Cabozantinib S-malate and Food

Cabozantinib should be taken on an empty stomach, one hour before or two hours after a meal. Do not consume grapefruit, grapefruit juice, or any supplements that contain grapefruit extract during treatment with cabozantinib unless directed otherwise by your doctor. Grapefruit juice can increase the blood levels of cabozantinib. You may be more likely to experience side effects such as nausea; vomiting; diarrhea; loss of appetite; weight loss; mouth sores; abdominal pain; skin rash (primarily on the palms of the hands and soles of the feet); delayed wound healing; high blood pressure; and impaired bone marrow function resulting in low numbers of different types of blood cells, which can increase the risk of bleeding problems and infections. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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.