Drug Interactions between belzutifan and Cycrin

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with belzutifan may decrease the plasma concentrations of hormonal contraceptives and possibly render them ineffective. The proposed mechanism is belzutifan-mediated induction of CYP450 3A4, the isoenzyme primarily responsible for the metabolic clearance of hormonal contraceptives. Concomitant use of belzutifan (120 mg once daily) with midazolam (a sensitive CYP450 3A4 substrate) decreased the midazolam systemic exposure (AUC) and peak plasma concentration (Cmax) by 40% and 34%, respectively. In patients with higher belzutifan concentrations (e.g., dual UGT 2B17 and CYP450 2C19 poor metabolizers) the AUC of midazolam is predicted to decrease by up to 70%. Belzutifan can cause fetal harm when administered to a pregnant woman.

MANAGEMENT: Hormonal contraceptives, including oral, injectable, transdermal, and implantable forms, may not be reliable during concomitant therapy with belzutifan. Women using hormonal contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant therapy with belzutifan. Because use of belzutifan may cause embryo-fetal harm, 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 belzutifan. Female patients of reproductive potential should use a highly effective, non-hormonal method of contraception during treatment and for 1 week after treatment. Male patients with female partners of reproductive potential should use effective contraception during treatment with belzutifan and for 1 week after treatment.

Switch to consumer interaction data