Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may 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. However, the extent to which less potent CYP450 3A4 inducers interact with ixabepilone is unknown.

MANAGEMENT: The potential for diminished pharmacologic effects of ixabepilone should be considered during coadministration with CYP450 3A4 inducers. Caution is advised if they are used with ixabepilone, and alternative treatments may be required if an interaction is suspected.

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.

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

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of rufinamide. In healthy volunteers, administration of a single 400 mg dose of rufinamide with food resulted in an approximately 56% increase in mean peak plasma concentration (Cmax) and a 34% increase in systemic exposure (AUC) compared to administration during a fasting state.

MANAGEMENT: To ensure maximal oral absorption, it is preferable to administer rufinamide with food. Patients receiving rufinamide should be advised to avoid consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how rufinamide affects them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.