, testosterone undecanoate [2] ---> SmPC of [2] of eMC

Concurrent administration of liver enzyme inducing may decrease the effect of testosterone undecanoate.

Rifampicin, tetracosactide

The enzymatic induction may increase the metabolism and decrease the plasma concentrations of released glucocorticoid

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%.

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

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.

Rifampicin, tiagabine

Rifampicin, enzymatic inductor, may accelerate the metabolism of tiagabine and decrease its plasma levels and effect

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.

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

Co-administration of ticagrelor with strong CYP3A4 inducers is discouraged, as co-administration may lead to a decrease in exposure and efficacy of ticagrelor

Rifampicin, 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

Rifampicin, timolol [2] ---> SmPC of [2] of eMC

The bioavailability of timolol will be reduced by co-administration with rifampicin.

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

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.

Rifampicin, tizanidine

The combination of tizanidine with rifampicin may decrease the plasma levels and the therapeutic effect or tizanidine

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

XELJANZ exposure is decreased when coadministered with potent CYP inducers (e.g., rifampicin). Coadministration of potent inducers of CYP3A4 with XELJANZ is not recommended.

Rifampicin, tolbutamide

Decreased hypoglycaemic effect may occur

Rifampicin, 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 should be exercised in co-administering CYP3A4 inducers with tolvaptan.

Rifampicin, 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

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

Verapamil concentrations may be reduced by rifampicin

Rifampicin, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Hepatic enzyme inducers may increase the metabolic clearance of triamcinolone

Rifampicin, triamcinolone [2] ---> SmPC of [2] of eMC

Hepatic enzyme inducers may increase the metabolic clearance of triamcinolone

Rifampicin, triazolam

Rifampicin causes induction of CYP3A4. The effect of triazolam coadministered with rifampicin is significantly reduced

Rifampicin, triiodthyronine

The enzymatic induction may decrease the plasma levels and the effect of liothyronine.

Rifampicin, trimethoprim [2] ---> SmPC of [2] of eMC

Rifampicin may decrease trimethoprim concentrations.

Rifampicin, trimethoprim/sulfamethoxazol [2] ---> SmPC of [2] of eMC

Concomitant use of cotrimoxazole and rifampicin can result in increased rifampicin serum levels and reduced plasma half-life of trimethoprim.

Rifampicin, trofosfamide

It has to be taken into account a prior or actual treatment with drugs that are enzyme inducers

Rifampicin, tropisetron

The enzymatic inductor may increase the metabolism of tropisetron and decrease its plasma levels

Rifampicin, tuberculosis vaccine

BCG bacteria are susceptible to tuberculostatic agents

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

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

The enzymatic inductor may increase the metabolism of valdecoxib and decrease its plasma levels

Rifampicin, valproic acid [2] ---> SmPC of [2] of eMC

Rifampicin may decrease the valproic acid blood levels resulting in a lack of therapeutic effect. Therefore, valproate dosage adjustment may be necessary when it is co-administered with rifampicin.

Rifampicin, valsartan ---> SmPC of [amlodipine/valsartan/hydrochlorothiazide] of EMA

The results of an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1. Co-administration of inhibitors of OATP1B1 may increase the systemic exposure to valsartan.

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

In healthy male subjects, the exposure to vandetanib was reduced by 40% when given together with the potent CYP3A4 inducer, rifampicin. Administration of vandetanib with potent CYP3A4 inducers should be avoided.

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

Concomitant administration of vemurafenib and potent inducers of CYP3A4 may lead to suboptimal exposure to vemurafenib and should be avoided.

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

Concomitant use of Venclyxto with strong CYP3A inducers or moderate CYP3A inducers should be avoided. Alternative treatments with less CYP3A induction should be considered.

Rifampicin, verapamil [2] ---> SmPC of [2] of eMC

Clinically significant interactions have been reported with inducers of CYP3A4 that have caused a lowering of plasma levels of verapamil, therefore, patients should be monitored for drug interactions.

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

The concomitant use of vinflunine and potent CYP3A4 inducers should be avoided since they may decrease vinflunine and DVFL concentrations

Rifampicin, 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 induces this iso-enzyme can affect the concentration of vinorelbine

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

Concomitant treatment with strong CYP inducers (e.g. rifampicin, carbamazepine or phenytoin) should be avoided, as a risk for decreased plasma concentrations and decreased efficacy of vismodegib cannot be excluded.

Rifampicin, vitamin K

Possible bleeding in newborn due to vitamin K deficiency

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

Co-administration of rifampin with vorapaxar substantially decreased the vorapaxar mean Cmax and AUC. Concomitant use of vorapaxar with strong (potent) inducers of CYP3A should be avoided.

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

The coadministration is contra-indicated since the CYP3A4 induction may decrease significantly the plasma concentrations of voriconazole

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

The strong CYP3A4 induction may decrease the AUC of vortioxetine. The co-administration may require an adjustment of the dose of vortioxetine

Rifampicin, xanthines

Rifampicin, enzymatic inductor, may increase the metabolism of xanthine and decrease its plasma levels and effect

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

Rifampicin, a strong inducer of several hepatic enzymes, including CYP3A4 resulted in a four fold reduction in zaleplon plasma concentration.

Rifampicin, zidovudine

The UGT induction may decrease the plasma concentration of zidovudine. The concomitant use should be avoided

Rifampicin, ziprasidone

The co-administration of ziprasidone with P glycoprotein inductors may decrease the plasma concentrations of ziprasidone

Rifampicin, zolpidem [2] ---> SmPC of [2] of eMC

The pharmacodynamic effect of zolpidem tartrate is decreased when it is administered with rifampicin (a CYP3A4 inducer).

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

Rifampicin is a potent CYP3A4 inducer. If co-administration is necessary, the patient should be closely monitored and the dose of Zonegran and other CYP3A4 substrates adjusted as needed.

Rifampicin, zopiclone [2] ---> SmPC of [2] of eMC

Plasma levels of zopiclone may be decreased when co-administered with CYP3A4 inducers

CONTRAINDICATIONS of Rifampicin

Rifadin is contra-indicated in patients who:

- are hypersensitive to any of the rifamycins or any of the excipients

- have jaundice;

- are concurrently receiving saquinavir/ritonavir therapy

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

Rifaximin

Activated charcoal, rifaximin

Rifaximin should be taken at least 2 hours after the administration of activated charcoal

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

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

Estrogens, rifaximin

Rifaximin may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.

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

As a precautionary measure, use of rifaximin during pregnancy is not recommended.

CONTRAINDICATIONS of Rifaximin

- Hypersensitivity to rifaximin, rifamycin]derivatives or to any of the excipients

- Cases of intestinal obstruction.

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

Rilonacept (Rilonacept Regeneron)

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

Vertigo may occur

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

A decision must be made to either discontinue breast-feeding or to discontinue/abstain from therapy.

CYP1A2 substrates with narrow therapeutic index, rilonacept [2] ---> SmPC of [2] of EMA

Rilonacept, IL-1 inhibitor, may normalize the formation of CYP450 enzymes. This is clinically relevant for CYP450 substrates with a narrow therapeutic index

CYP2B6 substrates with narrow therapeutic index, rilonacept [2] ---> SmPC of [2] of EMA

Rilonacept, IL-1 inhibitor, may normalize the formation of CYP450 enzymes. This is clinically relevant for CYP450 substrates with a narrow therapeutic index

CYP2C19 substrates with narrow therapeutic index, rilonacept [2] ---> SmPC of [2] of EMA

Rilonacept, IL-1 inhibitor, may normalize the formation of CYP450 enzymes. This is clinically relevant for CYP450 substrates with a narrow therapeutic index

CYP2C8 substrates with narrow therapeutic index, rilonacept [2] ---> SmPC of [2] of EMA

Rilonacept, IL-1 inhibitor, may normalize the formation of CYP450 enzymes. This is clinically relevant for CYP450 substrates with a narrow therapeutic index

CYP2C9 substrates with narrow therapeutic index, rilonacept [2] ---> SmPC of [2] of EMA

Rilonacept, IL-1 inhibitor, may normalize the formation of CYP450 enzymes. This is clinically relevant for CYP450 substrates with a narrow therapeutic index

Drugs primarily metabolised by CYP2D6 with narrow therapeutic index, rilonacept [2] ---> SmPC of [2] of EMA

Rilonacept, IL-1 inhibitor, may normalize the formation of CYP450 enzymes. This is clinically relevant for CYP450 substrates with a narrow therapeutic index

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, rilonacept [2] ---> SmPC of [2] of EMA

Rilonacept, IL-1 inhibitor, may normalize the formation of CYP450 enzymes. This is clinically relevant for CYP450 substrates with a narrow therapeutic index

IL-1 inhibitors, rilonacept [2] ---> SmPC of [2] of EMA

The concomitant use of rilonacept with other IL-1 inhibitors is not recommended because of increased risk of serious infections

IL-1 inhibitors, TNF inhibitors ---> SmPC of [rilonacept] of EMA

The concomitant administration of rilonacept with any TNF inhibitor is not recommended, because an increased incidence of serious infections has been associated with administration of another IL-1 blocker in combination with TNF inhibitors.

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

Treatment with immunosuppressants, including rilonacept, may result in an increase in the risk of malignancies

Neutropenia, rilonacept [2] ---> SmPC of [2] of EMA

Treatment with rilonacept should not be initiated in patients with neutropenia

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

Women who are pregnant or who desire to become pregnant should therefore only be treated after a thorough benefit-risk evaluation

Rilonacept [1], TNF inhibitors ---> SmPC of [1] of EMA

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

Live vaccines should not be given concurrently with rilonacept

CONTRAINDICATIONS of Rilonacept (Rilonacept Regeneron)

- Hypersensitivity to rilonacept or to any of the excipients.

- Active, severe infections

https://www.ema.europa.eu/en/documents/product-information/rilonacept-regeneron-epar-product-information_en.pdf 24/09/2012 (withdrawn)

Rilpivirine (Edurant)

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

No clinically relevant drug-drug interactions are expected. No dose adjustment is required.

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

Fatigue, dizziness and somnolence have been reported in some patients taking EDURANT and should be considered when assessing a patient's ability to drive or operate machinery.

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

The increase of gastric pH decreases absorption, plasma level and effect of rilpivirine. The antacid should be administered at least 2 h before or 4 h after rilpivirine

Aluminium, rilpivirine [2] ---> SmPC of [2] of EMA

The increase of gastric pH decreases absorption, plasma level and effect of rilpivirine. The antacid should be administered at least 2 h before or 4 h after rilpivirine

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

The increase of gastric pH decreases absorption, plasma level and effect of rilpivirine. The antacid should be administered at least 2 h before or 4 h after rilpivirine

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

Not studied. Increased exposure (inhibition of CYP3A enzymes) of rilpivirine is expected. No dose adjustment is required.

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

EVOTAZ is expected to increase rilpivirine plasma concentrations. The mechanism of interaction is CYP3A inhibition. Co-administration of EVOTAZ and rilpivirine can be used without dose adjustments

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

Not studied. Concomitant use of rilpivirine with ritonavir-boosted PIs (inhibition of CYP3A enzymes) causes an increase in the plasma concentrations of rilpivirine, but no dose adjustment is required.

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

No dose adjustment is required.

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

Not studied. Concomitant use of rilpivirine with azole antifungal agents (inhibition of CYP3A enzymes) may cause an increase in the plasma concentrations of rilpivirine. No dose adjustment is required.

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

The CYP3A4 inhibition increases the plasma concentrations of rilpivirine. No dosage adjustment necessary.

Boosted protease-inhibitors, rilpivirine [2] ---> SmPC of [2] of EMA

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

In order to avoid transmission of HIV to the infant it is recommended that women living with HIV do not breast-feed.

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

Because of the potential for adverse reactions in breastfed infants, mothers should be instructed not to breast-feed if they are receiving rilpivirine.

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

Rilpivirine did not significantly change cabotegravir plasma concentration. No dose adjustment of Vocabria injection is necessary when co-administered with rilpivirine.

Calcium carbonate, rilpivirine [2] ---> SmPC of [2] of EMA

The increase of gastric pH decreases absorption, plasma level and effect of rilpivirine. The antacid should be administered at least 2 h before or 4 h after rilpivirine

Calcium, rilpivirine [2] ---> SmPC of [2] of EMA

The increase of gastric pH decreases absorption, plasma level and effect of rilpivirine. The antacid should be administered at least 2 h before or 4 h after rilpivirine

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

Significant decreases in rilpivirine plasma concentrations are expected (induction of CYP3A enzymes). The co-administration is contraindicated

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

The increase of gastric pH decreases absorption, plasma level and effect of rilpivirine. The H2 antagonist should be administered at least 12 h before or 4 h after rilpivirine

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

The CYP3A4 inhibition by clarithromycin may increase the plasma concentrations of rilpivirine. Where possible, alternatives such as azithromycin should be considered.

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

Co-administration of rilpivirine and cobicistat is expected to increase the plasma concentration of rilpivirine. No dosage adjustment necessary.

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

It may not be completely excluded that rilpivirine can increase the exposure to drugs transported by P-glycoprotein. The combination of rilpivirine and dabigatran etexilate should be used with caution.

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

No dose adjustment is required

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

Boosted PREZISTA and rilpivirine can be used without dose adjustments.

Darunavir/cobicistat [1], rilpivirine ---> SmPC of [1] of EMA

Based on theoretical considerations REZOLSTA is expected to increase rilpivirine plasma concentrations. (CYP3A inhibition). Co-administration of REZOLSTA and rilpivirine can be used without dose adjustments

Darunavir/ritonavir, rilpivirine [2] ---> SmPC of [2] of EMA

Concomitant use of rilpivirine with ritonavir-boosted PIs (inhibition of CYP3A enzymes) causes an increase in the plasma concentrations of rilpivirine, but no dose adjustment is required.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, rilpivirine ---> SmPC of [dasabuvir] of EMA

Co-administration of Exviera and ombitasvir/paritaprevir/ritonavir with rilpivirine once daily should only be considered in patients without known QT-prolongation, and without other QT-prolongation coadministered medicinal products.

Delavirdine, rilpivirine [2] ---> SmPC of [2] of EMA

The co-administration of rilpivirine with another non-nucleoside reverse transcriptase inhibitor is not recommended

Dexamethasone, dolutegravir/rilpivirine ---> SmPC of [rilpivirine] of EMA

The CYP3A4 induction by dexamethasone may decrease the plasma concentrations and the therapeutic effect of rilpivirine. Contra-indicated (except as a single dose)

Dexamethasone, rilpivirine [2] ---> SmPC of [2] of EMA

The CYP3A4 induction by dexamethasone may decrease the plasma concentrations and the therapeutic effect of rilpivirine. Contra-indicated (except as a single dose)

Didanosine, rilpivirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required. Didanosine should be administered at least 2 hours before or at least 4 hours after rilpivirine.

Digoxin, rilpivirine [2] ---> SmPC of [2] of EMA

In a clinical study, rilpivirine did not significantly affect the pharmacokinetics of digoxin. No dose adjustment is required.

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

No dosage adjustment necessary.

Dolutegravir/abacavir/lamivudine [1], rilpivirine ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Dolutegravir/lamivudine [1], rilpivirine ---> SmPC of [1] of EMA

No dose adjustment is required.

Dolutegravir/rilpivirine [1], rilpivirine ---> SmPC of [1] of EMA

Juluca should not be taken with any other medicinal product containing dolutegravir or rilpivirine, except in case of co-administration with rifabutin

Dolutegravir/rilpivirine, torsades de pointes inducing drugs ---> SmPC of [rilpivirine] of EMA

Rilpivirine should be used with caution when co-administered with a medicinal product with a known risk of Torsade de Pointes.

Efavirenz, rilpivirine [2] ---> SmPC of [2] of EMA

The co-administration of rilpivirine with another non-nucleoside reverse transcriptase inhibitor is not recommended

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

No dose adjustment is required.

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

Co-administration of elvitegravir and rilpivirine is not expected to change elvitegravir plasma concentrations, therefore no dose adjustment of Vitekta is required.

Emtricitabine, rilpivirine [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interactions are expected. No dose adjustment is required.

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

Co-administration is likely to cause significant decreases in the plasma concentrations of tenofovir alafenamide (induction of P-gp). Co-administration is contraindicated.

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

Emtricitabine/rilpivirine/tenofovir should not be administered concomitantly with rilpivirine hydrochloride unless needed for dose adjustment with rifabutin

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

The recommended dose of Descovy is 200/25 mg once daily.

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

The CYP3A4 inhibition by erythromycin may increase the exposition of rilpivirine. Where possible, alternatives such as azithromycin should be considered.

Esomeprazole, rilpivirine [2] ---> SmPC of [2] of EMA

The increase of the gastric pH decreases the absorption, plasma level and therapeutic effect of rilpivirine. Rilpivirine must not be used with proton pump inhibitors

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

No dose adjustment is required.

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

Concomitant use of INTELENCE with rilpivirine may cause a decrease in the plasma concentration of rilpivirine and loss of therapeutic effect of rilpivirine. It is not recommended to co-administer INTELENCE with other NNRTIs.

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

The co-administration of rilpivirine with another non-nucleoside reverse transcriptase inhibitor is not recommended

Famotidine, rilpivirine [2] ---> SmPC of [2] of EMA

The increase of gastric pH decreases absorption, plasma level and effect of rilpivirine. The H2 antagonist should be administered at least 12 h before or 4 h after rilpivirine

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

No human data on the effect of rilpivirine on fertility are available. No clinically relevant effects on fertility were seen in animal studies (see section 5.3).

Fidaxomicin, rilpivirine

The inhibition of intestinal P-glycoprotein may increase the exposure to fidaxomicin

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

Foods, rilpivirine [2] ---> SmPC of [2] of EMA

Taking EDURANT in fasted condition or with only a nutritional drink may result in decreased plasma concentrations of rilpivirine, which could potentially reduce the therapeutic effect of EDURANT (see section 4.2).

Foods, rilpivirine [2] ---> SmPC of [2] of EMA

EDURANT must be taken with a meal to obtain optimal absorption

Fosamprenavir/ritonavir, rilpivirine [2] ---> SmPC of [2] of EMA

Ganciclovir, rilpivirine ---> SmPC of [valganciclovir] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Gastric pH increasing medication, rilpivirine [2] ---> SmPC of [2] of EMA

Co-administration of rilpivirine with medicinal products that increase gastric pH may result in decreased plasma concentrations of rilpivirine which could potentially reduce the therapeutic effect of rilpivirine.

H2 antagonists, rilpivirine [2] ---> SmPC of [2] of EMA

The increase of gastric pH decreases absorption, plasma level and effect of rilpivirine. The H2 antagonist should be administered at least 12 h before or 4 h after rilpivirine

Indinavir, rilpivirine [2] ---> SmPC of [2] of EMA

Not studied. Increased exposure (inhibition of CYP3A enzymes) of rilpivirine is expected. No dose adjustment is required.

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

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

Concomitant use of ketoconazole (inhibition of CYP3A enzymes) with rilpivirine (induction of CYP3A due to high rilpivirine dose in the study) decreases ketoconazole plasma levels and increases rilpivirine plasma levels. No dose adjustment is required.

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

No clinically relevant drug-drug interactions are expected. No dose adjustment is required.

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

The increase of the gastric pH decreases the absorption, plasma level and therapeutic effect of rilpivirine. Rilpivirine must not be used with proton pump inhibitors

Lanthanum carbonate, rilpivirine [2] ---> SmPC of [2] of EMA

The increase of the gastric pH decreases the absorption, plasma level and therapeutic effect of rilpivirine.

Lopinavir/ritonavir, rilpivirine [2] ---> SmPC of [2] of EMA

Concomitant use of lopinavir/ritonavir (inhibition of CYP3A enzymes) with rilpivirine causes an increase in the plasma concentrations of rilpivirine, but no dose adjustment is required.

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

The increase of gastric pH decreases absorption, plasma level and effect of rilpivirine. The antacid should be administered at least 2 h before or 4 h after rilpivirine

Magnesium, rilpivirine [2] ---> SmPC of [2] of EMA

The increase of gastric pH decreases absorption, plasma level and effect of rilpivirine. The antacid should be administered at least 2 h before or 4 h after rilpivirine

Maraviroc, rilpivirine [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required.

MATE-2K, rilpivirine [2] ---> SmPC of [2] of EMA

Rilpivirine is an in vitro inhibitor of the transporter MATE-2K with an IC50 of < 2.7 nM. The clinical implications of this finding are currently unknown.

Metformin, rilpivirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Methadone, rilpivirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Miconazole, rilpivirine

Oral miconazole is contraindicated with medicinal products that are metabolised by CYP3A4 and may prolong also the QT interval

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

Not studied. Increased exposure (inhibition of CYP3A enzymes) of rilpivirine is expected. No dose adjustment is required.

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

The concomitant administration of nevirapine with non-nucleoside reverse transcriptase inhibitors is not recommended.

Nevirapine, rilpivirine [2] ---> SmPC of [2] of EMA

The co-administration of rilpivirine with another non-nucleoside reverse transcriptase inhibitor is not recommended

Nizatidine, rilpivirine [2] ---> SmPC of [2] of EMA

The increase of gastric pH decreases absorption, plasma level and effect of rilpivirine. The H2 antagonist should be administered at least 12 h before or 4 h after rilpivirine

Non-nucleoside reverse transcriptase inhibitors, rilpivirine [2] ---> SmPC of [2] of EMA

The co-administration of rilpivirine with another non-nucleoside reverse transcriptase inhibitor is not recommended

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

No dose adjustment is required.

Nucleoside and nucleotide reverse transcriptase inhibitors, rilpivirine [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interactions are expected. No dose adjustment is required.

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

CYP3A4 inhibition by ritonavir. Co-administration of Viekirax with rilpivirine once daily should only be considered in patients without known QT prolongation, and without other QT-prolongation comedications.

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

The increase of the gastric pH decreases the absorption, plasma level and therapeutic effect of rilpivirine. Rilpivirine must not be used with proton pump inhibitors

Oxcarbazepine, rilpivirine [2] ---> SmPC of [2] of EMA

Significant decreases in rilpivirine plasma concentrations are expected (induction of CYP3A enzymes). The co-administration is contraindicated

P-glycoprotein substrates, rilpivirine [2] ---> SmPC of [2] of EMA

It may not be completely excluded that rilpivirine can increase the exposure to drugs transported by P-glycoprotein that are sensitive to intestinal P-gp inhibition

Pantoprazole, rilpivirine [2] ---> SmPC of [2] of EMA

The increase of the gastric pH decreases the absorption, plasma level and therapeutic effect of rilpivirine. Rilpivirine must not be used with proton pump inhibitors

Paracetamol, rilpivirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

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

Significant decreases in rilpivirine plasma concentrations are expected (induction of CYP3A enzymes). The co-administration is contraindicated

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

Significant decreases in rilpivirine plasma concentrations are expected (induction of CYP3A enzymes). The co-administration is contraindicated

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

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

The use of rilpivirine may be considered during pregnancy, if necessary.

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

The increase of the gastric pH decreases the absorption, plasma level and therapeutic effect of rilpivirine. Rilpivirine must not be used with proton pump inhibitors

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

Rilpivirine should be used with caution when co-administered with a medicinal product with a known risk of Torsade de Pointes.

Rabeprazole, rilpivirine [2] ---> SmPC of [2] of EMA

The increase of the gastric pH decreases the absorption, plasma level and therapeutic effect of rilpivirine. Rilpivirine must not be used with proton pump inhibitors

Raltegravir, rilpivirine [2] ---> SmPC of [2] of EMA

No dose adjustment is required

Ranitidine, rilpivirine [2] ---> SmPC of [2] of EMA

The increase of gastric pH decreases absorption, plasma level and effect of rilpivirine. The H2 antagonist should be administered at least 12 h before or 4 h after rilpivirine

Ribavirin, rilpivirine [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required.

Rifabutin, rilpivirine [2] ---> SmPC of [2] of EMA

Rifampicin, rilpivirine [2] ---> SmPC of [2] of EMA

The CYP3A4 induction by rifampicin may decrease the plasma concentrations and the therapeutic effect of rilpivirine. The co-administration is contraindicated

Rifapentine, rilpivirine [2] ---> SmPC of [2] of EMA

The CYP3A4 induction by rifapentine may decrease the plasma concentrations and the therapeutic effect of rilpivirine. The co-administration is contraindicated

Rilpivirine [1], saquinavir/ritonavir ---> SmPC of [1] of EMA

Rilpivirine [1], sildenafil ---> SmPC of [1] of EMA

No dose adjustment is required.

Rilpivirine [1], St. John's wort ---> SmPC of [1] of EMA

Significant decreases in rilpivirine plasma concentrations are expected (induction of CYP3A enzymes). Concomitant use is contraindicated

Rilpivirine [1], stavudine ---> SmPC of [1] of EMA

No clinically relevant drug-drug interactions are expected. No dose adjustment is required.

Rilpivirine [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Rilpivirine is primarily metabolised by cytochrome P450 (CYP)3A. Co-administration of rilpivirine and medicinal products that induce CYP3A has been observed to decrease the plasma concentrations of rilpivirine

Rilpivirine [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Rilpivirine is primarily metabolised by cytochrome P450 (CYP)3A. Co-administration of rilpivirine and medicinal products that inhibit CYP3A has been observed to increase the plasma concentrations of rilpivirine

Rilpivirine [1], tadalafil ---> SmPC of [1] of EMA

No dose adjustment is required.

Rilpivirine [1], tenofovir ---> SmPC of [1] of EMA

Increase in serum concentrations of tenofovir. No dose adjustment is required.

Rilpivirine [1], tipranavir/ritonavir ---> SmPC of [1] of EMA

Rilpivirine [1], torsades de pointes inducing drugs ---> SmPC of [1] of EMA

Rilpivirine should be used with caution when co-administered with a medicinal product with a known risk of Torsade de Pointes.

Rilpivirine [1], vardenafil ---> SmPC of [1] of EMA

No dose adjustment is required.

Rilpivirine [1], voriconazole ---> SmPC of [1] of EMA

Rilpivirine [1], zidovudine ---> SmPC of [1] of EMA

No clinically relevant drug-drug interactions are expected. No dose adjustment is required.

Rilpivirine, saquinavir [2] ---> SmPC of [2] of EMA

Switching directly from a rilpivirine containing regimen to Invirase/ritonavir is contraindicated as is concomitant use due to the potential for life threatening cardiac arrhythmia (see sections 4.3 and 4.4).

Rilpivirine, simeprevir [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Rilpivirine, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

Rilpivirine, sofosbuvir [2] ---> SmPC of [2] of EMA

No dose adjustment of sofosbuvir or rilpivirine is required when sofosbuvir and rilpivirine are used concomitantly.

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.

Rilpivirine, telaprevir [2] ---> SmPC of [2] of EMA

Decreased plasma levels of telaprevir. If co-administered, no dose adjustment is required.

Rilpivirine, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No dose adjustment of Vemlidy or rilpivirine is required.

Rilpivirine, valganciclovir [2] ---> SmPC of [2] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

CONTRAINDICATIONS of Rilpivirine (Edurant)

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

EDURANT should not be co-administered with the following medicinal products, as significant decreases in rilpivirine plasma concentrations may occur (due to CYP3A enzyme induction or gastric pH increase), which may result in loss of therapeutic effect of EDURANT:

- the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin

- the antimycobacterials rifampicin, rifapentine

- proton pump inhibitors, such as omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole

- the systemic glucocorticoid dexamethasone, except as a single dose treatment

- St John’s wort (Hypericum perforatum).

https://www.ema.europa.eu/en/documents/product-information/edurant-epar-product-information_en.pdf 23/10/2024

Other trade names: Rekambys,

Riluzole (Riluzole Zentiva)

Ability to drive, riluzole [2] ---> SmPC of [2] of EMA

Patients should be warned about the potential for dizziness or vertigo, and advised not to drive or operate machinery if these symptoms occur.

Amitriptyline, riluzole [2] ---> SmPC of [2] of EMA

Inhibitors of CYP 1A2 (e.g. caffeine, diclofenac, diazepam, nicergoline, clomipramine, imipramine, fluvoxamine, phenacetin, theophylline, amitriptyline and quinolones) could potentially decrease the rate of riluzole elimination

Breast-feeding, riluzole [2] ---> SmPC of [2] of EMA

Riluzole Zentiva is contraindicated in breast-feeding women (see sections 4.3 and 5.3). It is not known whether riluzole is excreted in human milk.

Caffeine, riluzole [2] ---> SmPC of [2] of EMA

Clomipramine, riluzole [2] ---> SmPC of [2] of EMA

CYP1A2 inductors, riluzole [2] ---> SmPC of [2] of EMA

Inducers of CYP 1A2 (e.g. cigarette smoke, charcoal-broiled food, rifampicin and omeprazole) could increase the rate of riluzole elimination.

CYP1A2 inhibitors, riluzole [2] ---> SmPC of [2] of EMA

Diazepam, riluzole [2] ---> SmPC of [2] of EMA

Diclofenac, riluzole [2] ---> SmPC of [2] of EMA

Fertility, riluzole [2] ---> SmPC of [2] of EMA

Fertility studies in rats revealed slight impairment of reproductive performance and fertility at doses of 15 mg/kg/day (which is higher than the therapeutic dose), probably due to sedation and lethargy.

Fluvoxamine, riluzole [2] ---> SmPC of [2] of EMA

Foods, riluzole [2] ---> SmPC of [2] of EMA

The rate and extent of absorption is reduced when riluzole is administered with high-fat meals (decrease in Cmax of 44%, decrease in AUC of 17%).

Grill, riluzole [2] ---> SmPC of [2] of EMA

Inducers of CYP 1A2 (e.g. cigarette smoke, charcoal-broiled food, rifampicin and omeprazole) could increase the rate of riluzole elimination.

Imipramine, riluzole [2] ---> SmPC of [2] of EMA

Nicergoline, riluzole [2] ---> SmPC of [2] of EMA

Nicotine, riluzole [2] ---> SmPC of [2] of EMA

Inducers of CYP 1A2 (e.g. cigarette smoke, charcoal-broiled food, rifampicin and omeprazole) could increase the rate of riluzole elimination.

Omeprazole, riluzole [2] ---> SmPC of [2] of EMA

Inducers of CYP 1A2 (e.g. cigarette smoke, charcoal-broiled food, rifampicin and omeprazole) could increase the rate of riluzole elimination.

Phenacetin, riluzole [2] ---> SmPC of [2] of EMA

Pregnancy, riluzole [2] ---> SmPC of [2] of EMA

Riluzole Zentiva is contraindicated in pregnancy (see sections 4.3 and 5.3). Clinical experience with riluzole in pregnant women is lacking.

Quinolones, riluzole [2] ---> SmPC of [2] of EMA

Rifampicin, riluzole [2] ---> SmPC of [2] of EMA

Inducers of CYP 1A2 (e.g. cigarette smoke, charcoal-broiled food, rifampicin and omeprazole) could increase the rate of riluzole elimination.

Riluzole [1], strong CYP1A2 inductors ---> SmPC of [1] of EMA

Inducers of CYP 1A2 (e.g. cigarette smoke, charcoal-broiled food, rifampicin and omeprazole) could increase the rate of riluzole elimination.

Riluzole [1], strong CYP1A2 inhibitors ---> SmPC of [1] of EMA

Riluzole [1], theophylline ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Riluzole (Riluzole Zentiva)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Hepatic disease or baseline transaminases greater than 3 times the upper limit of normal.

- Patients who are pregnant or breast-feeding.

https://www.ema.europa.eu/en/documents/product-information/riluzole-zentiva-epar-product-information_en.pdf 15/05/2025

Other trade names: Rilutek, Riluzol Accord, Riluzol Actavis, Riluzol Mylan, Riluzol Normon, Riluzol Panluetol, Riluzol PMCS, Riluzol Sandoz, Riluzol SUN, Riluzol Teva, Teglutik,

Rimegepant (Vydura)

BCRP inhibitors, rimegepant [2] ---> SmPC of [2] of EMA

Inhibitors of P-gp and BCRP efflux transporters may increase plasma concentrations of rimegepant.

Bosentan, rimegepant [2] ---> SmPC of [2] of EMA

Inducers of CYP3A4 decrease plasma concentrations of rimegepant. Concomitant administration of VYDURA with moderate CYP3A4 inducers (e.g., bosentan, efavirenz, modafinil) is not recommended

Breast-feeding, rimegepant [2] ---> SmPC of [2] of EMA

The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for VYDURA and any potential adverse reactions on the breastfed infant from rimegepant or from the underlying maternal condition.

Clarithromycin, rimegepant [2] ---> SmPC of [2] of EMA

Inhibitors of CYP3A4 increase plasma concentrations of rimegepant. Concomitant administration of rimegepant with strong CYP3A4 inhibitors (e.g., clarithromycin, itraconazole, ritonavir) is not recommended

Cyclosporine, rimegepant [2] ---> SmPC of [2] of EMA

Another dose of VYDURA within 48 hours should be avoided when it is concomitantly administered with strong inhibitors of P-gp (e.g., cyclosporine, verapamil, quinidine)

Diltiazem, rimegepant [2] ---> SmPC of [2] of EMA

Concomitant administration of rimegepant with medicinal products that moderately inhibit CYP3A4 (e.g., diltiazem, erythromycin, fluconazole) may increase exposure to rimegepant.

Efavirenz, rimegepant [2] ---> SmPC of [2] of EMA

Inducers of CYP3A4 decrease plasma concentrations of rimegepant. Concomitant administration of VYDURA with moderate CYP3A4 inducers (e.g., bosentan, efavirenz, modafinil) is not recommended

Erythromycin, rimegepant [2] ---> SmPC of [2] of EMA

Concomitant administration of rimegepant with medicinal products that moderately inhibit CYP3A4 (e.g., diltiazem, erythromycin, fluconazole) may increase exposure to rimegepant.

Fertility, rimegepant [2] ---> SmPC of [2] of EMA

Animal studies showed no clinically relevant impact on female and male fertility (see section 5.3).

Fluconazole, rimegepant [2] ---> SmPC of [2] of EMA

Concomitant administration of rimegepant with medicinal products that moderately inhibit CYP3A4 (e.g., diltiazem, erythromycin, fluconazole) may increase exposure to rimegepant.

Itraconazol, rimegepant [2] ---> SmPC of [2] of EMA

Modafinil, rimegepant [2] ---> SmPC of [2] of EMA

Inducers of CYP3A4 decrease plasma concentrations of rimegepant. Concomitant administration of VYDURA with moderate CYP3A4 inducers (e.g., bosentan, efavirenz, modafinil) is not recommended

Moderate CYP3A4 inductors, rimegepant [2] ---> SmPC of [2] of EMA

Inducers of CYP3A4 decrease plasma concentrations of rimegepant. The effect of CYP3A4 induction may last for up to 2 weeks after discontinuation of the strong or moderate CYP3A4 inducer.

Moderate CYP3A4 inhibitors, rimegepant [2] ---> SmPC of [2] of EMA

Another dose of rimegepant should be avoided within 48 hours when it is concomitantly administered with moderate inhibitors of CYP3A4

P-gp inhibitors, rimegepant [2] ---> SmPC of [2] of EMA

Inhibitors of P-gp and BCRP efflux transporters may increase plasma concentrations of rimegepant.

Phenobarbital, rimegepant [2] ---> SmPC of [2] of EMA

Inducers of CYP3A4 decrease plasma concentrations of rimegepant. Concomitant administration of VYDURA with strong CYP3A4 inducers (e.g., phenobarbital, rifampicin, St John's wort (Hypericum perforatum)) is not recommended

Pregnancy, rimegepant [2] ---> SmPC of [2] of EMA

As a precautionary measure, it is preferable to avoid the use of VYDURA during pregnancy.

Quinidine, rimegepant [2] ---> SmPC of [2] of EMA

Another dose of VYDURA within 48 hours should be avoided when it is concomitantly administered with strong inhibitors of P-gp (e.g., cyclosporine, verapamil, quinidine

Rifampicin, rimegepant [2] ---> SmPC of [2] of EMA

Rimegepant [1], ritonavir ---> SmPC of [1] of EMA

Rimegepant [1], St. John's wort ---> SmPC of [1] of EMA

Rimegepant [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Inducers of CYP3A4 decrease plasma concentrations of rimegepant. The effect of CYP3A4 induction may last for up to 2 weeks after discontinuation of the strong or moderate CYP3A4 inducer.

Rimegepant [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Rimegepant [1], verapamil ---> SmPC of [1] of EMA

Another dose of VYDURA within 48 hours should be avoided when it is concomitantly administered with strong inhibitors of P-gp (e.g., cyclosporine, verapamil, quinidine

CONTRAINDICATIONS of Rimegepant (Vydura)

- 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/vydura-epar-product-information_en.pdf 14/04/2025

Rimexolone

Ability to drive, rimexolone [2] ---> SmPC of [2] of eMC

If blurred vision or visual disturbances occur, the patient must wait until the vision clears before driving or using machinery.

Breast-feeding, rimexolone [2] ---> SmPC of [2] of eMC

A decision should be made whether to discontinue nursing or discontinue therapy, taking into consideration the importance of the drug to the mother.

Pregnancy, rimexolone [2] ---> SmPC of [2] of eMC

Rimexolone should not be used during pregnancy unless clearly necessary.

CONTRAINDICATIONS of Rimexolone

- Hypersensitivity to the active substance or any of the excipients.

