Drug Interactions between Duzallo and fluvoxamine

MONITOR: Coadministration with alcohol or other central nervous system (CNS) depressants may enhance the sedative effects of allopurinol and increase the likelihood and/or severity of central nervous system (CNS) side effects, such as drowsiness, somnolence, vertigo, and ataxia.

MANAGEMENT: Caution for increased CNS adverse effects is advised if allopurinol is coadministered with alcohol, other CNS depressants, or agents that cause dizziness or vertigo. Patients should not drive, operate machinery, or engage in hazardous activities requiring mental alertness and motor coordination until they know how the medications affect them.

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.