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 of imatinib with strong CYP450 3A4 inhibitors such as grapefruit juice, may significantly increase the plasma concentrations of imatinib, a known substrate of CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of imatinib by certain compounds present in grapefruits. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict. In a single-dose study, coadministration of imatinib with ketoconazole (a strong CYP450 3A4 inhibitor) increased imatinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 26% and 40%, respectively.

MANAGEMENT: Patients treated with imatinib should preferably avoid the consumption of grapefruit or grapefruit juice. If coadministration is unavoidable, monitor for prolonged and/or increased pharmacologic effects of imatinib, including edema, hematologic toxicity and immunosuppression.