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 can decrease the rate and extent of gastrointestinal absorption of sirolimus. Also, the consumption of grapefruit juice may result in increased sirolimus trough concentrations.

MANAGEMENT: Experts recommend that this drug be taken either at least one hour prior to eating or consistently with or without food to avoid variations in sirolimus blood levels. The manufacturer recommends against using grapefruit juice for dilution of sirolimus doses. Patients should be monitored for clinical and laboratory evidence of altered immunosuppressant effects.