Levetiracetam Use in Pregnancy

OBJECTIVE: To review data evaluating levetiracetam management of epilepsy during pregnancy. DATA SOURCES: A literature search of PubMed (1966-June 2009) was; performed using the terms pregnancy, epilepsy, levetiracetam, and anticonvulsants. Bibliographies of all articles retrieved were reviewed to identify additional relevant articles. STUDY SELECTION AND DATA EXTRACTION: All studies including humans and published in English with data describing levetiracetam management during pregnancy were included. DATA SYNTHESIS: The pharmacokinetic studies included in this review demonstrate that the clearance of levetiracetam increases during pregnancy, particularly during the third trimester, which subsequently leads to decreased serum levetiracetam concentrations. The increase in clearance is most likely due to an increase in renal blood flow. The teratogenic studies included in this review included a total of 147 patients. Of these patients, 2% experienced a major congenital malformation (MCM) and 4.8% experienced a minor anomaly. All of the patients who had either an MCM or a minor anomaly were receiving antiepileptic drug (AED) polytherapy. It was unknown whether 10.9% of the 147 patients discussed were receiving levetiracetam monotherapy or AED polytherapy. None of the published literature assessed adherence to AED therapy. Folic acid supplementation was addressed in only one of the case series presented. CONCLUSIONS: If levetiracetam is used during pregnancy, women should receive adequate amounts of folic acid (0.4-5 mg/day) and serum concentrations of levetiracetam should be determined before conception if possible and during each trimester, especially during the middle of the third trimester, to assess therapeutic concentrations. The dose may need to be increased during the third trimester to provide concentrations consistent with those before conception. Patients should be informed that there appears to be a small chance of malformations with levetiracetam, but that the data are limited.