Drug Interaction Report

Coadministration with brivaracetam at higher than recommended dosages may decrease the plasma concentrations of contraceptive hormones. The mechanism may involve weak induction of CYP450 3A4 metabolism by brivaracetam. In 24 healthy premenopausal women given an oral contraceptive containing ethinyl estradiol 30 mcg and levonorgestrel 150 mcg in combination with brivaracetam 200 mg twice daily (twice the recommended maximum daily dosage), a reduction in estrogen and progestin systemic exposure (AUC) of 27% and 23%, respectively, was observed without impact on suppression of ovulation. There was generally no difference in levels of the endogenous hormones estradiol, progesterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), and sex hormone binding globulin (SHBG) during the cycle with brivaracetam compared to the control cycle, and the combination was well tolerated. When the oral contraceptive was administered with brivaracetam 50 mg twice daily, no significant effects were observed on the pharmacokinetics of either ethinyl estradiol or levonorgestrel. Steady-state brivaracetam trough levels were also not affected by the oral contraceptive. Based on existing data, the interaction is not expected to be clinically relevant, and no particular precaution appears necessary when brivaracetam is used with oral contraceptives.