Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 2C9 may increase the plasma concentrations of lesinurad, which is primarily metabolized by the isoenzyme. According to the manufacturer, administration of lesinurad with the moderate CYP450 2C9 inhibitor fluconazole (200 mg daily) increased lesinurad peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 35% and 55%, respectively, compared to administration of lesinurad alone. In a cross-study pharmacogenomic analysis conducted in patients receiving single or multiple doses of lesinurad, patients who were deficient in CYP450 2C9 activity (i.e., CYP450 2C9 poor metabolizers) had an approximately 1.8-fold higher exposure to lesinurad at the 400 mg dose than extensive metabolizers.

MANAGEMENT: Caution is advised when lesinurad is prescribed with CYP450 2C9 inhibitors. Patients should be closely monitored for adverse renal effects such as serum creatinine elevations, renal function impairment, and nephrolithiasis. It may be advisable to avoid concomitant use with a potent CYP450 2C9 inhibitor such as gemfibrozil.

ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of asciminib. When a single 40 mg dose of asciminib was administered with a low-fat meal (400 calories; 25% fat) in healthy volunteers, asciminib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 35% and 30%, respectively, compared to asciminib administered in the fasted state. Administration with a high-fat meal (1000 calories; 50% fat) decreased the Cmax and AUC of asciminib by 68% and 62%, respectively.

MANAGEMENT: To ensure adequate asciminib exposures, food consumption should be avoided for at least 2 hours before and 1 hour after taking asciminib.