Pharmacokinetic drug interactions between oral contraceptives and second-generation anticonvulsants

Drug interactions between oral contraceptives (OCs) and traditional anticon vulsants 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, anticonvul sants are increasingly employed in the therapy of nonseizure-related disord ers, placing more women at risk of potential drug interactions that may lea d to contraceptive failure. Second-generation anticonvulsants include felbamate, gabapentin, lamotrigin e, oxcarbazepine, tiagabine, topiramate, vigabatrin and zonisamide, Most ha ve been approved for adjunctive management of seizures refractory to therap y with traditional anticonvulsants. On the basis of available study data in women receiving concomitant OC preparations, gabapentin, lamotrigine, tiag abine and vigabatrin may be administered without significant pharmacokineti c interactions that potentially diminish contraceptive efficacy. However, a dditional or alternative contraceptive measures, including using OCs with h igher 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 zonisamid e in women receiving OCs have yet to be reported. It is important to characterise the properties [e.g. substrate and enzyme a ctivity (particularly cytochrome P450 3A4 induction)] of new anticonvulsant s and recognise their potential to interfere with OCs. However, a pharmacok inetic interaction does not in itself indicate loss of OC efficacy. Contrac eptive failure should be measured by changes in ovarian hormone concentrati ons, maturation of ovarian follicle(s) or ovulation.