Drug Interaction Report

MONITOR: Coadministration with cenobamate may increase the plasma concentrations and therapeutic effects of drugs that are substrates of CYP450 2C19. The proposed mechanism is cenobamate-mediated inhibition of CYP450 2C19. According to the manufacturer, multiple doses of cenobamate (200 mg once daily) increased the mean Cmax and AUC of omeprazole, a CYP450 2C19 substrate, by 83% and 107%, respectively.

MANAGEMENT: Caution is advised when cenobamate is used concurrently with drugs that are substrates of CYP450 2C19, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever cenobamate is added to or withdrawn from therapy.

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.

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.