Practical considerations for the use of fenfluramine to manage patients with Dravet syndrome or Lennox-Gastaut syndrome in clinical practice.
Dravet syndrome
Lennox–Gastaut syndrome
antiseizure medications
fenfluramine
polytherapy
Journal
Epilepsia open
ISSN: 2470-9239
Titre abrégé: Epilepsia Open
Pays: United States
ID NLM: 101692036
Informations de publication
Date de publication:
04 Jul 2024
04 Jul 2024
Historique:
revised:
20
05
2024
received:
15
02
2024
accepted:
04
06
2024
medline:
4
7
2024
pubmed:
4
7
2024
entrez:
4
7
2024
Statut:
aheadofprint
Résumé
Fenfluramine (FFA), an antiseizure medication (ASM) with serotonergic and sigma-1 receptor activity, is used to manage patients with developmental and epileptic encephalopathies (DEEs). It is approved in the US for treating seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) in patients ≥2 years old and as add-on therapy for seizures associated with DS and LGS in the EU, UK, and Japan in similarly aged patients. Consensus guidelines for treatment of DS have recommended FFA to be an early-line ASM, and it has also shown efficacy in managing seizures associated with LGS. DS and LGS are DEEs associated with a range of seizure types, developmental impairments, and multiple comorbidities. Here we provide case vignettes describing 4 patients (3 DS and 1 LGS) aged 4-29 years old in whom up to 14 ASMs had previously failed, to illustrate real-world practice issues encountered by neurologists. This review provides guidance on the use of FFA in the context of ASM polytherapy and drug-drug interactions (DDIs), behavioral issues, dose titration, and adverse events. Along with data from the clinical trial program, these case vignettes emphasize the low risk of DDIs, a generally well-tolerated safety profile, and other seizure and nonseizure benefits (eg, improved cognition and sleep) associated with the use of FFA in DS or LGS. PLAIN LANGUAGE SUMMARY: Fenfluramine is used to treat seizures in individuals with Dravet syndrome and Lennox-Gastaut syndrome, but there are a range of issues that clinicians may face when treating patients. This review highlights four patients from the authors' everyday clinical work and offers guidance and practical considerations by neurologists with expertise in managing these complex conditions related to drug interactions, dosing, and side effects associated with fenfluramine.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : UCB Pharma
Informations de copyright
© 2024 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.
Références
Zuberi SM, Wirrell E, Yozawitz E, Wilmshurst JM, Specchio N, Riney K, et al. ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: position statement by the ILAE task force on nosology and definitions. Epilepsia. 2022;63(6):1349–1397.
Specchio N, Wirrell EC, Scheffer IE, Nabbout R, Riney K, Samia P, et al. International league against epilepsy classification and definition of epilepsy syndromes with onset in childhood: position paper by the ILAE task force on nosology and definitions. Epilepsia. 2022;63(6):1398–1442.
Wirrell EC, Hood V, Knupp KG, Meskis MA, Nabbout R, Scheffer I, et al. The international consensus on diagnosis and management of Dravet syndrome. Epilepsia. 2022;63(7):1761–1777.
Riva A, Coppola A, Bonaventura CD, Elia M, Ferlazzo E, Gobbi G, et al. An Italian consensus on the management of Lennox–Gastaut syndrome. Seizure. 2022;101:134–140.
Specchio N, Wirrell EC, Scheffer IE, Nabbout R, Riney K, Samia P, et al. ILAE classification and definition of epilepsy syndromes with onset in childhood: position paper by the ILAE task force on nosology and definitions. Epilepsia. 2022;63(6):1398–1442. Available from: https://www.ilae.org/files/dmfile/CHILDApril6withfigs.pdf. Accessed 1 March 2022
Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):512–521.
Marini C, Scheffer IE, Nabbout R, Suls A, De Jonghe P, Zara F, et al. The genetics of Dravet syndrome. Epilepsia. 2011;52(suppl 2):24–29.
Li W, Schneider AL, Scheffer IE. Defining Dravet syndrome: an essential pre‐requisite for precision medicine trials. Epilepsia. 2021;62(9):2205–2217.
