Drug Interaction Report

GENERALLY AVOID: Coadministration of topical chloramphenicol with other agents that can cause bone marrow depression, aplastic anemia, or agranulocytosis may increase the risk and/or severity of hematologic toxicity. Chloramphenicol may be absorbed systemically from the eye, ear, and vagina. Bone marrow hypoplasia, including aplastic anemia and death, has been reported following topical use of chloramphenicol. However, systemic absorption following topical, ophthalmic, otic, and vaginal administration is generally minimal, and data concerning the incidence of blood dyscrasias following the use of topical chloramphenicol are not available.

MANAGEMENT: Concurrent use of topical chloramphenicol formulations with other bone marrow depressing agents should generally be avoided. If concomitant use on a long-term or intermittent basis is considered necessary, patients should be monitored for the development of hematologic adverse effects. Monitoring via full blood counts before and periodically during therapy may also be advisable.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of copanlisib. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of copanlisib by certain compounds present in grapefruit. When a single 60 mg intravenous dose of copanlisib was administered to cancer patients in combination with the potent CYP450 3A4 and P-gp inhibitor, itraconazole (200 mg once daily for 10 days), mean copanlisib peak plasma concentration (Cmax) did not change but systemic exposure (AUC) increased by 53%. The interaction has not been studied with grapefruit juice. 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. Increased exposure to copanlisib may increase the risk of adverse effects such as nausea, vomiting, diarrhea, stomatitis, hyperglycemia, hypertension, noninfectious pneumonitis, cutaneous reactions (e.g., exfoliative dermatitis, maculopapular rash), anemia, neutropenia, thrombocytopenia, and infections.

MANAGEMENT: Patients should avoid the consumption of grapefruit and grapefruit juice during treatment with copanlisib.