Drug Interaction Report

GENERALLY AVOID: Coadministration with proton pump inhibitors 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 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. Since proton pump inhibitors affect pH of the upper gastrointestinal tract for an extended period, separation of doses may not eliminate the interaction.

MANAGEMENT: The concomitant use of bosutinib with proton pump inhibitors should generally be avoided. If acid-suppression therapy is required during bosutinib treatment, an H2-receptor antagonist (e.g., cimetidine, famotidine, ranitidine) or antacid may be taken up to 2 hours before or 2 hours after the bosutinib dose.

ADJUST DOSING INTERVAL: Food may interfere with the absorption of esomeprazole. The manufacturer reports that the area under the concentration-time curve for esomeprazole following a single 40 mg dose was 33% to 53% lower when administered after food intake as opposed to during fasting conditions.

MANAGEMENT: Esomeprazole should be taken at least one hour before meals. When administered to patients receiving continuous enteral nutrition, some experts recommend that the tube feeding should be interrupted for at least 1 hour before and 1 hour after the dose of esomeprazole is given.

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.