Drug Interaction Report

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

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: Due to induction of CYP450 1A2, the isoenzyme primarily responsible for the metabolic clearance of vorasidenib, smoking tobacco during treatment with vorasidenib may decrease its plasma concentrations and anti-tumor effect. Clinical and pharmacokinetic data are currently lacking.

MANAGEMENT: Patient should be advised to avoid smoking tobacco during treatment with vorasidenib because it may reduce efficacy of the therapy.

MONITOR: Coadministration of ethinyl estradiol may increase the plasma concentrations of drugs that are primarily metabolized by CYP450 1A2. In a study of 30 healthy volunteers administered the CYP450 1A2 substrate tizanidine, the systemic exposure (AUC) of tizanidine was 3.9 times greater in women using an oral contraceptive containing ethinyl estradiol.

MANAGEMENT: Patients should be monitored for increased adverse effects of the CYP450 1A2 substrate during concomitant use with ethinyl estradiol. Product labeling for the specific CYP450 1A2 substrate should be consulted for additional recommendations.

Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.

The central nervous system effects and blood levels of ethanol may be increased in patients taking oral contraceptives, although data are lacking and reports are contradictory. The mechanism may be due to enzyme inhibition. Consider counseling women about this interaction which is unpredictable.

The central nervous system effects and blood levels of ethanol may be increased in patients taking oral contraceptives, although data are lacking and reports are contradictory. The mechanism may be due to enzyme inhibition. Consider counseling women about this interaction which is unpredictable.