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.

MONITOR: Due to their gastrointestinal pharmacologic effects, somatostatin analogs (e.g., octreotide, lanreotide) may variously affect the absorption of dietary nutrients and concomitantly administered oral medications. Somatostatin analogs have been shown to prolong gastrointestinal transit time and inhibit intestinal absorption of some nutrients such as fat. Clinical data are limited, however. In case reports, octreotide has been reported to reduce the relative bioavailability of cyclosporine. Transplant rejection and significant reductions in cyclosporine levels, sometimes to undetectable levels, have been reported in association with the interaction. Vitamin K absorption was not affected when concomitantly administered with lanreotide according to the manufacturer.

MANAGEMENT: Clinicians should be aware of the potential for altered absorption of concomitantly administered oral medications during treatment with somatostatin analogs. Blood levels and clinical response should be monitored, particularly for drugs that have a narrow therapeutic index, and the dosages adjusted as necessary.

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.