Effect of eslicarbazepine acetate on the pharmacokinetics of a combined ethinylestradiol/levonorgestrel oral contraceptive in healthy women

•ESL significantly decreased the exposure to ethinylestradiol and levonorgestrel.•This effect is most likely mediated by an induction of CYP3A4 metabolism.•To avoid inadvertent pregnancy other methods of contraception should be used.

SummaryObjectiveTo investigate the effect of once-daily (QD) eslicarbazepine acetate (ESL) 800 mg and 1200 mg administration on pharmacokinetics of a combined ethinylestradiol/levonorgestrel oral contraceptive (OC) in women of childbearing potential.MethodsTwo two-way, crossover, two-period, randomized, open-label studies were performed in 20 healthy female subjects, each. In one period (ESL + OC period), subjects received ESL 800 mg QD in one study and ESL 1200 mg QD in the other study, for 15 days; concomitantly with the Day 14 ESL dose, an oral single dose of 30 μg ethinylestradiol and 150 μg levonorgestrel was administered. In the other period (OC alone), a single dose of 30 μg ethinylestradiol and 150 μg levonorgestrel was administered. Three weeks or more separated the periods. An analysis of variance (ANOVA) was used to test for differences between pharmacokinetic parameters of 30 μg ethinylestradiol and 150 μg levonorgestrel following ESL + OC and OC alone, and 90% confidence intervals (90%CI) for the ESL + OC/OC alone geometric mean ratio (GMR) were calculated.ResultsESL significantly decreased the systemic exposure to both ethinylestradiol and levonorgestrel. GMR (90%CI) for AUC0-24 of ethinylestradiol were 68% (64%; 71%) following 1200 mg ESL and 75% (71%; 79%) following 800 mg ESL. GMR (90%CI) for AUC0-24 of levonorgestrel were 76% (68%; 86%) following 1200 mg ESL and 89% (82%; 97%) following 800 mg ESL.ConclusionsA clinically relevant dose-dependent effect of ESL administration on the pharmacokinetics of ethinylestradiol and levonorgestrel was observed. Therefore, to avoid inadvertent pregnancy, women of childbearing potential should use other adequate methods of contraception during treatment with ESL, and, in case ESL treatment is discontinued, until CYP3A4 activity returns to normal.