Drug Interaction Report

GENERALLY AVOID: Coadministration of omacetaxine and drugs that interfere with platelet function or coagulation may potentiate the risk of bleeding complications. Treatment with omacetaxine is associated with a high frequency of thrombocytopenia. In one study, the overall incidence of grade 3 and 4 thrombocytopenia was 85% and 88%. Fatal cerebral hemorrhages occurred in 2% of patients receiving omacetaxine and nonfatal gastrointestinal hemorrhages occurred in 2%.

MANAGEMENT: Concomitant use of other medications that interfere with platelet function or coagulation should be avoided if the patient's platelet count is less than 50,000 per microliter. Close clinical and laboratory observation for bleeding complications is recommended during therapy. The CBC and platelet count should be monitored according to the manufacturer's recommendations. Patients should be advised to immediately report signs of hemorrhage including unusual bleeding, bruising, blood in the urine or feces, confusion, blurry vision, or slurred speech.

ADJUST DOSING INTERVAL: Food may alter the oral bioavailability of cabozantinib. When healthy subjects were given a single 140 mg oral dose with a high-fat meal, cabozantinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 41% and 57%, respectively, relative to administration under fasting conditions. In clinical studies, patients were administered cabozantinib without food.

GENERALLY AVOID: Coadministration with grapefruit juice is likely to increase the plasma concentrations of cabozantinib, 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: Cabozantinib should be administered at least one hour before or two hours after a meal. The consumption of grapefruit, grapefruit juice, and supplements that contain grapefruit extract should be avoided.