Treatment of Prolonged Seizure With Diazepam Nasal Spray: A Post Hoc Cohort Analysis
Randa Jarrar1, John Stern2, Danielle Becker3, Adrian Rabinowicz4, Enrique Carrazana5
1Phoenix Children’s Hospital, 2Geffen School of Medicine, University of California Los Angeles, 3Ohio State University Wexner Medical Center, 4Neurelis, Inc.; Center for Molecular Biology and Biotechnology, Charles E. Schmidt College of Science, 5Neurelis, Inc.; University of Hawaii, John A. Burns School of Medicine
Objective:
To assess the use of diazepam nasal spray (Valtoco®) in prolonged seizures in a seizure cluster (SC).
Background:
Benzodiazepines are first-line rescue therapy in seizure emergencies, including SCs and prolonged seizures, and can be used promptly when indicated. Diazepam nasal spray is indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, SCs) in patients with epilepsy aged ≥6 y. Diazepam nasal spray treatment of SCs within 5 minutes has been associated with seizure termination in ≤2 minutes.
Design/Methods:
This post hoc sensitivity analysis of data from a long-term safety study of diazepam nasal spray analyzed prolonged seizures within SCs (treated 5–15 min after seizure start) by age (<18 y, ≥18 y), epilepsy type (generalized, focal, unclassified), and SC burden (≥20 SCs). Second dose usage was a proxy for effectiveness.
Results:
In SCs treated 5–15 minutes after seizure start (n=727 events), an earlier analysis found that the median time from drug administration to seizure termination was 7 minutes. Sensitivity analyses reported generally similar results, with median times to seizure termination of 5 and 10 minutes for pediatric and adult patients; 6, 5, and 15 minutes for generalized, focal, and unclassified epilepsies; and 10 minutes in patients with ≥20 SCs. Second doses were administered in 9.3% of prolonged events; generally consistent across subgroups. 82.2% of patients had ≥1 treatment-emergent adverse event (TEAE) during 1.5 years on average. 30.7% patients had a serious TEAE, and 18.4% had TEAEs deemed related to study drug (none were serious). No cardiorespiratory depression was reported.
Conclusions:
If treatment is delayed (ie, a prolonged seizure within a SC), diazepam nasal spray rapidly terminates the SC with high first-dose effectiveness and a well-characterized safety profile. Diazepam nasal spray controls SCs when used promptly and when seizures are prolonged.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.