Approved November 14, 2008

RUFINAMIDE
(FDA Category 1S)

BANZEL(R) (Eisai, Inc) is an antiepileptic drug whose principal mechanism of action is thought to be through modulation of the activity of sodium channels, and in particular, prolongation of the inactive state of the channel.

DOSING INFORMATION: The initial dose for children 4 years and older is 10 mg/kg/day given in two equally divided doses. The dose should be increased by approximately 10 mg/kg increments every other day to a target dose of 45 mg/kg/day or 3200 mg/day, whichever is less, given in 2 equally divided doses. For adults, the initial dose is 400 to 800 mg/day given in 2 equally divided doses. The dose should be increased by 400 to 800 mg/day every 2 days to a maximum target dose of 3200 mg/day, given in 2 equally divided doses. Rufinamide should be taken with food.

PHARMACOKINETICS: Rufinamide is absorbed well after oral administration with a slowing of the rate and extent of absorption as the dose is increased. Food increases the oral bioavailability. The drug is 34% bound to plasma proteins, mostly to albumin (27%), and has an apparent volume of distribution of 50 liters. Rufinamide is extensively metabolized through enzymatic hydrolysis, with no active metabolites, and is not cytochrome P450 dependent. Approximately 85% of the dose is eliminated renally, with less than 2% excreted as unchanged drug. The plasma half-life is approximately 6 to 10 hours.

CAUTIONS: Contraindicated in patients with Familial Short QT syndrome. Serious adverse events include increased risk of depression and suicidal thoughts and behavior (suicidality), shortened QT interval, and multi-organ hypersensitivity reactions. Common adverse events include headache, dizziness, fatigue, somnolence, and nausea.

FDA APPROVED INDICATIONS: Rufinamide is indicated for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in children 4 years and older and adults.