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.

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ADJUST DOSING INTERVAL: Food may variably affect the bioavailability of different oral formulations and salt forms of erythromycin. The individual product package labeling should be consulted regarding the appropriate time of administration in relation to food ingestion. Grapefruit juice may increase the plasma concentrations of orally administered erythromycin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In an open-label, crossover study consisting of six healthy subjects, the coadministration with double-strength grapefruit juice increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single dose of erythromycin (400 mg) by 52% and 49%, respectively, compared to water. The half-life was not affected. The clinical significance of this potential interaction is unknown.

MANAGEMENT: In general, optimal serum levels are achieved when erythromycin is taken in the fasting state, one-half to two hours before meals. However, some erythromycin products may be taken without regard to meals.

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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.

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Ethanol, when combined with erythromycin, may delay absorption and therefore the clinical effects of the antibiotic. The mechanism appears to be due to slowed gastric emptying by ethanol. Data is available only for erythromycin ethylsuccinate. Patients should be advised to avoid ethanol while taking erythromycin salts.

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