- VEXOL is contraindicated in epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, and most other viral diseases of cornea and conjunctiva; mycobacterial infection of the eye; fungal diseases of the eye; acute purulent untreated infections which, like other diseases caused by microorganisms may be masked or enhanced by the presence of the steroid; red eye, where the diagnosis is unconfirmed; and amoebic infections.

http://www.medicines.org.uk/emc/

Rimonabant (Acomplia)

Breast-feeding, rimonabant [2] ---> SmPC of [2] of EMA

ACOMPLIA contraindicated during breast-feeding

Carbamazepine, rimonabant [2] ---> SmPC of [2] of EMA

It is expected that concomitant administration of potent CYP3A4 inducers may reduce the plasma concentration of rimonabant and may result in loss of efficacy.

Clarithromycin, rimonabant [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the exposition of rimonabant. Caution is advised during concomitant use of rimonabant and potent CYP3A4 inhibitors

Ethinyl estradiol/levonorgestrel, rimonabant [2] ---> SmPC of [2] of EMA

The steady-state pharmacokinetics of an ethinyl estradiol/levonorgestrel combination oral contraceptive were not significantly altered by concomitant administration of rimonabant.

Itraconazol, rimonabant [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the exposition of rimonabant. Caution is advised during concomitant use of rimonabant and potent CYP3A4 inhibitors

Ketoconazole, rimonabant [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the exposition of rimonabant. Caution is advised during concomitant use of rimonabant and potent CYP3A4 inhibitors

Nefazodone, rimonabant [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the exposition of rimonabant. Caution is advised during concomitant use of rimonabant and potent CYP3A4 inhibitors

Phenobarbital, rimonabant [2] ---> SmPC of [2] of EMA

It is expected that concomitant administration of potent CYP3A4 inducers may reduce the plasma concentration of rimonabant and may result in loss of efficacy.

Phenytoin, rimonabant [2] ---> SmPC of [2] of EMA

It is expected that concomitant administration of potent CYP3A4 inducers may reduce the plasma concentration of rimonabant and may result in loss of efficacy.

Pregnancy, rimonabant [2] ---> SmPC of [2] of EMA

Use in pregnancy is not recommended

Rifampicin, rimonabant [2] ---> SmPC of [2] of EMA

It is expected that concomitant administration of potent CYP3A4 inducers may reduce the plasma concentration of rimonabant and may result in loss of efficacy.

Rimonabant [1], ritonavir ---> 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

Rimonabant [1], St. John's wort ---> SmPC of [1] of EMA

It is expected that concomitant administration of potent CYP3A4 inducers may reduce the plasma concentration of rimonabant and may result in loss of efficacy.

Rimonabant [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

It is expected that concomitant administration of potent CYP3A4 inducers may reduce the plasma concentration of rimonabant and may result in loss of efficacy.

Rimonabant [1], strong CYP3A4 inhibitors ---> 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

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

CONTRAINDICATIONS of Rimonabant (Acomplia)

- Hypersensitivity to the active substance or to any of the excipients

- Lactation.

- Ongoing major depressive illness and/or ongoing antidepressive treatment

https://www.ema.europa.eu/en/documents/product-information/acomplia-epar-product-information_en.pdf 30/01/2009 (withdrawn)

Riociguat (Adempas)

Abacavir [1], ethanol ---> SmPC of [1] of EMA

Riociguat dose may need to be reduced. Consult the riociguat prescribing information for dosing recommendations.

Abacavir/lamivudine [1], riociguat ---> SmPC of [1] of EMA

Concomitant administration of a single dose of riociguat (0.5 mg) to HIV patients receiving the combination of abacavir/dolutegravir/lamivudine (600mg/50mg/300mg once daily) led to an approximately three-fold higher riociguat

Abacavir/lamivudine/zidovudine [1], riociguat ---> SmPC of [1] of EMA

Riociguat dose may need to be reduced. Consult the riociguat prescribing information for dosing recommendations.

Ability to drive, riociguat [2] ---> SmPC of [2] of EMA

Dizziness has been reported and may affect the ability to drive and use machines

Acetylsalicylic acid, riociguat [2] ---> SmPC of [2] of EMA

Riociguat did not potentiate the bleeding time caused by acetyl-salicylic acid or affect the platelet aggregation in humans.

Aluminium hydroxide, riociguat [2] ---> SmPC of [2] of EMA

Riociguat exhibits a reduced solubility at neutral pH vs. acidic medium. Co-medication of drugs increasing the upper GI pH may decrease oral riociguat bioavailability. Antacids should be taken at least 2 hours before, or 1 hour after riociguat.

Amyl nitrite, riociguat [2] ---> SmPC of [2] of EMA

Co-administration of riociguat with nitrates or nitric oxide donors (such as amyl nitrite) in any form, including recreational drugs called 'poppers', is contraindicated (see section 4.3).

Antacids, riociguat [2] ---> SmPC of [2] of EMA

Avanafil [1], riociguat ---> SmPC of [1] of EMA

The co-administration of type 5 phosphodiesterase (PDE5) inhibitors, including avanafil, with guanylate cyclase stimulators, such as riociguat is contraindicated as it may potentially lead to symptomatic hypotension

Azole antifungals, riociguat [2] ---> SmPC of [2] of EMA

Concomitant use of riociguat with strong multi-pathway CYP and P-gp/BCRP inhibitors is not recommended

Bosentan, riociguat [2] ---> SmPC of [2] of EMA

Bosentan, reported to be a moderate inducer of CYP3A4, led to a decrease of riociguat steady-state plasma concentrations in PAH patients by 27%

Breast-feeding, riociguat [2] ---> SmPC of [2] of EMA

A risk to the suckling child cannot be excluded. Breast-feeding should be discontinued during treatment with this medicinal product.

Carbamazepine, riociguat [2] ---> SmPC of [2] of EMA

The concomitant use of riociguat with strong CYP3A4 inducers may lead to decreased riociguat plasma concentration.

Coumarin anticoagulants, riociguat [2] ---> SmPC of [2] of EMA

The concomitant use of riociguat with other cumarin-derivatives (e.g. phenprocoumon) is also not expected to alter prothrombin time.

Cyclosporine, riociguat [2] ---> SmPC of [2] of EMA

Drugs strongly inhibiting P-gp/BCRP such as the immuno-suppressive cyclosporine A, should be used with caution

CYP450 isoforms, riociguat [2] ---> SmPC of [2] of EMA

From the recombinant CYP isoforms investigated in vitro CYP1A1 catalysed formation of riociguat's main metabolite most effectively.

Dolutegravir/abacavir/lamivudine [1], riociguat ---> SmPC of [1] of EMA

Riociguat dose may need to be reduced, consult the riociguat prescribing information for dosing recommendations.

Drugs primarily metabolised by CYP1A1, riociguat [2] ---> SmPC of [2] of EMA

Clinically relevant drug-drug interactions with co-medications which are significantly cleared by CYP1A1-mediated biotransformation cannot be ruled out.

Erlotinib, riociguat [2] ---> SmPC of [2] of EMA

The class of tyrosine kinase inhibitors was identified as potent inhibitors of CYP1A1, with erlotinib and gefitinib exhibiting the highest inhibitory potency in vitro.

Ethinyl estradiol/levonorgestrel, riociguat [2] ---> SmPC of [2] of EMA

Riociguat (2.5 mg 3 times per day) did not have a clinically meaningful effect on the plasma levels of combined oral contraceptives containing levonorgestrel and ethinyl estradiol when concomitantly administered to healthy female subjects.

Fertility, riociguat [2] ---> SmPC of [2] of EMA

In a reproduction toxicity study in rats, decreased testes weights were seen, but there were no effects on fertility (see section 5.3). The relevance of this finding for humans is unknown.

Foods, riociguat [2] ---> SmPC of [2] of EMA

However, if you are prone to having low blood pressure (hypotension), you should not switch from taking Adempas with food to taking Adempas without food because it may affect how you react to this medicine.

Gefitinib, riociguat [2] ---> SmPC of [2] of EMA

The class of tyrosine kinase inhibitors was identified as potent inhibitors of CYP1A1, with erlotinib and gefitinib exhibiting the highest inhibitory potency in vitro.

Granisetron, riociguat [2] ---> SmPC of [2] of EMA

Clinically relevant drug-drug interactions with co-medications which are significantly cleared by CYP1A1-mediated biotransformation cannot be ruled out.

Itraconazol, riociguat [2] ---> SmPC of [2] of EMA

Concomitant use of riociguat with strong multi-pathway CYP and P-gp/BCRP inhibitors is not recommended

Ketoconazole, riociguat [2] ---> SmPC of [2] of EMA

Concomitant use of riociguat with strong multi-pathway CYP and P-gp/BCRP inhibitors is not recommended

Lopinavir/ritonavir [1], riociguat ---> SmPC of [1] of EMA

Serum concentrations may be increased due to CYP3A and P-gp inhibition by Kaletra. The coadministration of riociguat with Kaletra is not recommended

Macitentan [1], riociguat ---> SmPC of [1] of EMA

Macitentan 10 mg once daily did not affect the pharmacokinetics of a BCRP substrate drug (riociguat 1 mg; rosuvastatin 10 mg).

Macitentan/tadalafil [1], riociguat ---> SmPC of [1] of EMA

In in vivo studies, macitentan 10 mg once daily did not affect the pharmacokinetics of a BCRP substrate drug (riociguat 1 mg; rosuvastatin 10 mg).

Macitentan/tadalafil [1], riociguat ---> 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 (see section 4.3).

Magnesium hydroxide, riociguat [2] ---> SmPC of [2] of EMA

Nicotine, riociguat [2] ---> SmPC of [2] of EMA

Plasma concentrations of riociguat in smokers are reduced compared to non-smokers. Dose adjustment may be necessary in patients who start or stop smoking during treatment with riociguat

Nirmatrelvir/ritonavir [1], riociguat ---> SmPC of [1] of EMA

Serum concentrations may be increased due to CYP3A and P-gp inhibition by ritonavir. The coadministration of riociguat with Paxlovid is not recommended (refer to riociguat SmPC).

Nitric oxide donors, riociguat [2] ---> SmPC of [2] of EMA

Co-administration of riociguat with nitrates or nitric oxide donors (such as amyl nitrite) in any form, including recreational drugs called 'poppers', is contraindicated (see section 4.3).

Nitroglycerine, riociguat [2] ---> SmPC of [2] of EMA

In a clinical study the highest dose of riociguat (2.5 mg tablets 3 times daily) potentiated the blood pressure lowering effect of sublingual nitroglycerin (0.4 mg) taken 4 and 8 hours after intake.

Oral contraceptives, riociguat [2] ---> SmPC of [2] of EMA

Organic nitrates, riociguat [2] ---> SmPC of [2] of EMA

Co-administration of riociguat with nitrates or nitric oxide donors (such as amyl nitrite) in any form, including recreational drugs called 'poppers', is contraindicated (see section 4.3).

PDE5 inhibitors, riociguat

Preclinical studies showed additive systemic blood pressure lowering effect when PDE5 inhibitors were combined with riociguat. Concomitant use of riociguat with PDE5 inhibitors, including vardenafil, is contraindicated

PDE5 inhibitors, riociguat

Concomitant use of riociguat with PDE5 inhibitors, including sildenafil, is contraindicated (see section 4.3).

PDE5 inhibitors, riociguat

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, riociguat [2] ---> SmPC of [2] of EMA

The concomitant use of riociguat with strong CYP3A4 inducers may lead to decreased riociguat plasma concentration.

Phenprocoumon, riociguat [2] ---> SmPC of [2] of EMA

The concomitant use of riociguat with other cumarin-derivatives (e.g. phenprocoumon) is also not expected to alter prothrombin time.

Phenytoin, riociguat [2] ---> SmPC of [2] of EMA

The concomitant use of riociguat with strong CYP3A4 inducers may lead to decreased riociguat plasma concentration.

Pregnancy, riociguat [2] ---> SmPC of [2] of EMA

Adempas is contraindicated during pregnancy. Monthly pregnancy tests are recommended. Patients must not get pregnant during riociguat therapy (see section 4.3).

Protease inhibitors, riociguat [2] ---> SmPC of [2] of EMA

Concomitant use of riociguat with strong multi-pathway CYP and P-gp/BCRP inhibitors is not recommended

Riociguat [1], ritonavir ---> SmPC of [1] of EMA

Serum concentrations may be increased due to CYP3A and P-gp inhibition by ritonavir. The coadministration of riociguat with Norvir is not recommended

Riociguat [1], smoking ---> SmPC of [1] of EMA

In cigarette smokers riociguat exposure is reduced by 50-60% (see section 5.2). Therefore, patients are advised to stop smoking (see section 4.2).

Riociguat [1], soluble guanylate cyclase stimulators ---> SmPC of [1] of EMA

Concomitant use of riociguat with other soluble guanylate cyclase stimulators is contraindicated (see section 4.3).

Riociguat [1], St. John's wort ---> SmPC of [1] of EMA

The concomitant use of riociguat with strong CYP3A4 inducers may lead to decreased riociguat plasma concentration.

Riociguat [1], strong BCRP inhibitors ---> SmPC of [1] of EMA

Concomitant use of riociguat with strong P-gp/BCRP inhibitors is not recommended

Riociguat [1], strong CYP1A1 inhibitors ---> SmPC of [1] of EMA

Drug-drug interactions by inhibition of CYP1A1 could result in increased riociguat exposure, especially in smokers. Strong CYP1A1 inhibitors should be used with caution

Riociguat [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

The concomitant use of riociguat with strong CYP3A4 inducers may lead to decreased riociguat plasma concentration.

Riociguat [1], strong multi pathway CYP and P-gp/BCRP inhibitors ---> SmPC of [1] of EMA

Concomitant administration of HAART combinations led to an increase in riociguat mean AUC of up to about 160% and to an approximate 30% increase in mean Cmax.

Riociguat [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

Concomitant use of riociguat with strong P-gp/BCRP inhibitors is not recommended

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

Riociguat [1], UGT1A1 inhibitors ---> SmPC of [1] of EMA

Inhibitors for the UDP-Glykosyltransferases (UGT) 1A1 and 1A9 may potentially increase the exposure of the riociguat metabolite M1, which is pharmacologically active

Riociguat [1], UGT1A9 inhibitors ---> SmPC of [1] of EMA

Inhibitors for the UDP-Glykosyltransferases (UGT) 1A1 and 1A9 may potentially increase the exposure of the riociguat metabolite M1, which is pharmacologically active

Riociguat [1], warfarin ---> SmPC of [1] of EMA

Concomitant treatment of riociguat and warfarin did not alter prothrombin time induced by the anticoagulant. Lack of pharmacokinetic interactions between riociguat and the CYP2C9 substrate warfarin was demonstrated in vivo.

Riociguat [1], women of childbearing potential ---> SmPC of [1] of EMA

Women and female adolescents of childbearing potential must use effective contraception during treatment with riociguat.

Riociguat, sildenafil [2] ---> SmPC of [2] of EMA

Concomitant use of riociguat with PDE5 inhibitors, including sildenafil, is contraindicated (see section 4.3).

Riociguat, vardenafil [2] ---> SmPC of [2] of EMA

CONTRAINDICATIONS of Riociguat (Adempas)

- Co-administration with PDE5 inhibitors (such as sildenafil, tadalafil, vardenafil) (see sections 4.2 and 4.5).

- Severe hepatic impairment (Child Pugh C).

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Pregnancy (see sections 4.4; 4.5 and 4.6).

- Co-administration with nitrates or nitric oxide donors (such as amyl nitrite) in any form including recreational drugs called 'poppers' (see section 4.5).

- Concomitant use with other soluble guanylate cyclase stimulators.

- Treatment initiation for

children aged 6 to < 12 years with systolic blood pressure < 90 mmHg,

patients ≥ 12 years with systolic blood pressure < 95 mmHg.

- Patients with pulmonary hypertension associated with idiopathic interstitial pneumonias (PHIIP) (see section 5.1)

https://www.ema.europa.eu/en/documents/product-information/adempas-epar-product-information_en.pdf 03/12/2025

Ripretinib (Qinlock)

Ability to drive, ripretinib [2] ---> SmPC of [2] of EMA

In some patients, fatigue has been reported following administration of QINLOCK. If a patient experiences fatigue, this may influence their ability to drive or use machines.

BCRP inhibitors, ripretinib [2] ---> SmPC of [2] of EMA

Based on in vitro data, medicinal products that are inhibitors of BCRP (e.g. cyclosporine A, eltrombopag) should be used with caution in combination with QINLOCK, as increased plasma concentrations of ripretinib or DP-5439 may be possible.

BCRP substrates, ripretinib [2] ---> SmPC of [2] of EMA

QINLOCK is to be used with caution with BCRP substrates (e.g. rosuvastatin, sulfasalazine and irinotecan) and MATE-1 substrates (e.g. metformin) as co-administration of QINLOCK with BCRP and MATE-1 substrates may lead to an increase of their exposure.

Breast-feeding, ripretinib [2] ---> SmPC of [2] of EMA

A risk to the breast-fed child cannot be excluded. Breast-feeding should be discontinued during treatment with QINLOCK and for at least 1 week after the final dose.

Cabotegravir, ripretinib [2] ---> SmPC of [2] of EMA

QINLOCK is to be used with caution in combination with clinical substrates of UGT1A enzymes (e.g. bictegravir, cabotegravir, dolutegravir, raltegravir, lamotrigine), as co-administration may lead to increased exposure of these substrates.

Carbamazepine, ripretinib [2] ---> SmPC of [2] of EMA

Concomitant use of QINLOCK with strong CYP3A inducers (e.g. carbamazepine, phenytoin, rifampicin, phenobarbital and St. John's wort) and moderate CYP3A inducers (e.g. efavirenz and etravirine) must therefore be avoided.

Cardiac failure, ripretinib [2] ---> SmPC of [2] of EMA

Cardiac failure (including cardiac failure, cardiac failure acute, acute left ventricular failure, and diastolic dysfunction) was observed with ripretinib (see section 4.8).

Clarithromycin, ripretinib [2] ---> SmPC of [2] of EMA

Strong inhibitors of CYP3A/P-gp (e.g. ketoconazole, erythromycin, clarithromycin, itraconazole, ritonavir, posaconazole, and voriconazole) are to be used with caution and patients should be monitored.

Cutaneous squamous cell carcinoma, ripretinib [2] ---> SmPC of [2] of EMA

Cutaneous squamous cell carcinoma (CuSCC) and melanoma were reported in patients receiving ripretinib (see section 4.8).

Cyclosporine, ripretinib [2] ---> SmPC of [2] of EMA

CYP1A2 substrates with narrow therapeutic index, ripretinib [2] ---> SmPC of [2] of EMA

Ripretinib and DP-5439 down-regulated CYP1A2 in vitro. Co-administration of ripretinib with CYP1A2 substrates with narrow therapeutic index (e.g. tizanidine) may lead to increased concentrations and monitoring is recommended.

CYP2B6 substrates with narrow therapeutic index, ripretinib [2] ---> SmPC of [2] of EMA

Co-administration of ripretinib with CYP2B6 substrates with narrow therapeutic index (e.g. efavirenz) may lead to loss of their efficacy.

Dabigatran, ripretinib [2] ---> SmPC of [2] of EMA

Medicinal products that are P-gp substrates with narrow therapeutic indices (e.g. digoxin, dabigatran etexilate) should be used with caution in combination with QINLOCK due to the likelihood of increased plasma concentrations of these substrates.

Digoxin, ripretinib [2] ---> SmPC of [2] of EMA

Dolutegravir, ripretinib [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP2C8, ripretinib [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, ripretinib [2] ---> SmPC of [2] 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).

Efavirenz, ripretinib [2] ---> SmPC of [2] of EMA

Eltrombopag, ripretinib [2] ---> SmPC of [2] of EMA

Embryofoetal toxicity, ripretinib [2] ---> SmPC of [2] of EMA

Based on findings from animal studies, ripretinib can cause foetal harm when administered to pregnant women (see sections 4.6 and 5.3).

Erythromycin, ripretinib [2] ---> SmPC of [2] of EMA

Etravirine, ripretinib [2] ---> SmPC of [2] of EMA

Fertility, ripretinib [2] ---> SmPC of [2] of EMA

Based on findings from animal studies, male and female fertility may be compromised by treatment with QINLOCK

Grapefruit juice, ripretinib [2] ---> SmPC of [2] of EMA

Ingestion of grapefruit juice is not recommended.

Hormonal contraceptives, ripretinib [2] ---> SmPC of [2] of EMA

It is unknown whether ripretinib may reduce the effectiveness of systemically acting hormonal contraceptives, and therefore women using systemically acting hormonal contraceptives should add a barrier method.

Hypertensive drugs, ripretinib [2] ---> SmPC of [2] of EMA

Hypertension was observed with ripretinib (see section 4.8). Ripretinib must not be initiated unless blood pressure is adequately controlled.

Irinotecan, ripretinib [2] ---> SmPC of [2] of EMA

Itraconazol, ripretinib [2] ---> SmPC of [2] of EMA

Ketoconazole, ripretinib [2] ---> SmPC of [2] of EMA

Lamotrigine, ripretinib [2] ---> SmPC of [2] of EMA

MATE1 substrates, ripretinib [2] ---> SmPC of [2] of EMA

Metformin, ripretinib [2] ---> SmPC of [2] of EMA

Midazolam, ripretinib [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inductors, ripretinib [2] ---> SmPC of [2] of EMA

P-glycoprotein substrates with small therapeutic index, ripretinib [2] ---> SmPC of [2] of EMA

Paclitaxel, ripretinib [2] ---> SmPC of [2] of EMA

Pantoprazole, ripretinib [2] ---> SmPC of [2] of EMA

No clinically significant differences in the plasma exposure to ripretinib and DP-5439 were observed when QINLOCK was co-administered with pantoprazole (a proton pump inhibitor).

Phenobarbital, ripretinib [2] ---> SmPC of [2] of EMA

Phenytoin, ripretinib [2] ---> SmPC of [2] of EMA

Phototoxicity, ripretinib [2] ---> SmPC of [2] of EMA

It is recommended to advise patients to avoid or minimise exposure to direct sunlight, sunlamps, and other sources of ultraviolet radiation due to the risk of phototoxicity associated with ripretinib.

Posaconazole, ripretinib [2] ---> SmPC of [2] of EMA

Pregnancy, ripretinib [2] ---> SmPC of [2] of EMA

The pregnancy status of females of reproductive potential is to be verified prior to initiating QINLOCK and during treatment.

Pregnancy, ripretinib [2] ---> SmPC of [2] of EMA

QINLOCK should not be used during pregnancy unless the clinical condition of the woman requires treatment with ripretinib.

Raltegravir, ripretinib [2] ---> SmPC of [2] of EMA

Repaglinide, ripretinib [2] ---> SmPC of [2] of EMA

Rifampicin, ripretinib [2] ---> SmPC of [2] of EMA

Ripretinib [1], ritonavir ---> SmPC of [1] of EMA

Ripretinib [1], rosuvastatin ---> SmPC of [1] of EMA

Ripretinib [1], St. John's wort ---> SmPC of [1] of EMA

Ripretinib [1], strong CYP3A4 and P-glycoprotein-inhibitors ---> SmPC of [1] of EMA

Ripretinib [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Ripretinib [1], sulfasalazine ---> SmPC of [1] of EMA

Ripretinib [1], surgery ---> SmPC of [1] of EMA

Treatment with ripretinib is to be withheld for at least 3 days prior to and after minor surgery and at least 5 days prior to and after major surgery. Ripretinib may then be resumed after surgery based on clinical judgment of adequate wound healing.

Ripretinib [1], tacrolimus ---> SmPC of [1] of EMA

Ripretinib [1], tizanidine ---> SmPC of [1] of EMA

Ripretinib [1], voriconazole ---> SmPC of [1] of EMA

Ripretinib [1], wound healing ---> SmPC of [1] of EMA

Impaired wound healing complications may occur in patients who receive medicinal products that inhibit the vascular endothelial growth factor (VEGF) signalling pathway. Therefore, ripretinib has the potential to adversely affect wound healing.

Ripretinib, women of childbearing potential [2] ---> SmPC of [2] of EMA

Women of childbearing potential and men with female partners of reproductive potential must be informed that QINLOCK may cause foetal harm and must ensure effective contraception during treatment and for at least 1 week after the final dose of QINLOCK

CONTRAINDICATIONS of Ripretinib (Qinlock)

- 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/qinlock-epar-product-information_en.pdf 15/10/2025

Risankizumab (Skyrizi)

Breast-feeding, risankizumab [2] ---> SmPC of [2] of EMA

A decision should be made whether to discontinue/abstain from risankizumab therapy, taking into account the benefit of breast-feeding to the child and the benefit of risankizumab therapy to the woman.

Fertility, risankizumab [2] ---> SmPC of [2] of EMA

The effect of risankizumab on human fertility has not been evaluated. Animal studies do not indicate direct or indirect harmful effects with respect to fertility.

Immunosuppressives, risankizumab [2] ---> SmPC of [2] of EMA

The safety and efficacy of risankizumab in combination with immunosuppressants, including biologics or phototherapy, have not been evaluated.

Pregnancy, risankizumab [2] ---> SmPC of [2] of EMA

As a precautionary measure, it is preferable to avoid the use of risankizumab during pregnancy.

Risankizumab [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

Patients treated with risankizumab should not receive live vaccines during treatment and for at least 21 weeks after treatment (see section 5.2).

Risankizumab [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 21 weeks after treatment.

CONTRAINDICATIONS of Risankizumab (Skyrizi)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Clinically important active infections (e.g. active tuberculosis, see section 4.4).

https://www.ema.europa.eu/en/documents/product-information/skyrizi-epar-product-information_en.pdf 25/11/2025

Risdiplam (Evrysdi)

Breast-feeding, risdiplam [2] ---> SmPC of [2] of EMA

Studies in rats show that risdiplam is excreted into milk (see section 5.3). As the potential for harm to the breastfed infant is unknown, it is recommended not to breastfeed during treatment.

CYP3A4 inhibitors, risdiplam [2] ---> SmPC of [2] of EMA

No dose adjustments are required when Evrysdi is coadministered with a CYP3A inhibitor.

CYP3A4 substrates, risdiplam [2] ---> SmPC of [2] of EMA

The extent of the interaction is not considered clinically relevant, and therefore no dose adjustment is required for CYP3A substrates.

Female fertility, risdiplam [2] ---> SmPC of [2] of EMA

Based on nonclinical data (see section 5.3), an impact of risdiplam on female fertility is not expected.

FMO1, risdiplam [2] ---> SmPC of [2] of EMA

No drug-drug interactions are expected via the FMO1 and FMO3 pathway.

Itraconazol, risdiplam [2] ---> SmPC of [2] of EMA

No dose adjustments are required when Evrysdi is coadministered with a CYP3A inhibitor.

Male fertility, risdiplam [2] ---> SmPC of [2] of EMA

Male fertility may be compromised while on treatment, based on nonclinical findings. Based on observations from animal studies, the effects on sperm cells are expected to be reversible upon discontinuation of risdiplam.

MATE1 substrates, risdiplam [2] ---> SmPC of [2] of EMA

The effect of co-administration of risdiplam on the pharmacokinetics of MATE1 and MATE2-K substrates in humans is unknown.

MATE2-K substrates, risdiplam [2] ---> SmPC of [2] of EMA

The effect of co-administration of risdiplam on the pharmacokinetics of MATE1 and MATE2-K substrates in humans is unknown.

Men, risdiplam [2] ---> SmPC of [2] of EMA

Male patients, and their female partners of childbearing potential, should both ensure that highly effective contraception is achieved during treatment and for at least 4 months after the last dose.

Metformin, risdiplam [2] ---> SmPC of [2] of EMA

Based on in vitro data, risdiplam may increase plasma concentrations of medicinal products eliminated via MATE1 or MATE2-K, such as metformin.

Midazolam, risdiplam [2] ---> SmPC of [2] of EMA

The extent of the interaction is not considered clinically relevant, and therefore no dose adjustment is required for CYP3A substrates.

Nusinersen, risdiplam [2] ---> SmPC of [2] of EMA

There is no efficacy or safety data to support the concomitant use of risdiplam and nusinersen.

OCT2 substrates, risdiplam [2] ---> SmPC of [2] of EMA

At therapeutic drug concentrations, no interaction is expected with OCT2 substrates.

Pregnancy, risdiplam [2] ---> SmPC of [2] of EMA

Evrysdi is not recommended during pregnancy and in women of childbearing potential not using contraception (see section 4.4).

Risdiplam [1], sperm ---> SmPC of [1] of EMA

Male patients may consider sperm preservation prior to treatment initiation or after a treatment-free period of at least 4 months. Male patients who wish to father a child should stop treatment for a minimum of 4 months.

Risdiplam [1], women of childbearing potential ---> SmPC of [1] of EMA

Female patients of childbearing potential should use highly effective contraception during treatment and for at least 1 month after the last dose.

CONTRAINDICATIONS of Risdiplam (Evrysdi)

- 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/evrysdi-epar-product-information_en.pdf 12/09/2024

Risedronate

Aluminium, risedronate [2] ---> SmPC of [2] of eMC

Concomitant ingestion of medications containing polyvalent cations (e.g. calcium, magnesium, iron and aluminium) will interfere with the absorption of risedronate sodium

Breast-feeding, risedronate [2] ---> SmPC of [2] of eMC

Risedronate sodium must not be used by breast-feeding women.

Calcium, risedronate [2] ---> SmPC of [2] of eMC

Concomitant ingestion of medications containing polyvalent cations (e.g. calcium, magnesium, iron and aluminium) will interfere with the absorption of risedronate sodium

Foods, risedronate [2] ---> SmPC of [2] of eMC

Foods interfere with the absorption of bisphosphonates and should not be taken at the same time

Iron, risedronate [2] ---> SmPC of [2] of eMC

Concomitant ingestion of medications containing polyvalent cations (e.g. calcium, magnesium, iron and aluminium) will interfere with the absorption of risedronate sodium

Magnesium, risedronate [2] ---> SmPC of [2] of eMC

Concomitant ingestion of medications containing polyvalent cations (e.g. calcium, magnesium, iron and aluminium) will interfere with the absorption of risedronate sodium

Pregnancy, risedronate [2] ---> SmPC of [2] of eMC

Risedronate sodium must not be used during pregnancy

CONTRAINDICATIONS of Risedronate

- Hypersensitivity to risedronate sodium or to any of the excipients.

- Hypocalcaemia

- Pregnancy and lactation.

- Severe renal impairment (creatinine clearance <30 ml/min).

http://www.medicines.org.uk/emc/

Risperidone (Okedi)

Ability to drive, risperidone [2] ---> SmPC of [2] of EMA

OKEDI can have minor or moderate influence on the ability to drive and use machines due to potential nervous system and visual effects (see section 4.8).

Abiraterone [1], risperidone ---> 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.

Abiraterone/niraparib [1], risperidone ---> SmPC of [1] of EMA

Examples of medicinal products metabolised by CYP2D6 include metoprolol, propranolol, desipramine, venlafaxine, haloperidol, risperidone, propafenone, flecainide, codeine, oxycodone and tramadol.

Alcohol, risperidone [2] ---> SmPC of [2] of EMA

OKEDI should be used with caution in combination with other centrally-acting substances, notably including alcohol, opiates, antihistamines and benzodiazepines due to the increased risk of sedation.

Amiodarone, risperidone [2] ---> SmPC of [2] of EMA

Caution is advised when prescribing OKEDI with medicinal products known to prolong the QT interval

Amitriptyline, risperidone [2] ---> SmPC of [2] of EMA

Caution is advised when prescribing OKEDI with medicinal products known to prolong the QT interval. Amitriptyline does not affect the pharmacokinetics of risperidone or the active antipsychotic fraction.

Antihistamines, risperidone [2] ---> SmPC of [2] of EMA

OKEDI should be used with caution in combination with other centrally-acting substances, notably including alcohol, opiates, antihistamines and benzodiazepines due to the increased risk of sedation.

Antihypertensives, risperidone [2] ---> SmPC of [2] of EMA

Clinically significant hypotension has been observed postmarketing with concomitant use of risperidone and antihypertensive treatment.

Aripiprazole, risperidone [2] ---> SmPC of [2] of EMA

Aripiprazole, a CYP2D6 and CYP3A4 substrate: Risperidone tablets or injections did not affect the pharmacokinetics of the sum of aripiprazole and its active metabolite, dehydroaripiprazole.

Atazanavir/cobicistat [1], risperidone ---> SmPC of [1] of EMA

Co-administration of neuroleptics with EVOTAZ may result in increased plasma concentrations of neuroleptics. The mechanism of interaction is inhibition of CYP3A4 and/or CYP2D6 by atazanavir and/or cobicistat

Benzodiazepines, risperidone [2] ---> SmPC of [2] of EMA

OKEDI should be used with caution in combination with other centrally-acting substances, notably including alcohol, opiates, antihistamines and benzodiazepines due to the increased risk of sedation.

Betablockers, risperidone [2] ---> SmPC of [2] of EMA

Some beta-blockers may increase the plasma concentrations of risperidone but not those of the active moiety.

Breast-feeding, risperidone [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from OKEDI therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Bupropion [1], risperidone ---> SmPC of [1] of eMC

Concomitant therapy of bupropion with medicinal products with narrow therapeutic indices that are mainly metabolised by CYP2D6 (bupropion inhibits CYP2D6) should be initiated at the lower end of the dose range of the concomitant medicine.

Carbamazepine, risperidone [2] ---> SmPC of [2] of EMA

When concomitant carbamazepine or another strong CYP3A4 and/or P-gp inducer is initiated or discontinued, the physician should re-evaluate the dosing of OKEDI.

Carbamazepine, risperidone [2] ---> SmPC of [2] of EMA

Carbamazepine, a strong CYP3A4 inducer and a P-gp inducer, has been shown to decrease the plasma concentrations of the active moiety.

Cimetidine, risperidone [2] ---> SmPC of [2] of EMA

Cimetidine and ranitidine, both weak inhibitors of CYP2D6 and CYP3A4, increased the bioavailability of risperidone, but only marginally that of the active moiety.

Citalopram [1], risperidone ---> SmPC of [1] of eMC

Caution is recommended when citalopram is co-administered with medicinal products that are mainly metabolised by CYP2D6, and that have a narrow therapeutic index

Clarithromycin, risperidone [2] ---> SmPC of [2] of eMC

The CYP3A4 and P-glycoprotein inhibition may increase the plasma levels of risperidone

Class IA antiarrhythmic agents, risperidone [2] ---> SmPC of [2] of EMA

Caution is advised when prescribing OKEDI with medicinal products known to prolong the QT interval

Class III antiarrhythmic agents, risperidone [2] ---> SmPC of [2] of EMA

Caution is advised when prescribing OKEDI with medicinal products known to prolong the QT interval

CNS depressants, risperidone [2] ---> SmPC of [2] of EMA

Risperidone should be used with caution in combination with CNS depressants due to the increased risk of sedation

Cobicistat [1], risperidone ---> SmPC of [1] of EMA

The co-administration may increase the plasma levels of neuroleptic

Cyclosporine, risperidone [2] ---> SmPC of [2] of eMC

The CYP3A4 and P-glycoprotein inhibition may increase the plasma levels of risperidone

CYP2D6 inhibitors, risperidone [2] ---> SmPC of [2] of eMC

It is expected that CYP 2D6 inhibitors increase the plasma concentrations of risperidone

CYP3A4 and P-glycoprotein inductors, risperidone [2] ---> SmPC of [2] of eMC

The CYP3A4 and P-glycoprotein induction may decrease the plasma levels of the active antipsychotic fraction of risperidone

Darunavir/cobicistat [1], risperidone ---> SmPC of [1] of EMA

REZOLSTA is expected to increase the neuroleptic plasma concentrations. (CYP2D6 inhibition). For this neuroleptics, consider reducing the dose of the neuroleptic upon co-administration with REZOLSTA.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], risperidone ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase these neuroleptic plasma concentrations. CYP2D6 inhibition

Darunavir/ritonavir, risperidone ---> SmPC of [darunavir] of EMA

Boosted darunavir is expected to increase the antipsychotic plasma concentrations. (CYP2D6 inhibition and/or P-gp)

Digoxin, risperidone [2] ---> SmPC of [2] of EMA

Risperidone does not show a clinically relevant effect on the pharmacokinetics of digoxin.

Disopyramide, risperidone [2] ---> SmPC of [2] of EMA

Caution is advised when prescribing OKEDI with medicinal products known to prolong the QT interval

Donepezil, risperidone [2] ---> SmPC of [2] of EMA

Donepezil and galantamine, both CYP2D6 and CYP3A4 substrates, do not show a clinically relevant effect on the pharmacokinetics of risperidone and the active moiety.

Dopamine agonists, risperidone [2] ---> SmPC of [2] of EMA

OKEDI may antagonise the effect of levodopa and other dopamine agonists. If this combination is deemed necessary, particularly in end-stage Parkinson's disease, the lowest effective dose of each treatment should be prescribed.

Drugs inducing bradycardia, risperidone [2] ---> SmPC of [2] of EMA

Caution is advised when prescribing OKEDI with medicinal products causing bradycardia

Drugs with high protein binding, risperidone [2] ---> SmPC of [2] of EMA

When risperidone is taken together with highly protein-bound medicinal products, there is no clinically relevant displacement of either medicine from the plasma proteins.

