Drug Interaction Report

Coadministration with certain antiepileptic agents (carbamazepine, phenobarbital, phenytoin, primidone, vigabatrin) has been shown to decrease the plasma concentrations of rufinamide. The mechanism of interaction is unknown, since the majority of rufinamide clearance is via a non-CYP450 pathway. In pharmacokinetic studies, carbamazepine reduced the concentrations of rufinamide by 19% to 26% in a dose-dependent manner. Phenobarbital, phenytoin, and primidone reduced the concentrations of rufinamide by 25% to 46%, and these alterations were not dependent on dose of the antiepileptic agent. In general, rufinamide had little effect on the pharmacokinetics of other antiepileptic agents. Any effects, when they occurred, have been more marked in the pediatric population.

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

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

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of rufinamide. In healthy volunteers, administration of a single 400 mg dose of rufinamide with food resulted in an approximately 56% increase in mean peak plasma concentration (Cmax) and a 34% increase in systemic exposure (AUC) compared to administration during a fasting state.

MANAGEMENT: To ensure maximal oral absorption, it is preferable to administer rufinamide with food. Patients receiving rufinamide should be advised to avoid consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how rufinamide affects them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.