Abstracts

Rationale: Fenfluramine (FFA), originally launched as an anorectic agent, has also been demonstrated to have anti-convulsive activity. However, FFA was removed from market due to cardiac side effects. In 2002, a Belgian Royal Decree permitted the further study of low-dose FFA as an add-on in pediatric patients with drug-resistant epilepsy. In 2012, Ceulemans et al. presented the results of FFA add-on therapy in Dravet syndrome (DS). In this cohort, no clinical or echocardiographic changes could be demonstrated after a mean treatment duration of 11 years and 4 months. In this prospective pilot study, we aimed to assess potential FFA-induced cardiovascular side effects using echocardiographic follow-up in DS patients on continuous low-dose FFA.Methods: Seven patients with DS were included in the FFA prospective pilot study. Echocardiography was performed before the start and at least every 6 months during the first 2 years and then yearly. Standardized valvular scoring systems were used (including regurgitation and restrictive function). Systolic pulmonary artery pressure was derived from the tricuspid regurgitant jet. The presence of pulmonary hypertension was further examined by echocardiography through a quantitative assessment of the cardiac hemodynamics, chamber size, and function.Results: Seven patients (Table 1) were included (ages 1 to 20 years old). All patients had been treated with low-dose FFA (5 to 15 mg daily) with a mean treatment duration of 22 months (SD 20.45 months). During the follow-up period, all the echocardiographic examinations remained normal without any signs of valvulopathy, pulmonary hypertension, or other abnormalities (Table 2). Statistical analysis showed no significant changes related to the cumulative dose or treatment duration with FFA for all the echocardiographic parameters.Conclusions: In this prospective pilot study, we did not see any clinical cardiovascular side effects or echocardiographic abnormalities in DS patients treated with FFA. By limiting the daily dose to a maximum of 20 mg per day, FFA seems to be a potentially safe anti-epileptic drug patients with this refractory epilepsy syndrome. Brabant Pharma and Zogenix, Inc. funded the study and its analysis. Medical writing assistance was provided by PharmaWrite (Princeton, NJ) and was funded by Zogenix Inc.