Duloxetine [1], risperidone ---> SmPC of [1] of EMA

Duloxetine is a moderate inhibitor of CYP2D6. Caution is advised if duloxetine is co-administered with medicinal products that are predominantly metabolised by CYP2D6

Electrolyte imbalance, risperidone [2] ---> SmPC of [2] of EMA

Caution is advised when prescribing OKEDI with medicines causing electrolyte imbalance (hypokalaemia, hypomagnesaemia)

Erythromycin, risperidone [2] ---> SmPC of [2] of EMA

Erythromycin, a moderate CYP3A4 inhibitor and P-gp inhibitor, does not change the pharmacokinetics of risperidone and the active moiety.

Escitalopram [1], risperidone ---> SmPC of [1] of eMC

Caution should be observed when co-administering escitalopram (CYP2D6 inhibitor) and drugs that are mainly metabolised by CYP2D6 and that have a narrow therapeutic index. Dosage adjustment may be warranted.

Fertility, risperidone [2] ---> SmPC of [2] of EMA

This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. There were no relevant effects observed in the non-clinical studies.

Fluoxetine, risperidone [2] ---> SmPC of [2] of EMA

Fluoxetine, a strong CYP2D6 inhibitor, increases the plasma concentration of risperidone, but less so of the active moiety.

Fluvoxamine, risperidone [2] ---> SmPC of [2] of EMA

Doses higher than 100 mg/day of sertraline or fluvoxamine may elevate concentrations of the risperidone active moiety.

Furosemide, risperidone [2] ---> SmPC of [2] of EMA

The increase in mortality in patients treated with furosemide plus risperidone was observed in two of the four clinical trials. Concomitant use of risperidone with other diuretics

Galantamine, risperidone [2] ---> SmPC of [2] of EMA

Donepezil and galantamine, both CYP2D6 and CYP3A4 substrates, do not show a clinically relevant effect on the pharmacokinetics of risperidone and the active moiety.

Hepatic metabolism, risperidone [2] ---> SmPC of [2] of EMA

Caution is advised when prescribing OKEDI with medicinal products which inhibit the hepatic metabolism of risperidone.

Hypnotics, risperidone [2] ---> SmPC of [2] of eMC

Risperidone should be used with caution in combination with other centrally-acting substances due to the increased risk of sedation.

Hypokalemia, risperidone [2] ---> SmPC of [2] of eMC

Caution is advised when prescribing OKEDI with medicines causing electrolyte imbalance (hypokalaemia, hypomagnesaemia)

Hypomagnesemia, risperidone [2] ---> SmPC of [2] of EMA

Caution is advised when prescribing OKEDI with medicines causing electrolyte imbalance (hypokalaemia, hypomagnesaemia)

Interferon, risperidone

Caution should be used when administering interferon with medicines mainly metabolised by hepatic cytochrome P450 and have a narrow therapeutic window

Itraconazol, risperidone [2] ---> SmPC of [2] of EMA

When concomitant itraconazole or another strong CYP3A4 and/or P-gp inhibitor is initiated or discontinued, the physician should re-evaluate the dosing of OKEDI.

Itraconazol, risperidone [2] ---> SmPC of [2] of EMA

Itraconazole, a strong CYP3A4 inhibitor and a P-gp inhibitor, at a dosage of 200 mg/day increased the plasma concentrations of the active moiety by about 70%, at risperidone doses of 2 to 8 mg/day.

Ketoconazole [1], risperidone ---> SmPC of [2] of EMA

Careful monitoring. Dose adjustment of risperidone may be required.

Ketoconazole, risperidone [2] ---> SmPC of [2] of EMA

Ketoconazole, a strong CYP3A4 inhibitor and a P-gp inhibitor, at a dosage of 200 mg/day increased the plasma concentrations of risperidone and decreased the plasma concentrations of 9-hydroxy-risperidone.

Lamotrigine [1], risperidone ---> SmPC of [1] of eMC

Multiple oral doses of lamotrigine 400 mg daily had no clinically significant effect on the single dose pharmacokinetics of 2 mg risperidone in 14 healthy adult volunteers.

Levodopa, risperidone ---> SmPC of [levodopa/carbidopa] of EMA

Dopamine D2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone), benzodiazepines and isoniazid may reduce the therapeutic effects of levodopa.

Levodopa/carbidopa [1], risperidone ---> SmPC of [1] of EMA

Dopamine D2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone), benzodiazepines and isoniazid may reduce the therapeutic effects of levodopa.

Lithium, risperidone [2] ---> SmPC of [2] of EMA

Risperidone does not show a clinically relevant effect on the pharmacokinetics of lithium.

Maprotiline, risperidone [2] ---> SmPC of [2] of EMA

Caution is advised when prescribing OKEDI with medicinal products known to prolong the QT interval

Mefloquine, risperidone [2] ---> SmPC of [2] of EMA

Caution is advised when prescribing OKEDI with medicinal products known to prolong the QT interval

Methylphenidate, risperidone [2] ---> SmPC of [2] of EMA

Caution is warranted in patients receiving both psychostimulants (e.g. methylphenidate) and risperidone concomitantly, as EPSs could emerge when adjusting one or both medicines. Gradual withdrawal of stimulant treatment is recommended (see section 4.5).

Naltrexone/bupropion [1], risperidone ---> SmPC of [1] of EMA

Co-administration of bupropion with drugs that are metabolised by CYP2D6 isozyme should be approached with caution and should be initiated at the lower end of the dose range of the concomitant medicinal product.

Neuroleptics, risperidone [2] ---> SmPC of [2] of eMC

Risperidone should be used with caution in combination with other centrally-acting substances due to the increased risk of sedation.

Nirmatrelvir/ritonavir [1], risperidone ---> SmPC of [1] of EMA

Ritonavir is likely to inhibit CYP2D6 and as a result is expected to increase concentrations of haloperidol, risperidone and thioridazine. Careful monitoring of therapeutic and adverse effects is recommended

Opiates, risperidone [2] ---> SmPC of [2] of EMA

OKEDI should be used with caution in combination with other centrally-acting substances, notably including alcohol, opiates, antihistamines and benzodiazepines due to the increased risk of sedation.

P-glycoprotein and CYP3A4 inhibitors, risperidone

The CYP3A4 and P-glycoprotein inhibition may increase the plasma levels of risperidone

Paliperidone [1], risperidone ---> SmPC of [1] of EMA

Concomitant use of INVEGA with oral risperidone is not recommended as paliperidone is the active metabolite of risperidone and the combination of the two may lead to additive paliperidone exposure.

Paliperidone, risperidone [2] ---> SmPC of [2] of EMA

Concomitant use of OKEDI with paliperidone is not recommended as paliperidone is the active metabolite of risperidone and the combination of the two may lead to additive active moiety exposure.

Paroxetine, risperidone [2] ---> SmPC of [2] of EMA

Higher doses of a strong CYP2D6 inhibitor may elevate concentrations of the risperidone active moiety (e.g., paroxetine, see below).

Phenobarbital, risperidone [2] ---> SmPC of [2] of EMA

Phenobarbital, a strong CYP3A4 inducer and a P-gp inducer, has been shown to decrease the plasma concentrations of the active moiety.

Phenothiazines, risperidone [2] ---> SmPC of [2] of EMA

Phenothiazines may increase the plasma concentrations of risperidone but not those of the active moiety.

Phenytoin, risperidone [2] ---> SmPC of [2] of EMA

Phenytoin, a strong CYP3A4 inducer and a P-gp inducer, has been shown to decrease the plasma concentrations of the active moiety.

Pregnancy, risperidone [2] ---> SmPC of [2] of EMA

OKEDI should not be used during pregnancy unless clearly necessary.

Procainamide, risperidone [2] ---> SmPC of [2] of EMA

Caution is advised when prescribing OKEDI with medicinal products known to prolong the QT interval

Prolactin, risperidone [2] ---> SmPC of [2] of EMA

Risperidone elevates prolactin level. Hyperprolactinaemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion.

Propafenone, risperidone

Caution is advised when prescribing OKEDI with medicinal products known to prolong the QT interval

Protease inhibitors, risperidone [2] ---> SmPC of [2] of EMA

No formal study data are available; however, since ritonavir is a strong CYP3A4 inhibitor and a weak CYP2D6 inhibitor, ritonavir and ritonavir-boosted protease inhibitors potentially raise concentrations of the risperidone active moiety.

Psychostimulants, risperidone [2] ---> SmPC of [2] of EMA

QT interval prolonging drugs, risperidone [2] ---> SmPC of [2] of EMA

Caution is advised when prescribing OKEDI with medicinal products known to prolong the QT interval

Quetiapine [1], risperidone ---> SmPC of [1] of eMC

The pharmacokinetics of quetiapine were not significantly altered by co-administration of the antipsychotics risperidone or haloperidol.

Quinidine, risperidone [2] ---> SmPC of [2] of EMA

When concomitant paroxetine, quinidine, or another strong CYP2D6 inhibitor, especially at higher doses, is initiated or discontinued, the physician should re-evaluate the dosing of OKEDI.

Quinidine, risperidone [2] ---> SmPC of [2] of EMA

Caution is advised when prescribing OKEDI with medicinal products known to prolong the QT interval

Quinine, risperidone [2] ---> SmPC of [2] of EMA

Caution is advised when prescribing OKEDI with medicinal products known to prolong the QT interval

Ranitidine, risperidone [2] ---> SmPC of [2] of EMA

Cimetidine and ranitidine, both weak inhibitors of CYP2D6 and CYP3A4, increased the bioavailability of risperidone, but only marginally that of the active moiety.

Rifampicin, risperidone [2] ---> SmPC of [2] of EMA

Rifampicin, a strong CYP3A4 inducer and a P-gp inducer, decreased the plasma concentrations of the active moiety.

Risperidone [1], ritonavir ---> SmPC of [1] of EMA

Ritonavir and ritonavir-boosted protease inhibitors potentially raise concentrations of the risperidone active moiety.

Risperidone [1], ritonavir-boosted protease inhibitors ---> SmPC of [1] of EMA

Risperidone [1], sertraline ---> SmPC of [1] of EMA

Doses higher than 100 mg/day of sertraline or fluvoxamine may elevate concentrations of the risperidone active moiety.

Risperidone [1], sotalol ---> SmPC of [1] of EMA

Caution is advised when prescribing OKEDI with medicinal products known to prolong the QT interval

Risperidone [1], strong CYP2D6 inhibitors ---> SmPC of [1] of EMA

Co-administration of OKEDI with a strong CYP2D6 inhibitor may increase the plasma concentrations of risperidone, but less so of the active moiety. Higher doses of a strong CYP2D6 inhibitor may elevate concentrations of the risperidone active moiety

Risperidone [1], strong CYP3A4 and P-glycoprotein inductors ---> SmPC of [1] of EMA

Co-administration of OKEDI with a strong CYP3A4 and/or P-gp inducer may decrease the plasma concentrations of the risperidone active moiety.

Risperidone [1], strong CYP3A4 and P-glycoprotein-inhibitors ---> SmPC of [1] of EMA

Co-administration of OKEDI with a strong CYP3A4 and/or P-gp inhibitor may substantially elevate plasma concentrations of the risperidone active moiety.

Risperidone [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Co-administration of OKEDI with a strong CYP3A4 and/or P-gp inducer may decrease the plasma concentrations of the risperidone active moiety.

Risperidone [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Co-administration of OKEDI with a strong CYP3A4 and/or P-gp inhibitor may substantially elevate plasma concentrations of the risperidone active moiety.

Risperidone [1], strong diuretic agents ---> SmPC of [1] of EMA

Caution should be exercised and the risks and benefits of this combination or co-treatment with other potent diuretics should be considered prior to the decision to use.

Risperidone [1], strong P-gp inductors ---> SmPC of [1] of EMA

Co-administration of OKEDI with a strong CYP3A4 and/or P-gp inducer may decrease the plasma concentrations of the risperidone active moiety.

Risperidone [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

Co-administration of OKEDI with a strong CYP3A4 and/or P-gp inhibitor may substantially elevate plasma concentrations of the risperidone active moiety.

Risperidone [1], tetracyclic antidepressant ---> SmPC of [1] of EMA

Caution is advised when prescribing OKEDI with medicinal products known to prolong the QT interval

Risperidone [1], topiramate ---> SmPC of [1] of EMA

Risperidone does not show a clinically relevant effect on the pharmacokinetics of valproate or topiramate.

Risperidone [1], tricyclic antidepressant ---> SmPC of [1] of EMA

Tricyclic antidepressants may increase the plasma concentrations of risperidone but not those of the active moiety. Amitriptyline does not affect the pharmacokinetics of risperidone or the active antipsychotic fraction.

Risperidone [1], valproate ---> SmPC of [1] of EMA

Risperidone does not show a clinically relevant effect on the pharmacokinetics of valproate or topiramate.

Risperidone [1], verapamil ---> SmPC of [1] of eMC

Verapamil, a moderate inhibitor of CYP3A4 and an inhibitor of P-gp, increases the plasma concentration of risperidone and the active moiety.

Risperidone, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir dosed as an antiretroviral agent is likely to inhibit CYP2D6 and as a result is expected to increase concentrations of haloperidol, risperidone and thioridazine.

Risperidone, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

Caution is recommended with CYP2D6 substrates combined with ropeginterferon alfa-2b. Ropeginterferon alfa-2b may inhibit the activity of CYP1A2 and CYP2D6 and thus may increase the blood concentrations of these medicinal products.

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.

Risperidone, topiramate [2] ---> SmPC of [2] of EMA

Topiramate modestly reduced the bioavailability of risperidone, but not that of the active moiety. Therefore, this interaction is unlikely to be of clinical significance.

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.

Risperidone, venlafaxine [2] ---> SmPC of [2] of eMC

Venlafaxine increased the risperidone AUC by 50%, but did not significantly alter the pharmacokinetic profile of the total active moiety (risperidone plus 9-hydroxyrisperidone). The clinical significance of this interaction is unknown.

CONTRAINDICATIONS of Risperidone (Okedi)

- 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/okedi-epar-product-information_en.pdf 14/10/2025

Other trade names: Arketin, Calmapride, Diaforin, Rispemylan Flas, Risperdal, Risperidona: Benel, Mylan, Actavis, Alter, Apotex, Aristo, Aurobindo, Bexal, Cinfa, Codramol, Curaxys, Farmalider, Flas Krka, Flas Ratiopharm, Flas Teva, Kern Pharma, Mabo, Mylan, Normon, Qualige

Ritlecitinib (Litfulo)

Antituberculosis therapy, ritlecitinib [2] ---> SmPC of [2] of EMA

Anti-TB therapy should be started prior to initiating therapy with ritlecitinib in patients with a new diagnosis of latent TB or previously untreated latent TB.

Blood-platelet count, ritlecitinib [2] ---> SmPC of [2] of EMA

Prior to initiating treatment with ritlecitinib, ALC and platelet counts should be performed. Treatment with ritlecitinib should not be initiated in patients with an ALC < 0.5 × 103/mm3 or a platelet count < 100 × 103/mm3.

Breast-feeding, ritlecitinib [2] ---> SmPC of [2] of EMA

A risk to newborns/infants cannot be excluded. Litfulo is contraindicated during breast-feeding (see section 4.3).

Caffeine, ritlecitinib [2] ---> SmPC of [2] of EMA

Multiple doses of 200 mg once daily ritlecitinib increased the AUCinf and Cmax of caffeine, a CYP1A2 substrate, by approximately 2.7-fold and 1.1-fold, respectively.

Colchicine, ritlecitinib [2] ---> SmPC of [2] of EMA

Dose adjustment recommendations for the CYP3A substrate (e.g., colchicine, everolimus, tacrolimus, sirolimus) should be considered.

Cyclosporine, ritlecitinib [2] ---> SmPC of [2] of EMA

Caution should be exercised with concomitant use of ritlecitinib with CYP3A substrates (e.g., quinidine, cyclosporine, dihydroergotamine, ergotamine, pimozide) where moderate concentration changes may lead to serious adverse reactions.

CYP inducers, ritlecitinib [2] ---> SmPC of [2] of EMA

This is not considered clinically significant and, therefore dose adjustment is not required when ritlecitinib is coadministered with inducers of CYP enzymes.

CYP1A2 substrates, ritlecitinib [2] ---> SmPC of [2] of EMA

Caution should be exercised with concomitant use of ritlecitinib with other CYP1A2 substrates (e.g., tizanidine) where moderate concentration changes may lead to serious adverse reactions.

CYP3A4 inhibitors, ritlecitinib [2] ---> SmPC of [2] of EMA

This is not considered clinically significant and, therefore dose adjustment is not required when ritlecitinib is coadministered with CYP3A inhibitors.

CYP3A4 substrates, ritlecitinib [2] ---> SmPC of [2] of EMA

Dihydroergotamine, ritlecitinib [2] ---> SmPC of [2] of EMA

Ergotamine, ritlecitinib [2] ---> SmPC of [2] of EMA

Everolimus, ritlecitinib [2] ---> SmPC of [2] of EMA

Dose adjustment recommendations for the CYP3A substrate (e.g., colchicine, everolimus, tacrolimus, sirolimus) should be considered.

Fertility, ritlecitinib [2] ---> SmPC of [2] of EMA

The effect of ritlecitinib on human fertility has not been evaluated. There were no effects on fertility in rats at clinically relevant exposures (see section 5.3).

Herpes zoster, ritlecitinib [2] ---> SmPC of [2] of EMA

Viral reactivations, including cases of herpes virus reactivation (e.g., herpes zoster), have been reported (see section 4.8).

Infection, ritlecitinib [2] ---> SmPC of [2] of EMA

Treatment with ritlecitinib must not be initiated in patients with an active, serious infection (see section 4.3).

Itraconazol, ritlecitinib [2] ---> SmPC of [2] of EMA

The coadministration of multiple 200 mg doses of itraconazole, a strong CYP3A inhibitor, increased the area under curve (AUC)inf of ritlecitinib by approximately 15%.

Midazolam, ritlecitinib [2] ---> SmPC of [2] of EMA

Multiple doses of 200 mg once daily ritlecitinib increased the AUCinf and Cmax of midazolam a CYP3A4 substrate, by approximately 2.7-fold and 1.8-fold, respectively.

Neoplasia, ritlecitinib [2] ---> SmPC of [2] of EMA

Malignancies, including non-melanoma skin cancer (NMSC) have been reported in patients receiving ritlecitinib.

OCT1 substrates, ritlecitinib [2] ---> SmPC of [2] of EMA

Caution should be exercised with concomitant use of ritlecitinib with OCT1 substrates where small concentration changes may lead to serious adverse reactions.

Oral contraceptives, ritlecitinib [2] ---> SmPC of [2] of EMA

Ritlecitinib did not produce clinically significant changes in the exposures of oral contraceptives (e.g., ethinyl oestradiol or levonorgestrel), CYP2B6 substrates (e.g., efavirenz), CYP2C substrates (e.g., tolbutamide)

Pimozide, ritlecitinib [2] ---> SmPC of [2] of EMA

Pirfenidone, ritlecitinib [2] ---> SmPC of [2] of EMA

Dose adjustment recommendations for the CYP1A2 substrate (e.g., theophylline, pirfenidone) should be considered.

Pregnancy, ritlecitinib [2] ---> SmPC of [2] of EMA

Studies in animals have shown reproductive toxicity (see section 5.3). Ritlecitinib was teratogenic in rats and rabbits at high doses (see section 5.3). Litfulo is contraindicated during pregnancy (see section 4.3).

Quinidine, ritlecitinib [2] ---> SmPC of [2] of EMA

Rifampicin, ritlecitinib [2] ---> SmPC of [2] of EMA

The coadministration of multiple 600 mg doses of rifampicin, a strong inducer of CYP enzymes, decreased the AUCinf of ritlecitinib by approximately 44%.

Ritlecitinib [1], rosuvastatin ---> SmPC of [1] of EMA

Ritlecitinib did not produce clinically significant changes in the exposures of substrates of organic anion transporter (OAT)P1B1, breast cancer resistant protein (BCRP), and OAT3 (e.g., rosuvastatin).

Ritlecitinib [1], sirolimus ---> SmPC of [1] of EMA

Dose adjustment recommendations for the CYP3A substrate (e.g., colchicine, everolimus, tacrolimus, sirolimus) should be considered.

Ritlecitinib [1], sumatriptan ---> SmPC of [1] of EMA

The coadministration of a single 400 mg dose of ritlecitinib increased the AUCinf of sumatriptan ([OCT]1 substrate) by approximately 1.3 to 1.5-fold. The increase in sumatriptan exposure is not considered clinically relevant.

Ritlecitinib [1], tacrolimus ---> SmPC of [1] of EMA

Dose adjustment recommendations for the CYP3A substrate (e.g., colchicine, everolimus, tacrolimus, sirolimus) should be considered.

Ritlecitinib [1], theophylline ---> SmPC of [1] of EMA

Dose adjustment recommendations for the CYP1A2 substrate (e.g., theophylline, pirfenidone) should be considered.

Ritlecitinib [1], thrombosis ---> SmPC of [1] of EMA

Events of venous and arterial thromboembolism, including MACE, have been reported in patients receiving ritlecitinib.

Ritlecitinib [1], tizanidine ---> SmPC of [1] of EMA

Caution should be exercised with concomitant use of ritlecitinib with other CYP1A2 substrates (e.g., tizanidine) where moderate concentration changes may lead to serious adverse reactions.

Ritlecitinib [1], vaccinations ---> SmPC of [1] of EMA

Use of live attenuated vaccines should be avoided during or immediately prior to ritlecitinib treatment.

Ritlecitinib [1], women of childbearing potential ---> SmPC of [1] of EMA

Ritlecitinib is not recommended in women of childbearing potential not using contraception. Women of childbearing potential have to use effective contraception during treatment and for 1 month following the final dose of Litfulo.

CONTRAINDICATIONS of Ritlecitinib (Litfulo)

- Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.

- Active serious infections, including tuberculosis (TB) (see section 4.4).

- Severe hepatic impairment (see section 4.2).

- Pregnancy and breast-feeding (see section 4.6).

https://www.ema.europa.eu/en/documents/product-information/litfulo-epar-product-information_en.pdf 06/06/2024

Ritodrine

Anaesthetics, ritodrine

Strong anesthetics may enhance the cardiovascular effects of intravenous ritodrine, specially arrhytmias or hypotension

Atropine, ritodrine

Concomitant use of ritodrine and parasympatholytic agents may cause an additive sympathomimetic efect and increase the possibility of developing adverse effects, including hypertension or heart problems

Beta-adrenergic agonists, ritodrine

Concomitant use of ritodrine and beta-adrenergic agonists may cause an additive sympathomimetic efect and increase the possibility of developing adverse effects, including hypertension or heart problems

Betablockers, ritodrine

The beta-blocker may decrease the activity of ritodrine. The co-administration should be avoided

Breast-feeding, ritodrine

Carefully control of possible effects of ritodrine is recommended

Corticosteroids, ritodrine

Risk of acute lung edema. Caution is recommended

Digital glycosides, ritodrine

In case of hypokaliemia, the co-administration of digitalis glycoside with ritodrine should be avoided due to hypokalaemia may potentiate the toxicity of digitalis glycoside

Electrolyte imbalance, ritodrine

Possible hypokaliemia

General anesthetics, ritodrine

Strong anesthetics may enhance the cardiovascular effects of intravenous ritodrine, specially arrhytmias or hypotension

Gliclazide [1], ritodrine ---> SmPC of [1] of eMC

The administration of gliclazide and i.v. ritodrine increases the blood glucose levels due to beta-2 agonist effects

Halogenated anaesthetics, ritodrine

Strong anesthetics may enhance the cardiovascular effects of intravenous ritodrine, specially arrhytmias or hypotension

Hypokalemia, ritodrine

Possible hypokaliemia

Insulin lispro [1], ritodrine ---> SmPC of [1] of EMA

Insulin requirements may be increased by medicinal products with hyperglycaemic activity

Insulin, ritodrine

Insulin requirements may be increased by medicinal products with hyperglycaemic activity

Loop diuretics, ritodrine

Possible hypokaliemia

Magnesium sulfate, ritodrine

Magnesium sulfate may enhance the cardiovascular effects of intravenous ritodrine, specially arrhytmias or hypotension

Oral antidiabetics, ritodrine

Antidiabetic drug requirements may be increased by medicinal products with hyperglycaemic activity

Parasympatholytics, ritodrine

Pethidine, ritodrine

Pethidine may enhance the cardiovascular effects of intravenous ritodrine, specially arrhytmias or hypotension

Pregnancy, ritodrine

Ritodrine passes the placenta. It should not be used in the first pregnancy trimester

Ritodrine, sympathomimetics

Concomitant use of ritodrine and sympathomimetic agents may cause an additive sympathomimetic efect and increase the possibility of developing adverse effects, including hypertension or heart problems

Ritodrine, thiazides

Possible hypokaliemia

Ritonavir (Norvir)

Abemaciclib, ritonavir [2] ---> SmPC of [2] of EMA

Co-administration of abemaciclib and Norvir should be avoided. If this co-administration is judged unavoidable, refer to the abemaciclib SmPC for dosage adjustment recommendations.

Ability to drive, ritonavir [2] ---> SmPC of [2] of EMA

Dizziness is a known undesirable effect that should be taken into account when driving or using machinery.

Acalabrutinib [1], ritonavir ---> 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

Acenocoumarol [1], ritonavir ---> SmPC of [1] of eMC

The co-administration may decrease the anticoagulant effect

Afatinib, ritonavir [2] ---> SmPC of [2] of EMA

Serum concentrations may be increased due to Breast Cancer Resistance Protein (BCRP) and acute P-gp inhibition by ritonavir. The extent of increase in AUC and Cmax depends on the timing of ritonavir administration.

Albendazole, ritonavir

The co-administration may decrease the plasma concentrations of active albendazole metabolite

Alectinib [1], ritonavir ---> SmPC of [1] of EMA

Appropriate monitoring is recommended for patients taking concomitant strong CYP3A inhibitors

Alfentanyl [1], ritonavir ---> SmPC of [1] of eMC

Alfentanil is metabolised mainly via the human cytochrome P450 3A4 enzyme. In vitro data suggest that cytochrome P450 3A4 enzyme inhibitors may inhibit the metabolism of alfentanil

Alfuzosin, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir co-administration is likely to result in increased plasma concentrations of alfuzosin and is therefore contraindicated

Alprazolam, ritonavir [2] ---> SmPC of [2] of EMA

Alprazolam metabolism was inhibited following the introduction of ritonavir. After ritonavir use for 10 days, no inhibitory effect of ritonavir was observed.

Aminophylline [1], ritonavir ---> SmPC of [1] of eMC

Ritonavir may decrease plasma theophylline concentrations

Amiodarone, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir co-administration with amiodarone is likely to result in increased plasma concentrations of amiodarone and is therefore contraindicated

Amitriptyline, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir dosed as an antiretroviral agent is likely to inhibit CYP2D6 and as a result is expected to increase concentrations of imipramine, amitriptyline, nortriptyline, fluoxetine, paroxetine or sertraline.

Amlodipine, ritonavir [2] ---> SmPC of [2] 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 calcium channel antagonists.

Amlodipine/valsartan [1], ritonavir ---> SmPC of [1] of EMA

Co-administration of inhibitors of the uptake transporter (rifampicin, ciclosporin) or efflux transporter (ritonavir) may increase the systemic exposure to valsartan.

Amlodipine/valsartan/hydrochlorothiazide [1], ritonavir ---> SmPC of [1] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure.

Amphetamine, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir dosed as an antiretroviral agent is likely to inhibit CYP2D6 and as a result is expected to increase concentrations of amphetamine and its derivatives.

Amprenavir, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir increases the serum levels of amprenavir as a result of CYP3A4 inhibition. Clinical trials confirmed the safety and efficacy of 600 mg amprenavir twice daily with ritonavir 100 mg twice daily.

Apalutamide, ritonavir [2] ---> SmPC of [2] of EMA

Apalutamide is a moderate to strong CYP3A4 inducer and this may lead to a decreased exposure of ritonavir and potential loss of virologic response.

Apixaban [1], ritonavir ---> SmPC of [1] of EMA

The use of apixaban is not recommended in patients receiving concomitant systemic treatment with strong inhibitors of both CYP3A4 and P-gp

Artesunate [1], ritonavir ---> SmPC of [1] of EMA

Co-administration of Artesunate Amivas with UGT inducers (e.g. nevirapine, ritonavir, rifampicin, carbamazepine, phenytoin) may decrease DHA exposures, leading to a reduction in, or loss of, efficacy. Co-administration should be avoided.

Astemizole, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir co-administration is likely to result in increased plasma concentrations of astemizole and terfenadine and is therefore contraindicated (see section 4.3).

Atazanavir, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir increases the serum levels of atazanavir as a result of CYP3A4 inhibition. Clinical trials confirmed the safety and efficacy of 300 mg atazanavir once daily with ritonavir 100 mg once daily in treatment experienced patients.

Atazanavir/cobicistat [1], ritonavir ---> SmPC of [1] of EMA

Co-administration of EVOTAZ with medicinal products containing ritonavir or cobicistat, which are strong inhibitors of CYP3A, may result in additional boosting and increased plasma concentration of atazanavir. Concomitant use not recommended

Atenolol/nifedipine [1], ritonavir ---> SmPC of [1] of eMC

Drugs known to inhibit the cytochrome P450 3A4 system when administered orally with nifedipine may substantial increase the systemic bioavailability of nifedipine due to a decreased first pass metabolism and a decreased elimination

Atogepant [1], ritonavir ---> SmPC of [1] of EMA

Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir) can significantly increase systemic exposure to atogepant.

Atorvastatin, ritonavir [2] ---> SmPC of [2] of EMA

Caution must also be exercised and reduced doses should be considered if ritonavir is used concurrently with atorvastatin, which is metabolised to a lesser extent by CYP3A.

Atovaquone, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent induces glucuronidation and as a result is expected to decrease the plasma concentrations of atovaquone.

Avacopan [1], ritonavir ---> SmPC of [1] of EMA

Strong CYP3A4 enzyme inhibitors should be used with caution in patients who are being treated with avacopan.

Avanafil [1], ritonavir ---> 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

Avapritinib [1], ritonavir ---> SmPC of [1] of EMA

Co-administration with strong or moderate CYP3A inhibitors should be avoided because it may increase the plasma concentration of avapritinib

Axitinib [1], ritonavir ---> 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.

Beclometasone/formoterol/glycopyrronium [1], ritonavir ---> SmPC of [1] of EMA

Beclometasone is less dependent on CYP3A metabolism than some other corticosteroids; however, the possibility of systemic effects with concomitant use of strong CYP3A inhibitors (e.g. ritonavir, cobicistat) cannot be excluded

Bedaquiline [1], ritonavir ---> SmPC of [1] of EMA

Due to the potential risk of adverse reactions due to an increase in systemic exposure, prolonged co-administration of bedaquiline and moderate or strong CYP3A4 inhibitors used systemically for more than 14 consecutive days should be avoided.

Benperidol [1], ritonavir ---> SmPC of [1] of eMC

Ritonavir may cause an increase in the plasma concentration of benperidol necessitating a dose modification.

Benzodiazepines, ritonavir [2] ---> SmPC of [2] of eMC

Ritonavir may inhibit benzodiazepine hepatic metabolism

Bepridil, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir co-administration with bepridil is likely to result in increased plasma concentrations of bepridil and is therefore contraindicated

Bilastine [1], ritonavir ---> SmPC of [1] of eMC

Concomitant intake of bilastine, substrate for P-gp, may likewise have the potential to increase plasma concentrations of bilastine.

Boceprevir [1], ritonavir ---> SmPC of [1] of EMA

When boceprevir is administered with ritonavir alone, boceprevir concentrations are decreased.

Bortezomib [1], ritonavir ---> SmPC of [1] of EMA

The strong CYP3A4 inhibition may increase the AUC of bortezomib. Patients should be closely monitored when given bortezomib in combination with potent CYP3A4 inhibitors

Bosentan [1], ritonavir ---> SmPC of [1] of EMA

The strong CYP3A4 inhibition may increase the plasma concentrations of bosentan. Co-administration is not recommended

Bosutinib [1], ritonavir ---> 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, ritonavir [2] ---> SmPC of [2] of EMA

Women living with HIV should not breast-feed their infants if they are receiving Norvir.

Brexpiprazole [1], ritonavir ---> SmPC of [1] of EMA

Based on results of interaction studies, dose adjustment of brexpiprazole to half the dose is recommended when administered concomitantly with strong CYP3A4 inhibitors

Brigatinib [1], ritonavir ---> SmPC of [1] of EMA

The concomitant use of strong CYP3A inhibitors with Alunbrig should be avoided

Brinzolamide [1], ritonavir ---> SmPC of [1] of EMA

It is expected that inhibitors of CYP3A4 will inhibit the metabolism of brinzolamide by CYP3A4. Caution is advised if CYP3A4 inhibitors are given concomitantly.

Brinzolamide/brimonidine [1], ritonavir ---> SmPC of [1] of EMA

It is expected that inhibitors of CYP3A4 will inhibit the metabolism of brinzolamide by CYP3A4. Caution is advised if CYP3A4 inhibitors are given concomitantly.

Brinzolamide/timolol [1], ritonavir ---> SmPC of [1] of EMA

It is expected that inhibitors of CYP3A4 will inhibit the metabolism of brinzolamide by CYP3A4. Caution is advised if CYP3A4 inhibitors are given concomitantly.

Budesonide, ritonavir [2] ---> SmPC of [2] of EMA

Concomitant use of ritonavir and budesonide/other glucocorticoids that are metabolised by CYP3A4, risk of systemic corticosteroid effects.

Bulevirtide [1], ritonavir ---> SmPC of [1] of EMA

In vitro, it has been shown, that certain medicinal products can inhibit bulevirtide target sodium- taurocholate co-transporting polypeptide (NTCP). The co-administration of such medicinal products is not recommended.

Buprenorphine, ritonavir [2] ---> SmPC of [2] of EMA

The increases of plasma levels of buprenorphine and its active metabolite did not lead to clinically significant pharmacodynamic changes in a population of opioid tolerant patients.

Buprenorphine/naloxone [1], ritonavir ---> SmPC of [1] of EMA

Medicines that inhibit the enzyme CYP3A4 may give rise to increased concentrations of buprenorphine. A reduction of the buprenorphine/naloxone dose may be needed.

Bupropion, ritonavir [2] ---> SmPC of [2] of EMA

Bupropion is primarily metabolised by CYP2B6. Concurrent administration of bupropion with repeated doses of ritonavir is expected to decrease bupropion levels.

Buspirone, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent inhibits CYP3A and as a result is expected to increase the plasma concentrations of buspirone.

Cabazitaxel [1], ritonavir ---> 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

Cabozantinib [1], ritonavir ---> SmPC of [1] of EMA

Co-administration of cabozantinib with strong CYP3A4 inhibitors (increased plasma cabozantinib exposure (AUC) should be approached with caution.

Calcium antagonists, ritonavir [2] ---> SmPC of [2] of EMA

Possible increase in the plasma concentrations of calcium channel antagonist. Careful monitoring of therapeutic and adverse effects is recommended.

Canagliflozin [1], ritonavir ---> SmPC of [1] of EMA

Enzyme inducers may give rise to decreased exposure of canagliflozin. These decreases in exposure to canagliflozin may decrease efficacy.

Canagliflozin/metformin [1], ritonavir ---> SmPC of [1] of EMA

Enzyme inducers may give rise to decreased exposure of canagliflozin. These decreases in exposure to canagliflozin may decrease efficacy.

Capmatinib [1], ritonavir ---> SmPC of [1] of EMA

Patients should be closely monitored for adverse reactions during co-administration of Tabrecta with strong CYP3A inhibitors

Carbamazepine, ritonavir [2] ---> SmPC of [2] 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 carbamazepine. Careful monitoring of therapeutic and adverse effects is recommended

Cariprazine [1], ritonavir ---> 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, ritonavir [2] ---> SmPC of [2] of EMA

Serum concentrations may be increased due to CYP3A and P-gp inhibition by ritonavir. Caution should be exercised in administering ceritinib with Norvir.

Ciclesonide [1], ritonavir ---> SmPC of [1] of eMC

The concomitant administration of ciclesonide with potent inhibitors of CYP 3A4 should be avoided unless the benefit outweighs the increased risk of systemic side effects of corticosteroids.

Cinacalcet [1], ritonavir ---> 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

Cinitapride, ritonavir

The strong CYP3A4 inhibition may increase the plasma concentrations of cinitapride

Cisapride, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir co-administration is likely to result in increased plasma concentrations of cisapride and is therefore contraindicated

Clarithromycin, ritonavir [2] ---> SmPC of [2] of EMA

Due to the large therapeutic window of clarithromycin no dose reduction should be necessary in patients with normal renal function.

Clobetasol, ritonavir

The co-administration of clobetasol with CYP3A4 inhibitors inhibits the metabolism of corticosteroid and increases its systemic bioavailability

Clobetasone [1], ritonavir ---> SmPC of [1] of eMC

Co-administered drugs that can inhibit CYP3A4 have been shown to inhibit the metabolism of corticosteroids leading to increased systemic exposure.

Clozapine, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir co-administration is likely to result in increased plasma concentrations of clozapine or pimozide and is therefore contraindicated (see section 4.3).

Cobicistat [1], ritonavir ---> SmPC of [1] of EMA

Cobicistat should not be used concurrently with ritonavir due to similar effects of cobicistat and ritonavir on CYP3A.

Cobimetinib [1], ritonavir ---> 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.

