Interaction between brivaracetam ( 100 mg/ day) and a combination oral contraceptive: A randomized, doubleblind, placebo-controlled study

This randomized, double-blind, placebo-controlled, two-way crossover study aimed to assess the pharmacokinetic interactions between brivaracetam 100mg/day and a combination oral contraceptive (OC) containing 30g ethinylestradiol and 150g levonorgestrel. The study was performed in 28 healthy women over five 28-day menstrual cycles: baseline (OC only), two treatment cycles with brivaracetam (50mg b.i.d.) or placebo coadministered with OC separated by a wash-out cycle (OC only), and a follow-up cycle (OC only). The OC was administered on days 1-21 of each cycle, and brivaracetam or placebo on days 1-28 of the treatment cycles. Pharmacokinetics of ethinylestradiol and levonorgestrel were determined on day 20; brivaracetam morning trough levels on days 20 (with OC) and 29 (without OC) were compared. C-max (maximum plasma concentration) and AUC (area under the plasma concentration versus time curve) ratios for brivaracetam versus placebo (90% confidence interval [CI]) were 0.96 (0.88-1.04) and 0.90 (0.86-0.95) for ethinylestradiol, and 0.95 (0.91-0.99) and 0.92 (0.88-0.97) for levonorgestrel, within predefined bioequivalence limits (0.80-1.25). Brivaracetam trough levels were similar on days 20 and 29 (ratio 1.08; 90% CI 0.98-1.18). No differences in breakthrough bleeding were seen across the five cycles. It was concluded that there were no interactions between brivaracetam 100mg/day and the OC. A PowerPoint slide summarizing this article is available for download in the Supporting Information section .