Abstracts

Lamotrigine is metabolized in the liver via glucuronidation and the clearance of Lamotrigine is considerably enhanced when taken concurrently with drugs that increase metabolism via the Uridine Diphosphat Glucuronosyltransferase system (UDP). Oral contraceptives may increase clearance of drugs that are metabolized via UDP, and retrospective studies suggest that oral contraceptives increase the metabolism of Lamotrigine. However, no formal controlled trials have assessed the the effect of oral contraceptives on Lamotrigine metabolism in patients with epilepsy. Women with epilepsy, aged 18 [ndash] 40 years, concurrently taking combination type oral contraceptives and Lamotrigine in monotherapy were eligible for participation in the study. In a blinded, crossover design, patients were randomly assigned continued use of oral contraceptives or placebo for one menstrual cycle. Throughout the study, patients were taking the same kind of combination type oral contraceptives (estrogen and progesterone (Cilest) or matching placebo). Barrier-type contraceptives were used throughout the study. Trough blood samples were taken at the end of each of the menstrual cycles and the Lamotrigine concentration analyzed. The primary outcome of the trial was the comparison of the Lamotrigine concentration after one menstrual cycle taking oral contraceptives and one menstrual cycle taking placebo. A total of 13 patients were included in the trial, but only six patients completed the entire trial. The mean concentration of Lamotrigine after one menstrual cycle taking placebo was 195% (95% Confidence Intervals: 146 [ndash] 245%, P [lt] 0.005) of the concentration after one menstrual cycle taking oral contraceptives. There were no pregnancies in the trial. Oral contraceptives significantly reduce the concentration of Lamotrigine. The reduction is large enough to expect that the interaction may influence safety and efficacy of Lamotrigine, and thus warrants further investigation. (Supported by Hede Nielsens Familiefond and Institue of Clinical Medicine, University of Aarhus supported the study. GSK supported presentation of the study.)