Codergocrin, ritonavir

The strong CYP3A4 inhibition may increase the exposition to codergocrin, which may cause a dopaminergic effect. Concomitant use should be avoided

Colchicine, ritonavir [2] ---> SmPC of [2] of EMA

Life-threatening and fatal drug interactions have been reported in patients treated with colchicine and strong inhibitors of CYP3A like ritonavir

Conjugated oestrogens/bazedoxifene [1], ritonavir ---> SmPC of [1] of EMA

Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

Crisaborole [1], ritonavir ---> SmPC of [1] of EMA

Based on in vitro data, concomitant administration of Staquis and CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, erythromycin, clarithromycin, ritonavir) can increase systemic crisaborole concentrations

Crizotinib [1], ritonavir ---> 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.

Cyclophosphamide, ritonavir

The CYP2B6 and CYP3A4 inhibition may decrease the efficacy of cyclophosphamide (prodrug)

Cyclosporine, ritonavir [2] ---> SmPC of [2] of EMA

Careful monitoring of therapeutic and adverse effects is recommended when these medicines are concomitantly administered with ritonavir.

CYP1A2 inductors, ritonavir

The CYP1A2 induction may decrease plasma concentrations of ritonavir, which has a narrow therapeutic index

CYP1A2 inhibitors, ritonavir

The CYP1A2 inhibition may increase plasma concentrations of ritonavir (narrow therapeutic index)

CYP2D6 inhibitors, ritonavir

The CYP2D6 inhibition may increase plasma concentrations of ritonavir (narrow therapeutic index)

Cyproterone [1], ritonavir ---> SmPC of [1] of eMC

Since cyproterone acetate is metabolised by CYP3A4, it is expected strong inhibitors of CYP3A4 inhibit the metabolism of cyproterone acetate.

Cyproterone/ethinylestradiol [1], ritonavir ---> 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.

Dabigatran etexilate, ritonavir [2] ---> SmPC of [2] of EMA

Clinical monitoring and/or dose reduction of the direct oral anticoagulants (DOAC) should be considered when a DOAC transported by P-gp but not metabolised by CYP3A4, including dabigatran etexilate and edoxaban, is co-administered with ritonavir.

Dabrafenib [1], ritonavir ---> 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.

Dapoxetine [1], ritonavir ---> SmPC of [1] of eMC

The strong CYP3A4 inhibition may increase the plasma concentrations of dapoxetine. Concomitant use of dapoxetine and potent CYP3A4 inhibitors is contraindicated

Daridorexant [1], ritonavir ---> SmPC of [1] of EMA

No clinical study was conducted with a strong CYP3A4 inhibitor. Concomitant use of QUVIVIQ with strong inhibitors of CYP3A4 (e.g., itraconazole, clarithromycin, ritonavir) is contraindicated

Darifenacin [1], ritonavir ---> SmPC of [1] of EMA

Concomitant treatment of darifenacin with potent CYP3A4 inhibitors is contraindicated

Darunavir, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir increases the serum levels of darunavir as a result of CYP3A4 inhibition. Darunavir must be given with ritonavir to ensure its therapeutic effect.

Darunavir/cobicistat [1], ritonavir ---> SmPC of [1] of EMA

REZOLSTA should not be used concurrently with products containing ritonavir or regimens containing ritonavir or cobicistat.

Dasatinib [1], ritonavir ---> 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.

Deferasirox [1], ritonavir ---> SmPC of [1] of EMA

The concomitant use of deferasirox with potent UGT inducers may result in a decrease in deferasirox efficacy.

Delamanid, ritonavir [2] ---> SmPC of [2] of EMA

Co-administration of delamanid with a strong inhibitor of CYP3A (ritonavir) may increase exposure to delamanid metabolite, which has been associated with QTc prolongation.

Delavirdine, ritonavir [2] ---> SmPC of [2] of EMA

Based on comparison to historical data, the pharmacokinetics of delavirdine did not appear to be affected by ritonavir. When used in combination with delavirdine, dose reduction of ritonavir may be considered.

Desipramine, ritonavir [2] ---> SmPC of [2] of EMA

The AUC and Cmax of the 2-hydroxy metabolite were decreased 15 and 67%, respectively. Dosage reduction of desipramine is recommended when co-administered with ritonavir dosed as an antiretroviral agent.

Desogestrel [1], ritonavir ---> SmPC of [1] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones

Dexamethasone, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent inhibits CYP3A and as a result is expected to increase the plasma concentrations of dexamethasone.

Dextromethorphan, ritonavir

The CYP2D6 inhibition may increase the plasma concentrations of dextromethorphan

Dextromethorphan/quinidine [1], ritonavir ---> 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.

Dextropropoxyphene, ritonavir

The co-administration may increase the plasma levels and toxicity of dextropropoxyphene

Diazepam, ritonavir [2] ---> SmPC of [2] of EMA

Increased plasma concentrations of diazepam, increasing the risk of extreme sedation and respiratory depression and is therefore contraindicated

Diclofenac, ritonavir

Plasma concentration of NSAID possibly increased

Didanosine, ritonavir [2] ---> SmPC of [2] of EMA

As ritonavir is recommended to be taken with food and didanosine should be taken on an empty stomach, dosing should be separated by 2.5 h.

Digitoxin, ritonavir

The CYP3A4 inhibition may increase the plasma levels of digitoxin

Digoxin, ritonavir [2] ---> SmPC of [2] of EMA

This interaction may be due to modification of P-glycoprotein mediated digoxin efflux by ritonavir dosed as an antriretroviral agent or as a pharmacokinetic enhancer.

Dihydroergotamine, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir co-administration is likely to result in increased plasma concentrations of ergot derivatives and is therefore contraindicated

Diltiazem, ritonavir [2] ---> SmPC of [2] 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 calcium channel antagonists.

Dipotassium clorazepate, ritonavir [2] ---> SmPC of [2] of EMA

Increased plasma concentrations of clorazepate, increasing the risk of extreme sedation and respiratory depression and is therefore contraindicated

Disopyramide, ritonavir [2] ---> SmPC of [2] of EMA

Cardiac and neurologic events have been reported when ritonavir has been co-administered with disopyramide. The possibility of drug interaction cannot be excluded

Divalproex sodium, ritonavir ---> SmPC of [indinavir] of EMA

Ritonavir, inductor of CYP2C9 and glucuronidation, may decrease the plasma concentrations of divalproex

Divalproex, ritonavir [2] ---> SmPC of [2] of EMA

As a result is expected to decrease the plasma concentrations of anticonvulsants. Careful monitoring of serum levels or therapeutic effects is recommended when these medicines are concomitantly administered with ritonavir.

Docetaxel [1], ritonavir ---> 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 [1], ritonavir ---> SmPC of [1] of EMA

The strong CYP3A4 inhibition may increase the plasma concentrations of dofetilide. The co-administration is contraindicated

Doravirine [1], ritonavir ---> SmPC of [1] of EMA

No dose adjustment is required.

Doxorubicine [1], ritonavir ---> SmPC of [1] of eMC

Elevated serum doxorubicin concentrations were reported after the concomitant administration of doxorubicin and ritonavir.

Dronedarone [1], ritonavir ---> SmPC of [1] of EMA

Concomitant use of dronedarone with strong CYP3A4 inhibitors increases dronedarone exposure. The combination of dronedarone with strong CYP3A4 inhibitors is contraindicated

Droperidol [1], ritonavir ---> SmPC of [1] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzyme CYP3A4 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Drospirenone/estetrol [1], ritonavir ---> SmPC of [1] of EMA

Medicinal products increasing the clearance of CHCs

Drugs primarily metabolised by CYP2D6, ritonavir [2] ---> SmPC of [2] of EMA

Co-administration of ritonavir and medicinal products primarily metabolised by CYP2D6 may result in increased plasma concentrations of the other medicinal product, which could increase or prolong its therapeutic and adverse effects.

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, ritonavir

Ritonavir, strong CYP3A4 inhibitor, should not be administered with medicinal products with narrow therapeutic windows and are primarily metabolised by CYP3A4

Drugs primarily metabolised by CYP3A4, ritonavir [2] ---> SmPC of [2] of EMA

Co-administration of ritonavir and medicinal products primarily metabolised by CYP3A may result in increased plasma concentrations of the other medicinal product, which could increase or prolong its therapeutic and adverse effects.

Drugs with high protein binding, ritonavir [2] ---> SmPC of [2] of EMA

As ritonavir is highly protein bound, the possibility of increased therapeutic and toxic effects due to protein binding displacement of concomitant medicinal products should be considered.

Dutasteride [1], ritonavir ---> SmPC of [1] of eMC

Long-term combination of dutasteride with drugs that are potent inhibitors of the enzyme CYP3A4 may increase serum concentrations of dutasteride.

Duvelisib [1], ritonavir ---> SmPC of [1] of EMA

Duvelisib dose should be reduced to 15 mg twice daily when co-administered with a strong CYP3A4 inhibitor

Dydrogesterone/estradiol [1], ritonavir ---> SmPC of [1] of eMC

Ritonavir, although known as strong inhibitor, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

Edoxaban, ritonavir [2] ---> SmPC of [2] of EMA

Efavirenz, ritonavir [2] ---> SmPC of [2] of EMA

A higher frequency of adverse reactions (e.g., dizziness, nausea, paraesthesia) and laboratory abnormalities (elevated liver enzymes) have been observed when efavirenz is co-administered with ritonavir dosed as an antiretroviral agent.

Eletriptan [1], ritonavir ---> SmPC of [1] of eMC

In clinical studies with potent inhibitors of CYP3A4 significant increases in eletriptan Cmax and AUC were observed. Eletriptan should not be used together with potent CYP3A4 inhibitors

Eliglustat [1], ritonavir ---> 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, ritonavir

Decreased plasma levels of eltrombopag

Eluxadoline [1], ritonavir ---> 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

Empagliflozin/linagliptin [1], ritonavir ---> SmPC of [1] of EMA

The changes in linagliptin pharmacokinetics were not considered to be clinically relevant.

Emtricitabine/tenofovir alafenamide [1], ritonavir ---> SmPC of [1] of EMA

Co-administration of Descovy with other medicinal products that inhibit P-gp (e.g., cobicistat, ritonavir, ciclosporin) are expected to increase the absorption and plasma concentration of tenofovir alafenamide.

Encainide, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir co-administration with encainide is likely to result in increased plasma concentrations of encainide and is therefore contraindicated

Encorafenib [1], ritonavir ---> 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).

Enfortumab vedotin [1], ritonavir ---> SmPC of [1] of EMA

Patients receiving concomitant strong CYP3A4 inhibitors should be monitored more closely for signs of toxicities.

Enfuvirtide [1], ritonavir ---> SmPC of [1] of EMA

Entrectinib [1], ritonavir ---> SmPC of [1] of EMA

Co-administration of entrectinib with CYP3A/P-gp inducers (including, but not limited to, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampicin, St. John's Wort -Hypericum perforatum-, apalutamide, ritonavir) should be avoided.

Entrectinib [1], ritonavir ---> SmPC of [1] of EMA

Co-administration of strong and moderate CYP3A inhibitors (including, but not limited to, ritonavir, saquinavir, ketoconazole, itraconazole, voriconazole, posaconazole, grapefruit or Seville oranges) should be avoided.

Enzalutamide [1], ritonavir ---> SmPC of [1] of EMA

Enzalutamide, enzymatic inductor, may increase the metabolism of ritonavir and decrease its plasma levels and effect

Eplerenone [1], ritonavir ---> 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

Ergonovine, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir co-administration is likely to result in increased plasma concentrations of ergot derivatives and is therefore contraindicated

Ergot derivatives, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir co-administration is likely to result in increased plasma concentrations of ergot derivatives and is therefore contraindicated

Ergotamine, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir co-administration is likely to result in increased plasma concentrations of ergot derivatives and is therefore contraindicated

Erythromycin, ritonavir [2] ---> SmPC of [2] 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 erythromycin and itraconazole.

Estazolam, ritonavir [2] ---> SmPC of [2] of EMA

Increased plasma concentrations of estazolam, increasing the risk of extreme sedation and respiratory depression and is therefore contraindicated

Estradiol valerate/norgestrel [1], ritonavir ---> SmPC of [1] of eMC

Ritonavir, although known as strong inhibitor, by contrast exhibits inducing properties when used concomitantly with steroid hormones

Estradiol [1], ritonavir ---> SmPC of [1] of eMC

Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

Estradiol/norethisterone [1], ritonavir ---> SmPC of [1] of eMC

Ritonavir, although known as strong inhibitor, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

Estriol [1], ritonavir ---> SmPC of [1] of eMC

Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

Estrogens, ritonavir ---> SmPC of [estradiol] of eMC

Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

Ethinyl estradiol, ritonavir [2] ---> SmPC of [2] of EMA

Due to reductions in ethinyl estradiol concentrations, barrier or other non-hormonal methods of contraception should be considered with concomitant ritonavir use when dosed as an antiretroviral agent or as a pharmacokinetic enhancer.

Ethinylestradiol/chlormadinone, ritonavir

Interactions can occur with drugs that induce hepatic enzymes which can result in increased clearance of sex hormones

Ethinylestradiol/desogestrel [1], ritonavir ---> 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], ritonavir ---> 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], ritonavir ---> 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], ritonavir ---> 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], ritonavir ---> SmPC of [1] of eMC

Ethosuximide, ritonavir

The co-administration of ethosuximide and ritonavir may increase the plasma levels of ethosuximide

Etonogestrel [1], ritonavir ---> 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

Everolimus [1], ritonavir ---> 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], ritonavir ---> 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.

Fedratinib [1], ritonavir ---> SmPC of [1] of EMA

If strong CYP3A4 inhibitors cannot be replaced, the dose of Inrebic should be reduced when administering with strong CYP3A4 inhibitors, (e.g. ketoconazole, ritonavir).

Felodipine, ritonavir ---> SmPC of [felodipine/metoprolol] of eMC

The strong CYP3A4 inhibition may increase the plasma concentrations of felodipine

Felodipine/metoprolol, ritonavir

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

Fentanyl, ritonavir [2] ---> SmPC of [2] 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 fentanyl.

Fertility, ritonavir [2] ---> SmPC of [2] of EMA

No human data on the effect of ritonavir on fertility are available. Animal studies do not indicate harmful effects of ritonavir on fertility (see section 5.3).

Fesoterodine [1], ritonavir ---> SmPC of [1] of EMA

The maximum dose of fesoterodine should be restricted to 4 mg when used concomitantly with potent CYP3A4 inhibitors

Fexofenadine, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir may modify P-glycoprotein mediated fexofenadine efflux when dosed as an antiretroviral agent or as a pharmacokinetic enhancer resulting in increased concentrations of fexofenadine.

Finerenone [1], ritonavir ---> SmPC of [1] of EMA

Concomitant use of Kerendia with strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, nelfinavir, cobicistat, telithromycin or nefazodone) is contraindicated (see section 4.3), since a marked increase in finerenone exposure is expected.

Flecainide, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir co-administration with flecainide is likely to result in increased plasma concentrations of flecainide and is therefore contraindicated

Fluoxetine, ritonavir [2] ---> SmPC of [2] of EMA

Flurazepam, ritonavir [2] ---> SmPC of [2] of EMA

Increased plasma concentrations of flurazepam, increasing the risk of extreme sedation and respiratory depression and is therefore contraindicated

Fluticasone furoate [1], ritonavir ---> SmPC of [1] of EMA

Coadministration with ritonavir is not recommended because of the risk of increased systemic exposure of fluticasone furoate.

Fluticasone furoate/umeclidinium/vilanterol [1], ritonavir ---> SmPC of [1] of EMA

Caution is advised when co-administering with strong CYP3A4 inhibitors as there is potential for increased systemic exposure to both fluticasone furoate and vilanterol, which could lead to an increased potential for adverse reactions.

Fluticasone furoate/vilanterol [1], ritonavir ---> SmPC of [1] of EMA

Caution is advised when co-administering with strong CYP 3A4 inhibitors as there is potential for increased systemic exposure to both fluticasone furoate and vilanterol, and concomitant use should be avoided.

Fluticasone, ritonavir [2] ---> SmPC of [2] of EMA

Significant increased plasma levels of fluticasone (metabolized by CYP3A4) with risk of systemic corticosteroid effects. Concomitant use not recommended

Fluvastatin, ritonavir [2] ---> SmPC of [2] of EMA

The metabolism of pravastatin and fluvastatin is not dependent on CYP3A, and interactions are not expected with ritonavir. If treatment with an HMG-CoA reductase inhibitor is indicated, pravastatin or fluvastatin is recommended.

Foods, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir is recommended to be taken with food

Fosamprenavir, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir increases the serum levels of amprenavir (from fosamprenavir) as a result of CYP3A4 inhibition. Fosamprenavir must be given with ritonavir to ensure its therapeutic effect.

Fosaprepitant [1], ritonavir ---> 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

Foscarnet [1], ritonavir ---> SmPC of [1] of eMC

Abnormal renal function has been reported in connection with the use of foscarnet in combination with ritonavir

Fostamatinib, ritonavir [2] ---> SmPC of [2] of EMA

Co-administration of fostamatinib with ritonavir may increase fostamatinib metabolite R406 exposure resulting in dose-related adverse events such as hepatotoxicity, neutropenia, hypertension, or diarrhoea.

Fostemsavir [1], ritonavir ---> SmPC of [1] of EMA

Temsavir (inhibition of CYP3A and P-gp). Ritonavir increased temsavir plasma concentrations. No dose adjustment of either medicinal product is necessary.

Fusidic acid, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir co-administration is likely to result in increased plasma concentrations of both fusidic acid and ritonavir and is therefore contraindicated

Galantamine [1], ritonavir ---> SmPC of [1] of eMC

The co-administration of galantamine with strong CYP3A4 inhibitors may increase the bioavailability of galantamine and the incidence of cholinergic adverse reactions, predominantly nausea and vomiting.

Glasdegib [1], ritonavir ---> 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.

Glecaprevir/pibrentasvir [1], ritonavir ---> SmPC of [1] of EMA

Co-administration of Maviret with medicinal products that inhibit P-gp and BCRP may slow elimination of glecaprevir and pibrentasvir and thereby increase plasma exposure of the antivirals.

Glucocorticoids metabolized by CYP3A4, ritonavir [2] ---> SmPC of [2] of EMA

Concomitant use of ritonavir and glucocorticoids that are metabolised by CYP3A4 is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects

Glucuronidation inductors, ritonavir

The glucuronidation induction may decrease the plasma concentrations of ritonavir

Glycopyrronium/indacaterol/mometasone [1], ritonavir ---> SmPC of [1] of EMA

However, there may be a potential for increased systemic exposure to mometasone furoate when strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, nelfinavir, ritonavir, cobicistat) are co-administered.

Guanfacin [1], ritonavir ---> 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.

H2 antagonists, protease inhibitors ---> SmPC of [ritonavir] of EMA

Proton pump inhibitors and H2-receptor antagonists (e.g. omeprazole or ranitidine) may reduce concentrations for co-administered protease inhibitors.

Halofantrine, ritonavir

Possible increase of plasma concentrations of halofantrine. Inherent risk of inducing torsades de pointes. The co-administration is not recommended

Haloperidol, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir dosed as an antiretroviral agent is likely to inhibit CYP2D6 and as a result is expected to increase concentrations of haloperidol, risperidone and thioridazine.

Hemp extract, ritonavir

The co-administration may increase the Cmax and THC and CBD.

Hydrocortisone [1], ritonavir ---> SmPC of [1] of EMA

Potent CYP 3A4 inhibitors can inhibit the metabolism of hydrocortisone, and thus increase blood levels.

Ibrutinib, ritonavir [2] ---> SmPC of [2] of EMA

Serum concentrations of ibrutinib may be increased due to CYP3A inhibition by ritonavir, resulting in increased risk for toxicity including risk of tumor lysis syndrome. Co-administration of ibrutinib and ritonavir should be avoided.

Imatinib [1], ritonavir ---> 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.

Imipramine, ritonavir [2] ---> SmPC of [2] of EMA

Indacaterol/mometasone [1], ritonavir ---> SmPC of [1] of EMA

There may be a potential for increased systemic exposure to mometasone furoate when strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, nelfinavir, ritonavir, cobicistat) are co-administered.

Indinavir, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir increases the serum levels of indinavir as a result of CYP3A4 inhibition. Minimal benefit of ritonavir-mediated pharmacokinetic enhancement is achieved with doses higher than 100 mg twice daily.

Indinavir/ritonavir, ritonavir ---> SmPC of [indinavir] 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.

Interferon, ritonavir

Caution should be used when administering interferon with medicines mainly metabolised by hepatic cytochrome P450 and have a narrow therapeutic window

Irinotecan [1], ritonavir ---> SmPC of [1] of EMA

Co-administration of ONIVYDE with other inhibitors of CYP3A4 may increase systemic exposure of ONIVYDE.

Isavuconazole [1], ritonavir ---> SmPC of [1] of EMA

Co-administration with high-dose ritonavir (>200 mg twice daily) is contraindicated, as at high doses ritonavir may induce CYP3A4/5 and decrease isavuconazole plasma concentrations

Isradipine [1], ritonavir ---> SmPC of [1] of eMC

Caution should be exercised when co-administering isradipine with strong CYP3A inhibitors

Itraconazol, ritonavir [2] ---> SmPC of [2] 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 erythromycin and itraconazole.

Ivabradine [1], ritonavir ---> 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

Ivosidenib [1], ritonavir ---> SmPC of [1] of EMA

Coadministration of moderate or strong CYP3A4 inhibitors increases ivosidenib plasma levels. This may increase the risk of QTc interval prolongation and suitable alternatives that are not moderate or strong CYP3A4 inhibitors should be considered

Ixabepilone, ritonavir

The strong CYP3A4 inhibition may increase the plasma concentrations of ixabepilone. The coadministration should be avoided

Ketoconazole, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir inhibits CYP3A-mediated metabolism of ketoconazole. Due to an increased incidence of gastrointestinal and hepatic adverse reactions, a dose reduction of ketoconazole should be considered

Lacosamide [1], ritonavir ---> SmPC of [1] of EMA

Caution is recommended in concomitant treatment of lacosamide with strong inhibitors of CYP3A4, which may lead to increased systemic exposure of lacosamide.

Lamotrigine, ritonavir [2] ---> SmPC of [2] of EMA

Lapatinib [1], ritonavir ---> 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.

Larotrectinib [1], ritonavir ---> SmPC of [1] of EMA

Co-administration of VITRAKVI with strong or moderate CYP3A inhibitors, P-gp and BCRP inhibitors may increase larotrectinib plasma concentrations (see section 4.2).

Lefamulin [1], ritonavir ---> SmPC of [1] of EMA

Medicinal products that are strong CYP3A and P-gp inhibitors may alter absorption of lefamulin and therefore increase lefamulin plasma concentrations. Co- administration is contraindicated

Lenacapavir [1], ritonavir ---> SmPC of [1] of EMA

No dose adjustment of lenacapavir is required.

Lercanidipine [1], ritonavir ---> SmPC of [1] of eMC

The strong CYP3A4 inhibition increases plasma concentrations of lercanidipine. Co-administration of lercanidipine with inhibitors of CYP3A4 should be avoided

Letermovir [1], ritonavir ---> SmPC of [1] of EMA

Co-treatment with moderate and strong inducers may give rise to subtherapeutic letermovir exposure

Letermovir [1], ritonavir ---> SmPC of [1] of EMA

Co-administration of PREVYMIS with medicinal products that are inhibitors of OATP1B1/3 transporters may result in increased letermovir plasma concentrations.

Levobupivacaine, ritonavir

In vitro studies indicate that the CYP3A4 isoform and CYP1A2 isoform mediate the metabolism of levobupivacaine. Metabolism of levobupivacaine may be affected by CYP3A4 inhibitors and CYP1A2 inhibitors

Levomethadone, ritonavir

The enzymatic induction may decrease the plasma levels of levomethadone and abstinence syndrome may occur

Levonorgestrel [1], ritonavir ---> SmPC of [1] of eMC

The metabolism of levonorgestrel is enhanced by concomitant use of liver enzyme inducers.

Levonorgestrel/ethinylestradiol [1], ritonavir ---> SmPC of [1] of eMC

Levothyroxine, ritonavir [2] ---> SmPC of [2] of EMA

Thyroid-stimulating hormone (TSH) should be monitored in patients treated with levothyroxine at least the first month after starting and/or ending ritonavir treatment.

Linagliptin [1], ritonavir ---> SmPC of [1] of EMA

Co-administration of a single 5 mg oral dose of linagliptin and multiple 200 mg oral doses of ritonavir, a potent inhibitor of P-glycoprotein and CYP3A4, increased the AUC and Cmax of linagliptin approximately twofold and threefold, respectively

Linagliptin/metformin [1], ritonavir ---> SmPC of [1] of EMA

The changes in linagliptin pharmacokinetics were not considered to be clinically relevant. Therefore, clinically relevant interactions would not be expected with other P-glycoprotein/CYP3A4 inhibitors.

Lofepramine [1], ritonavir ---> SmPC of [1] of eMC

The plasma concentrations of some tricyclic antidepressants may be increased by ritonavir.

Lonafarnib [1], ritonavir ---> SmPC of [1] of EMA

The concomitant use of lonafarnib and a strong CYP3A inducer should be avoided, and therapeutic alternatives sought

Loperamide [1], ritonavir ---> SmPC of [1] of eMC

Concomitant administration of loperamide (16 mg single dose) with ritonavir, which is P-glycoprotein inhibitor, resulted in a 2 to 3-fold increase in loperamide plasma levels.

Lopinavir, ritonavir

The strong CYP3A4 inhibition increases the plasma concentrations of lopinavir

Loratadine, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir, CYP3A4 inhibitor, may increase the plasma concentrations of loratadine. Careful monitoring of therapeutic and adverse effects is recommended

Lorlatinib [1], ritonavir ---> SmPC of [1] of EMA

CYP3A4/5 inhibitors may increase lorlatinib plasma concentrations and should be avoided

Lovastatine, ritonavir [2] ---> SmPC of [2] of EMA

Since increased concentrations of lovastatin and simvastatin may predispose patients to myopathies, including rhabdomyolysis, the combination of these medicinal products with ritonavir is contraindicated

Lumefantrine, ritonavir

Possible increase of plasma concentrations of lumefantrine. Inherent risk of inducing torsades de pointes. The co-administration is not recommended

Lurasidone, ritonavir [2] ---> SmPC of [2] of EMA

Due to CYP3A inhibition by ritonavir, concentrations of lurasidone are expected to increase. The concomitant administration with lurasidone is contraindicated (see section 4.3).

Macitentan [1], ritonavir ---> SmPC of [1] of EMA

Caution should be exercised when macitentan (by CYP3A4 metabolized) is administered concomitantly with strong CYP3A4 inhibitors

Maraviroc, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir increases the serum levels of maraviroc as a result of CYP3A inhibition. Maraviroc may be given with ritonavir to increase the maraviroc exposure.

Mebendazol, ritonavir

A long-term treatment with ritonavir cause a significant decrease in mebendazole uptake

Medroxyprogesterone, ritonavir ---> SmPC of [estradiol/norethisterone] of eMC

Ritonavir, although known as strong inhibitor, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

Meperidine, ritonavir

Increased plasma concentrations of normeperidine and is therefore contraindicated

Meptazinol [1], ritonavir ---> SmPC of [1] of eMC

Avoid concomitant use with ritonavir as plasma concentration of meptazinol may be increased.

Methadone, ritonavir [2] ---> SmPC of [2] of EMA

Increased methadone dose may be necessary when concomitantly administered with ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer due to induction of glucuronidation.

Methylergometrine, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir co-administration is likely to result in increased plasma concentrations of ergot derivatives and is therefore contraindicated

Mexiletine, ritonavir [2] ---> SmPC of [2] of EMA

Cardiac and neurologic events have been reported when ritonavir has been co-administered with mexiletine. The possibility of drug interaction cannot be excluded

Midazolam, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir, CYP3A4 inhibitor, may increase the plasma concentrations of midazolam: oral contraindicated, caution on parenterally administered

Mirabegron [1], ritonavir ---> SmPC of [1] of EMA

The strong CYP3A4 inhibition may increase the exposition of mirabegron. No dose-adjustment is needed when mirabegron is combined with inhibitors of CYP3A and/or P-gp.

Mometasone [1], ritonavir ---> SmPC of [1] of eMC

There may be a potential for increased systemic exposure to mometasone furoate when strong CYP3A4 inhibitors are co-administered

Morphine, ritonavir [2] ---> SmPC of [2] of EMA

Morphine levels may be decreased due to induction of glucuronidation by co-administered ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer.

Naldemedine [1], ritonavir ---> SmPC of [1] of EMA

Concomitant use of strong CYP3A inhibitors should be avoided. If use with strong CYP3A inhibitors is unavoidable, monitor for adverse reactions

Naloxegol [1], ritonavir ---> 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

Naltrexone/bupropion [1], ritonavir ---> SmPC of [1] of EMA

Since bupropion is extensively metabolised, caution is advised when naltrexone/bupropion is co-administered with medicinal products known to induce CYP2B6 as these may affect the clinical efficacy of naltrexone/bupropion.

Nefazodone, ritonavir [2] ---> SmPC of [2] of EMA

Cardiac and neurologic events have been reported when ritonavir has been co-administered with nefazadone. The possibility of drug interaction cannot be excluded

Nelfinavir, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir increases the serum levels of nelfinavir as a result of CYP3A4 inhibition. Minimal benefit of ritonavir-mediated pharmacokinetic enhancement is achieved with doses higher than 100 mg twice daily.

Neratinib, ritonavir [2] ---> SmPC of [2] of EMA

Serum concentrations may be increased due to CYP3A4 inhibition by ritonavir. Concomitant use of neratinib with Norvir is contraindicated due to serious and/or life-threatening potential reactions including hepatotoxicity (see section 4.3).

Neuroleptics, ritonavir

An increase in plasma concentration of antipsychotic drugs may occur if taken with ritonavir.

Nevirapine, ritonavir [2] ---> SmPC of [2] of EMA

Co-administration of ritonavir with nevirapine does not lead to clinically relevant changes in the pharmacokinetics of either nevirapine or ritonavir.

Nifedipine, ritonavir [2] ---> SmPC of [2] 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 calcium channel antagonists.

Nilotinib [1], ritonavir ---> 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.

Nilvadipine, ritonavir

The strong CYP3A4 inhibition may increase the plasma concentrations of nilvadipine. Caution is recommended

Nimodipine [1], ritonavir ---> SmPC of [1] of eMC

Upon co-administration of nimodipine with CYP3A4 inhibitors the blood pressure should be monitored and, if necessary, an adaptation in the nimodipine dose should be considered.

Niraparib [1], ritonavir ---> SmPC of [1] of EMA

No dose adjustment for Zejula is required when administered concomitantly with medicinal products known to inhibit (e.g. itraconazole, ritonavir, and clarithromycin) or induce CYP enzymes (e.g. rifampin, carbamazepine, and phenytoin)

Nisoldipine, ritonavir

The co-administration of nisoldipine with medicinal products that inhibit the cytochrome P450 3A4-system may increase the bioavailability of nisoldipine. Concomitant use is contraindicated

Nitrendipine, ritonavir

The CYP3A4 inhibition may increase the plasma levels of nitrendipine

Nomegestrol/estradiol [1], ritonavir ---> SmPC of [1] of EMA

Interactions between oral contraceptives and enzyme-inducing medicinal products may lead to breakthrough bleeding and even contraceptive failure.

Norbuprenorphine, ritonavir [2] ---> SmPC of [2] of EMA

The increases of plasma levels of buprenorphine and its active metabolite did not lead to clinically significant pharmacodynamic changes in a population of opioid tolerant patients.

Norelgestromin/ethinylestradiol [1], ritonavir ---> 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, ritonavir

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

Nortriptyline, ritonavir [2] ---> SmPC of [2] of EMA

OATP1B1 substrates, ritonavir ---> SmPC of [darunavir] of EMA

Ritonavir inhibits the transporters OATP1B1, and co-administration with substrates of these transporters can result in increased plasma concentrations of these compounds

OATP1B3 substrates, ritonavir ---> SmPC of [darunavir] of EMA

Ritonavir inhibits the transporters OATP1B3, and co-administration with substrates of these transporters can result in increased plasma concentrations of these compounds

Olanzapine, ritonavir

Decrease of the olanzapine effect

Omeprazole, ritonavir [2] ---> SmPC of [2] of EMA

Concurrent administration of omeprazole or ranitidine does not significantly modify ritonavir efficacy as a pharmacokinetic enhancer despite a slight change of exposure (about 6 - 18%).

Opioid analgesics, ritonavir ---> SmPC of [codeine] of eMC

Ritonavir may increase plasma levels of opioid analgesics

Oral contraceptives, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir adversely interacts with oral contraceptives. Therefore, an alternative, effective and safe method of contraception should be used during treatment

Oxazepam, ritonavir

Ritonavir may inhibit benzodiazepine hepatic metabolism

P-glycoprotein and CYP3A4 inhibitors, ritonavir

The P-glycoprotein and CYP3A4 inhibition may increase the plasma concentrations of ritonavir

P-glycoprotein substrates, ritonavir ---> SmPC of [darunavir] of EMA

Co-administration of darunavir/ritonavir with medicinal products transported by P-gp may result in increased systemic exposure to such medicinal products, which could increase or prolong their therapeutic effect and adverse reactions.

Paclitaxel [1], ritonavir ---> SmPC of [1] of EMA

Caution should be exercised when administering paclitaxel concomitantly with medicines known to inhibit either CYP2C8 or CYP3A4 because toxicity of paclitaxel may be increased due to higher paclitaxel exposure.

Panobinostat [1], ritonavir ---> 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

Paroxetine, ritonavir [2] ---> SmPC of [2] of EMA

Pazopanib [1], ritonavir ---> SmPC of [1] of EMA

Concomitant treatment with strong inhibitors of CYP3A4 should be avoided due to risk of increased exposure to pazopanib

PDE5 inhibitors, ritonavir

The co-administration may increase the plasma levels und adverse effects (hypotension and prolonged erection) of PDE5 inhibitor

Pethidine, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir co-administration is likely to result in increased plasma concentrations of norpethidine and propoxyphene and is therefore contraindicated (see section 4.3).

Phenobarbital, ritonavir

The co-administration may decrease the plasma levels of protease inhibitor

Phenytoin, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir, inductor of CYP2C9 and glucuronidation, may decrease the plasma levels of phenytoin. Phenytoin may decrease the plasma levels of ritonavir

Pimozide, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir co-administration is likely to result in increased plasma concentrations of clozapine or pimozide and is therefore contraindicated (see section 4.3).

Piperaquine/artenimol [1], ritonavir ---> SmPC of [1] of EMA

Concomitant treatment with medicinal products which inhibit CYP3A4 may lead to a marked increase of piperaquine plasma concentration resulting in an exacerbation of the effect on QTc

Piroxicam, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir co-administration with piroxicam is likely to result in increased plasma concentrations of piroxicam and is therefore contraindicated

Pixantrone [1], ritonavir ---> SmPC of [1] of EMA

The inhibition of the transporters of the P-glycoprotein has the potential to decrease hepatic uptake and excretion efficiency of pixantrone.

Polatuzumab vedotin [1], ritonavir ---> SmPC of [1] of EMA

Patients receiving concomitant strong CYP3A4 inhibitors should be monitored more closely for signs of toxicities.

Ponatinib [1], ritonavir ---> 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)

PR interval prolonging drugs, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir has been shown to cause modest asymptomatic prolongation of the PR interval in some healthy adult subjects.

Pralsetinib [1], ritonavir ---> SmPC of [1] of EMA

Therefore, co-administration of pralsetinib with strong CYP3A4 inhibitors or combined P-gp and strong CYP3A4 inhibitors should be avoided. If co-administration cannot be avoided, reduce the current dose of pralsetinib

Pravastatine, ritonavir [2] ---> SmPC of [2] of EMA

Prednisolone, ritonavir [2] ---> SmPC of [2] of EMA

Careful monitoring of therapeutic and adverse effects is recommended when prednisolone is concomitantly administered with ritonavir.

Pregnancy, ritonavir [2] ---> SmPC of [2] of EMA

Norvir can be used during pregnancy if clinically needed.

Primidone, ritonavir

The co-administration may decrease the plasma levels of protease inhibitor

Promazine, ritonavir

An increase in plasma concentration of antipsychotic drugs may occur if taken with ritonavir.

Propafenone, ritonavir [2] ---> SmPC of [2] of EMA

The combination may increase the plasma concentrations of propafenone, increasing the risk of arrhythmias. The concomitant use is contra-indicated

Propoxyphene, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir co-administration is likely to result in increased plasma concentrations of norpethidine and propoxyphene and is therefore contraindicated (see section 4.3).

Protease inhibitors, proton pump inhibitors ---> SmPC of [ritonavir] of EMA

Proton pump inhibitors and H2-receptor antagonists (e.g. omeprazole or ranitidine) may reduce concentrations for co-administered protease inhibitors.

Protease inhibitors, ritonavir

Generally, dual therapy with protease inhibitors is not recommended

Proton pump inhibitors, ritonavir

The CYP2C9 induction decreases the plasma levels of proton pump inhibitor. The combined use is not recommended

Quetiapine, ritonavir [2] ---> SmPC of [2] of EMA

Due to CYP3A inhibition by ritonavir, concentrations of quetiapine are expected to increase. Concomitant administration of Norvir and quetiapine is contraindicated as it may increase quetiapine-related toxicity.

