Visanne Drug Interactions

Effects of Other Medicaments on Visanne: Individual Enzyme Inducers or Inhibitors (CYP3A4): Progestogens including dienogest are metabolized mainly by the cytochrome P450 (CYP450) 3A4 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 Visanne and may result in adverse effects eg, 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.
Substances with Enzyme-Inducing Properties: Interactions can occur with drugs (eg, phenytoin, barbiturates, primidone, carbamazepine, rifampicin and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin, nevirapine and products containing St. John's wort) that induce microsomal enzymes (eg, CYP450 enzymes) which can result in increased clearance of sex hormones.
Maximum enzyme induction is generally not seen for 2-3 weeks but may then be sustained for at least 4 weeks after the cessation of therapy.
The effect of the CYP3A4 inducer rifampicin was studied in healthy postmenopausal women. Co-administration of rifampicin with estradiol valerate/dienogest tablets led to significant decreases in steady state concentrations and systemic exposures of dienogest. The systemic exposure of dienogest at steady state, measured by AUC_{0-24 hrs}, was decreased by 83%.
Substances with Enzyme-Inhibiting Properties: Known CYP3A4 inhibitors eg, azole antifungals (eg, ketoconazole, itraconazole, fluconazole), cimetidine, verapamil, macrolides (eg, erythromycin, clarithromycin and roxithromycin), diltiazem, protease inhibitors (eg, ritonavir, saquinavir, indinavir, nelfinavir), antidepressants (eg, nefazodone, fluvoxamine, fluoxetine) and grapefruit juice may increase plasma levels of progestogens and result in adverse effects.
In a study investigating the effect of CYP3A4 inhibitors (ketoconazole, erythromycin) on the combination of estradiol valerate/dienogest, steady state dienogest plasma levels were increased. Co-administration with the strong inhibitor ketoconazole resulted in a 186% increase of AUC_{0-24 hrs} at steady state for dienogest. When co-administered with the moderate inhibitor erythromycin, the AUC_{0-24 hrs} of dienogest at steady state was increased by 62%. The clinical relevance of these interactions is unknown.
Effects of Dienogest on Other Medicaments: Based on in vitro inhibition studies, a clinically relevant interaction of Visanne with the CYP450 enzyme-mediated metabolism of other medicaments is unlikely.
Note: The prescribing information of concomitant medications should be consulted to identify potential interactions.
Drug-Food Interactions: A standardized high fat meal did not affect the bioavailability of Visanne.
Other Forms of Interactions: 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 eg, lipid/lipoprotein fractions, parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis. Changes generally remain within the normal laboratory range.