Drug Interaction Report

ADJUST DOSING INTERVAL: Concurrent administration of agents that increase gastric pH such as H2-receptor antagonists or antacids may decrease the oral bioavailability of bosutinib and reduce its concentrations in plasma. The solubility of bosutinib decreases rapidly when the pH is above 5, resulting in reduced absorption. In 24 healthy volunteers, administration of a single 400 mg oral dose of bosutinib in combination with multiple oral doses of the proton pump inhibitor lansoprazole (60 mg) under fasting conditions resulted in a 46% decrease in bosutinib peak plasma concentration (Cmax) and 26% decrease in systemic exposure (AUC) compared to administration of bosutinib alone. The interaction has not been studied with H2-receptor antagonists or antacids.

MANAGEMENT: To minimize the potential for interaction, H2-receptor antagonists or antacids should be administered at least 2 hours before or 2 hours after the bosutinib dose.

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.