Past and Future Perspectives for Seizure Cluster Treatment in Persons with Epilepsy
Abstract number :
3.308
Submission category :
7. Anti-seizure Medications / 7E. Other
Year :
2022
Submission ID :
2204632
Source :
www.aesnet.org
Presentation date :
12/5/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:26 AM
Authors :
William Tatum, DO – Mayo Clinic; Tracy Glauser, MD – Comprehensive Epilepsy Center; Jurriaan Peters, MD, PhD – Boston Children's Hospital; Amit Verma, MD – Houston Methodist Hospital; Sarah Weatherspoon, MD – University of Texas at Austin Dell Medical School; Selim Benbadis, MD – Comprehensive Epilepsy Program, University of South Florida & Tampa General Hospital; Danielle Becker, MD, MS – Case Western Reserve University School of Medicine; Vinay Puri, MBSS, MD – University of Louisville; Michael Smith, MD – Section of Epilepsy and Clinical Neurophysiology, Rush University; Sunita Misra, MD, PhD – Neurelis, Inc.; Adrian Rabinowicz, MD – Neurelis, Inc.; Enrique Carrazana, MD – Neurelis, Inc.; University of Hawaii John A. Burns School of Medicine
Rationale: Some patients with epilepsy experience seizure clusters while receiving daily antiseizure medication (ASM). Prior to the recent FDA approvals of two intranasal rescue therapies, rectal diazepam was the only available treatment for acute management of seizure clusters. There are, however, substantial practical and medical limitations to the rectal route of administration in the acute setting, and use of unapproved ASM and routes presents safety and efficacy concerns. Hence, traditional practices for rescue therapies are in need of reevaluation given changes in the treatment landscape.
Methods: We identified common practices and concerns regarding acute administration of rescue therapies for seizure clusters that we categorized by rescue therapy formulation, efficacy, and safety. The literature was evaluated for support or refutation of the underlying hypotheses.
Results: Regarding formulations of rescue ASM used for seizure clusters, use of oral ASM in adult patients and intravenous solutions administered intranasally with an atomizer have more discrete delivery routes than rectal administration. However, potential shortcomings of these off-label uses include aspiration risk, delayed time to efficacy with oral tablet use, inadvertent swallowing of intranasally administered formulations of intravenous solutions, and variations in bioavailability. Many of these concerns may be overcome by use of the recently available ASM rescue therapies (Table). Regarding efficacy, there is a misconception that all routes of administration are equally effective, which is not supported by the data. Further, it is a common practice that rescue therapy should be delivered 5 minutes into a seizure cluster. However, this time point is for identifying status epilepticus, and the efficacy of rescue benzodiazepines in treating seizure clusters may differ. Efficacy also has been evaluated using maximum concentration (Cmax) and time to Cmax (Tmax), although these parameters do not correlate with clinical efficacy (Table). Relative safety concerns include mucosal irritation with intranasal rescue ASM stemming from past experience encountered with use of atomized intravenous or prior investigational formulations. Therefore, recent intranasal rescue therapies have used different formulations to reduce the potential for nasal irritation. Importantly, concern for developing respiratory depression and tolerance have been carried over from studies of intravenous and daily benzodiazepine usage but have not yet been reported for intermittent use of appropriate rescue therapies in epilepsy (Table).
Conclusions: Knowledge of traditional delivery routes for administration of acute ASM needs to be updated to address beliefs and concerns relative to their use. Evolving practices based on currently available data for improved rescue therapies involving formulations, efficacy, and safety are emerging and are expected to improve acute management of persons with epilepsy who experience ongoing seizure clusters.
Funding: Neurelis, Inc.
Anti-seizure Medications