Abstracts

Rationale: To describe the postmarketing adverse event (AE) profile of rufinamide based on spontaneously reported data received from EU and USA. Methods: All serious and nonserious postmarketing AE data received by Eisai Pharmacovigilance from January 16, 2007, though March 15, 2009, were reviewed in order to describe the frequency of reported AEs and to assess potential safety signals. AEs were coded using the MedDRA dictionary. Results: A total of 95 AEs were reported in 55 patients during this 27-month period comprising 500,000 patient-days of rufinamide exposure. Twenty-two of the 55 patients (40%) experienced a total of 30 serious AEs. Twenty-four patients (44%) were aged 17 years or under. Rufinamide was discontinued due to AEs in 20 patients (36%), dosage was maintained or reduced in 22 patients (40%), and dosage was unknown in 13 patients (24%). Among those patients for whom the duration of treatment at the time of AE occurrence was recorded (34, 62%), the majority (24 of 34, 71%) experienced AEs within the first month of treatment, including13 (38%) within the first week. The most commonly reported AEs were referable to the nervous system (17 patients), skin and subcutaneous system (15 patients), gastrointestinal disorders (10 patients), and general disorders (9 patients). The most frequently recorded AEs were seizures, rash, vomiting, and decrease in weight. Seizures were reported in 10 patients; the majority (73%) was considered serious. They were described as increasing in frequency, breakthrough, or flurry in 4 patients; change in form and frequency in 1 patient; and severe or worsening in severity in 2 patients. In the remaining 3 patients status epilepticus led to discontinuation of rufinamide. Rash was reported in 10 patients, including 6 children. The majority of rashes was considered nonserious, occurred within the first 2 weeks of treatment, and improved or resolved when rufinamide was discontinued. There were no reports of toxic epidermal necrolysis or Stevens Johnson syndrome. Vomiting was reported in 6 patients; 3 were children. In 2 of the children the vomiting occurred during up-titration and improved with dose reduction; in 1 patient the outcome was reported as recovered, and in the remainder it was unknown. Five patients had a decrease in weight; 3 were children. All but 1 event, which was reported in a female of unknown age, were considered nonserious. The dose of rufinamide was reduced in 2 patients, maintained in 1 patient, and unknown in 2 patients. Seven events, including double vision, nausea, fatigue, vomiting, and status epilepticus, were attributed to a possible interaction between rufinamide and another antiepileptic drug, most often lamotrigine or valproate. There were no deaths, serious injuries, or serious sequelae reported. Conclusions: The type, severity, and timing of AEs reported in this 27-month survey was consistent with that observed in the rufinamide clinical trial program. No new safety issues were identified. Overall, rufinamide appears to be tolerated as adjunctive treatment of epilepsy.