Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of bosutinib, which is primarily metabolized by the isoenzyme. In 24 healthy volunteers, administration of a single 500 mg dose of bosutinib with the potent CYP450 3A4 inducer rifampin (600 mg/day for 6 days) under fed conditions resulted in an 86% decrease in bosutinib peak plasma concentration (Cmax) and 94% decrease in systemic exposure (AUC) compared to administration of bosutinib alone. No data are available for use with less potent CYP450 3A4 inducers.

MANAGEMENT: The potential for diminished pharmacologic effects of bosutinib should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of bosutinib. When given with a high-fat meal, bosutinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.8- and 1.7-fold, respectively.

GENERALLY AVOID: Coadministration with grapefruit juice is likely to increase the plasma concentrations of bosutinib, which is primarily metabolized by CYP450 3A4. However, the interaction has not been studied. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Bosutinib should be administered with a meal. The consumption of grapefruit, grapefruit juice, and supplements that contain grapefruit extract should be avoided.