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.

GENERALLY AVOID: Coadministration with grapefruit juice may increase the serum concentrations of colchicine. Clinical toxicity including myopathy, neuropathy, multiorgan failure, and pancytopenia may occur. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism and P-glycoprotein efflux in the gut wall by certain compounds present in grapefruits. A published case report describes an eight-year-old patient with familial Mediterranean fever who developed acute clinical colchicine intoxication after ingesting approximately one liter of grapefruit juice per day for two months prior to hospital admission while being treated with colchicine 2 mg/day. Her condition progressed to circulatory shock and multiorgan failure, but she recovered with supportive therapy after 24 days in the hospital. In a study of 21 healthy volunteers, administration of 240 mL grapefruit juice twice a day for 4 days was found to have no significant effect on the pharmacokinetics of a single 0.6 mg dose of colchicine. However, significant interactions have been reported with other CYP450 3A4 inhibitors such as clarithromycin, diltiazem, erythromycin, ketoconazole, ritonavir, and verapamil.

MANAGEMENT: Patients treated with colchicine should be advised to avoid the consumption of grapefruit and grapefruit juice, and to contact their physician if they experience symptoms of colchicine toxicity such as abdominal pain, nausea, vomiting, diarrhea, fatigue, myalgia, asthenia, hyporeflexia, paresthesia, and numbness.