Treatment of prolonged seizure with diazepam nasal spray: An exploratory post hoc cohort analysis.

Autor: Jarrar R; Department of Neurology, Phoenix Children's Hospital, 1919 E Thomas Rd Ambulatory Building, Floor 3, Phoenix, AZ 85016, USA. Electronic address: rjarrar@phoenixchildrens.com., Stern JM; Department of Neurology, Geffen School of Medicine, University of California Los Angeles, Los Angeles 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA. Electronic address: jstern@ucla.edu., Becker DA; Department of Neurology, Ohio State University, Wexner Medical Center 395 W. 12th Ave., 7th Floor, Columbus, OH 43210, USA. Electronic address: dbecker8@gmail.com., Davis C; CSD Biostatistics, Inc., 1005 W. Soft Wind Place, Oro Valley, AZ 85737, USA. Electronic address: csdbiostat@gmail.com., Rabinowicz AL; Clinical Development and Medical Affairs, Neurelis, Inc., 3430 Carmel Mountain Rd Suite 300, San Diego, CA 92121, USA; Center for Molecular Biology and Biotechnology, Charles E. Schmidt College of Science, Florida Atlantic University, 777 Glades Rd, SE-43, Boca Raton, FL 33431, USA. Electronic address: arabinowicz@neurelis.com., Carrazana E; Clinical Development and Medical Affairs, Neurelis, Inc., 3430 Carmel Mountain Rd Suite 300, San Diego, CA 92121, USA; Department of Family Medicine, John A. Burns School of Medicine, University of Hawaii, 651 Ilalo St, Honolulu, HI 96813, USA. Electronic address: ecarrazana@neurelis.com.
Jazyk: angličtina
Zdroj: Epilepsy & behavior : E&B [Epilepsy Behav] 2024 Oct; Vol. 159, pp. 109987. Date of Electronic Publication: 2024 Aug 23.
DOI: 10.1016/j.yebeh.2024.109987
Abstrakt: Background: Benzodiazepines are used in first-line rescue therapy as immediate-use seizure medication for the treatment of seizure clusters and prolonged seizures. Their use varies across clinical practices and conditions, and they can be used promptly when indicated. Clinical studies have demonstrated seizure termination within 2 min when diazepam nasal spray is used to treat seizure clusters within 5 min, but the response when treating longer duration seizures in a cluster remains to be characterized.
Objective: To describe and assess timing and dosing of diazepam nasal spray in the subset of prolonged seizures within seizure clusters in a larger dataset of all treated seizure clusters collected during a long-term safety study of diazepam nasal spray.
Methods: Using timing data recorded in seizure diaries, this post hoc analysis and associated sensitivity analyses focused on prolonged seizures treated 5 to 15 min after the seizure start. Measures included time to treatment administration and time to seizure termination. Second-dose data were used as a proxy for effectiveness.
Results: In this group of seizure clusters treated 5 to 15 min after seizure start, median time drug administration was 6 min after seizure start, median time from drug administration to seizure termination was 7 min, and median overall seizure duration was 15 min. Sensitivity analyses by age, epilepsy type, and high seizure frequency confirmed this pattern. Use of a second dose occurred in 9.3 % of episodes, with the majority of second doses administered ≤ 4 h after the first dose. Safety results from the overall study showed 82.2 % of patients had ≥ 1 treatment-emergent adverse event (TEAE) irrespective of relationship to treatment, during a mean participation of ∼ 1.5 years. In addition, 30.7 % patients had a serious TEAE, and 18.4 % had TEAEs deemed at least possibly related to the study drug, none of which were serious. No events of cardiorespiratory depression were reported.
Conclusions: Although immediate use of diazepam nasal spray (within 5 min) resulted in quicker seizure termination, a treatment delay of 5 to 15 min still produced rapid termination of the seizure cluster with high first-dose effectiveness and an overall acceptable safety profile. These findings suggest that diazepam nasal spray maintains effectiveness in prolonged seizures within a cluster with delayed treatment.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dr Jarrar is an advisor for Neurelis, Inc. Dr Stern is a consultant for Eisai; Jazz; Neurelis, Inc.; SK Life Science; and UCB. Dr Becker is a consultant/speaker for Neurelis, Inc; SK Life Science; and Jazz Pharmaceuticals. Dr Davis is a consultant to Neurelis, Inc. Dr Rabinowicz is an employee of and has received stock options from Neurelis, Inc. Dr Carrazana is an employee of and has received stock and stock options from Neurelis, Inc.].
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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