Drug Interaction Report

MONITOR: Coadministration with cenobamate may decrease the plasma concentrations and pharmacologic effects of CYP450 3A4 substrates. The proposed mechanism is cenobamate-mediated induction of the CYP450 3A4 isoenzyme. According to the manufacturer, multiple doses of cenobamate (200 mg once daily) reduced the mean Cmax and AUC of midazolam, a CYP450 3A4 substrate, by 61% and 72%, respectively.

MANAGEMENT: Caution is advised if cenobamate is used concomitantly with drugs that are substrates of CYP450 3A4, particularly those with a narrow therapeutic index. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever cenobamate is added to or withdrawn from therapy.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

GENERALLY AVOID: Acute ethanol ingestion may potentiate the CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MANAGEMENT: Patients should be advised to avoid alcohol during benzodiazepine therapy.