Allen AS, Berkovic SF, Cossette P, Delanty N, Dlugos D, Eichler EE, et al. De novo mutations in epileptic encephalopathies. Nature. 2013;501(7466):217–221.
Strzelczyk A, Schubert‐Bast S. Expanding the treatment landscape for Lennox–Gastaut syndrome: current and future strategies. CNS Drugs. 2021;35(1):61–83.
Fattorusso A, Matricardi S, Mencaroni E, Dell'Isola GB, Di Cara G, Striano P, et al. The pharmacoresistant epilepsy: an overview on existant and new emerging therapies. Front Neurol. 2021;12:674483.
Knupp KG, Wirrell EC. Treatment strategies for Dravet syndrome. CNS Drugs. 2018;32(4):335–350.
Verrotti A, Striano P, Iapadre G, Zagaroli L, Bonanni P, Coppola G, et al. The pharmacological management of Lennox–Gastaut syndrome and critical literature review. Seizure. 2018;63:17–25.
Vasquez A, Buraniqi E, Wirrell EC. New and emerging pharmacologic treatments for developmental and epileptic encephalopathies. Curr Opin Neurol. 2022;35(2):145–154.
Aras LM, Isla J, Mingorance‐Le MA. The European patient with Dravet syndrome: results from a parent‐reported survey on antiepileptic drug use in the European population with Dravet syndrome. Epilepsy Behav. 2015;44:104–109.
Knupp KG, Scheffer IE, Ceulemans B, Sullivan J, Nickels KC, Lagae L, et al. Fenfluramine provides clinically meaningful reduction in frequency of drop seizures in patients with Lennox–Gastaut syndrome: interim analysis of an open‐label extension study. Epilepsia. 2022;64(1):139–151.
Lagae L, Brambilla I, Mingorance A, Gibson E, Battersby A. Quality of life and comorbidities associated with Dravet syndrome severity: a multinational cohort survey. Dev Med Child Neurol. 2018;60(1):63–72.
Schubert‐Bast S, Wolff M, Wiemer‐Kruel A, von Spiczak S, Trollmann R, Reif PS, et al. Seizure management and prescription patterns of anticonvulsants in Dravet syndrome: a multicenter cohort study from Germany and review of literature. Epilepsy Behav. 2019;98(Pt A):88–95.
Arzimanoglou A, French J, Blume WT, Cross JH, Ernst JP, Feucht M, et al. Lennox–Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology. Lancet Neurol. 2009;8(1):82–93.
Cross JH, Auvin S, Falip M, Striano P, Arzimanoglou A. Expert opinion on the management of Lennox–Gastaut syndrome: treatment algorithms and practical considerations. Front Neurol. 2017;8:505.
Strzelczyk A, Zuberi SM, Striano P, Rosenow F, Schubert‐Bast S. The burden of illness in Lennox–Gastaut syndrome: a systematic literature review. Orphanet J Rare Dis. 2023;18(1):42.
Montouris G, Aboumatar S, Burdette D, Kothare S, Kuzniecky R, Rosenfeld W, et al. Expert opinion: proposed diagnostic and treatment algorithms for Lennox–Gastaut syndrome in adult patients. Epilepsy Behav. 2020;110:107146.
Nabbout R, Chemaly N, Chiron C, Kuchenbuch M. Safety considerations selecting antiseizure medications for the treatment of individuals with Dravet syndrome. Expert Opin Drug Saf. 2021;1‐16:561–576.
Strzelczyk A, Schubert‐Bast S. A practical guide to the treatment of Dravet syndrome with anti‐seizure medication. CNS Drugs. 2022;36(3):217–237.
UCB Inc. FINTEPLA® (fenfluramine) oral solution [prescribing information]. GA March: Smyrna; 2023.
Zogenix ROI Limited. Fintepla 2.2 mg/mL oral solution [summary of product characteristics]. Dublin, IE: Zogenix ROI Limited; 2023.
Medicines & Healthcare products Regulatory Agency. Orphan register. 2023 Available from: https://www.gov.uk/government/publications/orphan‐registered‐medicinal‐products/orphan‐register. [Accessed 7 November 2023]
UCB Japan Co. LTD. Fintepla Oral solution 2.2 mg/mL [prescribing information]. Tokyo, Japan: UCB Japan Co. LTD; 2022.
