Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of ixabepilone, which is primarily metabolized by the isoenzyme. According to the product labeling, administration of ixabepilone in combination with the CYP450 3A4 inhibitor ketoconazole resulted in a 79% increase in ixabepilone systemic exposure (AUC) compared to treatment without ketoconazole.

MANAGEMENT: Concomitant use of ixabepilone with potent CYP450 3A4 inhibitors should generally be avoided. If coadministration is necessary, a reduction of the ixabepilone dosage to 20 mg/m2 should be considered. Based on pharmacokinetic studies, this dosage is predicted to adjust the ixabepilone systemic exposure (AUC) to the range observed without inhibitors. However, clinical data are lacking. Following discontinuation of the potent CYP450 3A4 inhibitor, a washout period of approximately one week should be allowed before the ixabepilone dosage is adjusted upward to the indicated dosage.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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.