Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 1A2, CYP450 3A4, and P-glycoprotein may increase the plasma concentrations of pomalidomide, which has been shown to be primarily metabolized by these isoenzymes and also a substrate of the efflux transporter. Pomalidomide exposure is increased when given with a strong CYP450 1A2 inhibitor (e.g., fluvoxamine) in the presence of a strong CYP450 3A4 and P-gp inhibitor (e.g., ketoconazole). Coadministration with ketoconazole alone did not have a clinically significant effect on exposure to pomalidomide. However, the combination of pomalidomide and fluvoxamine in the presence of ketoconazole increased exposure to pomalidomide by 104% compared to pomalidomide plus ketoconazole.

MANAGEMENT: The use of pomalidomide with potent inhibitors of CYP450 1A2 (e.g., ciprofloxacin, fluvoxamine, tiabendazole) in the presence of strong CYP450 3A4 and P-gp inhibitors should generally be avoided. If coadministration is considered clinically necessary, the pomalidomide dose should be reduced by 50%. Dose reduction may also be required if pomalidomide is given with a strong inhibitor of CYP450 1A2 in the absence of a coadministered CYP450 3A4 and P-gp inhibitor. Patients should be monitored for occurrence of pomalidomide-related side effects, including nausea, diarrhea, and neutropenia.

MONITOR: Cigarette smoking may reduce pomalidomide exposure due to induction of CYP450 1A2, the isoenzyme that is responsible for the metabolic clearance of pomalidomide along with CYP450 3A4.

MANAGEMENT: Patients should be advised that smoking may reduce the efficacy of pomalidomide therapy. Pomalidomide should be taken on an empty stomach, at least 2 hours before or 2 hours after a meal.