Drug Interaction Report

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with bosentan may decrease the plasma concentrations and efficacy of contraceptive hormones. The mechanism is bosentan induction of CYP450 3A4, the isoenzyme primarily responsible for the metabolic clearance of sex hormones. In one study, coadministration of bosentan and an oral contraceptive containing ethinyl estradiol and norethindrone resulted in average decreases of 31% and 14%, respectively, in plasma levels of the hormones. However, decreases in exposure were as much as 66% for ethinyl estradiol and 56% for norethindrone in individual subjects.

MANAGEMENT: Hormonal contraceptives, including oral, injectable, transdermal, and implantable forms, may not be reliable during concomitant therapy with bosentan. Because use of bosentan is likely associated with major birth defects, it is particularly important that patients not become pregnant during treatment. Therefore, hormonal contraceptives should not be used as the sole method of birth control in women of childbearing potential treated with bosentan. Input from a gynecologist or similar expert on adequate contraception, including emergency contraception, should be sought as needed. Intrauterine systems are unlikely to be significantly affected because of their local action.