Drug Interaction Report

Since the aqueous solubility of axitinib is pH-dependent, with higher pH resulting in lower solubility, drugs that increase the pH of the upper gastrointestinal tract may reduce the oral bioavailability of axitinib. The interaction has been studied with rabeprazole. When given with rabeprazole (20 mg once daily for 5 days), axitinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by approximately 50% and 20%, respectively. These changes are not considered clinically significant. No dosage adjustment for axitinib is recommended during coadministration with proton pump inhibitors, H2-receptor antagonists, or antacids.

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.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of axitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Patients treated with axitinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Axitinib may be administered with or without food.