Drug Interactions between conjugated estrogens / medroxyprogesterone and vorasidenib

ADDITIONAL CONTRACEPTION RECOMMENDED: Concomitant use with vorasidenib may decrease the plasma concentrations and efficacy of contraceptive hormones. In vitro studies show that vorasidenib is an inducer of CYP450 3A, the isoenzyme primarily responsible for the metabolic clearance of sex hormones. Decreased hormone concentrations can result in contraception failure and/or increase in breakthrough bleeding. Vorasidenib 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 vorasidenib. Since the use of vorasidenib is likely associated with 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 vorasidenib. Women of childbearing potential should use a highly effective, non-hormonal method of contraception during treatment with vorasidenib and for 3 months after the last dose. Male patients with female partners of reproductive potential should use effective contraception during treatment with vorasidenib and for 3 months after the last dose

GENERALLY AVOID: Concomitant use with multiple doses of vorasidenib may decrease the plasma concentrations of drugs that are substrates of CYP450 3A. Vorasidenib is predicted to be an inducer of CYP450 3A resulting in decreased plasma concentrations of agents that are metabolized by the isoenzyme. The interaction may be significant for sensitive CYP450 3A4 substrates or those that demonstrate a narrow therapeutic index. Clinical and pharmacokinetic data are currently lacking.

MANAGEMENT: Concomitant use of vorasidenib with substrates of CYP450 3A should be avoided due to the potential for reduced efficacy