Riliz Drug Interactions

Drug Affecting Hepatic Microsomal Enzymes: Progestogens, including dienogest, are metabolized mainly by the cytochrome P450 system (CYP3A4) located both in the intestinal mucosa and in the liver. Therefore, inducers or inhibitors of CYP3A4 may affect the progestogen drug metabolism.
An increased clearance of sex hormones due to enzyme induction may reduce the therapeutic effect of dienogest and may result in adverse effects e.g., changes in the uterine bleeding profile.
A reduced clearance of sex hormones due to enzyme inhibition may increase the exposure to dienogest and may result in adverse effects.
Cytochrome P450 (CYP3A4) Inducers: Interactions may occur with drug substances (e.g., phenytoin, barbiturates, primidone, carbamazepine, rifampicin, and possibly also oxcarbazepine, topiramate, felbamate, and griseofulvin) that induce CYP3A4 enzymes which may result in increased clearance of sex hormones. Induction of hepatic microsomal enzymes may decrease plasma concentrations of dienogest. Enzyme induction can be observed after a few days of treatment. Maximum enzyme induction is generally seen within a few weeks. After the cessation of drug therapy, enzyme induction may be sustained for about 4 weeks.
Cytochrome P450 (CYP3A4) Inhibitors: Dienogest is a substrate of CYP3A4. Concomitant administration of strong and moderate CYP3A4 inhibitors such as azole antifungals (e.g., ketoconazole, itraconazole, voriconazole, fluconazole), macrolides (e.g., clarithromycin, erythromycin), diltiazem, and verapamil may increase plasma concentrations of dienogest.
HIV/HCV protease inhibitors (e.g., ritonavir, saquinavir, indinavir, nelfinavir, boceprevir): May increase or decrease plasma concentrations of dienogest. These changes may be clinically relevant in some cases.
Non-nucleoside reverse transcriptase inhibitors (e.g., nevirapine, efavirenz): May result in an increased clearance of dienogest.
Antacids (e.g., cimetidine, ranitidine): May increase plasma concentrations of dienogest.
Grapefruit juice: May increase plasma concentrations of dienogest.
St. John's wort (Hypericum perforatum): May induce CYP3A4 enzymes and can result in increased clearance of sex hormones.
Other Drugs: Based on in vitro inhibition studies, it is unlikely that dienogest will have clinically relevant effects on the cytochrome P450 enzyme-mediated metabolism of other medications.
Laboratory Tests: The use of progestogens may influence the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and renal function, plasma levels of (carrier) proteins (e.g., corticosteroid binding globulin and lipid/lipoprotein fractions), parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis. Changes generally remain within the normal laboratory range.