Abstracts

Rationale: Rufinamide is an antiepileptic drug that has been approved for Lennox-Gastaut syndrome (LGS) (2008 in US - 2007 in Europe). Rufinamide is usually initiates at 10mg/kg/day, followed by a titration of 10mg/kg/day every two days, until a maintenance dose of 45mg/kg/day.Methods: We conducted a retrospective study in the epilepsy unit of Robert-Debr Children University Hospital, Paris, France. We identified 22 patients treated with rufinamide for at least three months (January 2010-December 2012): n=10 LGS, n=6 infantile spasms and n=4 epileptic encephalopathy with tonic seizures. The patient with a decrease of 50% at least of the seizure frequency compare to the baseline was defined as responder (based on seizure diary).Results: Responder rate was 78.9% (19 patients). We observed that a long titration period was used (mean titration duration = 13.5 weeks). Initiation doses were lower than the recommended dose (mean dose: 3.6 mg/kg/day). Regarding the responders, the mean maintenance dose was 10.5 mg/kg/day (3-27 mg/kg/day): 7.9 mg/kg/day for LGS patients and 13.5 mg/kg/day for other epileptic syndromes. All responders was treated by concomitant AEDs. All responders received VPA (mean dose = 26.4 mg/kg/day). During the titration, 10/15 patients have experienced an increase of seizure frequency after a initial positive effect (same daily number of seizure or increase of the number of seizure compared to the baseline without rufinamide) at the mean dose of 13.2 mg/kg/day (5-25 mg/kg/day): 11.9 mg/kg/day for LGS patients and 16.5 mg/kg/day for other epileptic syndromes patients. No worsening of the seizure frequency was observed among the non-responders. All patients that experienced a worsening regain the positive effect on seizure frequency with a down titration. Conclusions: Rufinamide was effective in most of the patients. We observed an efficacy with a low dose of rufinamide. The final dose was found after the patients have experienced an increase of seizure frequency during the up-titration period.This might be related to pharmacological interaction (most of our patients started rufinamide in addition to valproate and lamotrigine). Our experience suggests the use of low dose and a slow titration in order to avoid to falsely conclude to the absence of effect of rufinamide.