Drug interactions with oral contraceptives

Drug-drug interactions (DDI) can alter the metabolism of oral contraceptives (OC) and lead to treatment failure and unintended pregnancies (OC as victim drugs). The likelihood of such a loss of efficacy increases if elimination of the OC is substantially accelerated through comedication and the maintenance dose of the contraceptive is low. Among the drugs that accelerate this elimination in a relevant manner (so-called inductors) are enzyme-inducing antiepileptics (e.g., carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin), rifamycin antibiotics (rifampicin, rifabutin), efavirenz, and over-the-counter medicines such as the antidepressant St. John's wort. Combined with these substances, effective hormonal contraception is no longer guaranteed and OC have to be replaced by other contraceptive methods. On the other hand, numerous drugs are known to inhibit the elimination of progestogens, which are mainly metabolized by the cytochrome P450 3A4 isozymes. Relevant inhibitors for this isozyme (perpetrator drugs) are triazoles (e.g., fluconazole), HIV protease inhibitors (e.g., ritonavir), and some macrolide antibiotics (such as clarithromycin, erythromycin). With the current low-dose OC formulations, the observed increase in drug exposure due to DDI neither leads to acute toxicity nor does it impair contraception. Finally, OC can also induce the elimination of co-administered drugs (OC as a perpetrator) and substantially decrease the plasma concentrations of antiepileptic drugs that are mainly eliminated by glucuronidation such as valproic acid and lamotrigine (potentially leading to seizure recurrence). If such combinations cannot be avoided, antiepileptic concentrations and effects must be closely monitored or alternative contraception methods should be selected.