Nippon Shinyaku Co. Ltd. UCB Japan obtained additional application of fintepla®(fenfluramine) for the treatment of seizures associated with Lennox–Gastaut syndrome in Japan. 2024. Available from: https://www.nippon‐shinyaku.co.jp/file/download.php?file_id=7484. [Accessed 28 March 2024]
Simon K, Sheckley H, Anderson CL, Liu Z, Carney PR. A review of fenfluramine for the treatment of Dravet syndrome patients. Curr Res Pharmacol Drug Discov. 2022;3:100078.
Sullivan J, Helen CJ. Raising the bar: fenfluramine sets new treatment standards for Dravet syndrome. Epilepsy Behav. 2021;121(Pt A):108061.
Sourbron J, Lagae L. Fenfluramine: a plethora of mechanisms? Front Pharmacol. 2023;14:1192022.
Knupp K, Scheffer I, Ceulemans B, Sullivan J, Nickels K, Lagae L, et al. Efficacy and safety of fenfluramine for the treatment of seizures associated with Lennox–Gastaut syndrome: a randomized clinical trial. JAMA Neurol. 2022;79(6):554–564.
Lagae L, Sullivan J, Knupp K, Laux L, Polster T, Nikanorova M, et al. Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, double‐blind, placebo‐controlled trial. Lancet. 2019;394(10216):2243–2254.
Nabbout R, Mistry A, Zuberi S, Villeneuve N, Gil‐Nagel A, Sanchez‐Carpintero R, et al. Fenfluramine for treatment‐resistant seizures in patients with Dravet syndrome receiving stiripentol‐inclusive regimens: a randomized clinical trial. JAMA Neurol. 2020;77(3):300–308.
Scheffer IE, Devinsky O, Thiele EA, Wirrell E, Auvin S, Polster T, et al. Interim safety analysis of an ongoing open‐label extension study of fenfluramine for Dravet syndrome [poster]. Presented at American Epilepsy Society annual meeting, December 2‐6, 2022, Nashville, TN.
Sullivan J, Lagae L, Cross JH, Devinsky O, Guerrini R, Knupp KG, et al. Fenfluramine in the treatment of Dravet syndrome: results of a third randomized, placebo‐controlled clinical trial. Epilepsia. 2023;64(10):2653–2666.
Sullivan J, Specchio N, Devinsky O, Auvin S, Perry MS, Strzelczyk A, et al. Fenfluramine significantly reduces day‐to‐day seizure burden by increasing number of seizure‐free days and time between seizures in patients with Dravet syndrome: a time‐to‐event analysis. Epilepsia. 2022;63(1):130–138.
Devinsky O, Gil‐Nagel A, Gunning B, Battaglia D, Riney K, Gammaitoni A, et al. ZX008 (fenfluramine HCl oral solution) significantly reduces frequency of generalized tonic‐ clonic seizures in dravet syndrome: pooled analysis from two phase 3 clinical trials [abstract]. Presented at Annual Meeting of the Child Neurology Society, October 23‐26, 2019, Charlotte, NC.
Devi N, Madaan P, Asrar MM, Sahu JK, Bansal D. Comparative short‐term efficacy and safety of add‐on anti‐seizure medications in Dravet syndrome: an indirect treatment comparison. Seizure. 2021;91:316–324.
Linley W, Hawkins N, Schwenkglenks M, Toward T. Comparative effectiveness of fenfluramine vs cannabidiol for the treatment of seizures in Dravet syndrome: a network meta‐analysis. Presented at: International Epilepsy Consortium, August 28–September 1, 2021, virtual; August 28–September 1.
Gil‐Nagel A, Falip M, Sánchez‐Carpintero R, Abad‐Sazatornil MR, Poveda JL, Aibar J, et al. The contribution of fenfluramine to the treatment of Dravet syndrome in Spain through multi‐criteria decision analysis. Epilepsy Behav. 2022;132:108711.
