Abstracts

The present analysis, based on the pooled analysis of the adverse event (AE) reports from clinical studies, was conducted to evaluate the short- and long-term safety of rufinamide in patients with epilepsy. Safety data was derived from 12 double-blind, placebo-controlled studies and 12 controlled or open-label studies of rufinamide for short- and long-term therapy, respectively. Analysis was performed on patients with epilepsy who received [ge]1 doses of study drug. Adverse events were analyzed using the Medical Dictionary for Regulatory Activities and were presented by system organ class (SOC). Common AEs that occurred in [ge]10% of patients were identified. Time to onset of common AEs was evaluated in double-blind, placebo-controlled studies. The short-term safety of rufinamide versus placebo was evaluated in 1240 rufinamide-treated patients and 635 placebo patients (mean ages, 31.7 and 28.6 y, respectively) who had a median duration of exposure of 2.8 and 3.0 months, respectively. The mean dose of rufinamide was 1373 mg/d. The most frequently reported AEs for rufinamide versus placebo patients included headache (22.9% vs 18.9%), dizziness (15.5% vs 9.4%), fatigue (13.6% vs 9.0%), somnolence (11.8% vs 9.1%), and nausea (11.4% vs 7.6%). The time to onset of these AEs was comparable between the groups and suggested an early onset with quick resolution. Serious AEs occurred in 6.3% of rufinamide-treated and 3.9% of placebo patients, with epilepsy-related events such as convulsions the most commonly reported. A higher percentage of patients in the rufinamide group (8.1%) than the placebo group (4.3%) discontinued treatment due to AEs.
Rufinamide as long-term therapy was assessed in 1978 patients (mean age, 31.3 y) in controlled or open studies of [lt]1 month to [gt]4 years in duration; 47% of patients were given the drug for [ge]12 months. Mean daily dose of rufinamide was 1700 mg/d (maximum daily dose, 7200 mg/d). Adverse events occurred most commonly within the SOCs of the nervous system (64.7%) and gastrointestinal disorders (42.3%). The most frequently reported AEs with long-term follow-up were headache (29.5%), dizziness (22.5%), and fatigue (17.7%); 13.1% of patients discontinued rufinamide due to AEs. Serious AEs were reported in 13.2% of patients; convulsion, status epilepticus, and pneumonia were the most common. The rates of AEs generally increased as the median dose of rufinamide increased. The differences by dose may be confounded by the duration of treatment, since patients who were given higher doses were treated at those doses for longer periods of time. Rufinamide was well tolerated in over 1000 patients with epilepsy. The time frame of common AEs suggested an early onset of events with rapid resolution. In the long term, rufinamide was safe and well tolerated in a large population of patients with epilepsy. (Supported by Eisai Inc.)