Drug Interactions between Omeclamox-Pak and zuranolone

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.

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.