Authors :
Presenting Author: Pringsheim Milka, MD – Schön Klinik Vogtareuth, Germany, PMU Salzburg, Austria, TUM Klinikum Munich, German Heart centre, Germany
Gerhard Kluger, Prof – Schön Klinik Vogtareuth, Germany, PMU Salzburg, Austria
Adam strzelczyk, Professor – Epilepsy center Frankfurt Rhine-Main Frankfurt, germany
Susanne Schubert-Bast, Professor – Epilepsy center Frankfurt Rhine-Main Frankfurt, germany
Thomas Mayer, Professor – Epilepsy center Kleinwachau, Dresden-Radeberg, Germany
Benjamin Glauche, MD – Epilepsy center Kleinwachau, Dresden-Radeberg, Germany
Hiltrud Muhle, Professor – Deparment of neuropediatrics, Chritian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Germany
Michael Alber, Professor – Department of Neuropediatrics, University of Tübingen, Germany
Hartwig Spors, Professor – Deparment of Neuropediatrics, Justus-Lieig-University Giessen,Germany
Tilman Polster, MD – Krankenhaus Mara, Bethel Epilepsy Center, Medical School OWL, Bielefeld University
Regina Trollmann, Professor – Department of Neuropedatrics, Friedrich-Alexander University Erlangen, Germany
Gerhard Kurlemann, Professor – St. Bonifatius Hospital Lingen, Germany
Markus Berndt, MD – University Hospital LMU Munich, Germany
Kerstin Alexandra Klotz, MD – University Hospital of Bonn, Member of the ERN EpiCARE; Medical Center–University of Freiburg, Faculty of Medicine, University of Freiburg
Rationale:
To assess 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:
Data on 22 patients (median age 8.9 years (range 2.2–26.7)) treated with BR were available. 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/d (SD 699) vs. 1755 (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.
Conclusions:
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 minimizing the risk of adverse events.
Funding: No Funding.