Drug Interaction Report

MONITOR: Coadministration with enasidenib may alter the plasma concentrations of hormonal contraceptives. In vitro, enasidenib has been found to both inhibit and induce CYP450 3A4, the isoenzyme primarily responsible for the metabolic clearance of contraceptive hormones. The clinical significance is unknown.

MANAGEMENT: Because use of enasidenib may be associated with fetal harm, it is important that patients not become pregnant during treatment. It may be advisable to monitor patients for potentially altered effects of their hormonal contraceptive during and after treatment with enasidenib. 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.

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.