Quinidine, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir co-administration with quinidine is likely to result in increased plasma concentrations of quinidine and is therefore contraindicated

Raltegravir, ritonavir [2] ---> SmPC of [2] of EMA

Co-administration of ritonavir and raltegravir results in a minor reduction in raltegravir levels

Ranitidine, ritonavir [2] ---> SmPC of [2] of EMA

Concurrent administration of omeprazole or ranitidine does not significantly modify ritonavir efficacy as a pharmacokinetic enhancer despite a slight change of exposure (about 6 - 18%).

Ranolazine, ritonavir [2] ---> SmPC of [2] of EMA

Increased plasma concentrations of ranolazine which may increase the potential for serious and/or life-threatening reactions

Ribociclib, ritonavir [2] ---> SmPC of [2] 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, ritonavir [2] ---> SmPC of [2] of EMA

Due to the large increase in rifabutin AUC, the concomitant use of rifabutin with ritonavir dosed as an antiretroviral agent is contraindicated (see section 4.3).

Rifampicin, ritonavir [2] ---> SmPC of [2] of EMA

The inducing effect of rifampicin (next to that of ritonavir itself) is small and may have no clinical relevant effect on ritonavir levels

Rimegepant [1], ritonavir ---> SmPC of [1] of EMA

Rimonabant [1], ritonavir ---> 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

Riociguat [1], ritonavir ---> SmPC of [1] of EMA

Serum concentrations may be increased due to CYP3A and P-gp inhibition by ritonavir. The coadministration of riociguat with Norvir is not recommended

Ripretinib [1], ritonavir ---> SmPC of [1] of EMA

Risperidone, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir dosed as an antiretroviral agent is likely to inhibit CYP2D6 and as a result is expected to increase concentrations of haloperidol, risperidone and thioridazine.

Ritonavir [1], rivaroxaban ---> SmPC of [1] of EMA

Inhibition of CYP3A and P-gp lead to increased plasma levels and pharmacodynamic effects of rivaroxaban which may lead to an increased bleeding risk. Therefore, the use of ritonavir is not recommended in patients receiving rivaroxaban.

Ritonavir [1], rosuvastatin ---> SmPC of [1] of EMA

While rosuvastatin elimination is not dependent on CYP3A, an elevation of rosuvastatin exposure has been reported with ritonavir co-administration.

Ritonavir [1], salmeterol ---> SmPC of [1] of EMA

Ritonavir inhibits CYP3A4 and as a result a pronounced increase in the plasma concentrations of salmeterol is expected. Therefore concomitant use is not recommended.

Ritonavir [1], saquinavir ---> SmPC of [1] of EMA

Ritonavir increases the serum levels of saquinavir as a result of CYP3A4 inhibition. Saquinavir should only be given in combination with ritonavir.

Ritonavir [1], sertraline ---> SmPC of [1] of EMA

Ritonavir [1], sildenafil ---> SmPC of [1] of EMA

Based on these pharmacokinetic results co-administration of sildenafil with ritonavir is not advised (see section 4.4) and in any event the maximum dose of sildenafil should under no circumstances exceed 25 mg within 48 hours.

Ritonavir [1], simvastatine ---> SmPC of [1] of EMA

Ritonavir [1], sirolimus ---> SmPC of [1] of EMA

Ritonavir, CYP3A4 inhibitor, may increase the plasma concentrations of sirolimus. More frequent monitoring is recommended

Ritonavir [1], St. John's wort ---> SmPC of [1] of EMA

Serum levels of ritonavir can be reduced by concomitant use of herbal preparations containing St John's wort (Hypericum perforatum). This is due to the induction of medicinal product metabolising enzymes by St John's wort.

Ritonavir [1], sulfamethoxazol/trimethoprim ---> SmPC of [1] of EMA

Dose alteration of sulfamethoxazole/trimethoprim during concomitant ritonavir therapy should not be necessary.

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 [1], terfenadine ---> SmPC of [1] of EMA

Ritonavir co-administration is likely to result in increased plasma concentrations of astemizole and terfenadine and is therefore contraindicated (see section 4.3).

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.

Ritonavir [1], thioridazine ---> SmPC of [1] of EMA

Ritonavir dosed as an antiretroviral agent is likely to inhibit CYP2D6 and as a result is expected to increase concentrations of haloperidol, risperidone and thioridazine.

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.

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 [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

Ritonavir [1], trimethoprim/sulfamethoxazol ---> SmPC of [1] of EMA

Dose alteration of sulfamethoxazole/trimethoprim during concomitant ritonavir therapy should not be necessary.

Ritonavir [1], vardenafil ---> SmPC of [1] of EMA

Increased plasma concentrations of vardenafil. Concomitant use of vardenafil with ritonavir is contraindicated

Ritonavir [1], vinblastine ---> SmPC of [1] of EMA

Serum concentrations of vinblastine may be increased when co-administered with ritonavir resulting in the potential for increased incidence of adverse events.

Ritonavir [1], vincristine ---> SmPC of [1] of EMA

Serum concentrations of vincristine may be increased when co-administered with ritonavir resulting in the potential for increased incidence of adverse events.

Ritonavir [1], vorapaxar ---> SmPC of [1] of EMA

Serum concentrations may be increased due to CYP3A inhibition by ritonavir. The coadministration of vorapaxar with Norvir is not recommended

Ritonavir [1], voriconazole ---> SmPC of [1] of EMA

Concomitant use of ritonavir dosed as an antiretroviral agent and voriconazole is contraindicated due to reduction in voriconazole concentrations

Ritonavir [1], warfarin ---> SmPC of [1] of EMA

Ritonavir, inductor of CYP1A2 and CYP2C9, may decrease the levels of R warfarin and may lead to reduced anticoagulation. Monitoring the anticoagulation parameters.

Ritonavir [1], zidovudine ---> SmPC of [1] of EMA

Ritonavir may induce the glucuronidation of zidovudine, resulting in slightly decreased levels of zidovudine. Dose alterations should not be necessary.

Ritonavir [1], zolpidem ---> SmPC of [1] of EMA

Zolpidem and ritonavir may be co-administered with careful monitoring for excessive sedative effects.

Ritonavir, ruxolitinib [2] ---> SmPC of [2] 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

Ritonavir, sacituzumab govitecan [2] ---> SmPC of [2] of EMA

Sacituzumab govitecan should be used with caution in patients receiving UGT1A1 inducers (e.g. carbamazepine, phenytoin, rifampicin, ritonavir, tipranavir).

Ritonavir, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

Ritonavir, salmeterol/fluticasone propionate [2] ---> SmPC of [2] of EMA

Ritonavir can greatly increase the concentration of fluticasone propionate in plasma. Therefore, concomitant use should be avoided, unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.

Ritonavir, selpercatinib [2] ---> SmPC of [2] of EMA

If strong CYP3A and/or P-gp inhibitors, e. g. ketoconazole, itraconazole, voriconazole, ritonavir, saquinavir, telithromycin, posaconazole and nefazodone, have to be coadministered, the dose of selpercatinib should be reduced

Ritonavir, silodosin [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the plasma levels of silodosin. Concomitant use of silodosin with potent CYP3A4 inhibitors is not recommended

Ritonavir, simeprevir [2] ---> SmPC of [2] of EMA

The strong CYP3A4 enzyme inhibition by may increase the exposition of active principles. It is not recommended to co-administer OLYSIO with ritonavir.

Ritonavir, sitagliptin [2] ---> SmPC of [2] of EMA

It is possible that potent CYP3A4 inhibitors (i.e. ketoconazole, itraconazole, ritonavir, clarithromycin) could alter the pharmacokinetics of sitagliptin in patients with severe renal impairment or ESRD.

Ritonavir, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

It is possible that potent CYP3A4 inhibitors (i.e., ketoconazole, itraconazole, ritonavir, clarithromycin) could alter the pharmacokinetics of sitagliptin in patients with severe renal impairment or ESRD.

Ritonavir, sitaxentan [2] ---> SmPC of [2] of EMA

The extent of interaction with other OATP inhibitors (except cyclosporine) is unknown but could result in raised plasma levels of sitaxentan.

Ritonavir, solifenacin [2] ---> SmPC of [2] of eMC

The CYP3A4 inhibition may increase the plasma levels of solifenacin. Simultaneous treatment of solifenacin and a potent CYP3A4 inhibitor is contra-indicated in patients with severe renal impairment or moderate hepatic impairment

Ritonavir, sonidegib [2] ---> SmPC of [2] 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

Ritonavir, sotagliflozin [2] ---> SmPC of [2] of EMA

If an enzyme inducer (e.g., rifampicin, phenytoin, phenobarbital, ritonavir) must be co-administered with sotagliflozin, consider frequent monitoring of glucose level.

Ritonavir, steroid hormones ---> SmPC of [estradiol] of eMC

Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

Ritonavir, strong CYP2D6 inhibitors

The strong CYP2D6 inhibition may increase plasma concentrations of ritonavir (narrow therapeutic index)

Ritonavir, strong CYP3A4 inductors

The strong CYP3A4 induction may decrease the plasma concentrations of ritonavir

Ritonavir, strong CYP3A4 inhibitors

The strong CYP3A4 inhibition may increase the plasma concentrations of ritonavir

Ritonavir, sufentanil [2] ---> SmPC of [2] of EMA

Sufentanil is primarily metabolised by the CYP3A4. Ketoconazole, a potent CYP3A4 inhibitor, can significantly increase the systemic exposure to sublingual sufentanil. Similar effects with other potent CYP3A4 inhibitors cannot be excluded.

Ritonavir, sunitinib [2] ---> SmPC of [2] of EMA

Administration of sunitinib with potent CYP3A4 inhibitors may increase sunitinib concentrations. Combination with CYP3A4 inhibitors should therefore be avoided

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

Ritonavir, talazoparib [2] ---> SmPC of [2] of EMA

Concomitant use of strong P-gp inhibitors during treatment with talazoparib should be avoided.

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.

Ritonavir, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

It cannot be ruled out that strong inhibitors of CYP3A4 may increase the plasma concentrations of amlodipine. Amlodipine should be used with caution together with CYP3A4 inhibitors.

Ritonavir, temsirolimus [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inhibitors may increase blood concentrations of the active moieties, temsirolimus and its metabolite, sirolimus. Therefore, concomitant treatment with agents that have strong CYP3A4 inhibition potential should be avoided.

Ritonavir, tepotinib [2] ---> SmPC of [2] of EMA

Concomitant use of TEPMETKO with dual strong CYP3A and P-gp inhibitors (e.g. itraconazole, ketoconazole, ritonavir, saquinavir, nelfinavir) should be avoided.

Ritonavir, ticagrelor [2] ---> SmPC of [2] of EMA

Co-administration of ticagrelor with strong CYP3A4 inhibitors is contraindicated, as co-administration may lead to a substantial increase in exposure to ticagrelor

Ritonavir, 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.

Ritonavir, 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

Ritonavir, 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

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.

Ritonavir, tricyclic antidepressant

Ritonavir may increase the plasma levels of antidepressant

Ritonavir, trofosfamide

The inhibition of CYP3A4 may increase the formation of a trofosfamide metabolite which is related with nephrotoxicity and CNS toxicity

Ritonavir, ulipristal [2] ---> SmPC of [2] of EMA

Ritonavir, 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

Ritonavir, valproate semisodium

Possible decreased plasma concentrations of anticonvulsant

Ritonavir, valsartan [2] ---> SmPC of [2] of eMC

Co-administration of inhibitors of the uptake transporter OATP1B1/OATP1B3 (eg. rifampin, ciclosporin) or efflux transporter (eg. ritonavir) may increase the systemic exposure to valsartan.

Ritonavir, vandetanib [2] ---> SmPC of [2] of EMA

In healthy subjects, no clinically significant interaction was shown between vandetanib (a single dose of 300 mg) and the potent CYP3A4 inhibitor, itraconazole

Ritonavir, 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

Ritonavir, venetoclax [2] ---> SmPC of [2] of EMA

Concomitant use of venetoclax with strong CYP3A inhibitors at initiation and during the dose-titration phase is contraindicated due to increased risk for TLS

Ritonavir, 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.

Ritonavir, verapamil [2] ---> SmPC of [2] of eMC

Clinically significant interactions have been reported with inhibitors of CYP3A4 causing elevation of plasma levels of verapamil hydrochloride, therefore, patients should be monitored for drug interactions.

Ritonavir, vilanterol ---> SmPC of [umeclidinium/vilanterol] of EMA

Concomitant administration of strong CYP3A4 inhibitors may inhibit the metabolism of, and increase the systemic exposure to, vilanterol. Care is advised

Ritonavir, vinflunine [2] ---> SmPC of [2] of EMA

The concomitant use of vinflunine and potent CYP3A4 inhibitors should be avoided since they may increase vinflunine and DVFL concentrations

Ritonavir, vinorelbine [2] ---> SmPC of [2] of eMC

As vinca-alkaloids are known as substrates for P-glycoprotein, caution should be exercised when combining vinorelbine with strong modulators of this membrane transporter.

Ritonavir, 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.

Ritonavir, ziconotide [2] ---> SmPC of [2] of EMA

Angiotensin converting enzyme inhibitors (e.g., benazepril, lisinopril and moexipril) and HIV protease inhibitors (e.g., ritonavir, saquinavir, indinavir), have no readily apparent effect on plasma ziconotide exposure.

Ritonavir, ziprasidone

The co-administration of ziprasidone with P glycoprotein inhibitors may increase the plasma concentrations of ziprasidone

Ritonavir, 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

Ritonavir-boosted protease inhibitors, trazodone [2] ---> SmPC of [2] of EMA

CYP3A4 inhibitors increase the exposure of lomitapide, with strong inhibitors increasing exposure approximately 27-fold. Concomitant use of Norvir with lomitapide is contraindicated

CONTRAINDICATIONS of Ritonavir (Norvir)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- When ritonavir is used as a pharmacokinetic enhancer of other PIs, consult the SPC of the co-administered protease inhibitor for contraindications

- Ritonavir should not be given as a pharmacokinetic enhancer or as an antiretroviral agent to patients with decompensated liver disease.

- In vitro and in vivo studies have demonstrated that ritonavir is a potent inhibitor of CYP3A-and CYP2D6-mediated biotransformations. The following medicines are contraindicated when used with ritonavir and unless otherwise noted, the contraindication is based on the potential for ritonavir to inhibit metabolism of the co-administered medicinal product, resulting in increased exposure to the co-administered medicinal product and risk of clinically significant adverse effects.

- The enzyme-modulating effect of ritonavir may be dose dependent. For some products, contraindications may be more relevant when ritonavir is used as an antiretroviral agent than when ritonavir is used as a pharmacokinetic enhancer (e.g. rifabutin and voriconazole):

See Table of 4.3 und Section 4.5

https://www.ema.europa.eu/en/documents/product-information/norvir-epar-product-information_en.pdf. 25/10/2023

Rituximab (MabThera)

Breast-feeding, rituximab [2] ---> SmPC of [2] of EMA

As these data are limited and the long-term outcomes of breastfed infants remain unknown, breastfeeding is not recommended while being treated with rituximab and optimally for 6 months following rituximab treatment.

Cyclophosphamide, rituximab [2] ---> SmPC of [2] of EMA

In CLL patients, co-administration with MabThera did not appear to have an effect on the pharmacokinetics of fludarabine or cyclophosphamide. In addition, there was no apparent effect of fludarabine and cyclophosphamide on the pharmacokinetics of MabThera

Fertility, rituximab [2] ---> SmPC of [2] of EMA

Animal studies did not reveal deleterious effects of rituximab on reproductive organs.

Fludarabine, rituximab [2] ---> SmPC of [2] of EMA

Imlifidase [1], rituximab ---> SmPC of [1] of EMA

Recommended time interval after administration of 0.25 mg/kg imlifidase: 4 days

Infection, rituximab [2] ---> SmPC of [2] of EMA

In these patients the rate of clinically relevant infection while on MabThera was 6.01 per 100 patient years compared to 4.97 per 100 patient years following treatment with the biologic DMARD.

Methotrexate, rituximab [2] ---> SmPC of [2] of EMA

Co-administration with methotrexate had no effect on the pharmacokinetics of MabThera in rheumatoid arthritis patients.

Monoclonal antibodies, rituximab [2] ---> SmPC of [2] of EMA

Patients with human anti-mouse antibody (HAMA) or anti-drug antibody (ADA) titres may have allergic or hypersensitivity reactions when treated with other diagnostic or therapeutic monoclonal antibodies.

Pregnancy, rituximab [2] ---> SmPC of [2] of EMA

MabThera should not be administered to pregnant women unless the possible benefit outweighs the potential risk.

Rituximab [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

The safety of immunisation with live viral vaccines, following MabThera therapy has not been studied for NHL and CLL patients and vaccination with live virus vaccines is not recommended.

Rituximab [1], women of childbearing potential ---> SmPC of [1] of EMA

Due to the long retention time of rituximab in B cell depleted patients, women of childbearing potential should use effective contraceptive methods during and for 12 months following treatment with MabThera.

Rituximab, vedolizumab [2] ---> SmPC of [2] of EMA

No vedolizumab clinical trial data are available for patients previously treated with natalizumab or rituximab. Caution should be exercised when considering the use of Entyvio in these patients.

CONTRAINDICATIONS of Rituximab (MabThera)

Contraindications for use in non-Hodgkin's lymphoma and chronic lymphocytic leukaemia

- Hypersensitivity to the active substance or to murine proteins, or to any of the other excipients listed in section 6.1.

- Active, severe infections (see section 4.4).

- Patients in a severely immunocompromised state.

Contraindications for use in rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis and pemphigus vulgaris

- Hypersensitivity to the active substance or to murine proteins, or to any of the other excipients listed in section 6.1.

- Active, severe infections (see section 4.4).

- Patients in a severely immunocompromised state.

- Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease (see section 4.4 regarding other cardiovascular diseases).

https://www.ema.europa.eu/en/documents/product-information/mabthera-epar-product-information_en.pdf 06/05/2025

Other trade names: Blitzima, Ritemvia, Rituzena (previously Tuxella), Rixathon, Riximyo, Ruxience, Truxima,

Rivaroxaban (Xarelto)

Ability to drive, rivaroxaban [2] ---> SmPC of [2] of EMA

Adverse reactions like syncope (frequency: uncommon) and dizziness (frequency: common) have been reported. Patients experiencing these adverse reactions should not drive or use machines.

Acetylsalicylic acid, rivaroxaban [2] ---> SmPC of [2] of EMA

No clinically significant pharmacokinetic or pharmacodynamic interactions were observed when rivaroxaban was co-administered with 500 mg acetylsalicylic acid.

Anticoagulants, rivaroxaban [2] ---> SmPC of [2] of EMA

Concomitant treatment with any other anticoagulants is contraindicated, except under specific circumstances of switching anticoagulant therapy or when UFH is given at doses necessary to maintain an open central venous or arterial catheter.

Apixaban [1], rivaroxaban ---> SmPC of [1] of EMA

Due to an increased bleeding risk, concomitant treatment of apixaban with any other anticoagulants is contraindicated

Atazanavir/cobicistat [1], rivaroxaban ---> SmPC of [1] of EMA

Co-administration of EVOTAZ and rivaroxaban may result in increased exposure to rivaroxaban and may lead to increased bleeding. The mechanism of interaction is CYP3A4 and P-gp inhibition by cobicistat. Avoid concomitant use of EVOTAZ and rivaroxaban.

Atorvastatin, rivaroxaban [2] ---> SmPC of [2] of EMA

No clinically significant pharmacokinetic or pharmacodynamic interactions were observed when rivaroxaban was co-administered with atorvastatin

Avanafil [1], rivaroxaban ---> SmPC of [1] of EMA

Although specific interactions of avanafil with rivaroxaban and apixaban (both CYP3A4 substrates) have not been studied, an interaction is not expected.

Azole antifungals, rivaroxaban [2] ---> SmPC of [2] of EMA

Therefore, the use of Xarelto is not recommended in patients receiving concomitant systemic treatment with azole-antimycotics such as ketoconazole, itraconazole, voriconazole and posaconazole or HIV protease inhibitors.

Bleeding risk, rivaroxaban [2] ---> SmPC of [2] of EMA

As with other anticoagulants, patients taking Xarelto are to be carefully observed for signs of bleeding. It is recommended to be used with caution in conditions with increased risk of haemorrhage.

Boceprevir, rivaroxaban

The inhibition of the transporters of the P-glycoprotein and breast cancer resistant protein (BCRP) may increase the plasma concentrations of boceprevir.

Breast-feeding, rivaroxaban [2] ---> SmPC of [2] of EMA

Xarelto is contraindicated during breast feeding. A decision must be made whether to discontinue breast feeding or to discontinue/abstain from therapy.

Carbamazepine, rivaroxaban [2] ---> SmPC of [2] of EMA

Clarithromycin, rivaroxaban [2] ---> SmPC of [2] of EMA

The interaction with clarithromycin is likely not clinically relevant in most patients but can be potentially significant in high-risk patients. (For patients with renal impairment: see section 4.4).

Clopidogrel, rivaroxaban [2] ---> SmPC of [2] of EMA

Clopidogrel (300 mg loading dose followed by 75 mg maintenance dose) did not show a pharmacokinetic interaction with rivaroxaban (15 mg) but a relevant increase in bleeding time was observed in a subset of patients

Cobicistat [1], rivaroxaban ---> SmPC of [1] of EMA

Inhibition of CYP3A and intestinal P-gp may lead to increased plasma levels and pharmacodynamic effects of rivaroxaban which may lead to an increased bleeding risk.

CYP3A4 and P-glycoprotein-inhibitors, rivaroxaban [2] ---> SmPC of [2] of EMA

Cytochrome P450, rivaroxaban [2] ---> SmPC of [2] of EMA

Rivaroxaban neither inhibits nor induces any major CYP isoforms like CYP3A4.

Dabigatran etexilate [1], rivaroxaban ---> SmPC of [1] of EMA

Concomitant treatment of dabigatran with any other anticoagulants is contraindicated, except under specific circumstances of switching anticoagulant therapy or when UFH is given at doses necessary to maintain an open central venous or arterial catheter

Dalteparin, rivaroxaban [2] ---> SmPC of [2] of EMA

Darunavir/cobicistat [1], rivaroxaban ---> SmPC of [1] of EMA

Co-administration of REZOLSTA with this anticoagulant may increase concentrations of the anticoagulant. (CYP3A and/or P-glycoprotein inhibition). Co-administration of REZOLSTA and this anticoagulant is not recommended.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], rivaroxaban ---> SmPC of [1] of EMA

Based on theoretical considerations co-administration of DRV/COBI with this anticoagulant may increase concentrations of the anticoagulant. (CYP3A and/or P-glycoprotein inhibition). Co-administration of Symtuza and this anticoagulant is not recommended.

Darunavir/ritonavir, rivaroxaban ---> SmPC of [darunavir] of EMA

Co-administration of boosted darunavir (CYP3A and/or P-gp inhibition) with this anticoagulant may increase concentrations of the anticoagulant. The use of boosted darunavir and the anticoagulant is not recommended.

Defibrotide [1], rivaroxaban ---> SmPC of [1] of EMA

The use of defibrotide with antithrombotic/fibrinolytic medicinal products is not recommended. However, if used, in exceptional cases, caution should be exercised by closely monitoring the coagulation parameters (see section 4.4).

Digoxin, rivaroxaban [2] ---> SmPC of [2] of EMA

No clinically significant pharmacokinetic or pharmacodynamic interactions were observed when rivaroxaban was co-administered with digoxin

Dronedarone, rivaroxaban [2] ---> SmPC of [2] of EMA

Given the limited clinical data available with dronedarone, co-administration with rivaroxaban should be avoided.

Enoxaparin, rivaroxaban [2] ---> SmPC of [2] of EMA

Enoxaparin did not affect the pharmacokinetics of rivaroxaban. Due to the increased bleeding risk care is to be taken if patients are treated concomitantly with any other anticoagulants (see sections 4.3 and 4.4).

Erythromycin, rivaroxaban [2] ---> SmPC of [2] of EMA

The interaction with erythromycin is likely not clinically relevant in most patients but can be potentially significant in high-risk patients.

Fertility, rivaroxaban [2] ---> SmPC of [2] of EMA

No specific studies with rivaroxaban in humans have been conducted to evaluate effects on fertility. In a study on male and female fertility in rats no effects were seen (see section 5.3).

Fluconazole, rivaroxaban [2] ---> SmPC of [2] of EMA

The interaction with fluconazole is likely not clinically relevant in most patients but can be potentially significant in high risk patients. (For patients with renal impairment: see section 4.4).

Fondaparinux, rivaroxaban [2] ---> SmPC of [2] of EMA

Foods, rivaroxaban [2] ---> SmPC of [2] of EMA

No clinically relevant interaction with food was observed (see section 4.2).

Haemostasis, rivaroxaban [2] ---> SmPC of [2] of EMA

Care is to be taken if patients are treated concomitantly with medicinal products affecting haemostasis such as non-steroidal anti-inflammatory medicinal products

Itraconazol, rivaroxaban [2] ---> SmPC of [2] of EMA

Ketoconazole, rivaroxaban [2] ---> SmPC of [2] of EMA

Co-administration of rivaroxaban with ketoconazole (400 mg once a day) or ritonavir (600 mg twice a day) led to a 2.6 fold / 2.5 fold increase in mean rivaroxaban AUC and a 1.7 fold / 1.6 fold increase in mean rivaroxaban Cmax

Laboratory, rivaroxaban [2] ---> SmPC of [2] of EMA

Clotting parameters (e.g. PT, aPTT, HepTest) are affected as expected by the mode of action of rivaroxaban (see section 5.1).

Lenacapavir [1], rivaroxaban ---> SmPC of [1] of EMA

Plasma concentration of DOAC may be increased when co-administered with lenacapavir. Due to potential bleeding risk, dose adjustment of DOAC may be required.

Lopinavir/ritonavir [1], rivaroxaban ---> SmPC of [1] of EMA

The inhibition of CYP3A4 and P-gp by lopinavir/ritonavir may increase the rivaroxaban plasma levels and the bleeding risk. The combination is not recommended

Low molecular weight heparins, rivaroxaban [2] ---> SmPC of [2] of EMA

Midazolam, rivaroxaban [2] ---> SmPC of [2] of EMA

No clinically significant pharmacokinetic or pharmacodynamic interactions were observed when rivaroxaban was co-administered with midazolam (substrate of CYP3A4)

Naproxen, rivaroxaban [2] ---> SmPC of [2] of EMA

No clinically relevant prolongation of bleeding time was observed after concomitant administration of rivaroxaban and naproxen. Nevertheless, there may be individuals with a more pronounced pharmacodynamic response.

Neoplasia, rivaroxaban [2] ---> SmPC of [2] of EMA

In patients with malignant neoplasms at high risk of bleeding, the use of rivaroxaban is contraindicated (see section 4.3).

Nirmatrelvir/ritonavir [1], rivaroxaban ---> SmPC of [1] of EMA

NSAID, rivaroxaban [2] ---> SmPC of [2] of EMA

Care is to be taken if patients are treated concomitantly with NSAIDs (including acetylsalicylic acid) and platelet aggregation inhibitors because these medicinal products typically increase the bleeding risk (see section 4.4).

Omeprazole, rivaroxaban [2] ---> SmPC of [2] of EMA

No clinically significant pharmacokinetic or pharmacodynamic interactions were observed when rivaroxaban was co-administered with omeprazole (proton pump inhibitor).

Parecoxib [1], rivaroxaban ---> SmPC of [1] of EMA

The concomitant use of NSAIDs with oral anticoagulants increases the risk of bleeding. Oral anticoagulants include warfarin/coumarin-type and novel oral anticoagulants (e.g. apixaban, dabigatran, and rivaroxaban)

Patiromer [1], rivaroxaban ---> SmPC of [1] of EMA

In vitro studies have shown no potential interaction of patiromer with the other active substances

Pazopanib, rivaroxaban

Care should be taken when pazopanib (BCRP and P-gp inhibitor) is co-administered with other oral BCRP and P-gp substrates

Phenobarbital, rivaroxaban [2] ---> SmPC of [2] of EMA

Phenytoin, rivaroxaban [2] ---> SmPC of [2] of EMA

Platelet aggregation inhibitors, rivaroxaban [2] ---> SmPC of [2] of EMA

Posaconazole, rivaroxaban [2] ---> SmPC of [2] of EMA

Pregnancy, rivaroxaban [2] ---> SmPC of [2] of EMA

Due to the potential reproductive toxicity, the intrinsic risk of bleeding and the evidence that rivaroxaban passes the placenta, Xarelto is contraindicated during pregnancy

Protease inhibitors, rivaroxaban [2] ---> SmPC of [2] of EMA

Rifampicin, rivaroxaban [2] ---> SmPC of [2] of EMA

Ritonavir [1], rivaroxaban ---> SmPC of [1] of EMA

Ritonavir, rivaroxaban [2] ---> SmPC of [2] of EMA

Rivaroxaban [1], SSNRI ---> SmPC of [1] of EMA

As with other anticoagulants the possibility may exist that patients are at increased risk of bleeding in case of concomitant use with SSRIs or SNRIs due to their reported effect on platelets.

Rivaroxaban [1], SSRI ---> SmPC of [1] of EMA

As with other anticoagulants the possibility may exist that patients are at increased risk of bleeding in case of concomitant use with SSRIs or SNRIs due to their reported effect on platelets.

Rivaroxaban [1], St. John's wort ---> SmPC of [1] of EMA

Rivaroxaban [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Rivaroxaban [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Active substances strongly inhibiting only one of the rivaroxaban elimination pathways, either CYP3A4 or P-gp, are expected to increase rivaroxaban plasma concentrations to a lesser extent.

Rivaroxaban [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

Active substances strongly inhibiting only one of the rivaroxaban elimination pathways, either CYP3A4 or P-gp, are expected to increase rivaroxaban plasma concentrations to a lesser extent.

Rivaroxaban [1], unfractionated heparins ---> SmPC of [1] of EMA

Rivaroxaban [1], voriconazole ---> SmPC of [1] of EMA

Rivaroxaban [1], warfarin ---> SmPC of [1] of EMA

Rivaroxaban [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of child bearing potential should avoid becoming pregnant during treatment with rivaroxaban.

Rivaroxaban, sugammadex [2] ---> SmPC of [2] of EMA

In in vitro experiments a pharmacodynamic interaction (aPTT and PT prolongation) was noted with vitamin K antagonists, unfractionated heparin, low molecular weight heparinoids, rivaroxaban and dabigatran (see section 4.4).

CONTRAINDICATIONS of Rivaroxaban (Xarelto)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Active clinically significant bleeding.

- Lesion or condition, if considered to be a significant risk for major bleeding. This may include current or recent gastrointestinal ulceration, presence of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities.

- Concomitant treatment with any other anticoagulants e.g. unfractionated heparin (UFH), low molecular weight heparins (enoxaparin, dalteparin, etc.), heparin derivatives (fondaparinux, etc.), oral anticoagulants (warfarin, dabigatran etexilate, apixaban, etc.) except under specific circumstances of switching anticoagulant therapy (see section 4.2) or when UFH is given at doses necessary to maintain an open central venous or arterial catheter

- Concomitant treatment of ACS with antiplatelet therapy in patients with a prior stroke or a transient ischaemic attack (TIA)

- Concomitant treatment of CAD/PAD with ASA in patients with previous haemorrhagic or lacunar stroke, or any stroke within a month (see section 4.4).

- Hepatic disease associated with coagulopathy and clinically relevant bleeding risk including cirrhotic patients with Child Pugh B and C

- Pregnancy and breast feeding

https://www.ema.europa.eu/en/documents/product-information/xarelto-epar-product-information_en.pdf 12/09/2024

Other trade names: Rivaroxaban Accord, Rivaroxaban Viatris (previously Rivaroxaban Mylan),

Rivastigmine (Prometax)

Ability to drive, rivastigmine [2] ---> SmPC of [2] of EMA

Rivastigmine can induce dizziness and somnolence, mainly when initiating treatment or increasing the dose. As a consequence, rivastigmine has minor or moderate influence on the ability to drive and use machines.

Amisulpride, rivastigmine [2] ---> SmPC of [2] of EMA

The combination of rivastigmine with QT prolongation- or torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Anticholinergics, rivastigmine [2] ---> SmPC of [2] of EMA

Rivastigmine might interfere with the activity of anticholinergic medicinal products (e.g oxybutynin, tolterodine).

Atenolol, rivastigmine [2] ---> SmPC of [2] of EMA

Additive effects leading to bradycardia (which may result in syncope) have been reported with the combined use of various beta-blockers (including atenolol) and rivastigmine.

Benzamides, rivastigmine [2] ---> SmPC of [2] of EMA

The combination of rivastigmine with QT prolongation- or torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Betablockers, rivastigmine [2] ---> SmPC of [2] of EMA

Caution should be exercised when rivastigmine is combined with beta-blockers and also other bradycardia agents

Breast-feeding, rivastigmine [2] ---> SmPC of [2] of EMA

Women on rivastigmine should not breast-feed.

Butyrylcholinesterase, rivastigmine [2] ---> SmPC of [2] of EMA

According to its metabolism, metabolic interactions with other medicinal products appear unlikely, although rivastigmine may inhibit the butyrylcholinesterase mediated metabolism of other substances.

Calcium antagonists, rivastigmine [2] ---> SmPC of [2] of EMA

Caution should be exercised when rivastigmine is combined with beta-blockers and also other bradycardia agents

Carteolol, rivastigmine

Risk of excessive bradycardia (addition of bradycardic effects)

Chlorpromazine, rivastigmine [2] ---> SmPC of [2] of EMA

The combination of rivastigmine with QT prolongation- or torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Cholinergic agents, rivastigmine [2] ---> SmPC of [2] of EMA

In view of its pharmacodynamic effects and possible additive effects, rivastigmine should not be given concomitantly with other cholinomimetic substances. Rivastigmine might interfere with the activity of anticholinergic medicinal products

Cholinomimetics, rivastigmine [2] ---> SmPC of [2] of EMA

In view of its pharmacodynamic effects and possible additive effects, rivastigmine should not be given concomitantly with other cholinomimetic substances.

Cisapride, rivastigmine [2] ---> SmPC of [2] of EMA

The combination of rivastigmine with QT prolongation- or torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Citalopram, rivastigmine [2] ---> SmPC of [2] of EMA

The combination of rivastigmine with QT prolongation- or torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Class III antiarrhythmic agents, rivastigmine [2] ---> SmPC of [2] of EMA

Caution should be exercised when rivastigmine is combined with beta-blockers and also other bradycardia agents

Depolarizing muscle relaxants, rivastigmine [2] ---> SmPC of [2] of EMA

As a cholinesterase inhibitor, rivastigmine may exaggerate the effects of succinylcholine-type muscle relaxants during anaesthesia.

Digital glycosides, rivastigmine [2] ---> SmPC of [2] of EMA

Caution should be exercised when rivastigmine is combined with beta-blockers and also other bradycardia agents

Digoxin, rivastigmine [2] ---> SmPC of [2] of EMA

No untoward effects on cardiac conduction were observed following concomitant administration of digoxin and rivastigmine.

Diphemanil, rivastigmine [2] ---> SmPC of [2] of EMA

The combination of rivastigmine with QT prolongation- or torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Droperidol, rivastigmine [2] ---> SmPC of [2] of EMA

The combination of rivastigmine with QT prolongation- or torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Drugs inducing bradycardia, rivastigmine [2] ---> SmPC of [2] of EMA

Caution should be exercised when rivastigmine is combined with beta-blockers and also other bradycardia agents

Fertility, rivastigmine [2] ---> SmPC of [2] of EMA

No adverse effects of rivastigmine were observed on fertility or reproductive performance in rats (see section 5.3). Effects of rivastigmine on human fertility are not known.

Foods, rivastigmine [2] ---> SmPC of [2] of EMA

Administration of rivastigmine with food delays absorption (tmax) by 90 min and lowers Cmax and increases AUC by approximately 30%.

Galantamine [1], rivastigmine ---> SmPC of [1] of eMC

Because of its mechanism of action, galantamine should not be given concomitantly with other cholinomimetics

Halofantrine, rivastigmine [2] ---> SmPC of [2] of EMA

The combination of rivastigmine with QT prolongation- or torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Haloperidol, rivastigmine [2] ---> SmPC of [2] of EMA

The combination of rivastigmine with QT prolongation- or torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Hydroquinidine, rivastigmine

Risk excessive bradycardia due to the bradycardic effects of both active ingredients may be additive

Levomepromazine, rivastigmine [2] ---> SmPC of [2] of EMA

The combination of rivastigmine with QT prolongation- or torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Metabolised by plasma cholinesterase, rivastigmine [2] ---> SmPC of [2] of EMA

Rivastigmine may inhibit the butyrylcholinesterase mediated metabolism of other substances.

Methadone, rivastigmine [2] ---> SmPC of [2] of EMA

The combination of rivastigmine with QT prolongation- or torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Mizolastine, rivastigmine [2] ---> SmPC of [2] of EMA

The combination of rivastigmine with QT prolongation- or torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Moxifloxacin, rivastigmine [2] ---> SmPC of [2] of EMA

The combination of rivastigmine with QT prolongation- or torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Oxybutynine, rivastigmine [2] ---> SmPC of [2] of EMA

Rivastigmine might interfere with the activity of anticholinergic medicinal products (e.g oxybutynin, tolterodine).

