Drug Interactions between ethinyl estradiol and nevirapine

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with nevirapine may decrease the plasma concentrations of contraceptive hormones, although the available evidence is conflicting. The proposed mechanism is nevirapine-medicated induction of CYP450 3A4, the isoenzyme partially responsible for the metabolic clearance of sex hormones and other steroids. In ten HIV-positive subjects, nevirapine (200 mg once a day for 2 weeks followed by 200 mg twice a day for 2 weeks) decreased the area under the plasma concentration-time curve (AUC) of ethinyl estradiol (administered as ethinyl estradiol-norethindrone 0.035 mg-1 mg) by 20% compared to administration of the oral contraceptive alone. The AUC and peak plasma concentration (Cmax) of norethindrone decreased by 19% and 16%, respectively. In a different study, levonorgestrel concentrations were found to be 1.4-4.9-fold higher when used in combination with nevirapine. Furthermore, clinical outcomes studies have not found a significant difference in the rate of pregnancy among women using hormonal contraceptives on nevirapine-based antiretroviral therapy (ART) and those not receiving ART.

MANAGEMENT: Women using hormonal contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant therapy with nevirapine. Some authorities do not suggest any dose adjustments for hormonal contraceptives when used in combination with nevirapine. Alternative or additional methods of birth control should be considered during and for at least two weeks after short-term and 4 weeks after long-term (greater than 4 weeks) nevirapine therapy if an interaction is suspected. Although breakthrough bleeding is not necessarily indicative of low ethinyl estradiol serum levels or increased risk of ovulation, some clinicians suggest that women who experience breakthrough bleeding during enzyme-inducing therapy may be prescribed an increased dose of ethinyl estradiol above 50 mcg daily by combining more than one formulation of contraceptive pill if necessary. No precautions or recommendations are available for women using hormone-releasing intrauterine systems, but a significant interaction with these systems is thought to be unlikely due to their local action.