Pharmacokinetic interactions between contraceptives and antiepileptic drugs

The occurrence of bi-directional drug interactions between antiepileptic drugs (AEDs) and combined oral contraceptives (OCs) pose potential risks of un-intended pregnancy and as well as seizure deterioration. It is well established that several of the older AEDs (carbamazepine, phenytoin and phenobarbital), are strong inducers of the hepatic cytochrome P450 (CYP) 3A4 enzyme system, and are associated with increased the risk of contraceptive failure. In addition, it is demonstrated that also some of the newer AEDs, oxcarbazepine and topiramate influence on the pharmacokinetics of OCs, which is thought to be due to a more selective induction of subgroups of the hepatic enzyme system. Estrogens containing OCs induce the glucuronosyltransferase and may reduce the plasma levels and the effect of AEDs cleared by glucuronidation. This has been most intensively studied for lamotrigine but also other AEDs, which undergoes glucuronidation processes, such as valproate and oxcarbazepine, may be affected by OCs. The magnitude of the drug-drug interactions show in general wide inter-individual variability and the change in the elimination rate is often unpredictable and can be influenced by a number of co-variants such as co-medication of other drugs, as well as genetic and environmental factors. It is therefore recommended that change in OC use is assisted by AED monitoring whenever possible.