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: Grapefruit and grapefruit juice may increase the plasma concentrations of lumateperone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit but has been reported for other CYP450 3A4 inhibitors. In a drug interaction study, the strong CYP450 3A4 inhibitor itraconazole increased lumateperone peak plasma concentration (Cmax) and systemic exposure (AUC) approximately 3.5- and 4-fold, respectively, while diltiazem (a moderate CYP450 3A4 inhibitor) increased lumateperone Cmax and AUC approximately 2- and 2.5-fold, respectively. 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.

When administered with a high-fat meal, lumateperone Cmax decreased by 33% while its AUC increased by 9% and its median time to peak plasma concentration (Tmax) was delayed by about 1 hour.

MANAGEMENT: Lumateperone should be administered with food. Coadministration of grapefruit or grapefruit juice with lumateperone should be avoided.