Drug Interaction Report

MONITOR: Coadministration with lesinurad may decrease the plasma concentrations of drugs that are sensitive CYP450 3A4 substrates. Lesinurad is a weak CYP450 3A4 inducer. In drug interaction studies conducted in healthy subjects, lesinurad reduced systemic exposure (AUC) to sildenafil and amlodipine, both CYP450 3A4 substrates, by approximately 30% to 40%. In contrast, lesinurad had no clinically significant effects on the pharmacokinetics of atorvastatin and colchicine, also CYP450 3A4 substrates.

MANAGEMENT: Patients receiving concomitant drugs that are sensitive CYP450 3A4 substrates or substrates with narrow therapeutic ranges should be monitored for potentially diminished therapeutic response to those drugs during treatment with lesinurad. Alternative treatments or dosage adjustments may be required if an interaction is suspected.

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.