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.

ADJUST DOSING INTERVAL: Food may enhance the oral bioavailability of bexarotene. In one clinical study, bexarotene peak plasma concentration (Cmax) and systemic exposure (AUC) resulting from a 75 to 300 mg dose were 35% and 48% higher, respectively, when administered after a fat-containing meal relative to a glucose solution. In all clinical trials, patients were instructed to take bexarotene with or immediately following a meal.

Coadministration with inhibitors of CYP450 3A4 such as grapefruit juice may theoretically increase the plasma concentrations of bexarotene. In vitro studies suggest that bexarotene is metabolized by CYP450 3A4. However, concomitant administration with multiple doses of ketoconazole, a potent CYP450 3A4 inhibitor, did not alter bexarotene plasma concentrations, which would imply that bexarotene elimination is not substantially dependent on CYP450 3A4 metabolism in vivo.

MANAGEMENT: Because safety and efficacy data are based upon administration with food, bexarotene should be administered once daily with a meal. Patients may want to avoid consuming large amounts of grapefruit or grapefruit juice.