Abstracts

Rationale: Serum concentrations of first generation AEDs are known to fall during pregnancy. This is particularly true for phenobarbital and phenytoin during the first trimester and carbamazepine in the third trimester. This is related to protein binding. Little is known about changes in serum concentrations involving second generation AEDs. Many of these are renally excreted (topamax, oxcarbazepine, levetiracitam). As a result, renal clearance and GRF increase during pregnancy. Oral contraceptives are known to decrease lamotrigine levels because of glucuronidation. The same appears to occur during pregnancy. Therefore, close monitoring of both renally excreted second generation AEDs and lamotrigine is required to sustain seizure control during pregnancy. Elevation in post-partum serum concentrations are seen in first generation AEDs, approximately 10 to 14 days post-partum. In contrast, as renal clearance and glucuronidation revert to the pre-gestational state, the risk of toxicity from renally excreted second generation AEDs and lamotrigine may occur immediately post-partum. Methods: Twenty women with epilepsy, yielding twenty-three pregnancies, were followed over the last three years at Boston Medical Center. Serum levels yielding seizure freedom were established pre-gestationally and served as the individual's therapeutic level. Serum concentrations were monitored throughout pregnancy and when below this established therapeutic level, dose adjustments were made to achieve seizure control. Serum concentrations were checked on the day of delivery and one day post-partum when possible. Results: Frequent dose adjustments were required to maintain each individual's therapeutic level and prevent seizures. Only patients with refractory epilepsy had breakthrough seizures during pregnancy. All those who were seizure free pre-gestationally remained seizure free during pregnancy. Levels one day post-partum were markedly higher than the individual's established therapeutic level, as well as the previously obtained level during pregnancy. This required immediate dose adjustments to avoid toxicity. Conclusions: It is highly recommended that serum concentrations of both first and second generation AEDs be monitored throughout pregnancy and appropriate dose adjustments be made. It is also imperative that immediate post-partum levels of second generation AEDs be monitored to prevent toxicity. Dose adjustments may need to be made day of delivery and/or one day post-partum.