Abstract
OBJECTIVE: To assess the efficacy and tolerability of fenfluramine (FFA) with concomitant potassium bromide (BR) in patients with Dravet syndrome (DS). METHODS: This multicenter retrospective study, conducted within the German compassionate use program, analyzed BR doses and serum levels before and after FFA initiation, adverse events (AEs), seizure reduction, and symptoms changes using the Clinical Global Impression of Change (CGIC) scale. Timepoints were defined as T0 (baseline), T1 (FFA initiation), T2 and T3 (first and second BR level measurement after FFA initiation). RESULTS: Twenty-two patients (median age 8.9 years, range 2.2-26.7) treated with BR were included. Median duration of BR-FFA combination therapy was 7 months (range 0-28). BR doses were reduced at least once in 11 patients (50%) as a precaution or because of increased serum levels. At T3, mean BR dose was significantly lower compared to T0 (1217 mg/day, SD = 699 vs. 1755 mg/day, SD = 752.2; p = 0.04), but BR levels showed no significant difference between T2 or T3 and baseline. In contrast, for patients with stable BR doses (n = 14), mean BR level significantly increased from baseline (1376 mg/L, SD = 345.7) to T2 (1762 mg/L, SD = 553.3; p = 0.04). AEs were reported in 15 patients (68.2%) during the combination therapy, with the most common being somnolence (59.1%) and loss of appetite (22.7%). In 40.9% either FFA or BR were discontinued due to sedation. The responder rate for seizure reduction was 68.4% at 3 months and 76.9% at 6 months. SIGNIFICANCE: BR levels increased significantly after FFA initiation when BR doses were not reduced, contributing to adverse events-primarily somnolence-and resulting in the discontinuation of BR or FFA in some patients. Close monitoring of BR levels is crucial to minimize the risk of adverse events. PLAIN LANGUAGE SUMMARY: This study investigated the combination of fenfluramine (FFA) and potassium BR in treating Dravet syndrome. It was found that it is effective in reducing seizures, but BR levels often went up after starting FFA, which caused side effects like drowsiness in many patients. In some cases, these side effects were serious enough that physicians had to stop either BR or FFA. The study highlights the need for careful monitoring of BR levels when using this combination to avoid potential side effects by reducing the BR dose early if needed.