Drug Interaction Report

GENERALLY AVOID: Theoretical concerns exist that chemotherapeutic agents and other bone marrow depressants may potentiate the myelosuppressive effects of samarium sm 153 lexidronam. In clinical trials, white blood cell and platelet counts decreased to a nadir of approximately 40% to 50% of baseline in 95% of patients within three to five weeks after administration of samarium sm 153 lexidronam, and tended to return to pretreatment levels by eight weeks. The potential for additive bone marrow toxicity with myelotoxic treatments including chemotherapy or external beam radiation has not been studied.

MANAGEMENT: The manufacturer recommends avoiding concomitant use of samarium sm 153 lexidronam with chemotherapy or external beam radiation therapy unless benefits are anticipated to outweigh the risks. Moreover, samarium sm 153 lexidronam should not be given after either of these treatments until there has been time for adequate marrow recovery. Caution and close monitoring of bone marrow function are advisable if coadministration with other myelotoxic agents is required. Patients should be advised to contact their physician if they develop signs and symptoms of myelosuppression such as pallor, dizziness, fatigue, lethargy, fainting, unusual bleeding or bruising, or signs of infection such as fever, chills, diarrhea, sore throat, muscle aches, shortness of breath, blood in phlegm, weight loss, red or inflamed skin, body sores, and pain or burning during urination.

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.