Drug Interaction Report

MONITOR: Agents that cause urinary alkalinization can reduce serum salicylate concentrations in patients receiving anti-inflammatory dosages of aspirin or other salicylates. The mechanism involves reduction in salicylate renal tubular reabsorption due to increased urinary pH, resulting in increased renal salicylate clearance especially above urine pH of 7. This interaction is sometimes exploited in the treatment of salicylate toxicity.

MANAGEMENT: Patients treated chronically with urinary alkalinizers and large doses of salicylates (i.e. 3 g/day or more) should be monitored for potentially diminished or inadequate analgesic and anti-inflammatory effects, and the salicylate dosage adjusted if necessary.

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.

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.

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.