EFFECTS OF FELBAMATE ON THE PHARMACOKINETICS OF A LOW-DOSE COMBINATION ORAL-CONTRACEPTIVE

The effects of felbamate on the pharmacokinetics of a low-dose combina tion oral contraceptive containing 30 mu g ethinyl estradiol and 75 mu g gestodene were assessed in a randomized, double-blind, placebo-cont rolled parallel-group study in healthy premenopausal female volunteers established in a regimen of oral contraceptive use. They received eit her placebo or 2400 mg/day felbamate from midcycle (day 15) to midcycl e (day 14) of two consecutive oral contraceptive cycles (months 1 and 2). Pharmacokinetic assessments of ethinyl estradiol and gestodene wer e performed on day 14 of both cycles. To determine whether ovulation o ccurred, plasma progesterone and urinary luteinizing hormone levels we re measured, and diaries recording vaginal bleeding were kept. Felbama te treatment resulted in a significant 42% decrease in gestodene area under the plasma concentration-time curve (0 to 24 hours) (p = 0.018) compared with baseline, whereas a minor but not clinically relevant ef fect was observed on the pharmacokinetic parameters of ethinyl estradi ol. There were no changes in the pharmacokinetics of ethinyl estradiol or gestodene after placebo treatment. No volunteer showed hormonal ev idence of ovulation; however, one volunteer reported the onset of inte rmenstrual bleeding during felbamate treatment. Because of the effect of felbamate on the pharmacokinetics of gestodene and the report of in termenstrual bleeding, it is possible that the contraceptive efficacy of low-dose combination oral contraceptives may be adversely affected during felbamate treatment.