PMID- 33181890 OWN - NLM STAT- MEDLINE DCOM- 20210414 LR - 20210414 IS - 1525-5069 (Electronic) IS - 1525-5050 (Linking) VI - 112 DP - 2020 Nov TI - Long-term safety and tolerability of adjunctive eslicarbazepine acetate in children with focal seizures. PG - 107458 LID - S1525-5050(20)30638-7 [pii] LID - 10.1016/j.yebeh.2020.107458 [doi] AB - OBJECTIVE: The objective of this study was to evaluate long-term safety and tolerability outcomes in two open-label extension (OLE) studies of adjunctive eslicarbazepine acetate (ESL) in children with focal seizures. METHODS: Safety data from patients aged 4-17 years in OLEs of Studies 2093-208 and -305 were pooled and analyzed. Studies 208 and 305 were randomized, double-blind, placebo-controlled studies of adjunctive treatment with ESL in children with focal seizures refractory to treatment with 1-2 antiseizure drugs; patients could continue into uncontrolled OLEs (up to 5 years total duration). The OLEs evaluated the safety and tolerability of ESL (10-30 mg/kg/day; maximum 1200 mg/day). RESULTS: The 1-year OLE and post-1-year OLE safety populations comprised 337 and 177 ESL-treated patients, respectively. The overall incidence of treatment-emergent adverse events (TEAEs) with ESL was 64.1% during the 1-year OLE and 52.5% during the post-1-year OLE. Nasopharyngitis, partial seizures, vomiting, pyrexia, headache, somnolence, and respiratory tract infection were the most frequently reported TEAEs during the 1-year OLE. The overall incidence of serious adverse events (AEs) was 8.9% during the 1-year OLE and 10.2% during the post-1-year OLE. Partial seizures (1.2%) and pneumonia (1.2%) were the most frequently reported serious AEs during the 1-year OLE. The overall incidence of TEAEs leading to discontinuation was 4.2% during the 1-year OLE and 0.6% during the post-1-year OLE. Partial seizures (1.5%) was the most frequently reported TEAE leading to discontinuation during the 1-year OLE. CONCLUSIONS: Overall, long-term treatment with ESL was generally well tolerated in pediatric patients aged 4-17 years with focal seizures. TEAEs were comparable to those observed in adults with no new events of concern. CI - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Sankar, Raman AU - Sankar R AD - David Geffen School of Medicine, UCLA Mattel Children's Hospital, Los Angeles, CA, USA. Electronic address: rsankar@ucla.edu. FAU - Kirkham, Fenella J AU - Kirkham FJ AD - University Hospital Southampton, Southampton, UK; UCL Great Ormond Street Institute of Child Health, London, UK. Electronic address: fenella.kirkham@ucl.ac.uk. FAU - Holmes, Gregory L AU - Holmes GL AD - College of Medicine, University of Vermont, Burlington, VT, USA. Electronic address: gregory.holmes@med.uvm.edu. FAU - Pina-Garza, J Eric AU - Pina-Garza JE AD - Centennial Children's Hospital, Nashville, TN, USA. Electronic address: jesus.pinagarza@hcahealthcare.com. FAU - Wheless, James AU - Wheless J AD - UTHSC Pediatric Neurology, Le Bonheur Children's Hospital, Memphis, TN, USA. Electronic address: jwheless@uthsc.edu. FAU - Gama, Helena AU - Gama H AD - BIAL - Portela & C feminine, S.A., Coronado (S. Romao e S. Mamede), Portugal. Electronic address: Helena.gama@bial.com. FAU - Moreira, Joana AU - Moreira J AD - BIAL - Portela & C feminine, S.A., Coronado (S. Romao e S. Mamede), Portugal. Electronic address: joana.moreira@bial.com. FAU - Cantu, David AU - Cantu D AD - Sunovion Pharmaceuticals Inc., Fort Lee, NJ, USA. Electronic address: David.Cantu@sunovion.com. FAU - Tosiello, Robert AU - Tosiello R AD - Sunovion Pharmaceuticals Inc., Marlborough, MA, USA. Electronic address: rtosiello@comcast.net. FAU - Blum, David AU - Blum D AD - Sunovion Pharmaceuticals Inc., Marlborough, MA, USA. Electronic address: davideblum@gmail.com. FAU - Grinnell, Todd AU - Grinnell T AD - Sunovion Pharmaceuticals Inc., Marlborough, MA, USA. Electronic address: todd.grinnell@sunovion.com. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200924 PL - United States TA - Epilepsy Behav JT - Epilepsy & behavior : E&B JID - 100892858 RN - 0 (Anticonvulsants) RN - 0 (Dibenzazepines) RN - BEA68ZVB2K (eslicarbazepine acetate) SB - IM MH - Adolescent MH - Adult MH - *Anticonvulsants/adverse effects MH - Child MH - Child, Preschool MH - *Dibenzazepines/adverse effects MH - Double-Blind Method MH - Humans MH - Seizures/drug therapy MH - Treatment Outcome OTO - NOTNLM OT - Antiseizure drug OT - Eslicarbazepine acetate OT - Open-label extension OT - Pediatric OT - Safety OT - Tolerability COIS- Declaration of competing interest RS reports employment at the University of California; receiving honoraria from Sunovion Pharmaceuticals Inc., Supernus, Eisai, Greenwich Biosciences, UCB, LivaNova, BioMarin, and Encoded; receiving consulting fees from Sunovion Pharmaceuticals Inc., Supernus, UCB, BioMarin, Encoded, West Therapeutic Development, and Aquestive Therapeutics; and receiving grants or funds from SK Life Science. FK reports being on advisory councils or committees and receiving honoraria from BIAL and Eisai; and receiving grants from Action Medical Research. GH reports being on advisory councils or committees for Eisai (Data Safety Monitoring Board), Marinus, Ovid, and Zogenix. JEP-G reports being on an advisory council or committee for and receiving honoraria and consulting fees from Aquestive, Eisai, Greenwich, Sunovion Pharmaceuticals Inc., Supernus, and UCB. JW reports receiving grants from Shainberg Foundation, Mallinckrodt, LivaNova, Eisai, Aquestive, Greenwich, Neuralis, Zogenix, and NeuroPace; consultancy for West, Mallinckrodt, Eisai, Supernus, Aquestive, Greenwich, Neuralis, and BioMarin; and is a speaker's bureau member for Mallinckrodt, LivaNova, Eisai, Supernus, Greenwich, UCB, and BioMarin. HG and JM report employment with BIAL - Portela & C feminine, S.A. DC, RT, and TG report employment with Sunovion Pharmaceuticals Inc. DB reports that at the time of the research, he was an employee of Sunovion Pharmaceuticals Inc.; and currently receives consulting fees from Sunovion Pharmaceuticals Inc. EDAT- 2020/11/14 06:00 MHDA- 2021/04/15 06:00 CRDT- 2020/11/13 01:00 PHST- 2020/05/26 00:00 [received] PHST- 2020/08/26 00:00 [revised] PHST- 2020/08/31 00:00 [accepted] PHST- 2020/11/13 01:00 [entrez] PHST- 2020/11/14 06:00 [pubmed] PHST- 2021/04/15 06:00 [medline] AID - S1525-5050(20)30638-7 [pii] AID - 10.1016/j.yebeh.2020.107458 [doi] PST - ppublish SO - Epilepsy Behav. 2020 Nov;112:107458. doi: 10.1016/j.yebeh.2020.107458. Epub 2020 Sep 24.