Diane 35 Drug Interactions

Note: The prescribing information of concomitant medications should be consulted to identify potential interactions.
Effects of other medicinal products on Cyproterone acetate + Ethinylestradiol (Diane 35): Interactions can occur with drugs that induce microsomal enzymes which can result in increased clearance of sex hormones and which may lead to breakthrough bleeding and/or contraceptive failure.
Enzyme induction can already be observed after a few days of treatment. Maximal enzyme induction is generally seen within a few weeks. After the cessation of drug therapy enzyme induction may be sustained for about 4 weeks.
Women on treatment with any of these drugs should temporarily use a barrier method in addition to Cyproterone acetate + Ethinylestradiol (Diane 35) or choose another method of contraception. The barrier method should be used during the time of concomitant drug administration and for 28 days after their discontinuation. If the period during which the barrier method is used runs beyond the end of the tablets in the Cyproterone acetate + Ethinylestradiol (Diane 35) pack, the next pack should be started without the usual tablet-free interval.
Substances increasing the clearance of Cyproterone acetate + Ethinylestradiol (Diane 35) [diminished efficacy of Cyproterone acetate + Ethinylestradiol (Diane 35) by enzyme-induction], e.g.: Phenytoin, barbiturates, primidone, carbamazepine, rifampicin, and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin and products containing St. John's wort.
Substances with variable effects on the clearance of Cyproterone acetate + Ethinylestradiol (Diane 35), e.g.: When co-administered with Cyproterone acetate + Ethinylestradiol (Diane 35), many HIV/HCV protease inhibitors and non-nucleoside reverse transcriptase inhibitors can increase or decrease plasma concentrations of estrogen or progestin. These changes may be clinically relevant in some cases.
Substances decreasing the clearance of Diane 35 (enzyme inhibitors): Strong and moderate CYP3A4 inhibitors such as azole antifungals (e.g. itraconazole, voriconazole, fluconazole), verapamil, macrolides (e.g. clarithromycin, erythromycin), diltiazem and grapefruit juice can increase plasma concentrations of the estrogen or the progestin or both.
Etoricoxib doses of 60 to 120 mg/day have been shown to increase plasma concentrations of ethinylestradiol 1.4 to 1.6-fold, respectively when taken concomitantly with a combined hormonal contraceptive containing 0.035 mg ethinylestradiol.
Effects of estrogen/progestogen combinations on other medicinal products: Estrogen/progestogen combinations like Cyproterone acetate + Ethinylestradiol (Diane 35) may affect the metabolism of certain other drugs. Accordingly, plasma and tissue concentrations may either increase (e.g. cyclosporin) or decrease (e.g. lamotrigine).
In vitro, ethinylestradiol is a reversible inhibitor of CYP2C19, CYP1A1 and CYP1A2 as well as a mechanism based inhibitor of CYP3A4/5, CYP2C8, and CYP2J2. In clinical studies, administration of a hormonal contraceptive containing ethinylestradiol did not lead to any increase or only to a weak increase in plasma concentrations of CYP3A4 substrates (e.g. midazolam) while plasma concentrations of CYP1A2 substrates can increase weakly (e.g. theophylline) or moderately (e.g. melatonin and tizanidine).
Pharmacodynamic interaction: Co-administration of ethinylestradiol-containing medicinal products with direct-acting antiviral (DAA) medicinal products containing ombitasvir, paritaprevir, or dasabuvir, and combinations of these has been shown to be associated with increases in ALT levels to greater than 20 times the upper limit of normal in healthy female subjects and HCV infected women (see Contraindications).
Other forms of interaction: Laboratory tests: The use of preparations like Cyproterone acetate + Ethinylestradiol (Diane 35) 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.