Pharmacokinetic drug interactions between oral contraceptives and second-generation anticonvulsants

Drug interactions between oral contraceptives (OCs) and traditional anticonvulsants have been well described. However, in the past decade, a number of new anticonvulsants have been developed, as well as modifications made in the composition of the OC preparations themselves. Additionally, anticonvulsants are increasingly employed in the therapy of nonseizure-related disorders, placing more women at risk of potential drug interactions that may lead to contraceptive failure. Second-generation anticonvulsants include felbamate, gabapentin, lamotrigine, oxcarbazepine, tiagabine, topiramate, vigabatrin and zonisamide. Most have been approved for adjunctive management of seizures refractory to therapy with traditional anticonvulsants. On the basis of available study data in women receiving concomitant OC preparations, gabapentin, lamotrigine, tiagabine and vigabatrin may be administered without significant pharmacokinetic interactions that potentially diminish contraceptive efficacy. However, additional or alternative contraceptive measures, including using OCs with higher estrogen content, are recommended when using felbamate, oxcarbazepine and topiramate, as these agents have demonstrated enzyme-inducing activity leading to reduced plasma steroid concentrations. The effects of zonisamide in women receiving OCs have yet to be reported. It is important to characterise the properties [e.g. substrate and enzyme activity (particularly cytochrome P450 3A4 induction)] of new anticonvulsants and recognise their potential to interfere with OCs. However, a pharmacokinetic interaction does not in itself indicate loss of OC efficacy. Contraceptive failure should be measured by changes in ovarian hormone concentrations, maturation of ovarian follicle(s) or ovulation.