Efficacy and safety of Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: A real‐world study
Abstract
Objective: Dravet syndrome (DS) is a drug‐resistant, infantile onset epilepsy syndrome with multiple seizure types and developmental delay. In recently published randomized controlled trials, fenfluramine (FFA) proved to be safe and effective in DS. Methods: DS patients were treated with FFA in the Zogenix Early Access Program at four Italian pediatric epilepsy centers. FFA was administered as add‐on, twice daily at an initial dose of 0.2 mg/kg/d up to 0.7 mg/kg/d. Seizures were recorded in a diary. Adverse events and cardiac safety (with Doppler echocardiography) were investigated every 3 to 6 months. Results: Fifty‐two patients were enrolled, with a median age of 8.6 years (interquartile range [IQR] = 4.1‐13.9). Forty‐five (86.5%) patients completed the efficacy analysis. The median follow‐up was 9.0 months (IQR = 3.2‐9.5). At last follow‐up visit, there was a 77.4% median reduction in convulsive seizures. Thirty‐two patients (71.1%) had a ≥50% reduction of convulsive seizures, 24 (53.3%) had a ≥75% reduction, and five (11.1%) were seizure‐free. The most common adverse event was decreased appetite (n = 7, 13.4%). No echocardiographic signs of cardiac valvulopathy or pulmonary hypertension were observed. There was no correlation between type of genetic variants and response to FFA. Significance: In this real‐world study, FFA provided a clinically meaningful reduction in convulsive seizure frequency in the majority of patients with DS and was well tolerated.
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Subsequent studies of fenfluramine in Dravet syndrome demonstrated dose-dependent clinically meaningful effects on regulating behaviour, emotion, cognition, and everyday executive functions in preschool age and sustained efficacy and safety in children, adolescents and adults in real-world practice.
“Subsequent studies of fenfluramine in Dravet syndrome demonstrated dosedependent clinically meaningful effects on regulating behaviour, emotion, cognition, and everyday executive functions in preschool age 199 and sustained efficacy and safety in children, adolescents and adults in real-world practice 200,201 .”
From Developmental and epileptic encephalopathies (2024) · cites this paper as [200]
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Developmental and epileptic encephalopathies
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- Authors
- Specchio, N., Pietrafusa, N., Doccini, V., Trivisano, M., Darra, F., Ragona, F., Cossu, A., Spolverato, S., Battaglia, D., Quintiliani, M., Luigia Gambardella, M., Rosati, A., Mei, D., Granata, T., Dalla Bernardina, B., Vigevano, F., & Guerrini, R.
- Affiliations
- Bambino Gesù Children's Hospital (IT)
- Meyer Children's Hospital (IT)
- University of Verona (IT)
- Fondazione IRCCS Istituto Neurologico Carlo Besta (IT)
- Università Cattolica del Sacro Cuore (IT)
- Pediatric Neurology Department of Woman and Child Health and Public Health Child Health Area A. Gemelli University Polyclinic Foundation IRCCS Catholic University of the Sacred Heart Rome Italy
- Child Neuropsychiatry Department of Surgical Sciences Dentistry, Gynecology, and Pediatrics University of Verona Verona Italy
- Corresponding author
- Specchio, Nicola
- ORCID
- Venue
- Epilepsia
- Publisher
- Wiley
- Published
- 2020-09-18
- Volume
- 61
- Issue
- 11
- Pages
- 2405-2414
- ISSN
- 0013-9580 (ISSN-L)
- 1528-1167
- OpenAlex
- W3087269728
- Cited by
- 56
- References
- 32
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 11 · 2023: 12 · 2022: 15 · 2021: 9
- FWCI
- 6.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Epilepsia (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Health Sciences › Medicine › Physiology › Diet and metabolism studies
- Keywords
- Dravet syndrome, fenfluramine, convulsions, seizure reduction, drug-resistant epilepsy, pediatric epilepsy, cardiac safety, valvulopathy, pulmonary hypertension, adverse events, appetite loss, genetic variants, real-world effectiveness
- MeSH terms
- Adolescent, Adult, Anorexia, Anticonvulsants, Child, Child, Preschool, Epilepsies, Myoclonic, Female, Fenfluramine, Follow-Up Studies, Humans, Male, Prospective Studies, Seizures, Treatment Outcome, Selective Serotonin Reuptake Inhibitors, Young Adult
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