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.

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of orally administered everolimus. The mechanism is inhibition of CYP450 3A4 and P-glycoprotein activity in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Patients treated with everolimus should avoid consumption of grapefruit and grapefruit juice.