Drug Interactions between ethinyl estradiol / norelgestromin and perampanel

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with certain anticonvulsants, such as rufinamide and perampanel, may reduce the efficacy of contraceptive hormones. The interaction stems from accelerated clearance of contraceptive hormones as well as decreased plasma concentrations of unbound (active) hormones due to induction of hepatic CYP450 enzymatic activity by the anticonvulsants. Pharmacokinetic studies have found that dosages of rufinamide 800 mg twice daily for 14 days reduced ethinyl estradiol and norethindrone systemic exposure (AUC) by 22% and 14%, respectively, and the Cmax by 31% and 18%, respectively. Perampanel doses of 12 mg once daily for 21 days with ethinyl estradiol-levonorgestrel reduced levonorgestrel systemic exposure and Cmax by 40% and 42%, respectively, and did not affect ethinyl estradiol exposure whilst it reduced the Cmax by 18%. The clinical significance is unknown.

MANAGEMENT: Women using hormonal contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant therapy with enzyme-inducing anticonvulsants. In general, alternative or additional methods of birth control should be used during and for at least two weeks after short-term and 4 weeks after long-term (greater than 4 weeks) anticonvulsant therapy. Intrauterine systems are unlikely to be significantly affected because of their local action. Input from a gynecologist or similar expert on adequate contraception, including emergency contraception, should be sought as needed.

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with certain anticonvulsants, such as rufinamide and perampanel, may reduce the efficacy of contraceptive hormones. The interaction stems from accelerated clearance of contraceptive hormones as well as decreased plasma concentrations of unbound (active) hormones due to induction of hepatic CYP450 enzymatic activity by the anticonvulsants. Pharmacokinetic studies have found that dosages of rufinamide 800 mg twice daily for 14 days reduced ethinyl estradiol and norethindrone systemic exposure (AUC) by 22% and 14%, respectively, and the Cmax by 31% and 18%, respectively. Perampanel doses of 12 mg once daily for 21 days with ethinyl estradiol-levonorgestrel reduced levonorgestrel systemic exposure and Cmax by 40% and 42%, respectively, and did not affect ethinyl estradiol exposure whilst it reduced the Cmax by 18%. The clinical significance is unknown.

MANAGEMENT: Women using hormonal contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant therapy with enzyme-inducing anticonvulsants. In general, alternative or additional methods of birth control should be used during and for at least two weeks after short-term and 4 weeks after long-term (greater than 4 weeks) anticonvulsant therapy. Intrauterine systems are unlikely to be significantly affected because of their local action. Input from a gynecologist or similar expert on adequate contraception, including emergency contraception, should be sought as needed.