Guerrini R, Chiron C, Vandame D, Linley W, Toward T. Comparative efficacy and safety of stiripentol, cannabidiol and fenfluramine as first‐line add‐on therapies for seizures in Dravet syndrome: a network meta‐analysis. Epilepsia Open. 2024;9(2):689–703.
Lattanzi S, Trinka E, Russo E, Del Giovane C, Matricardi S, Meletti S, et al. Pharmacotherapy for Dravet syndrome: a systematic review and network meta‐analysis of randomized controlled trials. Drugs. 2023;83(15):1409–1424.
Tong J, Ji T, Liu T, Liu J, Chen Y, Li Z, et al. Efficacy and safety of six new antiseizure medications for adjunctive treatment of focal epilepsy and epileptic syndrome: a systematic review and network meta‐analysis. Epilepsy Behav. 2024;152:109653.
Wu J, Zhang L, Zhou X, Wang J, Zheng X, Hu H, et al. Efficacy and safety of adjunctive antiseizure medications for Dravet syndrome: a systematic review and network meta‐analysis. Front Pharmacol. 2022;13:980937.
Xia D, Zhang P, Chen Y, Liu X, Chen Y. Efficacy of pharmacological treatments for Dravet syndrome: systematic review and network meta‐analysis. Seizure. 2024;117:90–97.
Kassaï B, Chiron C, Augier S, Cucherat M, Rey E, Gueyffier F, et al. Severe myoclonic epilepsy in infancy: a systematic review and a meta‐analysis of individual patient data. Epilepsia. 2008;49(2):343–348.
Chiron C, Marchand MC, Tran A, Rey E, d'Athis P, Vincent J, et al. Stiripentol in severe myoclonic epilepsy in infancy: a randomised placebo‐controlled syndrome‐dedicated trial. STICLO Study Group Lancet. 2000;356(9242):1638–1642.
Thanh TN, Chiron C, Dellatolas G, Rey E, Pons G, Vincent J, et al. Long‐term efficacy and tolerance of stiripentaol in severe myoclonic epilepsy of infancy (Dravet's syndrome). Article in French. Arch Pediatr. 2002;9(11):1120–1127.
Nabbout R, Chiron C. Stiripentol: an example of antiepileptic drug development in childhood epilepsies. Eur J Paediatr Neurol. 2012;16(suppl 1):S13–S17.
Linley W, Hawkins N, Schwenkglenks M, Toward T. Comparative effectiveness of fenfluramine vs cannabidiol for the treatment of seizures in Dravet syndrome (DS): a network meta‐analysis (NMA). Epilepsia. 2021;62(S3):154.
Sullivan J, Scheffer IE, Lagae L, Nabbout R, Pringsheim M, Talwar D, et al. Fenfluramine HCl (Fintepla®) provides long‐term clinically meaningful reduction in seizure frequency: analysis of an ongoing open‐label extension study. Epilepsia. 2020;61(11):2396–2404.
Lagae L, Schoonjans AS, Gammaitoni AR, Galer BS, Ceulemans B. A pilot, open‐label study of the effectiveness and tolerability of low‐dose ZX008 (fenfluramine HCl) in Lennox–Gastaut syndrome. Epilepsia. 2018;59(10):1881–1888.
Auvin S. Paediatric epilepsy and cognition. Dev Med Child Neurol. 2022;64(12):1444–1452.
Johannessen Landmark C, Patsalos PN. Drug interactions involving the new second‐ and third‐generation antiepileptic drugs. Expert Rev Neurother. 2010;10(1):119–140.
Martin P, Czerwiński M, Limaye PB, Muranjan S, Ogilvie BW, Smith S, et al. In vitro evaluation of fenfluramine and norfenfluramine as victims of drug interactions. Pharmacol Res Perspect. 2022;10(3):e00958.
Samanta D. Fenfluramine: a review of pharmacology, clinical efficacy, and safety in epilepsy. Children (Basel). 2022;9(8):1159.
Zogenix Inc. FINTEPLA® (fenfluramine) oral solution, CIV [prescribing information]. CA March: Emeryville; 2022.
Greenwich Biosciences, Inc. EPIDIOLEX® (cannabidiol) oral solution, CV [prescribing information]. Carlsbad, CA: Greenwich Biosciences, Inc; 2018.