Pasireotide [1], rivastigmine ---> SmPC of [1] of EMA

Clinical monitoring of heart rate, notably at the beginning of treatment, is recommended in patients receiving pasireotide concomitantly with bradycardic medicinal products

Pentamidine, rivastigmine [2] ---> SmPC of [2] of EMA

The combination of rivastigmine with QT prolongation- or torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Pharmacokinetics, rivastigmine [2] ---> SmPC of [2] of EMA

No pharmacokinetic interaction was observed between rivastigmine and digoxin, warfarin, diazepam or fluoxetine in studies in healthy volunteers. The increase in prothrombin time induced by warfarin is not affected by administration of rivastigmine.

Pilocarpine, rivastigmine [2] ---> SmPC of [2] of EMA

Caution should be exercised when rivastigmine is combined with beta-blockers and also other bradycardia agents

Pimozide, rivastigmine [2] ---> SmPC of [2] of EMA

The combination of rivastigmine with QT prolongation- or torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Pregnancy, rivastigmine [2] ---> SmPC of [2] of EMA

Rivastigmine should not be used during pregnancy unless clearly necessary.

QT interval prolonging drugs, rivastigmine [2] ---> SmPC of [2] of EMA

The combination of rivastigmine with QT prolongation- or torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Rivastigmine [1], succinylcholine ---> SmPC of [1] of EMA

As a cholinesterase inhibitor, rivastigmine may exaggerate the effects of succinylcholine-type muscle relaxants during anaesthesia.

Rivastigmine [1], sulpiride ---> SmPC of [1] of EMA

The combination of rivastigmine with QT prolongation- or torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Rivastigmine [1], sultopride ---> SmPC of [1] of EMA

The combination of rivastigmine with QT prolongation- or torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Rivastigmine [1], tiapride ---> SmPC of [1] of EMA

The combination of rivastigmine with QT prolongation- or torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Rivastigmine [1], tolterodine ---> SmPC of [1] of EMA

Rivastigmine might interfere with the activity of anticholinergic medicinal products (e.g oxybutynin, tolterodine).

Rivastigmine [1], torsades de pointes inducing drugs ---> SmPC of [1] of EMA

The combination of rivastigmine with QT prolongation- or torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Rivastigmine [1], veralipride ---> SmPC of [1] of EMA

The combination of rivastigmine with QT prolongation- or torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Rivastigmine [1], warfarin ---> SmPC of [1] of EMA

The increase in prothrombin time induced by warfarin is not affected by administration of rivastigmine.

Rivastigmine, sotalol

Bradycardia-inducing medicinal products enhance the risk of torsades de pointes

CONTRAINDICATIONS of Rivastigmine (Prometax)

- Hypersensitivity to the active substance rivastigmine, to other carbamate derivatives or to any of the excipients listed in section 6.1.

- Previous history of application site reactions suggestive of allergic contact dermatitis with rivastigmine patch (see section 4.4).

https://www.ema.europa.eu/en/documents/product-information/prometax-epar-product-information_en.pdf 10/09/2024

Other trade names: Exelon, Laro, Nimvastid, Nofleban, Rivastigmine 1 A Pharma, Rivastigmine 3M Health Care Ltd, Rivastigmine Actavis, Rivastigmine Hexal, Rivastigmine Sandoz, Rivastigmine Teva,

Rizatriptan

Ability to drive, rizatriptan [2] ---> SmPC of [2] of eMC

Migraine or the treatment may cause somnolence in some patients. Dizziness has also been reported

Breast-feeding, rizatriptan [2] ---> SmPC of [2] of eMC

Caution should be exercised when administering rizatriptan to women who are breast-feeding. Infant exposure should be minimized by avoiding breast-feeding for 24 hours after treatment.

Drugs primarily metabolised by CYP2D6, rizatriptan [2] ---> SmPC of [2] of eMC

The potential for interaction should be considered when rizatriptan is administered to patients taking CYP 2D6 substrates.

Ergot derivatives, rizatriptan [2] ---> SmPC of [2] of eMC

Due to an additive effect, the concomitant use increases the risk of coronary artery vasoconstriction and hypertensive effects. This combination is contraindicated

Ergotamine, rizatriptan [2] ---> SmPC of [2] of eMC

Due to an additive effect, the concomitant use increases the risk of coronary artery vasoconstriction and hypertensive effects. This combination is contraindicated

IMAOs, rizatriptan [2] ---> SmPC of [2] of eMC

Due to a risk of coronary artery vasoconstriction and hypertensive episodes, administration of rizatriptan to patients taking inhibitors of MAO is contraindicated.

Linezolid, rizatriptan [2] ---> SmPC of [2] of eMC

Due to a risk of coronary artery vasoconstriction and hypertensive episodes, administration of rizatriptan to patients taking inhibitors of MAO is contraindicated.

Methysergide, rizatriptan [2] ---> SmPC of [2] of eMC

Due to an additive effect, the concomitant use increases the risk of coronary artery vasoconstriction and hypertensive effects. This combination is contraindicated

Naratriptan, rizatriptan [2] ---> SmPC of [2] of eMC

Due to an additive effect, the concomitant use increases the risk of coronary artery vasoconstriction and hypertensive effects. This combination is contraindicated

Pregnancy, rizatriptan [2] ---> SmPC of [2] of eMC

Rizatriptan should be used during pregnancy only if clearly needed.

Propranolol, rizatriptan [2] ---> SmPC of [2] of eMC

Plasma concentrations of rizatriptan may be increased by concomitant administration of propranolol.

Rizatriptan [1], serotonin agonists ---> SmPC of [1] of eMC

Due to an additive effect, the concomitant use increases the risk of coronary artery vasoconstriction and hypertensive effects. This combination is contraindicated

Rizatriptan [1], SNRIs ---> SmPC of [1] of eMC

There have been reports describing patients with symptoms compatible with serotonin syndrome following the use of serotonin noradrenaline reuptake inhibitors (SNRIs) and triptans.

Rizatriptan [1], SSNRI ---> SmPC of [1] of eMC

There have been reports describing patients with symptoms compatible with serotonin syndrome following the use of serotonin noradrenaline reuptake inhibitors (SNRIs) and triptans.

Rizatriptan [1], SSRI ---> SmPC of [1] of eMC

There have been reports describing patients with symptoms compatible with serotonin syndrome following the use of selective serotonin reuptake inhibitors (SSRIs) and triptans.

Rizatriptan [1], St. John's wort ---> SmPC of [1] of eMC

Undesirable effects may be more common during concomitant use of triptans (5-HT1B/1D agonists) and herbal preparations containing St John's wort (Hypericum perforatum)

Rizatriptan [1], sumatriptan ---> SmPC of [1] of eMC

Due to an additive effect, the concomitant use increases the risk of coronary artery vasoconstriction and hypertensive effects. This combination is contraindicated

Rizatriptan [1], triptans ---> SmPC of [1] of eMC

Due to an additive effect, the concomitant use increases the risk of coronary artery vasoconstriction and hypertensive effects. This combination is contraindicated

Rizatriptan [1], zolmitriptan ---> SmPC of [1] of eMC

Due to an additive effect, the concomitant use increases the risk of coronary artery vasoconstriction and hypertensive effects. This combination is contraindicated

SSNRI, triptans ---> SmPC of [rizatriptan] of eMC

There have been reports describing patients with symptoms compatible with serotonin syndrome following the use of serotonin noradrenaline reuptake inhibitors (SNRIs) and triptans.

CONTRAINDICATIONS of Rizatriptan

- Hypersensitivity to rizatriptan or to any of the excipients.

- Concurrent administration of monoamine oxidase (MAO) inhibitors or use within 2 weeks of discontinuation of MAO inhibitor therapy.

- Rizatriptan is contra-indicated in patients with severe hepatic or severe renal insufficiency.

- It is contra-indicated in patients with a previous cerebrovascular accident (CVA) or transient ischaemic attack (TIA).

- Moderately severe or severe hypertension or untreated mild hypertension.

- Established coronary artery disease, including ischaemic heart disease (angina pectoris, history of myocardial infarction, or documented silent ischaemia), signs and symptoms of ischaemic heart disease, or Prinzmetal's angina.

- Peripheral vascular disease.

- Concomitant use of rizatriptan and ergotamine, ergot derivatives (including methysergide), or other 5-HT1B/1D receptor agonists.

http://www.medicines.org.uk/emc/

Rocuronium

Ability to drive, rocuronium [2] ---> SmPC of [2] of eMC

Since this medicine is used as an adjunct to general anaesthesia, the usual precautionary measures after a general anaesthesia should be taken for ambulatory patients.

Acylamino-penicillins, rocuronium [2] ---> SmPC of [2] of eMC

Recurarisation has been reported after post-operative administration of acylamino-penicillin antibiotics

Aminoglycoside antibiotics, rocuronium [2] ---> SmPC of [2] of eMC

Recurarisation has been reported after post-operative administration of aminoglycoside

Anticholinesterase, rocuronium [2] ---> SmPC of [2] of eMC

Reversal of the block with acetylcholinesterase inhibitors could be inhibited.

Betablockers, rocuronium [2] ---> SmPC of [2] of eMC

The acute administration of a beta-blocker increases rocuronium effects

Breast-feeding, rocuronium [2] ---> SmPC of [2] of eMC

This medicine should be given to lactating women only when the attending physician decides that the benefits outweigh the risks.

Calcium antagonists, rocuronium [2] ---> SmPC of [2] of eMC

Increased rocuronium effects

Carbamazepine, rocuronium [2] ---> SmPC of [2] of eMC

The prior chronic administration of carbamazepine decreases rocuronium effects

Corticosteroids, rocuronium [2] ---> SmPC of [2] of eMC

Long-term concomitant use of corticosteroids and rocuronium in the ICU may result in prolonged duration of neuromuscular block or myopathy

Diuretics, rocuronium [2] ---> SmPC of [2] of eMC

Increased rocuronium effects

Halogenated anaesthetics, rocuronium [2] ---> SmPC of [2] of eMC

Halogenated volatile anaesthetics potentiate the neuromuscular block of rocuronium. The effect only becomes apparent with maintenance dosing

Lidocaine, rocuronium [2] ---> SmPC of [2] of eMC

Rocuronium combined with lidocaine may result in a quicker onset of action of lidocaine.

Lithium, rocuronium [2] ---> SmPC of [2] of eMC

Increased rocuronium effects

Local anaesthetics, rocuronium [2] ---> SmPC of [2] of eMC

Increased rocuronium effects

Magnesium, rocuronium [2] ---> SmPC of [2] of eMC

Recurarisation has been reported after post-operative administration of magnesium salts

Muscle relaxants (non-depolarizing), rocuronium [2] ---> SmPC of [2] of eMC

Administration of other non-depolarising neuromuscular blocking agents in combination with rocuronium may produce attenuation or potentiation of the neuromuscular

Neostigmine, rocuronium

Decreased effect of rocuronium

Phenytoin, rocuronium [2] ---> SmPC of [2] of eMC

The acute administration of phenytoin increases rocuronium effects and the prior chronic administration decreases them.

Polypeptide antibiotics, rocuronium [2] ---> SmPC of [2] of eMC

Recurarisation has been reported after post-operative administration of polypeptide

Pregnancy, rocuronium [2] ---> SmPC of [2] of eMC

Caution should be exercised when prescribing this medicine to pregnant women.

Primidone [1], rocuronium ---> SmPC of [1] of eMC

Primidone therapy may lead to altered pharmacokinetics in concomitantly administered drugs, whose metabolism may be increased and lead to lowered plasma levels and/or a shorter half-life.

Pyridostigmine, rocuronium

Decreased effect of rocuronium

Quinidine, rocuronium [2] ---> SmPC of [2] of eMC

Recurarisation has been reported after post-operative administration of quinidine

Quinine, rocuronium [2] ---> SmPC of [2] of eMC

Recurarisation has been reported after post-operative administration of quinine

Rocuronium [1], succinylcholine ---> SmPC of [1] of eMC

Suxamethonium given after the administration of rocuronium may produce potentiation or attenuation of the neuromuscular blocking effect of rocuronium.

Rocuronium [1], suxamethonium ---> SmPC of [1] of eMC

Suxamethonium given after the administration of rocuronium may produce potentiation or attenuation of the neuromuscular blocking effect of rocuronium.

Rocuronium [1], ureidopenicillin ---> SmPC of [1] of eMC

Increased rocuronium effects

CONTRAINDICATIONS of Rocuronium

- Hypersensitivity to rocuronium or to the bromide ion or to any of the excipients.

http://www.medicines.org.uk/emc/

Roflumilast (Daxas)

Aluminium hydroxide, roflumilast [2] ---> SmPC of [2] of EMA

Co-administration with an antacid (combination of aluminium hydroxide and magnesium hydroxide) did not alter the absorption or pharmacokinetics of roflumilast or its N-oxide.

Antacids, roflumilast [2] ---> SmPC of [2] of EMA

Co-administration with an antacid (combination of aluminium hydroxide and magnesium hydroxide) did not alter the absorption or pharmacokinetics of roflumilast or its N-oxide.

Aprepitant, roflumilast

A transient moderate increase followed by a mild decrease in exposure of immunosuppressants metabolised by CYP3A4 is expected

Breast-feeding, roflumilast [2] ---> SmPC of [2] of EMA

Available pharmacokinetic data in animals have shown excretion of roflumilast or its metabolites in milk. A risk to the breastfed infant cannot be excluded. Roflumilast should not be used during breast-feeding.

Carbamazepine, roflumilast [2] ---> SmPC of [2] of EMA

Cimetidine, roflumilast [2] ---> SmPC of [2] of EMA

A combination of roflumilast with cimetidine might lead to an increase of exposure and persistent intolerability. In this case, roflumilast treatment should be reassessed

Enoxacin, roflumilast [2] ---> SmPC of [2] of EMA

A combination of roflumilast with enoxacin might lead to an increase of exposure and persistent intolerability. In this case, roflumilast treatment should be reassessed

Erythromycin, roflumilast [2] ---> SmPC of [2] of EMA

Clinical interaction studies with CYP3A4 inhibitor erythromycin showed increases of 9% of the total PDE4 inhibitory activity. No dose adjustment is necessary

Ethinyl estradiol, roflumilast [2] ---> SmPC of [2] of EMA

In an interaction study with an oral contraceptive containing gestodene and ethinyl oestradiol, the total PDE4 inhibitory activity was increased by 17%. No dose adjustment is necessary

Ethinylestradiol/gestodene, roflumilast [2] ---> SmPC of [2] of EMA

In an interaction study with an oral contraceptive containing gestodene and ethinyl oestradiol, the total PDE4 inhibitory activity was increased by 17%. No dose adjustment is necessary

Fertility, roflumilast [2] ---> SmPC of [2] of EMA

In a human spermatogenesis study, roflumilast 500 micrograms had no effects on semen parameters or reproductive hormones during the 3-month treatment period and the following 3-month off-treatment period.

Fluvoxamine, roflumilast [2] ---> SmPC of [2] of EMA

A combination of roflumilast with fluvoxamine might lead to an increase of exposure and persistent intolerability. In this case, roflumilast treatment should be reassessed

Gestodene, roflumilast [2] ---> SmPC of [2] of EMA

In an interaction study with an oral contraceptive containing gestodene and ethinyl oestradiol, the total PDE4 inhibitory activity was increased by 17%. No dose adjustment is necessary

Interactions, roflumilast [2] ---> SmPC of [2] of EMA

No interactions were observed with inhaled salbutamol, formoterol, budesonide and oral montelukast, digoxin, warfarin, sildenafil and midazolam.

Ketoconazole, roflumilast [2] ---> SmPC of [2] of EMA

Clinical interaction studies with CYP3A4 inhibitor ketoconazole showed increases of 9% of the total PDE4 inhibitory activity. No dose adjustment is necessary

Magnesium hydroxide, roflumilast [2] ---> SmPC of [2] of EMA

Co-administration with an antacid (combination of aluminium hydroxide and magnesium hydroxide) did not alter the absorption or pharmacokinetics of roflumilast or its N-oxide.

Phenobarbital, roflumilast [2] ---> SmPC of [2] of EMA

Phenytoin, roflumilast [2] ---> SmPC of [2] of EMA

Pregnancy, roflumilast [2] ---> SmPC of [2] of EMA

Roflumilast is not recommended during pregnancy. Roflumilast has been demonstrated to cross the placenta in pregnant rats.

Rifampicin, roflumilast [2] ---> SmPC of [2] of EMA

Roflumilast [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

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

Roflumilast [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing age should be advised to use an effective method of contraception during treatment. Roflumilast is not recommended in women of childbearing potential not using contraception.

Roflumilast, strong CYP1A2 inhibitors

The potent CYP1A2 inhibition may increase the plasma concentrations of roflumilast

Roflumilast, strong CYP3A4 inhibitors

The strong CYP3A4 inhibition may increase the plasma concentrations of roflumilast

CONTRAINDICATIONS of Roflumilast (Daxas)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Moderate or severe hepatic impairment (Child-Pugh B or C)

https://www.ema.europa.eu/en/documents/product-information/daxas-epar-product-information_en.pdf 07/10/2025

Other trade names: Daliresp, Libertek,

Rolapitant (Varuby)

Ability to drive, rolapitant [2] ---> SmPC of [2] of EMA

Varuby has minor influence on the ability to drive and use machines. Dizziness and fatigue may occur following administration of rolapitant

Aprepitant, rolapitant [2] ---> SmPC of [2] of EMA

The efficacy and safety of rolapitant with concurrent use of another NK1 receptor antagonist (e.g. aprepitant and a combination of netupitant and palonosetron hydrochloride) is not established and therefore not recommended (see section 4.4).

BCRP substrates, rolapitant [2] ---> SmPC of [2] of EMA

Rolapitant is an inhibitor of Breast-Cancer-Resistance Protein (BCRP). Increased plasma concentrations of BCRP substrates may result in potential adverse reactions.

Bendamustine, rolapitant [2] ---> SmPC of [2] of EMA

Rolapitant is an inhibitor of Breast-Cancer-Resistance Protein (BCRP). Increased plasma concentrations of BCRP substrates may result in potential adverse reactions.

Breast-feeding, rolapitant [2] ---> SmPC of [2] of EMA

Breast-feeding is not recommended during treatment with Varuby

Caffeine, rolapitant [2] ---> SmPC of [2] of EMA

Rolapitant had no effects on the pharmacokinetics of caffeine (a CYP1A2 substrate) when an oral dose of 200 mg caffeine was administered with a single dose of 180 mg rolapitant on Day 1, and without rolapitant on Day 8 and Day 15.

Carbamazepine, rolapitant [2] ---> SmPC of [2] of EMA

Varuby in patients who require chronic administration of strong inducers (e.g. rifampicin, carbamazepine, enzalutamide, phenytoin) is not recommended

Colchicine, rolapitant [2] ---> SmPC of [2] of EMA

Rolapitant is an inhibitor of P-glycoprotein (P-gp). Clinical monitoring of adverse reactions and, if possible, biological monitoring are recommended when rolapitant is combined with digoxin or with other P-gp substrates

Dabigatran, rolapitant [2] ---> SmPC of [2] of EMA

Dexamethasone, rolapitant [2] ---> SmPC of [2] of EMA

Rolapitant had no significant effects on the pharmacokinetics of dexamethasone when oral dexamethasone was administered on Days 1 to 3 after a single 180 mg dose of rolapitant was co-administered on Day 1.

Dextromethorphan, rolapitant [2] ---> SmPC of [2] of EMA

A 3-fold increase in the exposure of dextromethorphan, a CYP2D6 substrate, was observed 7 days after a single oral dose of rolapitant and may last longer.

Digoxin, rolapitant [2] ---> SmPC of [2] of EMA

Doxorubicine, rolapitant [2] ---> SmPC of [2] of EMA

Rolapitant is an inhibitor of Breast-Cancer-Resistance Protein (BCRP). Increased plasma concentrations of BCRP substrates may result in potential adverse reactions.

Drugs metabolised by CYP2D6, rolapitant [2] ---> SmPC of [2] of EMA

Rolapitant is a moderate CYP2D6 inhibitor. Increased plasma concentration of CYP2D6 substrates may result in potential adverse reactions.

Efavirenz, rolapitant [2] ---> SmPC of [2] of EMA

The effect of moderate inducers (e.g. efavirenz, rifabutin) is not established; therefore, the use of rolapitant in patients already given a moderate inducer is not recommended

Enzalutamide, rolapitant [2] ---> SmPC of [2] of EMA

Varuby in patients who require chronic administration of strong inducers (e.g. rifampicin, carbamazepine, enzalutamide, phenytoin) is not recommended

Fertility, rolapitant [2] ---> SmPC of [2] of EMA

Rolapitant did not affect the fertility or general reproductive performance of male rats. Decreases in the number of corpora lutea and implantation sites were observed in the female rat fertility and early embryonic development study (see section 5.3).

Irinotecan, rolapitant [2] ---> SmPC of [2] of EMA

Rolapitant is an inhibitor of Breast-Cancer-Resistance Protein (BCRP). Increased plasma concentrations of BCRP substrates may result in potential adverse reactions.

Ketoconazole, rolapitant [2] ---> SmPC of [2] of EMA

No clinically significant effect was seen on the pharmacokinetics of rolapitant when ketoconazole, a strong CYP3A4 inhibitor was administered with rolapitant.

Metabolized by CYP2D6 with narrow therapeutic index, rolapitant [2] ---> SmPC of [2] of EMA

Caution should be taken when rolapitant is combined with a medicinal product metabolised by CYP2D6, notably those having a narrow therapeutic margin

Methotrexate, rolapitant [2] ---> SmPC of [2] of EMA

Rolapitant is an inhibitor of Breast-Cancer-Resistance Protein (BCRP). Increased plasma concentrations of BCRP substrates may result in potential adverse reactions.

Metoprolol, rolapitant [2] ---> SmPC of [2] of EMA

Caution should be taken when rolapitant is combined with a medicinal product metabolised by CYP2D6, notably those having a narrow therapeutic margin

Midazolam, rolapitant [2] ---> SmPC of [2] of EMA

A single dose of 180 mg rolapitant had no significant effects on the pharmacokinetics of midazolam compared to oral midazolam 3 mg alone on Day 1, Day 8 and Day 11.

Mitoxantrone, rolapitant [2] ---> SmPC of [2] of EMA

Rolapitant is an inhibitor of Breast-Cancer-Resistance Protein (BCRP). Increased plasma concentrations of BCRP substrates may result in potential adverse reactions.

Moderate CYP3A4 inductors, rolapitant [2] ---> SmPC of [2] of EMA

The effect of moderate inducers (e.g. efavirenz, rifabutin) is not established; therefore, the use of rolapitant in patients already given a moderate inducer is not recommended

OATP1B3 substrates, rolapitant [2] ---> SmPC of [2] of EMA

Caution should be observed when rolapitant is combined with an OATP1B3 substrate (e.g. statins, bosentan, fexofenadine).

Ondansetron, rolapitant [2] ---> SmPC of [2] of EMA

Rolapitant had no significant effects on the pharmacokinetics of intravenous ondansetron when concomitantly administered with a single 180 mg dose of rolapitant on the same day

P-glycoprotein substrates, rolapitant [2] ---> SmPC of [2] of EMA

Phenytoin, rolapitant [2] ---> SmPC of [2] of EMA

Varuby in patients who require chronic administration of strong inducers (e.g. rifampicin, carbamazepine, enzalutamide, phenytoin) is not recommended

Pimozide, rolapitant [2] ---> SmPC of [2] of EMA

Caution should be taken when rolapitant is combined with a medicinal product metabolised by CYP2D6, notably those having a narrow therapeutic margin

Pregnancy, rolapitant [2] ---> SmPC of [2] of EMA

Varuby should not be used during pregnancy unless clearly necessary.

Propafenone, rolapitant [2] ---> SmPC of [2] of EMA

Caution should be taken when rolapitant is combined with a medicinal product metabolised by CYP2D6, notably those having a narrow therapeutic margin

Rifabutin, rolapitant [2] ---> SmPC of [2] of EMA

The effect of moderate inducers (e.g. efavirenz, rifabutin) is not established; therefore, the use of rolapitant in patients already given a moderate inducer is not recommended

Rifampicin, rolapitant [2] ---> SmPC of [2] of EMA

Varuby in patients who require chronic administration of strong inducers (e.g. rifampicin, carbamazepine, enzalutamide, phenytoin) is not recommended

Rifampicin, rolapitant [2] ---> SmPC of [2] of EMA

Concomitant administration of rifampicin, a strong enzyme inducer significantly decreased the systemic exposure to rolapitant and to its active metabolite.

Rolapitant [1], rosuvastatin ---> 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.

Rolapitant [1], St. John's wort ---> SmPC of [1] of EMA

Due to its strong inducing effect, St John's wort is contraindicated with rolapitant

Rolapitant [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Varuby in patients who require chronic administration of strong inducers (e.g. rifampicin, carbamazepine, enzalutamide, phenytoin) is not recommended

Rolapitant [1], sulfasalazine ---> 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.

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

Rolapitant [1], thioridazine ---> 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

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.

Rolapitant [1], UGT1A1 substrates ---> SmPC of [1] of EMA

Rolapitant modestly inhibited UGT1A1 and UGT2B7 in vitro. Therefore, the potential interactions associated with the inhibition of these UGT enzymes in the intestine cannot be excluded.

Rolapitant [1], UGT2B7 substrates ---> SmPC of [1] of EMA

Rolapitant modestly inhibited UGT1A1 and UGT2B7 in vitro. Therefore, the potential interactions associated with the inhibition of these UGT enzymes in the intestine cannot be excluded.

CONTRAINDICATIONS of Rolapitant (Varuby)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- In combination with St John’s wort (see section 4.5)

https://www.ema.europa.eu/en/documents/product-information/varuby-epar-product-information_en.pdf 02/03/2020 (withdrawn)

Romiplostim (Nplate)

Ability to drive, romiplostim [2] ---> SmPC of [2] of EMA

Nplate has moderate influence on the ability to drive and use machines. In clinical trials, mild to moderate, transient bouts of dizziness were experienced by some patients.

Azathioprine, romiplostim [2] ---> SmPC of [2] of EMA

Corticosteroids, danazol, and azathioprine use may be reduced or discontinued when given in combination with romiplostim (see section 5.1).

Breast-feeding, romiplostim [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from romiplostim therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Corticosteroids, romiplostim [2] ---> SmPC of [2] of EMA

Corticosteroids, danazol, and azathioprine use may be reduced or discontinued when given in combination with romiplostim (see section 5.1).

Danazol, romiplostim [2] ---> SmPC of [2] of EMA

Corticosteroids, danazol, and azathioprine use may be reduced or discontinued when given in combination with romiplostim (see section 5.1).

Drugs with high protein binding, romiplostim [2] ---> SmPC of [2] of EMA

The potential interactions of romiplostim with co-administered medicinal products due to binding to plasma proteins remain unknown.

Fertility, romiplostim [2] ---> SmPC of [2] of EMA

There is no data available on fertility.

Other medicinal product, romiplostim [2] ---> SmPC of [2] of EMA

Platelet counts should be monitored when combining romiplostim with other medicinal products for the treatment of ITP in order to avoid platelet counts outside of the recommended range (see section 4.2).

Pregnancy, romiplostim [2] ---> SmPC of [2] of EMA

Romiplostim is not recommended during pregnancy and in women of childbearing potential not using contraception.

Romiplostim [1], treatment of ITP ---> SmPC of [1] of EMA

Medicinal products used in the treatment of ITP in combination with romiplostim in clinical trials included corticosteroids, danazol, and/or azathioprine, intravenous immunoglobulin (IVIG), and anti-D immunoglobulin.

CONTRAINDICATIONS of Romiplostim (Nplate)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or to E. coli derived proteins.

https://www.ema.europa.eu/en/documents/product-information/nplate-epar-product-information_en.pdf 15/10/2025

Romosozumab (Evenity)

Breast-feeding, romosozumab [2] ---> SmPC of [2] of EMA

Romosozumab is not indicated for use in breast-feeding women.

Fertility, romosozumab [2] ---> SmPC of [2] of EMA

No data are available on the effect of romosozumab on human fertility. Animal studies in female and male rats did not show any effects on fertility endpoints (see section 5.3).

Palopegteriparatide [1], romosozumab ---> SmPC of [1] of EMA

Other medicinal products can exert effects on serum calcium and may alter the therapeutic response to Yorvipath. Patients should be monitored for changes in serum calcium when treated concomitantly with these medicinal products.

Pharmacokinetics, romosozumab [2] ---> SmPC of [2] of EMA

No pharmacokinetic drug interactions are expected with romosozumab.

Pregnancy, romosozumab [2] ---> SmPC of [2] of EMA

Romosozumab is not indicated for use in women of child-bearing potential or in pregnant women.

CONTRAINDICATIONS of Romosozumab (Evenity)

- Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1 (see section 4.4)

- Hypocalcaemia (see section 4.4)

- History of myocardial infarction or stroke (see section 4.4)

https://www.ema.europa.eu/en/documents/product-information/evenity-epar-product-information_en.pdf 07/05/2025

Ropeginterferon alfa-2b (Besremi)

Ability to drive, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

Besremi has minor influence on the ability to drive and use machines. Patients who experience dizziness, somnolence or hallucination (see section 4.8) during Besremi therapy should avoid driving or using machines.

Breast-feeding, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast- feeding or to discontinue/abstain from ropeginterferon alfa-2b therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Chemotherapeutic agents, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

Caution must be exercised when administering ropeginterferon alfa-2b in combination with other potentially myelosuppressive/chemotherapeutic agents.

CYP1A2 substrates with narrow therapeutic index, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

Care should be taken when ropeginterferon alfa-2b is co-administered with CYP1A2 substrates notably those having a narrow therapeutic margin such as theophylline or methadone.

Decompensated cirrhosis of the liver, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

Ropeginterferon alfa-2b is contraindicated in patients with decompensated cirrhosis of the liver (see section 4.3).

Drugs metabolised by CYP1A2, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

Ropeginterferon alfa-2b may inhibit the activity of CYP1A2 and CYP2D6 and thus may increase the blood concentrations of these medicinal products.

Drugs metabolised by CYP2C19, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

No dose adaptions for ropeginterferon alfa-2b should be necessary when concomitantly administered with medicinal products metabolised via CYP2C9/19, CYP3A4 or by N-acetyltransferase.

Drugs metabolised by CYP2C9, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

No dose adaptions for ropeginterferon alfa-2b should be necessary when concomitantly administered with medicinal products metabolised via CYP2C9/19, CYP3A4 or by N-acetyltransferase.

Drugs metabolised by CYP2D6, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

Ropeginterferon alfa-2b may inhibit the activity of CYP1A2 and CYP2D6 and thus may increase the blood concentrations of these medicinal products.

Drugs metabolised by CYP3A4, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

No dose adaptions for ropeginterferon alfa-2b should be necessary when concomitantly administered with medicinal products metabolised via CYP2C9/19, CYP3A4 or by N-acetyltransferase.

Eye disorder, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

Discontinuation of ropeginterferon alfa-2b should be considered in patients who develop new or worsening eye disorders.

Fertility, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

There are no data on the effect of ropeginterferon alfa-2b therapy on the fertility of females or males.

Hypnotics, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

Narcotics, hypnotics or sedatives must be administered with caution when used concomitantly with ropeginterferon alfa-2b.

Liver decompensation, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

In patients who develop evidence of hepatic decompensation during treatment, ropeginterferon alfa-2b should be discontinued.

Methadone, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

Care should be taken when ropeginterferon alfa-2b is co-administered with CYP1A2 substrates notably those having a narrow therapeutic margin such as theophylline or methadone.

Myelosuppressive agents, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

Caution must be exercised when administering ropeginterferon alfa-2b in combination with other potentially myelosuppressive/chemotherapeutic agents.

Narcotics, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

Narcotics, hypnotics or sedatives must be administered with caution when used concomitantly with ropeginterferon alfa-2b.

Phlebotomy, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

Phlebotomy as rescue treatment to normalise blood hyperviscosity may be necessary.

Pregnancy, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

As ropeginterferon alfa-2b may have the same effect, Besremi is not recommended during pregnancy and in women of childbearing potential not using contraception.

Renal disease, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

If renal function decreases during treatment, ropeginterferon alfa-2b therapy should be discontinued. Ropeginterferon alfa-2b is contraindicated in patients with end stage renal disease (see section 4.3).

Respiratory system, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

Patients who develop respiratory symptoms should be monitored closely and if necessary, ropeginterferon alfa-2b therapy should be discontinued.

Risperidone, ropeginterferon alfa-2b [2] ---> SmPC of [2] of EMA

Ropeginterferon alfa-2b [1], sedatives ---> SmPC of [1] of EMA

Narcotics, hypnotics or sedatives must be administered with caution when used concomitantly with ropeginterferon alfa-2b.

Ropeginterferon alfa-2b [1], skin disorder ---> SmPC of [1] of EMA

In case of appearance or worsening of this skin disorders, the stop of the treatment must be envisaged.

Ropeginterferon alfa-2b [1], stroke ---> SmPC of [1] of EMA

This medicinal product is contraindicated in patients with severe preexisting cardiovascular disease or patients who had recently suffered from a stroke or myocardial infarction (see section 4.3).

Ropeginterferon alfa-2b [1], teeth ---> SmPC of [1] of EMA

Patients should brush their teeth thoroughly twice daily and have regular dental examinations.

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

Ropeginterferon alfa-2b [1], theophylline ---> SmPC of [1] of EMA

Care should be taken when ropeginterferon alfa-2b is co-administered with CYP1A2 substrates notably those having a narrow therapeutic margin such as theophylline or methadone.

Ropeginterferon alfa-2b [1], vortioxetine ---> SmPC of [1] of EMA

Ropeginterferon alfa-2b [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential must use effective contraception during the treatment with ropeginterferon alfa-2b, unless otherwise discussed with the physician.

CONTRAINDICATIONS of Ropeginterferon alfa-2b (Besremi)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1

- Pre-existing thyroid disease unless it can be controlled with conventional treatment

- Existence of, or history of severe psychiatric disorders, particularly severe depression, suicidal ideation or suicide attempt

- Severe pre-existing cardiovascular disease, (i.e. uncontrolled hypertension, congestive heart failure (≥ NYHA class 2), serious cardiac arrhythmia, significant coronary artery stenosis, unstable angina) or recent stroke or myocardial infarction

- History or presence of autoimmune disease

- Immunosuppressed transplant recipients

- Combination with telbivudine (see section 4.5)

- Decompensated cirrhosis of the liver (Child-Pugh B or C)

- End stage renal disease (GFR <15 mL/min)

https://www.ema.europa.eu/en/documents/product-information/besremi-epar-product-information_en.pdf 24/10/2025

Ropinirole

Ability to drive, ropinirole [2] –––> SmPC of [2] of eMC

Somnolence and/or sudden sleep episodes may occur

Alcohol, ropinirole

It is recommended to avoid alcohol use

Amisulpride [1], ropinirole –––> SmPC of [1] of eMC

Amisulpride may oppose the effect of dopamine agonists. The combination is contraindicated

Breast–feeding, ropinirole [2] –––> SmPC of [2] of eMC

Ropinirole should not be used in nursing mothers as it may inhibit lactation.

Chlorpromazine [1], ropinirole –––> SmPC of [1] of eMC

Reciprocal antagonism of dopaminergic antiparkinsonian agent and chlorpromazine. The combination is not recommended

Cimetidine, ropinirole

The CYP1A2 inhibition may increase plasma concentrations of ropinirol

Ciprofloxacin, ropinirole [2] –––> SmPC of [2] of eMC

Ropinirole is principally metabolised by the CYP1A2. A pharmacokinetic study revealed that ciprofloxacin increased the Cmax and AUC of ropinirole by 60% and 84% respectively, with a potential risk of adverse events.

CYP1A2 inhibitors, ropinirole [2] –––> SmPC of [2] of eMC

Domperidone, ropinirole

Domperidone antagonises the dopaminergic actions of ropinirole peripherally

Dopamine antagonists, ropinirole [2] –––> SmPC of [2] of eMC

Neuroleptics and other centrally active dopamine antagonists, such as sulpiride or metoclopramide, may diminish the effectiveness of ropinirole and therefore, concomitant use of these medicinal products should be avoided.

Drugs primarily metabolised by CYP1A2, ropinirole

It is unlikely that ropinirol competes with the metabolism of other drugs metabolized by CYP1A2

Enoxacin, ropinirole [2] –––> SmPC of [2] of eMC

The CYP1A2 inhibition may increase plasma concentrations of ropinirol

Estrogens, ropinirole [2] –––> SmPC of [2] of eMC

Increased plasma concentrations of ropinirole have been observed in patients treated with high doses of oestrogens.

Fluvoxamine [1], ropinirole –––> SmPC of [1] of eMC

As plasma concentrations of ropinirole may be increased in combination with fluvoxamine thus increasing the risk of overdose

Levomepromazine, ropinirole

Due to the possibility of mutual antagonism, the co–administration is contraindicated except in case of Parkinson disease

Metoclopramide, ropinirole [2] –––> SmPC of [2] of eMC

Neuroleptics, ropinirole [2] –––> SmPC of [2] of eMC

Nicotine [1], ropinirole –––> SmPC of [1] of eMC

Smoking but not nicotine is associated with increased CYP1A2 activity. After stopping smoking there may be increased plasma levels of some medicinal products of potential clinical importance because of their narrow therapeutic window

Niraparib [1], ropinirole –––> 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).

