Drug Interaction Report

GENERALLY AVOID: Coadministration of chloramphenicol with other agents that can cause bone marrow depression, aplastic anemia, or agranulocytosis can increase the risk and/or severity of hematologic toxicity. Serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia, and bone marrow depression) have been reported after short-term and long-term systemic therapy with chloramphenicol. In addition, chloramphenicol is considered a moderate CYP450 3A4 inhibitor and may increase the plasma concentrations and risk of adverse effects of immunosuppressant drugs that are also substrates of this isoenzyme.

MANAGEMENT: Concurrent use of chloramphenicol with other agents that can cause bone marrow depression, aplastic anemia, or agranulocytosis that are also CYP450 3A4 substrates such as ruxolitinib, ibrutinib, idelalisib, olaparib, irinotecan, docetaxel, acalabrutinib, and fostamatinib, should be avoided. Some authorities consider coadministration of chloramphenicol with such medications to be contraindicated. The prescribing information for individual immunosuppressive agents should be consulted for more specific recommendations.

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.