Martin P, Czerwiński M, Limaye PB, Ogilvie BW, Smith S, Boyd B. In vitro evaluation suggests fenfluramine and norfenfluramine are unlikely to act as perpetrators of drug interactions. Pharmacol Res Perspect. 2022;10(3):e00959.
Wheless JW, Fulton SP, Mudigoudar BD. Dravet syndrome: a review of current management. Pediatr Neurol. 2020;107:28–40.
Perucca E. Clinically relevant drug interactions with antiepileptic drugs. Br J Clin Pharmacol. 2006;61(3):246–255.
Biocodex. DIACOMIT (stiripentol) capsules, for oral use. DIACOMIT (stiripentol) powder, for oral suspension [prescribing information]. Beauvais, France: Biocodex; 2018.
Strzelczyk A, Pringsheim M, Mayer T, Polster T, Klotz KA, Muhle H, et al. Efficacy, tolerability, and retention of fenfluramine for the treatment of seizures in patients with Dravet syndrome: compassionate use program in Germany. Epilepsia. 2021;62(10):2518–2527.
Specchio N, Pietrafusa N, Doccini V, Trivisano M, Darra F, Ragona F, et al. Efficacy and safety of fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a real‐world study. Epilepsia. 2020;61(11):2405–2414.
Valls Carbó A, Beltrán Á, Sánchez‐Miranda Román I, Cabal B, Gómez‐Porro P, Aledo‐Serrano Á, et al. What have we learned from the real‐world efficacy of FFA in DS and LGS? A post‐marketing study in clinical practice. Epilepsy Behav. 2024;151:109620.
Lundbeck. ONFI® (clobazam) tablets, for oral use, CIV. ONFI® (clobazam) oral suspension, CIV [prescribing information]. Deerfield, IL: Lundbeck; 2016.
Löscher W, Klein P. The pharmacology and clinical efficacy of antiseizure medications: from bromide salts to cenobamate and beyond. CNS Drugs. 2021;35(9):935–963.
Schoonjans AS, Roosens L, Dewals W, Paelinck BP, Ceulemans B. Therapeutic drug monitoring of fenfluramine in clinical practice: pharmacokinetic variability and impact of concomitant antiseizure medications. Epilepsia. 2022;63(3):686–696.
Guerrini R, Specchio N, Aledo‐Serrano Á, Pringsheim M, Darra F, Mayer T, et al. An examination of the efficacy and safety of fenfluramine in adults, children, and adolescents with Dravet syndrome in a real‐world practice setting: a report from the fenfluramine European early access program. Epilepsia Open. 2022;7(4):578–587.
Esteban D, Perry S. Long‐term seizure freedom in Dravet syndrome using fenfluramine monotherapy [Abstract]. Presented at Southern Pediatric Neurology Society Meeting, March 11, 2023; New Orleans, LA.
Besag FMC, Vasey MJ. Neurocognitive effects of antiseizure medications in children and adolescents with epilepsy. Paediatr Drugs. 2021;23(3):253–286.
Strzelczyk A, Schubert‐Bast S. Psychobehavioural and cognitive adverse events of anti‐seizure medications for the treatment of developmental and epileptic encephalopathies. CNS Drugs. 2022;36(10):1079–1111.
Jensen MP, Gammaitoni AR, Galer BS, Salem R, Wilkie D, Amtmann D. Fenfluramine treatment for Dravet syndrome: real‐world benefits on quality of life from the caregiver perspective. Epilepsy Res. 2022;185:106976.
Jensen MP, Gammaitoni AR, Salem R, Wilkie D, Lothe A, Amtmann D. Fenfluramine treatment for Dravet syndrome: caregiver‐ and clinician‐reported benefits on the quality of life of patients, caregivers, and families living in Germany, Spain, Italy, and the United Kingdom. Epilepsy Res. 2023;190:107091.
Bishop KI, Isquith PK, Gioia GA, Gammaitoni AR, Farfel G, Galer BS, et al. Improved everyday executive functioning following profound reduction in seizure frequency with fenfluramine: analysis from a phase 3 long‐term extension study in children/young adults with Dravet syndrome. Epilepsy Behav. 2021;121(Pt A):108024.
