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: Bowel cleansing products can increase the gastrointestinal transit rate. Oral medications administered within one hour of the start of administration of the bowel cleansing solution may be flushed from the gastrointestinal tract and not properly absorbed.

MANAGEMENT: Patients should be advised that absorption of oral medications may be impaired during bowel cleansing treatment. Oral medications (e.g., anticonvulsants, oral contraceptives, antidiabetic agents, antibiotics) should not be administered during and within one hour of starting bowel cleansing treatment whenever possible. However, if concomitant use cannot be avoided, monitoring for reduced therapeutic effects may be advisable.

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.