Drug Interaction Report

GENERALLY AVOID: Coadministration of zuranolone with CYP450 3A4 inducers may significantly reduce the plasma concentrations and systemic effects of zuranolone. The proposed mechanism is induction of the CYP450 3A4-mediated metabolism of zuranolone, which is primarily metabolized by this isoenzyme. Drug interaction studies have shown that coadministration with the potent CYP450 3A4 inducer rifampin decreased the systemic exposure (AUC) and peak plasma concentration (Cmax) by approximately 80% and 70%, respectively. However, data for less potent CYP450 3A4 inducers are lacking.

MANAGEMENT: Concomitant use of zuranolone with potent CYP450 3A4 inducers should generally be avoided. In addition, until further information is available, concomitant use with moderate CYP450 3A4 inducers should also be avoided.

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of zuranolone. When administered with a low-fat meal (e.g., 400 to 500 calories, 25% fat), zuranolone peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 3.5- and 1.8-fold, respectively, compared to administration under fasted conditions. Zuranolone was administered with food in the premarketing study population. The efficacy of zuranolone when administered in the fasted state is unknown.

GENERALLY AVOID: Concomitant use of zuranolone with central nervous system (CNS) depressants, including alcohol, may potentiate adverse effects such as somnolence, confusion, dizziness, and gait disturbance.

MANAGEMENT: Zuranolone must be administered with fat-containing food (e.g., 400 to 1,000 calories, 25% to 50% fat) according to the manufacturer. Patients should also be advised to avoid or limit consumption of alcohol and to avoid activities requiring mental alertness such as driving or operating hazardous machinery until at least 12 hours after administration of zuranolone.