Drug Interaction Report

MONITOR: Treatment with metreleptin, a recombinant analog of human leptin, may affect the pharmacokinetics of drugs that are primarily metabolized by CYP450 isoenzymes. In leptin-deficient obese mice, administration of leptin has been shown to alter the hepatic levels of some CYP450 isoenzymes.

MANAGEMENT: Caution is advised when metreleptin is prescribed to patients receiving drugs with a narrow therapeutic index that are substrates of CYP450 isoenzymes, such as macrolide immunosuppressants, oral contraceptives, cyclosporine, theophylline, and warfarin. Clinical and laboratory monitoring are recommended following the initiation, discontinuation or change of dosage of metreleptin, and the individual dosage of the concomitant agents adjusted as needed.

ADJUST DOSING INTERVAL: Consumption of food has led to a 27% decrease in the bioavailability of orally administered tacrolimus.

MANAGEMENT: Tacrolimus should be administered at least one hour before or two hours after meals.

GENERALLY AVOID: Grapefruit juice has been reported to increase tacrolimus trough concentrations. Data are limited, but inhibition of the CYP450 enzyme system appears to be involved.

MANAGEMENT: The clinician may want to recommend that the patient avoid ingesting large amounts of grapefruit juice while taking tacrolimus.