Drug Interaction Report

GENERALLY AVOID: Coadministration with potent or moderate inducers of CYP450 isoenzymes may significantly decrease the plasma concentrations of ganaxolone. According to the prescribing information, ganaxolone is metabolized by CYP450 3A4/5, 2B6, 2C19, and 2D6. In healthy study subjects, coadministration of ganaxolone with rifampin, a potent inducer of CYP450 2C19 and 3A4 and a moderate inducer of CYP450 2B6, decreased ganaxolone peak plasma concentration (Cmax) and systemic exposure (AUC) by 57% and 68%, respectively. Reduced efficacy of ganaxolone may occur. The interaction has not been studied with moderate or weak CYP450 inducers.

MONITOR CLOSELY: Central nervous system depressant or toxic effects may be additively or synergistically increased in patients taking ganaxolone with certain other drugs (such as other CNS-active agents or efavirenz) that cause these effects, especially in elderly or debilitated patients.

MANAGEMENT: Concomitant use of ganaxolone with potent or moderate CYP450 3A4 inducers should be avoided when possible. If coadministration is necessary, a dosage increase of ganaxolone should be considered; however, the maximum recommended dosage should not be exceeded. In patients on a stable ganaxolone dosage who are initiating or increasing their dosage(s) of enzyme-inducing antiepileptic drug(s) such as carbamazepine, phenytoin, phenobarbital or primidone, an increase in the ganaxolone dosage may be required, not to exceed the maximum daily dosage. Additionally, patients treated with any medication that can cause CNS toxicity symptoms should be advised to seek prompt medical attention if they experience symptoms. Patients should be advised to avoid driving, operating machinery, or engaging in potentially hazardous activities requiring mental alertness and motor coordination until they know how the medications affect them.

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.

Administration with food may delay the absorption of modafinil (the racemate) and armodafinil (the R-enantiomer) without significantly affecting their overall bioavailability. According to the product labeling, modafinil's absorption may be delayed by approximately one hour if taken with food. Similarly, the time to reach peak plasma concentration (Tmax) of armodafinil may be delayed by approximately 2 to 4 hours in the fed state.