Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of ixabepilone, which is primarily metabolized by the isoenzyme. According to the manufacturer, coadministration of ixabepilone with the potent CYP450 3A4 inducer rifampin decreased ixabepilone systemic exposure (AUC) by 43% compared to administration of ixabepilone alone. Reduced efficacy of ixabepilone may occur.

MANAGEMENT: The use of ixabepilone in combination with potent CYP450 3A4 inducers should generally be avoided. If coadministration is required, the manufacturer recommends increasing the ixabepilone dosage from 40 mg/m2 to 60 mg/m2 as tolerated. Following discontinuation of the potent CYP450 3A4 inducer, the dosage of ixabepilone should be returned to that used prior to initiation of the inducer.

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of ixabepilone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients treated with ixabepilone should avoid the consumption of grapefruit or grapefruit juice.