Drug Interactions between ixabepilone and Prezcobix

MONITOR: Coadministration with inhibitors of CYP450 3A4 may 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 potent inhibitor ketoconazole resulted in a 79% increase in ixabepilone systemic exposure (AUC) compared to treatment without ketoconazole. The effect of mild or moderate inhibitors such as erythromycin, fluconazole, or verapamil on exposure to ixabepilone has not been studied.

MANAGEMENT: Caution is advised when ixabepilone is prescribed with CYP450 3A4 inhibitors. Pharmacologic response to ixabepilone should be monitored more closely whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy, and the ixabepilone dosage adjusted as necessary. Frequent monitoring of peripheral blood counts between treatment cycles is recommended, and patients should be advised to contact their physician if they experience signs and symptoms of ixabepilone toxicities such as infection or burning, tingling, or numbness in the hands and feet.

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.