Norfloxacin, ropinirole [2] –––> SmPC of [2] of eMC

The CYP1A2 inhibition may increase plasma concentrations of ropinirol

Pregnancy, ropinirole [2] –––> SmPC of [2] of eMC

It is recommended that ropinirole is not used during pregnancy unless the potential benefit to the patient outweighs the potential risk to the foetus.

Ropinirole [1], strong CYP1A2 inhibitors –––> SmPC of [1] of eMC

Ropinirole [1], sulpiride –––> SmPC of [1] of eMC

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.

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

Ropinirole, vitamin K antagonists

Cases of INR imbalance have been reported in patients receiving ropinirol and vitamin K antagonists

CONTRAINDICATIONS of Ropinirole

– Hypersensitivity to the active substance or to any of the excipients

– Severe renal impairment (creatinine clearance < 30 ml/min) without regular haemodialysis.

– Hepatic impairment

http://www.medicines.org.uk/emc/

Ropivacaine

Ability to drive, ropivacaine [2] ---> SmPC of [2] of eMC

Depending on the dose, local anaesthetics may have a minor influence on mental function and co-ordination even in the absence of overt CNS toxicity and may temporarily impair locomotion and alertness.

Breast-feeding, ropivacaine [2] ---> SmPC of [2] of eMC

There are no data available concerning the excretion of ropivacaine into human milk.

Class III antiarrhythmic agents, ropivacaine [2] ---> SmPC of [2] of eMC

Specific interaction studies with ropivacaine and anti-arrhythmic drugs class III (e.g. amiodarone) have not been performed, but caution is advised

Enoxacin, ropivacaine [2] ---> SmPC of [2] of eMC

The strong CYP1A2 inhibition may decrease the plasma clearance of ropivacaine. Prolonged administration of ropivacaine with strong CYP1A2 inhibitors should be avoided

Fluvoxamine, ropivacaine [2] ---> SmPC of [2] of eMC

The strong CYP1A2 inhibition may decrease the plasma clearance of ropivacaine. Prolonged administration of ropivacaine with strong CYP1A2 inhibitors should be avoided

General anesthetics, ropivacaine [2] ---> SmPC of [2] of eMC

Simultaneous use of ropivacaine with general anaesthetics may potentiate each others (adverse) effects

Lidocaine, ropivacaine [2] ---> SmPC of [2] of eMC

Ropivacaine should be used with caution in patients receiving agents structurally related to amide-type local anaesthetics, since the systemic toxic effects are additive.

Local anaesthetics, ropivacaine [2] ---> SmPC of [2] of eMC

Ropivacaine should be used with caution in patients receiving other local anaesthetics, since the systemic toxic effects are additive.

Mexiletine, ropivacaine [2] ---> SmPC of [2] of eMC

Ropivacaine should be used with caution in patients receiving agents structurally related to amide-type local anaesthetics, since the systemic toxic effects are additive.

Opiates, ropivacaine [2] ---> SmPC of [2] of eMC

Simultaneous use of ropivacaine with opioids may potentiate each others (adverse) effects

Pregnancy, ropivacaine [2] ---> SmPC of [2] of eMC

Apart from epidural administration for obstetrical use, there are no adequate data on the use of ropivacaine in human pregnancy

Ropivacaine [1], strong CYP1A2 inhibitors ---> SmPC of [1] of eMC

The strong CYP1A2 inhibition may decrease the plasma clearance of ropivacaine. Prolonged administration of ropivacaine with strong CYP1A2 inhibitors should be avoided

CONTRAINDICATIONS of Ropivacaine

- Hypersensitivity to ropivacaine or to other local anaesthetics of the amide type.

- General contraindications related to epidural anaesthesia, regardless of the local anaesthetic used, should be taken into account.

- Intravenous regional anaesthesia.

- Obstetric paracervical anaesthesia.

- Hypovolaemia.

http://www.medicines.org.uk/emc/

Rosiglitazone (Avandia)

Ability to drive, rosiglitazone/glimepiride [2] ---> SmPC of [2] of EMA

The potential for hypoglycaemia should be borne in mind

Alcohol, rosiglitazone [2] ---> SmPC of [2] of EMA

Moderate ingestion of alcohol with rosiglitazone has no effect on glycaemic control.

Avanafil [1], rosiglitazone ---> SmPC of [1] of EMA

Further clinical studies using omeprazole, rosiglitazone and desipramine did not reveal clinically relevant interactions with CYPs 2C19, 2C8/9 and 2D6.

Breast-feeding, rosiglitazone [2] ---> SmPC of [2] of EMA

Should not be used during lactation

Breast-feeding, rosiglitazone/glimepiride [2] ---> SmPC of [2] of EMA

Should not be used during lactation

Breast-feeding, rosiglitazone/metformin [2] ---> SmPC of [2] of EMA

Should not be used during lactation

Carbamazepine, rosiglitazone [2] ---> SmPC of [2] of EMA

It cannot be excluded that other inducers (e.g. phenytoin, carbamazepine, phenobarbital, St John's wort) may also affect rosiglitazone exposure. The rosiglitazone dose may need to be increased. Close monitoring of glycaemic control should be considered

CYP2C8 inductors, rosiglitazone [2] ---> SmPC of [2] of EMA

CYP2C8 inhibitors, rosiglitazone [2] ---> SmPC of [2] of EMA

Rosiglitazone should be used with caution during concomitant administration of CYP2C8 inhibitors (e.g. gemfibrozil). Glycaemic control should be monitored closely.

CYP2C9 inhibitors, rosiglitazone [2] ---> SmPC of [2] of EMA

Clinically significant interactions with CYP2C9 substrates or inhibitors are not anticipated.

Darunavir/ritonavir, rosiglitazone ---> SmPC of [darunavir] of EMA

Drugs metabolised by CYP2C9, rosiglitazone [2] ---> SmPC of [2] of EMA

Clinically significant interactions with CYP2C9 substrates are not anticipated.

Ethinyl estradiol, rosiglitazone [2] ---> SmPC of [2] of EMA

No clinically relevant interactions with digoxin, the CYP2C9 substrate warfarin, the CYP3A4 substrates nifedipine, ethinylestradiol or norethindrone were observed after co-administration with rosiglitazone.

Febuxostat [1], rosiglitazone ---> SmPC of [1] of EMA

Co-administration of febuxostat with rosiglitazone or other CYP2C8 substrates is not expected to require any dose adjustment for those compounds.

Gemfibrozil, rosiglitazone [2] ---> SmPC of [2] of EMA

Co-administration of rosiglitazone with gemfibrozil (an inhibitor of CYP2C8) resulted in a twofold increase in rosiglitazone plasma concentrations.

Icosapent ethyl [1], rosiglitazone ---> SmPC of [1] of EMA

No interactions were observed.

Ivacaftor [1], rosiglitazone ---> SmPC of [1] of EMA

Ivacaftor has been studied with the CYP2C8 substrate rosiglitazone. No significant effect on rosiglitazone exposure was found. Therefore, no dose adjustment of CYP2C8 substrates such as rosiglitazone is necessary.

Ketoconazole, rosiglitazone

Ketoconazole increases the effect of rosiglitazone

Leflunomide [1], rosiglitazone ---> SmPC of [1] of EMA

Monitoring patients with concomitant use of medicinal products metabolised by CYP2C8, such as repaglinide, paclitaxel, pioglitazone or rosiglitazone, is recommended as they may have higher exposure.

Metformin, rosiglitazone [2] ---> SmPC of [2] of EMA

Concomitant administration with the oral anti-diabetic agents metformin, glibenclamide and acarbose did not result in any clinically relevant pharmacokinetic interactions with rosiglitazone.

Phenobarbital, rosiglitazone [2] ---> SmPC of [2] of EMA

Phenytoin, rosiglitazone [2] ---> SmPC of [2] of EMA

Pirtobrutinib [1], rosiglitazone ---> SmPC of [1] of EMA

Since pirtobrutinib can increase the plasma concentrations of CYP2C8 substrates, caution is advised when co-administering with CYP2C8 substrates (e.g. repaglinide, dasabuvir, selexipag, rosiglitazone, pioglitazone, and montelukast).

Pixantrone [1], rosiglitazone ---> SmPC of [1] of EMA

Although a risk to inhibition of pixantrone towards CYP2C8 could not be ascertained, caution should be observed when co-administering substances that are primarily metabolised via CYP2C8

Pregnancy, rosiglitazone [2] ---> SmPC of [2] of EMA

Rosiglitazone has been reported to cross the human placenta and to be detectable in foetal tissues. It should not be used during pregnancy

Pregnancy, rosiglitazone/glimepiride [2] ---> SmPC of [2] of EMA

Rosiglitazone has been reported to cross the human placenta and to be detectable in foetal tissues. It should not be used during pregnancy

Pregnancy, rosiglitazone/metformin [2] ---> SmPC of [2] of EMA

Rosiglitazone has been reported to cross the human placenta and to be detectable in foetal tissues. It should not be used during pregnancy

Proteolytic enzymes enriched in bromelain [1], rosiglitazone ---> 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

Rifampicin, rosiglitazone [2] ---> SmPC of [2] of EMA

Co-administration of rosiglitazone with rifampicin (an inducer of CYP2C8) resulted in a 66 % decrease in rosiglitazone plasma concentrations.

Rosiglitazone [1], St. John's wort ---> SmPC of [1] of EMA

Rosiglitazone [1], strong CYP2C8 inhibitors ---> SmPC of [1] of EMA

Rosiglitazone should be used with caution during concomitant administration of CYP2C8 inhibitors (e.g. gemfibrozil). Glycaemic control should be monitored closely.

Rosiglitazone, selpercatinib [2] ---> SmPC of [2] of EMA

Rosiglitazone, sitagliptin [2] ---> SmPC of [2] of EMA

In clinical studies, sitagliptin did not meaningfully alter the pharmacokinetics, providing in vivo evidence of a low propensity for causing interactions with substrates of CYP3A4, CYP2C8, CYP2C9, and organic cationic transporter (OCT).

Rosiglitazone, somatropin

Somatropin may antagonize the hypoglycemic effect of rosiglitazone

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.

Rosiglitazone, trimethoprim

The co-administration of trimethoprim may increase the plasma levels of rosiglitazone and enhance its hypoglycemic effect

Rosiglitazone, vismodegib [2] ---> SmPC of [2] of EMA

The systemic exposure of rosiglitazone (a CYP2C8 substrate) is not altered when co-administered with vismodegib. Thus inhibition of CYP enzymes by vismodegib in vivo may be excluded.

Rosiglitazone, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration with vorapaxar did not alter the single-dose pharmacokinetics of rosiglitazone (8 mg), a CYP2C8 substrate.

CONTRAINDICATIONS of Rosiglitazone (Avandia)

Use of rosiglitazone is contraindicated in patients with:

- known hypersensitivity to rosiglitazone or to any of the excipients

- cardiac failure or history of cardiac failure (NYHA class I to IV)

- an Acute Coronary Syndrome (unstable angina, non-ST segment elevation myocardial infarction and ST segment elevation myocardial infarction

- hepatic impairment

- diabetic ketoacidosis or diabetic pre-coma.

https://www.ema.europa.eu/en/documents/product-information/avandia-epar-product-information_en.pdf 08/06/2016 (withdrawn)

Rosuvastatin

Ability to drive, rosuvastatin [2] ---> SmPC of [2] of eMC

When driving vehicles or operating machines, it should be taken into account that dizziness may occur during treatment.

Afatinib [1], rosuvastatin ---> SmPC of [1] of EMA

In vitro studies indicated that afatinib is a substrate and an inhibitor of the transporter BCRP. Afatinib may increase the bioavailability of orally administered BCRP substrates (including but not limited to rosuvastatin and sulfasalazine).

Alcohol, rosuvastatin [2] ---> SmPC of [2] of eMC

Rosuvastatin should be used with caution in patients who consume excessive quantities of alcohol

Algeldrate/magnesium hydroxide, rosuvastatin ---> SmPC of [aluminium oxide/magnesium hydroxide] of eMC

The simultaneous dosing of rosuvastatin with an antacid suspension containing magnesium hydroxide resulted in a decrease in rosuvastatin plasma concentration of approximately 50%.

Aluminium hydroxide, rosuvastatin [2] ---> SmPC of [2] of eMC

The simultaneous dosing of rosuvastatin with an antacid suspension containing aluminium hydroxide resulted in a decrease in rosuvastatin plasma concentration of approximately 50%.

Aluminium oxide/magnesium hydroxide, rosuvastatin

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Antacids, rosuvastatin [2] ---> SmPC of [2] of eMC

The simultaneous dosing of rosuvastatin with an antacid suspension containing magnesium hydroxide resulted in a decrease in rosuvastatin plasma concentration of approximately 50%.

Ataluren [1], rosuvastatin ---> SmPC of [1] of EMA

Caution should be exercised when ataluren is co-administered with medicinal products that are substrates of UGT1A9, OAT1, OAT3, or OATP1B3 because of the risk of increase concentration of these medicinal products

Atazanavir/cobicistat [1], rosuvastatin ---> SmPC of [1] of EMA

Concomitant use may increase rosuvastatin exposition. The mechanism of interaction is potential inhibition of the transporter OATP1B1 by cobicistat. The risk of myopathy, including rhabdomyolysis, may be increased.

Atazanavir/ritonavir, rosuvastatin [2] ---> SmPC of [2] of eMC

Increased systemic exposure to rosuvastatin has been observed in subjects receiving rosuvastatin concomitantly with various protease inhibitors in combination with ritonavir.

BCRP inhibitors, rosuvastatin [2] ---> SmPC of [2] of eMC

Concomitant administration of rosuvastatin with medicinal products that are inhibitors of BCRP may result in increased rosuvastatin plasma concentrations and an increased risk of myopathy

Breast-feeding, rosuvastatin [2] ---> SmPC of [2] of eMC

Rosuvastatin is contraindicated in lactation.

Brigatinib [1], rosuvastatin ---> SmPC of [1] of EMA

Coadministration of brigatinib with substrates of P-gp, BCRP may increase their plasma concentrations. Patients should be closely monitored when Alunbrig is coadministered with substrates of these transporters with a narrow therapeutic index

Canagliflozin [1], rosuvastatin ---> SmPC of [1] of EMA

Inhibition of BCRP by canagliflozin cannot be excluded at an intestinal level and increased exposure may therefore occur for medicinal products transported by BCRP, e.g. certain statins like rosuvastatin and some anti-cancer medicinal products.

Canagliflozin/metformin [1], rosuvastatin ---> SmPC of [1] of EMA

Inhibition of BCRP by canagliflozin cannot be excluded at an intestinal level and increased exposure may therefore occur for medicinal products transported by BCRP, e.g., certain statins like rosuvastatin and some anti-cancer medicinal products.

Ceritinib [1], rosuvastatin ---> 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.

Cobicistat [1], rosuvastatin ---> SmPC of [1] of EMA

Plasma concentrations of HMG Co-A reductase inhibitors may be increased when co-administered with cobicistat

Coumarin anticoagulants, rosuvastatin [2] ---> SmPC of [2] of eMC

The co-administration may increase the international normalised ratio (INR). Appropriate monitoring of INR is desirable.

Cyclosporine, rosuvastatin [2] ---> SmPC of [2] of eMC

The co-administration increases significantly the plasma levels of rosuvastatin. The co-administration is contraindicated

Daclatasvir [1], rosuvastatin ---> SmPC of [1] of EMA

Inhibition of OATP 1B1 and BCRP by daclatasvir may increase plasma concentration of rosuvastatin. Caution should be used when daclatasvir is coadministered with rosuvastatin or other substrates of OATP 1B1 or BCRP.

Darunavir/cobicistat [1], rosuvastatin ---> SmPC of [1] of EMA

Concomitant use of a HMG CoA reductase inhibitor and darunavir/cobicistat may increase plasma concentrations of the lipid lowering agent, which may lead to adverse events such as myopathy.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], rosuvastatin ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase these HMG Co-A reductase inhibitor plasma concentrations. CYP3A inhibition and/or transport

Darunavir/ritonavir, rosuvastatin ---> SmPC of [darunavir] of EMA

The co-administration may increase the plasma levels of rosuvastatin

Dasabuvir with ombitasvir/paritaprevir/ritonavir, rosuvastatin ---> SmPC of [dasabuvir] of EMA

OATP1B inhibition by paritaprevir and BCRP inhibition by dasabuvir, paritaprevir, and ritonavir. The maximum daily dose of rosuvastatin should be 5 mg

Digoxin, rosuvastatin [2] ---> SmPC of [2] of eMC

Based on data from specific interaction studies no clinically relevant interaction with digoxin is expected

Efavirenz [1], rosuvastatin ---> SmPC of [1] of EMA

No dose adjustment is necessary for either medicinal product.

Efavirenz/emtricitabine/tenofovir disoproxil [1], rosuvastatin ---> SmPC of [1] of EMA

Atripla and rosuvastatin can be co-administered without dose adjustment.

Elbasvir/grazoprevir [1], rosuvastatin ---> SmPC of [1] of EMA

Intestinal BCRP inhibition. The dose of rosuvastatin should not exceed a daily dose of 10 mg when co-administered with ZEPATIER.

Eltrombopag [1], rosuvastatin ---> SmPC of [1] of EMA

When co-administered with eltrombopag, a reduced dose of statins should be considered and careful monitoring for statin adverse reactions should be undertaken

Eluxadoline [1], rosuvastatin ---> SmPC of [1] of EMA

Eluxadoline increases the exposure of the co-administered OATP1B1 substrate; rosuvastatin by up to 40% of the total exposure which is usually not considered to be clinically relevant.

Eluxadoline [1], rosuvastatin ---> SmPC of [1] of EMA

The effect on other statins which are more sensitive OATP1B1 substrates (e.g. simvastatin and atorvastatin), however, may be more pronounced.

Elvitegravir [1], rosuvastatin ---> SmPC of [1] of EMA

No dose adjustment is required when Vitekta is co-administered with rosuvastatin.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [1], rosuvastatin ---> SmPC of [1] of EMA

Dose modifications are not necessary when rosuvastatin is administered in combination with Genvoya.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], rosuvastatin ---> SmPC of [1] of EMA

Concentrations of rosuvastatin are transiently increased when administered with elvitegravir and cobicistat. Dose modifications are not necessary

Encorafenib [1], rosuvastatin ---> SmPC of [1] of EMA

Agents that are substrates of BCRP (such as methotrexate, rosuvastatin) may have increased exposure and should be therefore co-administered with caution.

Erythromycin, rosuvastatin [2] ---> SmPC of [2] of eMC

Concomitant use of rosuvastatin and erythromycin resulted in a 20% decrease in AUC and a 30% decrease in Cmax of rosuvastatin. This interaction may be caused by the increase in gut motility caused by erythromycin.

Eslicarbazepine [1], rosuvastatin ---> SmPC of [1] of EMA

The co-administration may decrease the systemic exposure of rosuvastatin. The monitoring of response to therapy is recommended.

Ethinyl estradiol, rosuvastatin ---> SmPC of [ethinylestradiol/norgestimate] of eMC

Increase in plasma hormone levels associated with co-administered drug

Ethinylestradiol/norgestimate [1], rosuvastatin ---> SmPC of [1] of eMC

Increase in plasma hormone levels associated with co-administered drug

Etravirine [1], rosuvastatin ---> SmPC of [1] of EMA

Rosuvastatin is metabolised by CYP2C9 and co-administration with etravirine may result in higher plasma concentrations of the HMG Co-A reductase inhibitor. Dose adjustments for this HMG Co-A reductase inhibitor may be necessary.

Ezetimibe, rosuvastatin [2] ---> SmPC of [2] of eMC

Very rare cases of rhabdomyolysis have been reported with the use of ezetimibe in combination with HMG-CoA reductase inhibitors. A pharmacodynamic interaction cannot be excluded and caution should be exercised with their combined use

Fenofibrate, rosuvastatin [2] ---> SmPC of [2] of eMC

Fibrates increase the risk of myopathy when given concomitantly with HMG-CoA reductase inhibitors, probably because they can produce myopathy when given alone. Concomitant use is contraindicated

Fibrates, rosuvastatin [2] ---> SmPC of [2] of eMC

Fibrates increase the risk of myopathy when given concomitantly with HMG-CoA reductase inhibitors, probably because they can produce myopathy when given alone. Concomitant use is contraindicated

Fidaxomicin [1], rosuvastatin ---> SmPC of [1] of EMA

Fidaxomicin does not have a clinically significant effect on the exposure of rosuvastatin, a substrate for the transporters OATP2B1 and BCRP.

Fluconazole, rosuvastatin [2] ---> SmPC of [2] of eMC

No clinically relevant interactions have been observed between rosuvastatin and fluconazole (an inhibitor of CYP2C9 and CYP3A4)

Fusidic acid, rosuvastatin [2] ---> SmPC of [2] of eMC

Combination with rosuvastatin and fusidic acid is not recommended. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving this combination

Gemfibrozil [1], rosuvastatin ---> SmPC of [1] of eMC

One study indicated that the co-administration of a single rosuvastatin dose to healthy volunteers on gemfibrozil resulted in a 2.2-fold increase in mean C max and a 1.9-fold increase in mean AUC of rosuvastatin.

Glecaprevir/pibrentasvir [1], rosuvastatin ---> SmPC of [1] of EMA

Caution is recommended.

Ibrutinib [1], rosuvastatin ---> SmPC of [1] of EMA

Ibrutinib may also inhibit BCRP in the liver and increase the exposure of drugs that undergo BCRP-mediated hepatic efflux, such as rosuvastatin.

Indinavir [1], rosuvastatin ---> SmPC of [1] of EMA

Combination not recommended.

Ketoconazole, rosuvastatin [2] ---> SmPC of [2] of eMC

No clinically relevant interactions have been observed between rosuvastatin and ketoconazole (an inhibitor of CYP2A6 and CYP3A4).

Lapatinib, rosuvastatin [2] ---> SmPC of [2] of eMC

Concomitant administration of rosuvastatin with medicinal products that are inhibitors of BCRP may result in increased rosuvastatin plasma concentrations and an increased risk of myopathy

Ledipasvir/sofosbuvir [1], rosuvastatin ---> SmPC of [1] of EMA

Co-administration may significantly increase the concentration of rosuvastatin which is associated with increased risk of myopathy, including rhabdomyolysis. Co-administration is contraindicated

Letermovir [1], rosuvastatin ---> SmPC of [1] of EMA

Letermovir may substantially increase plasma concentrations of these statins. Concomitant use is not recommended with PREVYMIS alone. When PREVYMIS is co-administered with cyclosporine, use of these statins is contraindicated.

Lopinavir/ritonavir [1], rosuvastatin ---> SmPC of [1] of EMA

The combination increases the rosuvastatin plasma levels. Caution should be exercised

Magnesium hydroxide, rosuvastatin [2] ---> SmPC of [2] of eMC

The simultaneous dosing of rosuvastatin with an antacid suspension containing magnesium hydroxide resulted in a decrease in rosuvastatin plasma concentration of approximately 50%.

Metabolized by cytochrome P450, rosuvastatin [2] ---> SmPC of [2] of eMC

Drug interactions resulting from cytochrome P450-mediated metabolism are not expected.

Myopathy, rosuvastatin

The risk of myopathy (contraindication with rosuvastatin) might be increased at concomitant administration of rosuvastatin with other medicinal products that have a potential to induce myopathy

Neratinib [1], rosuvastatin ---> SmPC of [1] of EMA

Patients who are treated with BCRP inhibitors (e.g., rosuvastatin and sulfasalazine) should be monitored carefully.

Niacin, rosuvastatin [2] ---> SmPC of [2] of eMC

An increased risk of myopathy and/or rhabdomyolysis has been observed in patients receiving HMG-CoA reductase inhibitors together with niacin. The combination should only be used with caution

Norgestrel, rosuvastatin [2] ---> SmPC of [2] of eMC

The co-administration increases the plasma concentrations of norgestrel

OATP1B1 inhibitors, rosuvastatin [2] ---> SmPC of [2] of eMC

Concomitant administration of rosuvastatin with medicinal products that are inhibitors of OATP1B1 may result in increased rosuvastatin plasma concentrations and an increased risk of myopathy

Olaparib [1], rosuvastatin ---> SmPC of [1] of EMA

Olaparib is an inhibitor of BCRP. It cannot be excluded that olaparib may increase the exposure to substrates of BCRP

Ombitasvir/paritaprevir/ritonavir [1], rosuvastatin ---> SmPC of [1] of EMA

OATP1B inhibition by paritaprevir and BCRP inhibition by paritaprevir, ritonavir or dasabuvir. The maximum daily dose of rosuvastatin should be 10 mg. No dose adjustment needed for Viekirax.

Oral contraceptives, rosuvastatin [2] ---> SmPC of [2] of eMC

Concomitant use of rosuvastatin and an oral contraceptive resulted in an increase in ethinyl estradiol and norgestrel AUC of 26% and 34%, respectively. These increased plasma levels should be considered when selecting oral contraceptive doses

Osimertinib [1], rosuvastatin ---> SmPC of [1] of EMA

In a clinical PK study, co-administration of TAGRISSO with rosuvastatin (sensitive BCRP substrate) increased the AUC and Cmax of rosuvastatin by 35% and 72%, respectively.

Padeliporfin [1], rosuvastatin ---> SmPC of [1] of EMA

Palbociclib [1], rosuvastatin ---> SmPC of [1] of EMA

Administration of palbociclib with medicinal products that are substrates of BCRP (e.g., rosuvastatin, sulfasalazine) may increase their therapeutic effect and adverse reactions.

Ponatinib [1], rosuvastatin ---> SmPC of [1] of EMA

In vitro, ponatinib is an inhibitor of BCRP. Therefore, ponatinib may have the potential to increase plasma concentrations of co-administered substrates of BCRP and may increase their therapeutic effect and adverse reactions.

Pregnancy, rosuvastatin [2] ---> SmPC of [2] of eMC

Rosuvastatin is contraindicated in pregnancy.

Protease inhibitors, rosuvastatin [2] ---> SmPC of [2] of eMC

Increased systemic exposure to rosuvastatin has been observed in subjects receiving rosuvastatin concomitantly with various protease inhibitors in combination with ritonavir.

Regorafenib [1], rosuvastatin ---> SmPC of [1] of EMA

Ribociclib [1], rosuvastatin ---> SmPC of [1] of EMA

Caution and monitoring for toxicity are advised during concomitant treatment with sensitive substrates of this transporter which exhibit a narrow therapeutic index

Ritonavir [1], rosuvastatin ---> SmPC of [1] of EMA

While rosuvastatin elimination is not dependent on CYP3A, an elevation of rosuvastatin exposure has been reported with ritonavir co-administration.

Rolapitant [1], rosuvastatin ---> 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.

Rosuvastatin [1], vitamin K antagonists ---> SmPC of [1] of eMC

The co-administration may increase the international normalised ratio (INR). Appropriate monitoring of INR is desirable.

Rosuvastatin [1], warfarin ---> SmPC of [1] of eMC

The co-administration may increase the international normalised ratio (INR). Appropriate monitoring of INR is desirable.

Rosuvastatin, rucaparib [2] ---> SmPC of [2] of EMA

Rucaparib is an inhibitor of the BCRP with IC50 value suggesting potential BCRP inhibition and increased exposures of medicinal products that are BCRP substrate (e.g., rosuvastatin).

Rosuvastatin, ruxolitinib [2] ---> SmPC of [2] of EMA

Ruxolitinib may inhibit P-glycoprotein and breast cancer resistance protein (BCRP) in the intestine. This may result in increased systemic exposure of substrates of these transporters

Rosuvastatin, simeprevir [2] ---> SmPC of [2] of EMA

OATP1B1/3, BCRP transporter inhibition. Titrate the rosuvastatin dose carefully and use the lowest necessary dose while monitoring for safety when co-administered with OLYSIO.

Rosuvastatin, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Inhibition of OATP1B and BCRP. Co-administration of Epclusa with rosuvastatin increases the concentration of rosuvastatin, which is associated with increased risk of myopathy, including rhabdomyolysis.

Rosuvastatin, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Dabigatran etexilate (P-gp substrate) and rosuvastatin (OATP1B and BCRP substrate) are contraindicate

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

Rosuvastatin, 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.

Rosuvastatin, telaprevir [2] ---> SmPC of [2] of EMA

The inhibition of CYP3A and OATPs by telaprevir may increase statin concentration. Caution is warranted and clinical monitoring is recommended.

Rosuvastatin, 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

Rosuvastatin, 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

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

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.

Rosuvastatin, vemurafenib [2] ---> SmPC of [2] of EMA

The effects of vemurafenib on drugs that are substrates of BCRP are unknown. It cannot be excluded that vemurafenib may increase the exposure of medicines transported by BCRP (e.g. methotrexate, mitoxantrone, rosuvastatin).

Rosuvastatin, 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 Rosuvastatin

Crestor is contraindicated:

- in patients with hypersensitivity to rosuvastatin or to any of the excipients.

- in patients with active liver disease including unexplained, persistent elevations of serum transaminases and any serum transaminase elevation

exceeding 3 x the upper limit of normal (ULN).

- in patients with severe renal impairment (creatinine clearance < 30 ml/min).

- in patients with myopathy.

- in patients receiving concomitant ciclosporin.

- during pregnancy and lactation and in women of childbearing potential not using appropriate contraceptive measures.

The 40 mg dose is contraindicated in patients with pre-disposing factors for myopathy/rhabdomyolysis. Such factors include:

- moderate renal impairment (creatinine clearance < 60 ml/min)

- hypothyroidism

- personal or family history of hereditary muscular disorders

- previous history of muscular toxicity with another HMG-CoA reductase inhibitor or fibrate

- alcohol abuse

- situations where an increase in plasma levels may occur

- Asian patients

- concomitant use of fibrates.

http://www.medicines.org.uk/emc/

Rotavirus vaccine (live) (Rotarix)

Breast-feeding, rotavirus vaccine (live) [2] ---> SmPC of [2] of EMA

Based on evidence generated in clinical trials, breast-feeding does not reduce the protection against rotavirus gastro-enteritis afforded by Rotarix. Therefore, breast-feeding may be continued during the vaccination schedule.

Food intake, rotavirus vaccine (live) [2] ---> SmPC of [2] of EMA

There are no restrictions on the infant's consumption of food or liquid, either before or after vaccination.

Oral polio vaccine, rotavirus vaccine (live) [2] ---> SmPC of [2] of EMA

Concomitant administration of Rotarix and oral polio vaccine (OPV) does not affect the immune response to the polio antigens.

Pregnancy, rotavirus vaccine (live) [2] ---> SmPC of [2] of EMA

Rotarix is not intended for use in adults. There are no data on the use of Rotarix during pregnancy and lactation.

CONTRAINDICATIONS of Rotavirus vaccine (live) (Rotarix)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Hypersensitivity after previous administration of rotavirus vaccines.

- History of intussusception.

- Subjects with uncorrected congenital malformation of the gastrointestinal tract that would predispose for intussusception.

- Subjects with Severe Combined Immunodeficiency (SCID) disorder

- Administration of Rotarix should be postponed in subjects suffering from acute severe febrile illness. The presence of a minor infection is not a contra-indication for immunisation.

- The administration of Rotarix should be postponed in subjects suffering from diarrhoea or vomiting.

https://www.ema.europa.eu/en/documents/product-information/rotarix-epar-product-information_en.pdf 07/01/2026

Rotavirus vaccine (live, oral (RotaTeq)

Breast-feeding, rotavirus vaccine (live, oral) [2] ---> SmPC of [2] of EMA

RotaTeq is intended for use in infants only. Thus human data on use during pregnancy or lactation are not available and animal fertility or reproduction studies have not been performed.

Poliomyelitis vaccine, rotavirus vaccine (live, oral) [2] ---> SmPC of [2] of EMA

Concomitant administration of RotaTeq and oral poliomyelitis vaccine (OPV) did not affect the immune response to the poliovirus antigens.

Pregnancy, rotavirus vaccine (live, oral) [2] ---> SmPC of [2] of EMA

RotaTeq is intended for use in infants only. Thus human data on use during pregnancy or lactation are not available and animal fertility or reproduction studies have not been performed.

Rotavirus vaccine (live [1], oral), vaccinations ---> SmPC of [1] of EMA

RotaTeq can be given concomitantly with monovalent or combination infant vaccines containing one or more of the following antigens: DTaP, Hib, IPV or OPV, HBV, PCV and MenCC.

CONTRAINDICATIONS of Rotavirus vaccine (live, oral) (RotaTeq)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Hypersensitivity after previous administration of rotavirus vaccines.

- Previous history of intussusception.

- Subjects with congenital malformation of the gastrointestinal tract that could predispose to intussusception.

- Infants who have known or suspected immunodeficiency (see sections 4.4 and 4.8).

- Administration of RotaTeq should be postponed in infants suffering from acute severe febrile illness.

- The presence of a minor infection is not a contraindication for immunisation.

- The administration of RotaTeq should be postponed in subjects suffering from acute diarrhoea or vomiting.

https://www.ema.europa.eu/en/documents/product-information/rotateq-epar-product-information_en.pdf 18/12/2025

Rotigotine (Neupro)

Ability to drive, rotigotine [2] ---> SmPC of [2] of EMA

Rotigotine may have major influence on the ability to drive and use machines. Patients being treated with rotigotine and presenting with somnolence and/or sudden sleep episodes must be informed not to drive or engage in activities

Alcohol, rotigotine [2] ---> SmPC of [2] of EMA

Because of possible additive effects, caution should be advised when patients are taking sedating medicinal products or other CNS (central nervous system) depressants or alcohol in combination with rotigotine.

Antidepressants, rotigotine [2] ---> SmPC of [2] of EMA

Benzodiazepines, rotigotine [2] ---> SmPC of [2] of EMA

Breast-feeding, rotigotine [2] ---> SmPC of [2] of EMA

Because rotigotine decreases prolactin secretion in humans, inhibition of lactation is expected. In the absence of human data, breast-feeding should be discontinued.

Butyrophenones, rotigotine [2] ---> SmPC of [2] of EMA

Because rotigotine is a dopamine agonist, it is assumed that dopamine antagonists, such as neuroleptics or metoclopramide, may diminish the effectiveness of rotigotine, and co-administration should be avoided.

Carbidopa, rotigotine [2] ---> SmPC of [2] of EMA

Co-administration of L-dopa and carbidopa with rotigotine had no effect on the pharmacokinetics of rotigotine, and rotigotine had no effect on the pharmacokinetics of L-dopa and carbidopa.

CNS depressants, rotigotine [2] ---> SmPC of [2] of EMA

Domperidone, rotigotine [2] ---> SmPC of [2] of EMA

Co-administration of domperidone with rotigotine had no effect on the pharmacokinetics of rotigotine.

Dopamine agonists, rotigotine [2] ---> SmPC of [2] of EMA

Rotigotine may potentiate the dopaminergic adverse reaction of L-dopa and may cause and/or exacerbate pre-existing dyskinesia, as described with other dopamine agonists.

Dopamine antagonists, rotigotine [2] ---> SmPC of [2] of EMA

Ethinyl estradiol, rotigotine [2] ---> SmPC of [2] of EMA

Co-administration of rotigotine (3 mg/24 h) did not affect the pharmacodynamics and pharmacokinetics of oral contraceptives (0.03 mg ethinylestradiol, 0.15 mg levonorgestrel).

Fertility, rotigotine [2] ---> SmPC of [2] of EMA

For information on fertility studies, please see section 5.3.

Levodopa, rotigotine [2] ---> SmPC of [2] of EMA

Co-administration of L-dopa and carbidopa with rotigotine had no effect on the pharmacokinetics of rotigotine, and rotigotine had no effect on the pharmacokinetics of L-dopa and carbidopa.

Levodopa/carbidopa, rotigotine [2] ---> SmPC of [2] of EMA

Co-administration of L-dopa and carbidopa with rotigotine had no effect on the pharmacokinetics of rotigotine, and rotigotine had no effect on the pharmacokinetics of L-dopa and carbidopa.

Levonorgestrel, rotigotine [2] ---> SmPC of [2] of EMA

Co-administration of rotigotine (3 mg/24 h) did not affect the pharmacodynamics and pharmacokinetics of oral contraceptives (0.03 mg ethinylestradiol, 0.15 mg levonorgestrel).

Metoclopramide, rotigotine [2] ---> SmPC of [2] of EMA

Neuroleptics, rotigotine [2] ---> SmPC of [2] of EMA

Omeprazole, rotigotine [2] ---> SmPC of [2] of EMA

Co-administration of omeprazole (inhibitor of CYP2C19), in doses of 40 mg/day, had no effect on the pharmacokinetics and metabolism of rotigotine in healthy volunteers.

Oral contraceptives, rotigotine [2] ---> SmPC of [2] of EMA

Co-administration of rotigotine (3 mg/24 h) did not affect the pharmacodynamics and pharmacokinetics of oral contraceptives (0.03 mg ethinylestradiol, 0.15 mg levonorgestrel).

Phenothiazines, rotigotine [2] ---> SmPC of [2] of EMA

Pregnancy, rotigotine [2] ---> SmPC of [2] of EMA

Rotigotine should not be used during pregnancy.

Rotigotine [1], sedatives ---> SmPC of [1] of EMA

Rotigotine [1], thioxanthenes ---> SmPC of [1] of EMA

Rotigotine [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should use effective contraception to prevent pregnancy during treatment with rotigotine.

