Yaz Drug Interactions

Note: The prescribing information of concomitant medications should be consulted to identify potential interactions.
Effects of other medicinal products on Drospirenone + Ethinylestradiol (Yaz): 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 the COC 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 hormone-containing light pink film-coated tablets in the COC pack, the hormone-free white film-coated tablets should be omitted and the next COC pack be started.
Substances increasing the clearance of COCs (diminished efficacy of COCs 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 COCs, e.g.: When co-administered with COCs, 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 COCs (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 COCs on other medicinal products: COCs may affect the metabolism of certain other drugs. Accordingly, plasma and tissue concentrations may either increase (e.g. cyclosporin) or decrease (e.g. lamotrigine).
Based on in vivo interaction studies in female volunteers using omeprazole, simvastatin or midazolam as marker substrates, a clinically relevant interaction of drospirenone at doses of 3 mg with the cytochrome P450 mediated metabolism of other drugs is unlikely.
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 interactions: 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 interactions: Serum potassium: There is a theoretical potential for an increase in serum potassium in women taking Drospirenone + Ethinylestradiol (Yaz) hormone-containing light pink film-coated tablets with other drugs that may increase serum potassium levels. Such drugs include angiotensin-II-receptor antagonists, potassium-sparing diuretics, and aldosterone antagonists. However, in studies evaluating the interaction of drospirenone (combined with estradiol) with an ACE inhibitor or indomethacin, no clinically or statistically significant differences in serum potassium concentrations were observed.
Laboratory tests: The use of contraceptive steroids 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. Drospirenone causes an increase in plasma renin activity and plasma aldosterone induced by its mild antimineralocorticoid activity.