Drug Interaction Report

Coadministration with inhibitors of CYP450 3A4 is not expected to have clinically significant effects on the pharmacokinetics of ganaxolone. According to the prescribing information, ganaxolone is metabolized by CYP450 3A4/5, 2B6, 2C19, and 2D6. When ganaxolone was administered to healthy study subjects with itraconazole, a potent CYP450 3A4 inhibitor, ganaxolone systemic exposure (AUC) increased by just 17% while peak plasma concentration (Cmax) did not change.

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of ganaxolone. When administered with a high-fat meal, ganaxolone peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 3- and 2-fold, respectively, compared to administration under fasted conditions. Ganaxolone was administered with food in the premarketing study population. The efficacy of ganaxolone when administered in the fasted state is unknown.

GENERALLY AVOID: Concomitant use of ganaxolone with central nervous system (CNS) depressants, including alcohol, may potentiate adverse effects such as somnolence and sedation.

MANAGEMENT: Ganaxolone must be administered with food according to the manufacturer. Patients should be advised to avoid or limit consumption of alcohol and to avoid activities requiring mental alertness such as driving or operating hazardous machinery until they know how the medication affects them.