CONTRAINDICATIONS of Rotigotine (Neupro)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Magnetic resonance imaging or cardioversion

https://www.ema.europa.eu/en/documents/product-information/neupro-epar-product-information_en.pdf. 27/02/2020

Other trade names: Leganto,

Roxadustat (Evrenzo)

Ability to drive, roxadustat [2] ---> SmPC of [2] of EMA

Seizures have been reported during treatment with Evrenzo (see section 4.4). Therefore, caution should be exercised when driving or using machines.

Aluminium, roxadustat [2] ---> SmPC of [2] of EMA

Roxadustat should be taken at least 1 hour after administration of phosphate binders or other medicinal products or supplements containing multivalent cations

Atorvastatin, roxadustat [2] ---> SmPC of [2] of EMA

Co-administration of 200 mg of roxadustat with atorvastatin increased the AUC and Cmax of atorvastatin 2.0-and 1.3-fold, respectively.

BCRP substrates, roxadustat [2] ---> SmPC of [2] of EMA

Roxadustat may increase the plasma exposure of other medicinal products that are substrates of BCRP or OATP1B1. Monitor for possible adverse reactions of co-administered medicinal products and adjust dose accordingly.

Breast-feeding, roxadustat [2] ---> SmPC of [2] of EMA

Available animal data have shown excretion of roxadustat in milk (for details see section 5.3). Evrenzo is contraindicated during breast-feeding (see sections 4.3 and 5.3).

Calcium acetate, roxadustat [2] ---> SmPC of [2] of EMA

Roxadustat should be taken at least 1 hour after administration of phosphate binders or other medicinal products or supplements containing multivalent cations

Calcium, roxadustat [2] ---> SmPC of [2] of EMA

Roxadustat should be taken at least 1 hour after administration of phosphate binders or other medicinal products or supplements containing multivalent cations

Erythropoiesis-stimulating agents, roxadustat [2] ---> SmPC of [2] of EMA

It is not recommended to combine administration of roxadustat and ESAs as the combination has not been studied.

Fertility, roxadustat [2] ---> SmPC of [2] of EMA

Women of childbearing potential must use highly effective contraception during treatment and for at least one week after the last dose of Evrenzo.

Gemfibrozil, roxadustat [2] ---> SmPC of [2] of EMA

Roxadustat is a substrate of CYP2C8 and UGT1A9. Monitor Hb levels when initiating or discontinuing concomitant treatment with gemfibrozil, probenecid, other strong inhibitors or inducers of CYP2C8 or other strong inhibitors of UGT1A9.

Iron, roxadustat [2] ---> SmPC of [2] of EMA

Roxadustat should be taken at least 1 hour after administration of phosphate binders or other medicinal products or supplements containing multivalent cations

Lanthanum carbonate, roxadustat [2] ---> SmPC of [2] of EMA

This restriction does not apply to lanthanum carbonate, as the co-administration of roxadustat with lanthanum carbonate did not result in a clinically meaningful change in the plasma exposure of roxadustat.

Magnesium, roxadustat [2] ---> SmPC of [2] of EMA

Roxadustat should be taken at least 1 hour after administration of phosphate binders or other medicinal products or supplements containing multivalent cations

OATP1B1 substrates, roxadustat [2] ---> SmPC of [2] of EMA

Phosphate binders, roxadustat [2] ---> SmPC of [2] of EMA

Roxadustat should be taken at least 1 hour after administration of phosphate binders or other medicinal products or supplements containing multivalent cations

Polyvalent cations, roxadustat [2] ---> SmPC of [2] of EMA

Roxadustat should be taken at least 1 hour after administration of phosphate binders or other medicinal products or supplements containing multivalent cations

Pregnancy, roxadustat [2] ---> SmPC of [2] of EMA

If pregnancy occurs while Evrenzo is being administered, treatment should be discontinued and switched to alternative treatments, if appropriate (see section 4.3).

Pregnancy, roxadustat [2] ---> SmPC of [2] of EMA

Roxadustat is contraindicated during the third trimester of pregnancy (see sections 4.3 and 4.4). Roxadustat is not recommended during the first and second trimester of pregnancy (see section 4.4).

Probenecide, roxadustat [2] ---> SmPC of [2] of EMA

Rosuvastatin, roxadustat [2] ---> SmPC of [2] of EMA

Co-administration of 200 mg of roxadustat with rosuvastatin increased the AUC and Cmax of rosuvastatin 2.9-and 4.5-fold, respectively.

Roxadustat [1], sevelamer carbonate ---> SmPC of [1] of EMA

Roxadustat should be taken at least 1 hour after administration of phosphate binders or other medicinal products or supplements containing multivalent cations

Roxadustat [1], simvastatine ---> SmPC of [1] of EMA

The concentrations of simvastatin and simvastatin acid also increased when simvastatin was administered 2 hours before or 4 or 10 hours after roxadustat.

Roxadustat [1], statins ---> SmPC of [1] of EMA

When co-administered with roxadustat, consider this interaction, monitor for adverse reactions associated with statins and for the need of statin dose reduction.

Roxadustat [1], strong CYP2C8 inductors ---> SmPC of [1] of EMA

Roxadustat [1], strong CYP2C8 inhibitors ---> SmPC of [1] of EMA

Roxadustat [1], strong UGT1A9 inhibitors ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Roxadustat (Evrenzo)

Evrenzo is contraindicated in the following conditions:

- Hypersensitivity to the active substance, peanut, soya or to any of the excipients listed in section 6.1.

- Third trimester of pregnancy (see sections 4.4 and 4.6).

- Breast-feeding (see section 4.6).

https://www.ema.europa.eu/en/documents/product-information/evrenzo-epar-product-information_en.pdf 16/04/2024

Roxithromycin

Ability to drive, roxithromycin

Dizziness may occur

Amiodarone, roxithromycin

Caution is warranted for concomitant use of roxitromycin with other QT interval prolonging medicines

Astemizole, roxithromycin

Roxitromycin, moderate CYP3A4 inhibitor, may increase the plasma levels of astemizole, cisapride, pimozide y terfenadine (QT-interval prolongation). The co-administration is contraindicated

Bactericides, macrolide antibiotics

The macrolide may interfere with the bactericidal effects of beta-lactamic antibiotic.

Bactericides, roxithromycin

The macrolide may interfere with the bactericidal effects of beta-lactamic antibiotic.

Breast-feeding, roxithromycin

A decision must be made whether to discontinue breastfeeding or to abstain from roxitromycin therapy

Bromocriptine, roxithromycin

Roxitromycin may increase significantly the absolute bioavailibility and the plasma levels of bromocriptine

Cardiac glycosides, roxithromycin

Roxitromycin may increase the absorption and the plasma levels of cardiac glycoside

Cisapride, roxithromycin

Roxitromycin, moderate CYP3A4 inhibitor, may increase the plasma levels of astemizole, cisapride, pimozide y terfenadine (QT-interval prolongation). The co-administration is contraindicated

Citalopram, roxithromycin

Caution is warranted for concomitant use of roxitromycin with other QT interval prolonging medicines

Class IA antiarrhythmic agents, roxithromycin

Caution is warranted for concomitant use of roxitromycin with other QT interval prolonging medicines

Class III antiarrhythmic agents, roxithromycin

Caution is warranted for concomitant use of roxitromycin with other QT interval prolonging medicines

Cyclosporine, roxithromycin

The co-administration may increase the plasma levels of cyclosporine

CYP3A4 substrates with narrow therapeutic index, roxithromycin

Roxitromycin, moderate CYP3A4 inhibitor, may increase the plasma levels of astemizole, cisapride, pimozide y terfenadine (QT-interval prolongation). The co-administration is contraindicated

Digoxin, roxithromycin

Roxitromycin may increase the absorption and the plasma levels of digoxin

Dihydroergotamine, roxithromycin

It has been reported cases of severe vasoconstriction (ergotism) with possibility of necrosis of the extremities with the co-administration of macrolides and rye ergots

Disopyramide, roxithromycin

Caution is warranted for concomitant use of roxitromycin with other QT interval prolonging medicines

Dofetilide, roxithromycin

Caution is warranted for concomitant use of roxitromycin with other QT interval prolonging medicines

Drugs inducing bradycardia, roxithromycin

Caution is warranted for concomitant use of roxitromycin with clinical relevant bradycardia

Ergot derivatives, roxithromycin

It has been reported cases of severe vasoconstriction (ergotism) with possibility of necrosis of the extremities with the co-administration of macrolides and rye ergots

Ergotamine, roxithromycin

It has been reported cases of severe vasoconstriction (ergotism) with possibility of necrosis of the extremities with the co-administration of macrolides and rye ergots

Fluconazole, roxithromycin

Caution is warranted for concomitant use of roxitromycin with other QT interval prolonging medicines

Hypokalemia, roxithromycin

Caution is warranted for concomitant use of roxitromycin with hypokaliemia or hypomagnesemia

Hypomagnesemia, roxithromycin

Caution is warranted for concomitant use of roxitromycin with hypokaliemia or hypomagnesemia

Lomitapide [1], roxithromycin ---> 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.

Metabolized by CYP3A4 and prolong QT, roxithromycin

The risk of rhythm disorders is higher with substances which may prolong the QT interval and their plasma levels can be increased by roxitromycin. These substances must not be coadministered with roxitromycin

Methadone, roxithromycin

Caution is warranted for concomitant use of roxitromycin with other QT interval prolonging medicines

Metildigoxin, roxithromycin

Increased plasma levels of metildigoxin

Midazolam, roxithromycin

The moderate CYP3A4 inhibition may increase the plasma concentrations of midazolam. A careful monitoring is recommended

Moxifloxacin, roxithromycin

Caution is warranted for concomitant use of roxitromycin with other QT interval prolonging medicines

Pentamidine, roxithromycin

Caution is warranted for concomitant use of roxitromycin with other QT interval prolonging medicines

Phenothiazines, roxithromycin

Caution is warranted for concomitant use of roxitromycin with other QT interval prolonging medicines

Pimozide, roxithromycin

Roxitromycin, moderate CYP3A4 inhibitor, may increase the plasma levels of astemizole, cisapride, pimozide y terfenadine (QT-interval prolongation). The co-administration is contraindicated

Pregnancy, roxithromycin

The administration of roxitromycin to pregnant women would be done after careful assessment of the benefit-risk

Procainamide, roxithromycin

Caution is warranted for concomitant use of roxitromycin with other QT interval prolonging medicines

QT interval prolonging drugs, roxithromycin

Caution is warranted for concomitant use of roxitromycin with other QT interval prolonging medicines

Quinidine, roxithromycin

Caution is warranted for concomitant use of roxitromycin with other QT interval prolonging medicines

Quinolones, roxithromycin

Caution is warranted for concomitant use of roxitromycin with other QT interval prolonging medicines

Rifabutin, roxithromycin

Roxithromycin may increase the plasma levels of rifabutin

Roxithromycin, statins

The concomitant use of roxithromycin and a statin may increase the risk of muscular adverse effects due to the possible increasing in the statin exposition

Roxithromycin, telaprevir

Caution is warranted for concomitant use of roxitromycin with other QT interval prolonging medicines

Roxithromycin, terfenadine

Roxitromycin, moderate CYP3A4 inhibitor, may increase the plasma levels of astemizole, cisapride, pimozide y terfenadine (QT-interval prolongation). The co-administration is contraindicated

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

Roxithromycin, tricyclic antidepressant

Caution is warranted for concomitant use of roxitromycin with other QT interval prolonging medicines

Roxithromycin, vitamin K antagonists

The co-administration may increase the prothrombin time or the international normalized ratio (INR)

Roxithromycin, warfarin

The co-administration may increase the prothrombin time or the international normalized ratio (INR)

Rozanolixizumab (Rystiggo)

Breast-feeding, rozanolixizumab [2] ---> SmPC of [2] of EMA

A risk to breast-fed infants cannot be excluded during this short period. Afterwards, use of rozanolixizumab could be considered during breast-feeding only if the clinical benefit outweighs the risks.

Fertility, rozanolixizumab [2] ---> SmPC of [2] of EMA

The effect of rozanolixizumab on human fertility is not known. Animal studies do not indicate harmful effects with respect to fertility (see section 5.3).

Immunoadsorption, rozanolixizumab [2] ---> SmPC of [2] of EMA

Treatment with IV or SC immunoglobulins, PLEX/plasmapheresis and immunoadsorption may reduce circulating levels of rozanolixizumab.

Immunoglobulin G, rozanolixizumab [2] ---> SmPC of [2] of EMA

As rozanolixizumab interferes with the FcRn recycling mechanism of immunoglobulin G (IgG), the serum concentrations of IgG-based medicinal products (e.g. monoclonal antibodies and intravenous immunoglobulin [IVIg]) and Fc-peptide fusion proteins are expected to be decreased if administered concomitantly or within 2 weeks after administration of rozanolixizumab.

Pregnancy, rozanolixizumab [2] ---> SmPC of [2] of EMA

Treatment of pregnant women with rozanolixizumab should only be considered if the clinical benefit outweighs the risks.

Rozanolixizumab [1], vaccinations ---> SmPC of [1] of EMA

Because rozanolixizumab causes a reduction in IgG levels, vaccination with live-attenuated or live vaccines is not recommended during treatment with rozanolixizumab (see sections 4.4 and 5.3).

Rozanolixizumab [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

Therefore, risks and benefits of administering live / live attenuated vaccines to infants exposed to rozanolixizumab in utero should be considered

CONTRAINDICATIONS of Rozanolixizumab (Rystiggo)

- 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/rystiggo-epar-product-information_en.pdf 24/10/2025

Rucaparib (Rubraca)

Ability to drive, rucaparib [2] ---> SmPC of [2] of EMA

Rubraca has minor influence on the ability to drive and use machines. Caution when driving or using machines is advised for patients who report fatigue, nausea, or dizziness during treatment with Rubraca (see section 4.8).

Alfentanyl, rucaparib [2] ---> SmPC of [2] 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.

Astemizole, rucaparib [2] ---> SmPC of [2] of EMA

BCRP substrates, rucaparib [2] ---> SmPC of [2] of EMA

No dose adjustment is recommended for co-administered medicinal products that are BCRP substrates.

Breast-feeding, rucaparib [2] ---> SmPC of [2] of EMA

Because of the potential for serious adverse reactions in breast-fed infants from rucaparib, breast-feeding is contraindicated during treatment with Rubraca and for 2 weeks after the final dose

Cisapride, rucaparib [2] ---> SmPC of [2] of EMA

Cyclosporine, rucaparib [2] ---> SmPC of [2] of EMA

CYP1A2 substrates with narrow therapeutic index, rucaparib [2] ---> SmPC of [2] 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.

CYP2C9 substrates with narrow therapeutic index, rucaparib [2] ---> SmPC of [2] of EMA

When co-administering medicinal products that are CYP2C9 substrates with a narrow therapeutic index (e.g., warfarin, phenytoin), dose adjustments may be considered, if clinically indicated.

Dihydroergotamine, rucaparib [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP1A2, rucaparib [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP2C19, rucaparib [2] ---> SmPC of [2] of EMA

No dose adjustment is considered necessary for co-administered medicinal products that are CYP2C19 substrates.

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, rucaparib [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by UGT1A1, rucaparib [2] ---> SmPC of [2] of EMA

Caution should be used when rucaparib is co-administered with UGT1A1 substrates (i.e. irinotecan) to patients with UGT1A1*28 (poor metabolizer) due to a possible increase in the exposure of SN-38 and associated toxicities.

Ergotamine, rucaparib [2] ---> SmPC of [2] of EMA

Fentanyl, rucaparib [2] ---> SmPC of [2] of EMA

Fertility, rucaparib [2] ---> SmPC of [2] of EMA

Based on the animal studies, impact on fertility associated with the use of rucaparib cannot be ruled out (see section 5.3). Moreover, according to its mechanism of action, rucaparib may impact human fertility.

Irinotecan, rucaparib [2] ---> SmPC of [2] of EMA

Metformin, rucaparib [2] ---> SmPC of [2] of EMA

Caution is advised when metformin is co-administered with rucaparib.

Omeprazole, rucaparib [2] ---> SmPC of [2] of EMA

No dose adjustment is considered necessary for co-administered medicinal products that are CYP2C19 substrates.

Oral contraceptives, rucaparib [2] ---> SmPC of [2] of EMA

No dose adjustment is recommended for coadministered oral contraceptives.

P-glycoprotein substrates, rucaparib [2] ---> SmPC of [2] of EMA

No dose adjustment is recommended for co-administered medicinal products that are P-gp substrates.

Phenytoin, rucaparib [2] ---> SmPC of [2] of EMA

When co-administering medicinal products that are CYP2C9 substrates with a narrow therapeutic index (e.g., warfarin, phenytoin), dose adjustments may be considered, if clinically indicated.

Pimozide, rucaparib [2] ---> SmPC of [2] of EMA

Pregnancy, rucaparib [2] ---> SmPC of [2] of EMA

Based on its mechanism of action and preclinical data, rucaparib may cause fetal harm when administered to a pregnant woman. A pregnancy test before initiating treatment is recommended in women of reproductive potential.

Quinidine, rucaparib [2] ---> SmPC of [2] of EMA

Rosuvastatin, rucaparib [2] ---> SmPC of [2] of EMA

Rucaparib is an inhibitor of the BCRP with IC50 value suggesting potential BCRP inhibition and increased exposures of medicinal products that are BCRP substrate (e.g., rosuvastatin).

Rucaparib [1], sirolimus ---> SmPC of [1] of EMA

Rucaparib [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Caution should be used for concomitant use of strong CYP3A4 inhibitors or inducers.

Rucaparib [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Caution should be used for concomitant use of strong CYP3A4 inhibitors or inducers.

Rucaparib [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

Caution is recommended when rucaparib is co-administered with medicinal products that are strong inhibitors of P-gp.

Rucaparib [1], tacrolimus ---> SmPC of [1] of EMA

Rucaparib [1], terfenadine ---> SmPC of [1] of EMA

Rucaparib [1], theophylline ---> SmPC of [1] of EMA

Rucaparib [1], tizanidine ---> SmPC of [1] of EMA

Rucaparib [1], warfarin ---> SmPC of [1] of EMA

When co-administering medicinal products that are CYP2C9 substrates with a narrow therapeutic index (e.g., warfarin, phenytoin), dose adjustments may be considered, if clinically indicated.

Rucaparib [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should be advised to avoid becoming pregnant while receiving rucaparib. Patients should be advised to use effective contraception during treatment and for 6 months following the last dose of rucaparib

CONTRAINDICATIONS of Rucaparib (Rubraca)

- 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/rubraca-epar-product-information_en.pdf 27/11/2025

Rufinamide (Inovelon)

Ability to drive, rufinamide [2] ---> SmPC of [2] of EMA

Inovelon may cause dizziness, somnolence and blurred vision. Depending on the individual sensitivity, rufinamide may have a minor to major influence on the ability to drive and use machines.

Alcohol, rufinamide [2] ---> SmPC of [2] of EMA

No data on the interaction of rufinamide with alcohol are available.

Antiepileptics, rufinamide [2] ---> SmPC of [2] of EMA

Rufinamide concentrations are not subject to clinically relevant changes on co-administration with known enzyme inducing antiepileptic medicinal products.

Benzodiazepines, rufinamide [2] ---> SmPC of [2] of EMA

No significant changes in rufinamide concentration are observed following co-administration with lamotrigine, topiramate or benzodiazepines.

Breast-feeding, rufinamide [2] ---> SmPC of [2] of EMA

It is not known if rufinamide is excreted in human breast milk. Due to the potential harmful effects for the breast-fed infant, breast-feeding should be avoided during maternal treatment with rufinamide.

Carbamazepine, rufinamide [2] ---> SmPC of [2] of EMA

Rufinamide appears not to have a clinically relevant effect on carbamazepine, lamotrigine, phenobarbital, topiramate, phenytoin or valproate steady state concentrations.

CYP3A4 substrates with narrow therapeutic index, rufinamide [2] ---> SmPC of [2] of EMA

It is recommended that patients treated with substances that are metabolised by the CYP3A4 enzyme system are to be carefully monitored for two weeks at the start of, or after the end of treatment with rufinamide, or after any marked change in the dose.

Cytochrome P450, rufinamide [2] ---> SmPC of [2] of EMA

Clinically significant interactions mediated through inhibition of cytochrome P450 system by rufinamide are unlikely to occur.

Digoxin, rufinamide [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP3A4, rufinamide [2] ---> SmPC of [2] of EMA

Rufinamide has been shown to induce the cytochrome P450 enzyme CYP3A4 and may therefore reduce the plasma concentrations of substances which are metabolised by this enzyme.

Ethinyl estradiol, rufinamide [2] ---> SmPC of [2] of EMA

Possible decreased AUC of ethinyl estradiol

Ethinylestradiol/norgestimate [1], rufinamide ---> SmPC of [1] of eMC

Fertility, rufinamide [2] ---> SmPC of [2] of EMA

No data are available on the effects on fertility following treatment with rufinamide.

Foods, rufinamide [2] ---> SmPC of [2] of EMA

As a food effect was observed, Inovelon should be administered with food

Isavuconazole [1], rufinamide ---> SmPC of [1] of EMA

Caution is warranted when prescribing CRESEMBA to patients taking other medicinal products known to decrease the QT interval, such as rufinamide.

Lamotrigine, rufinamide [2] ---> SmPC of [2] of EMA

No significant changes in rufinamide concentration are observed following co-administration with lamotrigine, topiramate or benzodiazepines.

Lurasidone [1], rufinamide ---> SmPC of [1] of EMA

Coadministration of lurasidone with mild inducers of CYP3A4 would be expected to give a <2-fold reduction in lurasidone exposure during co-administration and for up to 2 weeks after discontinuation of mild or moderate CYP3A4 inducers.

Norelgestromin/ethinylestradiol [1], rufinamide ---> SmPC of [1] of EMA

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

Norethisterone, rufinamide [2] ---> SmPC of [2] of EMA

Possible decreased AUC of norethisterone

Olanzapine, rufinamide [2] ---> SmPC of [2] of EMA

A specific interaction study in healthy subjects revealed no influence of rufinamide at a dose of 400 mg twice daily on the pharmacokinetics of olanzapine, a CYP1A2 substrate.

Oral contraceptives, rufinamide [2] ---> SmPC of [2] of EMA

Women of child-bearing potential using hormonal contraceptives are advised to use an additional safe and effective contraceptive method

Phenobarbital, rufinamide [2] ---> SmPC of [2] of EMA

Rufinamide appears not to have a clinically relevant effect on carbamazepine, lamotrigine, phenobarbital, topiramate, phenytoin or valproate steady state concentrations.

Phenytoin, rufinamide [2] ---> SmPC of [2] of EMA

Rufinamide appears not to have a clinically relevant effect on carbamazepine, lamotrigine, phenobarbital, topiramate, phenytoin or valproate steady state concentrations.

Pregnancy, rufinamide [2] ---> SmPC of [2] of EMA

Rufinamide should not be used during pregnancy, or in women of childbearing age not using contraceptive measures, unless clearly necessary.

Primidone, rufinamide

Possible decreased rufinamide plasma concentrations

Rufinamide [1], sodium valproate ---> SmPC of [1] of EMA

For patients on Inovelon treatment who have administration of valproate initiated, significant increases in rufinamide plasma concentrations may occur.

Rufinamide [1], topiramate ---> SmPC of [1] of EMA

No significant changes in rufinamide concentration are observed following co-administration with lamotrigine, topiramate or benzodiazepines.

Rufinamide [1], valproic acid ---> SmPC of [1] of EMA

Rufinamide appears not to have clinically relevant effect on valproate steady state concentrations

Rufinamide [1], warfarin ---> SmPC of [1] of EMA

Rufinamide [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential must use contraceptive measures during treatment with rufinamide.

Rufinamide, vigabatrin

Possible decreased rufinamide plasma concentrations

CONTRAINDICATIONS of Rufinamide (Inovelon)

- Hypersensitivity to the active substance, triazole derivatives or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/inovelon-epar-product-information_en.pdf. 06/12/2023

Rupatadine

Ability to drive, rupatadine [2] ---> SmPC of [2] of eMC

Care should be taken before driving or using machinery until the patient's individual reaction on rupatadine has been established.

Breast-feeding, rupatadine [2] ---> SmPC of [2] of eMC

Due to the lack of human data, caution should be exercised when prescribing rupatadine to lactating milk.

Clarithromycin, rupatadine [2] ---> SmPC of [2] of eMC

The concomitant administration of rupatadine with inhibitors of the isozyme CYP3A4 increases the systemic exposure to rupatadine. Rupatadine should be used with caution when it is administered concomitantly with inhibitors of CYP3A4.

CNS depressants, rupatadine [2] ---> SmPC of [2] of eMC

As with other antihistamines, interactions with CNS depressants cannot be excluded.

Diltiazem, rupatadine [2] ---> SmPC of [2] of eMC

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, rupatadine

With substrates of CYP3A4 and small therapeutic index may be necessary a dosage adjustment due to rupatadine may increase the plasma concentrations of the medicinal products

Erythromycin, rupatadine [2] ---> SmPC of [2] of eMC

Fluconazole, rupatadine [2] ---> SmPC of [2] of eMC

Grapefruit juice, rupatadine [2] ---> SmPC of [2] of eMC

The concomitant administration of rupatadine and grapefruit juice increased 3.5 times the systemic exposure of rupatadine. Grapefruit juice should not be taken simultaneously.

Grapefruit, rupatadine [2] ---> SmPC of [2] of eMC

The concomitant administration of rupatadine and grapefruit juice increased 3.5 times the systemic exposure of rupatadine. Grapefruit juice should not be taken simultaneously.

Itraconazol, rupatadine [2] ---> SmPC of [2] of eMC

Ketoconazole, rupatadine [2] ---> SmPC of [2] of eMC

Moderate CYP3A4 inhibitors, rupatadine [2] ---> SmPC of [2] of eMC

Nefazodone, rupatadine [2] ---> SmPC of [2] of eMC

Posaconazole, rupatadine [2] ---> SmPC of [2] of eMC

Pregnancy, rupatadine [2] ---> SmPC of [2] of eMC

Caution should be exercised when prescribing rupatadine to pregnant women.

Protease inhibitors, rupatadine [2] ---> SmPC of [2] of eMC

Rupatadine [1], statins ---> SmPC of [1] of eMC

The risk of interactions with statins, some of which are also metabolised by the cytochrome P450 CYP3A4 isoenzyme, is unknown. For these reasons, rupatadine should be used with caution when it is coadministered with statins.

Rupatadine [1], strong CYP3A4 inhibitors ---> SmPC of [1] of eMC

Rupatadine [1], voriconazole ---> SmPC of [1] of eMC

CONTRAINDICATIONS of Rupatadine

- Hypersensitivity to rupatadine or to any of the excipients.

http://www.medicines.org.uk/emc/

Rurioctocog alfa pegol (Adynovi)

Breast-feeding, rurioctocog alfa pegol [2] ---> SmPC of [2] of EMA

Factor VIII should be used during pregnancy and lactation only if clearly indicated.

Medicinal products, rurioctocog alfa pegol [2] ---> SmPC of [2] of EMA

No interactions of human coagulation factor VIII (rDNA) products with other medicinal products have been reported.

Pregnancy, rurioctocog alfa pegol [2] ---> SmPC of [2] of EMA

Factor VIII should be used during pregnancy and lactation only if clearly indicated.

CONTRAINDICATIONS of Rurioctocog alfa pegol (Adynovi)

- Hypersensitivity to the active substance, to the parent molecule octocog alfa or to any of the excipients listed in section 6.1.

- Known allergic reaction to mouse or hamster protein.

https://www.ema.europa.eu/en/documents/product-information/adynovi-epar-product-information_en.pdf 15/01/2025

Ruxolitinib (Jakavi)

Ability to drive, ruxolitinib [2] ---> SmPC of [2] of EMA

Jakavi has no or negligible sedating effect. However, patients who experience dizziness after the intake of Jakavi should refrain from driving or using machines.

Amprenavir, ruxolitinib [2] ---> SmPC of [2] of EMA

Mild or moderate CYP3A4 inhibitors may increase ruxolitinib exposition. No dose adjustment is recommended when ruxolitinib is co-administered with mild or moderate CYP3A4 inhibitors

Avasimibe, ruxolitinib [2] ---> SmPC of [2] of EMA

The strong CYP3A4 induction may reduce the AUC of ruxolitinib. It is possible that an increase of the ruxolitinib dose is needed with strong CYP3A4 inductors

BCRP substrates, ruxolitinib [2] ---> SmPC of [2] of EMA

Ruxolitinib may inhibit P-glycoprotein and breast cancer resistance protein (BCRP) in the intestine. This may result in increased systemic exposure of substrates of these transporters

Boceprevir, ruxolitinib [2] ---> SmPC of [2] 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.

Breast-feeding, ruxolitinib [2] ---> SmPC of [2] of EMA

Jakavi must not be used during breast-feeding and breast-feeding should therefore be discontinued when treatment is started.

Carbamazepine, ruxolitinib [2] ---> SmPC of [2] of EMA

The strong CYP3A4 induction may reduce the AUC of ruxolitinib. It is possible that an increase of the ruxolitinib dose is needed with strong CYP3A4 inductors

Cimetidine, ruxolitinib [2] ---> SmPC of [2] of EMA

Mild or moderate CYP3A4 inhibitors may increase ruxolitinib exposition. No dose adjustment is recommended when ruxolitinib is co-administered with mild or moderate CYP3A4 inhibitors

Ciprofloxacin, ruxolitinib [2] ---> SmPC of [2] of EMA

Mild or moderate CYP3A4 inhibitors may increase ruxolitinib exposition. No dose adjustment is recommended when ruxolitinib is co-administered with mild or moderate CYP3A4 inhibitors

Clarithromycin, ruxolitinib [2] ---> SmPC of [2] 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.

Cyclosporine, ruxolitinib [2] ---> SmPC of [2] of EMA

Ruxolitinib may inhibit P-glycoprotein and breast cancer resistance protein (BCRP) in the intestine. This may result in increased systemic exposure of substrates of these transporters

CYP2C9 and CYP3A4 inhibitors, ruxolitinib [2] ---> SmPC of [2] of EMA

50% dose reduction should be considered when using medicinal products which are dual inhibitors of CYP2C9 and CYP3A4 enzymes (e.g. fluconazole). Avoid the concomitant use of ruxolitinib with fluconazole doses greater than 200 mg daily.

CYP3A4 and CYP2C9 inhibitors, ruxolitinib [2] ---> SmPC of [2] of EMA

CYP3A4 inhibitors, ruxolitinib [2] ---> SmPC of [2] of EMA

Mild or moderate CYP3A4 inhibitors may increase ruxolitinib exposition. No dose adjustment is recommended when ruxolitinib is co-administered with mild or moderate CYP3A4 inhibitors

Cytopenia, ruxolitinib [2] ---> SmPC of [2] of EMA

Patients should be closely monitored (e.g. twice weekly) for cytopenias and dose titrated based on safety and efficacy (see section 4.2).

Dabigatran etexilate, ruxolitinib [2] ---> SmPC of [2] of EMA

Ruxolitinib may inhibit P-glycoprotein and breast cancer resistance protein (BCRP) in the intestine. This may result in increased systemic exposure of substrates of these transporters

Dabigatran, ruxolitinib [2] ---> SmPC of [2] of EMA

Ruxolitinib may inhibit P-glycoprotein and breast cancer resistance protein (BCRP) in the intestine. This may result in increased systemic exposure of substrates of these transporters

Digoxin, ruxolitinib [2] ---> SmPC of [2] of EMA

Ruxolitinib may inhibit P-glycoprotein and breast cancer resistance protein (BCRP) in the intestine. This may result in increased systemic exposure of substrates of these transporters

Diltiazem, ruxolitinib [2] ---> SmPC of [2] of EMA

Mild or moderate CYP3A4 inhibitors may increase ruxolitinib exposition. No dose adjustment is recommended when ruxolitinib is co-administered with mild or moderate CYP3A4 inhibitors

Drugs metabolised by intestinal CYP3A4, ruxolitinib [2] ---> SmPC of [2] of EMA

A study in healthy subjects indicated that ruxolitinib did not inhibit the metabolism of the oral CYP3A4 substrate midazolam. Therefore, no increase in exposure of CYP3A4 substrates is anticipated when combining them with ruxolitinib.

Drugs primarily metabolised by CYP3A4, ruxolitinib [2] ---> SmPC of [2] of EMA

Erythromycin, ruxolitinib [2] ---> SmPC of [2] of EMA

Mild or moderate CYP3A4 inhibitors may increase ruxolitinib exposition. No dose adjustment is recommended when ruxolitinib is co-administered with mild or moderate CYP3A4 inhibitors

Fertility, ruxolitinib [2] ---> SmPC of [2] of EMA

There are no human data on the effect of ruxolitinib on fertility. In animal studies, no effect on fertility was observed.

Fluconazole, ruxolitinib [2] ---> SmPC of [2] of EMA

Hemopoietic growth factors, ruxolitinib [2] ---> SmPC of [2] of EMA

It is not known whether the Janus associated kinase (JAK) inhibition by ruxolitinib reduces the efficacy of the haematopoietic growth factors or whether the haematopoietic growth factors affect the efficacy of ruxolitinib

Indinavir, ruxolitinib [2] ---> SmPC of [2] 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.

Itraconazol, ruxolitinib [2] ---> SmPC of [2] 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.

Ketoconazole, ruxolitinib [2] ---> SmPC of [2] 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.

Lopinavir/ritonavir, ruxolitinib [2] ---> SmPC of [2] 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.

Mibefradil, ruxolitinib [2] ---> SmPC of [2] 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.

Midazolam, ruxolitinib [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inhibitors, ruxolitinib [2] ---> SmPC of [2] of EMA

Mild or moderate CYP3A4 inhibitors may increase ruxolitinib exposition. No dose adjustment is recommended when ruxolitinib is co-administered with mild or moderate CYP3A4 inhibitors

Nefazodone, ruxolitinib [2] ---> SmPC of [2] 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.

Nelfinavir, ruxolitinib [2] ---> SmPC of [2] 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.

Oral contraceptives, ruxolitinib [2] ---> SmPC of [2] of EMA

A study in healthy subjects indicated that ruxolitinib does not affect the pharmacokinetics of an oral contraceptive containing ethinylestradiol and levonorgestrel.

P-glycoprotein substrates, ruxolitinib [2] ---> SmPC of [2] of EMA

Ruxolitinib may inhibit P-glycoprotein and breast cancer resistance protein (BCRP) in the intestine. This may result in increased systemic exposure of substrates of these transporters

Phenobarbital, ruxolitinib [2] ---> SmPC of [2] of EMA

The strong CYP3A4 induction may reduce the AUC of ruxolitinib. It is possible that an increase of the ruxolitinib dose is needed with strong CYP3A4 inductors

Phenytoin, ruxolitinib [2] ---> SmPC of [2] of EMA

The strong CYP3A4 induction may reduce the AUC of ruxolitinib. It is possible that an increase of the ruxolitinib dose is needed with strong CYP3A4 inductors

Posaconazole, ruxolitinib [2] ---> SmPC of [2] 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.

Pregnancy, ruxolitinib [2] ---> SmPC of [2] of EMA

As a precautionary measure, the use of Jakavi during pregnancy is contraindicated

Rifabutin, ruxolitinib [2] ---> SmPC of [2] of EMA

The strong CYP3A4 induction may reduce the AUC of ruxolitinib. It is possible that an increase of the ruxolitinib dose is needed with strong CYP3A4 inductors

Rifampicin, ruxolitinib

The strong CYP3A4 induction may reduce the AUC of ruxolitinib. It is possible that an increase of the ruxolitinib dose is needed with strong CYP3A4 inductors

Rifampicin, ruxolitinib [2] ---> SmPC of [2] of EMA

The strong CYP3A4 induction may reduce the AUC of ruxolitinib. It is possible that an increase of the ruxolitinib dose is needed with strong CYP3A4 inductors

Ritonavir, ruxolitinib [2] ---> SmPC of [2] 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.

Rosuvastatin, ruxolitinib [2] ---> SmPC of [2] of EMA

Ruxolitinib may inhibit P-glycoprotein and breast cancer resistance protein (BCRP) in the intestine. This may result in increased systemic exposure of substrates of these transporters

Ruxolitinib [1], saquinavir ---> 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.

Ruxolitinib [1], St. John's wort ---> SmPC of [1] of EMA

The strong CYP3A4 induction may reduce the AUC of ruxolitinib. It is possible that an increase of the ruxolitinib dose is needed with strong CYP3A4 inductors

Ruxolitinib [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

The strong CYP3A4 induction may reduce the AUC of ruxolitinib. It is possible that an increase of the ruxolitinib dose is needed with strong CYP3A4 inductors

Ruxolitinib [1], strong CYP3A4 inhibitors ---> 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.

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.

Ruxolitinib [1], telithromycin ---> 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.

Ruxolitinib [1], voriconazole ---> 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.

Ruxolitinib [1], women of childbearing potential ---> SmPC of [1] of EMA

In case pregnancy should occur during treatment with Jakavi, a risk/benefit evaluation must be carried out on an individual basis with careful counselling regarding potential risks to the foetus (see section 5.3).

CONTRAINDICATIONS of Ruxolitinib (Jakavi)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Pregnancy and breast-feeding

https://www.ema.europa.eu/en/documents/product-information/jakavi-epar-product-information_en.pdf 10/11/2025

Other trade names: Opzelura,

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