Bishop KI, Isquith PK, Gioia GA, Knupp KG, Scheffer IE, Nabbout R, et al. Fenfluramine treatment is associated with improvement in everyday executive function in preschool‐aged children (<5 years) with Dravet syndrome. Epilepsy Behav. 2023;138:108994.
Bishop KI, Isquith PK, Gioia GA, Knupp KG, Scheffer IE, Sullivan J, et al. Fintepla (fenfluramine) treatment improves everyday executive functioning in patients with Lennox–Gastaut syndrome: analysis from a phase 3 clinical trial [oral presentation]. Presented at American Academy of Neurology Annual Meeting, April 17‐22, 2021, Virtual meeting.
Bishop KI, Isquith PK, Gioia GA, Knupp KG, Sullivan J, Nabbout R, et al. Fenfluramine (Fintepla®) treatment improves everyday executive functioning in patients with Lennox–Gastaut syndrome: analysis from a phase 3 clinical trial [poster]. Presented at American Academy of Neurology Annual Meeting, Seattle, WA, April 2‐7, 2022, 98.
Bishop KI, Isquith PK, Roth RM, Gioia GA, Knupp KG, Sullivan J, et al. Adults with Lennox–Gastaut syndrome have improved everyday executive functioning with fenfluramine (Fintepla®) [poster]. Presented at European Epilepsy Congress (EEC), Geneva, Switzerland, July 9‐13, 2022.
Bishop KI, Isquith P, Knupp K, Sullivan J, Nabbout R, Gil‐Nagel A, et al. Fenfluramine treatment is associated with improvement in everyday executive function in adults with Lennox–Gastaut syndrome: post‐hoc analysis of dose effects from a phase 3 trial rationale [poster]. Presented at American Epilepsy Society Annual Meeting, December 2‐6, 2022, Nashville, TN, 100.
Licheni SH, McMahon JM, Schneider AL, Davey MJ, Scheffer IE. Sleep problems in Dravet syndrome: a modifiable comorbidity. Dev Med Child Neurol. 2018;60(2):192–198.
Jansen FE, Sadleir LG, Harkin LA, Vadlamudi L, McMahon JM, Mulley JC, et al. Severe myoclonic epilepsy of infancy (Dravet syndrome): recognition and diagnosis in adults. Neurology. 2006;67(12):2224–2226.
Samanta D. Management of Lennox–Gastaut syndrome beyond childhood: a comprehensive review. Epilepsy Behav. 2021;114(part A):107612.
Kerr M, Kluger G, Philip S. Evolution and management of Lennox–Gastaut syndrome through adolescence and into adulthood: are seizures always the primary issue? Epileptic Disord. 2011;13(Suppl 1):S15–S26.
Gallop K, Wild D, Nixon A, Verdian L, Cramer JA. Impact of Lennox–Gastaut syndrome (LGS) on health‐related quality of life (HRQL) of patients and caregivers: literature review. Seizure. 2009;18(8):554–558.
Sinoo C, de Lange IM, Westers P, Gunning WB, Jongmans MJ, Brilstra EH. Behavior problems and health‐related quality of life in Dravet syndrome. Epilepsy Behav. 2019;90:217–227.
Makiello P, Feng T, Dunwoody B, Steckler F, Symonds J, Zuberi SM, et al. Comorbidities and predictors of health‐related quality of life in Dravet syndrome: a 10‐year, prospective follow‐up study. Epilepsia. 2023;64(4):1012–1020.
de Leon J, Santoro V, D'Arrigo C, Spina E. Interactions between antiepileptics and second‐generation antipsychotics. Expert Opin Drug Metab Toxicol. 2012;8(3):311–334.
Miziak B, Czuczwar SJ, Pluta R. Comorbid epilepsy and depression‐pharmacokinetic and pharmacodynamic drug interactions. Front Pharmacol. 2022;13:988716.
Seiden LG, Connor GS. The importance of drug titration in the management of patients with epilepsy. Epilepsy Behav. 2022;128:108517.
