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

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.

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.

The recommended maximum number of medicines in the 'dibenzazepine anticonvulsant agents' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'dibenzazepine anticonvulsant agents' category:

• carbamazepine
• rufinamide

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.