Drug Interaction Report

MONITOR: The concomitant use of anticoagulants may theoretically increase the risk of sunitinib-induced bleeding. Severe and life-threatening tumor hemorrhage, hemoptysis, and pulmonary hemorrhage, and nonserious epistaxis have occurred during treatment with sunitinib.

MANAGEMENT: Monitoring for clinical and laboratory signs of bleeding is recommended during concomitant therapy, including INR/PT and complete blood counts. Patients should be advised to promptly report any potential signs of bleeding to their doctor, including nosebleeds, pain, swelling, or headache.

GENERALLY AVOID: Consumption of grapefruit or grapefruit juice during sunitinib therapy may increase the plasma concentrations of sunitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruit.

MANAGEMENT: Although clinical data are lacking, it may be advisable to avoid the consumption of large amounts of grapefruit or grapefruit juice during sunitinib therapy.

ADJUST DOSING INTERVAL: Food reduces the oral bioavailability of betrixaban. When administered with a low-fat (900 calories; 20% fat) or high-fat (900 calories; 60% fat) meal, betrixaban peak plasma concentration (Cmax) and systemic exposure (AUC) decreased relative to administration in the fasting state by an average of 70% and 61%, respectively, with the low-fat meal and 50% and 48%, respectively, with the high-fat meal. The effect of food on betrixaban pharmacokinetics could be observed for up to 6 hours after meal intake.

MANAGEMENT: The manufacturer recommends taking betrixaban at the same time each day with food.