Knupp KG, Scheffer IE, Ceulemans B, Sullivan J, Nickels KC, Lagae L, et al. Impact of fenfluramine in patients with Lennox–Gastaut Syndrome: subgroup analysis of dose‐capping on drop seizure frequency reduction in the open‐label extension data [poster]. Presented at American Epilepsy Society Annual Meeting, December 2‐6, 2022, Nashville, TN.
Harden C, Tomson T, Gloss D, Buchhalter J, Cross JH, Donner E, et al. Practice guideline summary: sudden unexpected death in epilepsy incidence rates and risk factors: report of the guideline development, dissemination, and implementation subcommittee of the American Academy of Neurology and the American Epilepsy Society. Epilepsy Curr. 2017;17(3):180–187.
Kløvgaard M, Sabers A, Ryvlin P. Update on sudden unexpected death in epilepsy. Neurol Clin. 2022;40(4):741–754.
Sveinsson O, Andersson T, Mattsson P, Carlsson S, Tomson T. Clinical risk factors in SUDEP: a nationwide population‐based case‐control study. Neurology. 2020;94(4):e419–e429.
Whitney R, Donner EJ. Risk factors for sudden unexpected death in epilepsy (SUDEP) and their mitigation. Curr Treat Options Neurol. 2019;21(2):7.
Cross JH, Galer BS, Gil‐Nagel A, Devinsky O, Ceulemans B, Lagae L, et al. Impact of fenfluramine on the expected SUDEP mortality rates in patients with Dravet syndrome. Seizure. 2021;93:154–159.
Cooper MS, McIntosh A, Crompton DE, McMahon JM, Schneider A, Farrell K, et al. Mortality in Dravet syndrome. Epilepsy Res. 2016;128:43–47.
Buraniqi E, Dabaja H, Wirrell EC. Impact of antiseizure medications on appetite and weight in children. Paediatr Drugs. 2022;24(4):335–363.
Gil‐Nagel A, Sullivan J, Ceulemans B, Wirrell E, Devinsky O, Nabbout R, et al. Treatment with fenfluramine in patients with Dravet syndrome has no long‐term effects on weight and growth. Epilepsy Behav. 2021;122:108212.
Lai WW, Galer BS, Wong PC, Farfel G, Pringsheim M, Keane MG, et al. Cardiovascular safety of fenfluramine in the treatment of Dravet syndrome: analysis of an ongoing long‐term open‐label safety extension study. Epilepsia. 2020;61(11):2386–2395.
Agarwal A, Farfel GM, Gammaitoni AR, Wong PC, Pinto FJ, Galer BS. Long‐term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: findings from serial echocardiographic assessments. Eur J Paediatr Neurol. 2022;39:35–39.
Agarwal A, Farfel G, Gammaitoni AR, Wong PC, Pinto FJ, Galer BS. Long‐term cardiovascular safety of fenfluramine for Lennox–Gastaut syndrome: interim analysis of open‐label safety study [plenary presentation]. Presented at American Academy of Neurology April 2‐7, 2022, Seattle, WA, 98.
UCB. Periodic safety update report for active substance(s): fenfluramine ATC code(s): N03AX26. August 24 2023.
Hope OA, Harris KM. Management of epilepsy during pregnancy and lactation. BMJ. 2023;382:e074630.
Błaszczyk B, Miziak B, Pluta R, Czuczwar SJ. Epilepsy in pregnancy‐management principles and focus on valproate. Int J Mol Sci. 2022;23(3):1369.
Harden CL, Meador KJ, Pennell PB, Hauser WA, Gronseth GS, French JA, et al. Management issues for women with epilepsy‐focus on pregnancy (an evidence‐based review): II. Teratogenesis and perinatal outcomes: report of the quality standards subcommittee and therapeutics and Technology Subcommittee of the American Academy of neurology and the American Epilepsy Society. Epilepsia. 2009;50(5):1237–1246.
Nucera B, Brigo F, Trinka E, Kalss G. Treatment and care of women with epilepsy before, during, and after pregnancy: a practical guide. Ther Adv Neurol Disord. 2022;15:17562864221101687.
Meador KJ. Effects of maternal use of antiseizure medications on child development. Neurol Clin. 2022;40(4):755–768.