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Epilepsia. 2019 Jul 29. doi: 10.1111/epi.16300. [Epub ahead of print]

Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters: An open-label extension trial.

Author information

1
Le Bonheur Comprehensive Epilepsy Program & Neuroscience Institute, Le Bonheur Children's Hospital, Memphis, Tennessee.
2
Pediatric Neurology, University of Tennessee Health Science Center, Memphis, Tennessee.
3
Proximagen, Plymouth, Minnesota.
4
Department of Neurology, Yale Comprehensive Epilepsy Center, Yale School of Medicine, New Haven, Connecticut.

Abstract

OBJECTIVE:

To evaluate safety- and seizure-related outcomes with repeated intermittent use of a novel formulation of midazolam administered as a single-dose nasal spray (MDZ-NS) in the outpatient treatment of patients experiencing seizure clusters (SCs).

METHODS:

In this open-label extension trial (ClinicalTrials.gov NCT01529034), patients aged ≥12 years and on a stable regimen of antiepileptic drugs who completed the original phase III, randomized controlled trial were enrolled. Caregivers administered MDZ-NS 5 mg when patients experienced SCs; a second dose could be given if seizures did not terminate within 10 minutes or recurred within 10 minutes-6 hours. Patients were monitored for treatment-emergent adverse events (TEAEs) throughout, and the main seizure-related outcome was treatment success, defined as seizure termination within 10 minutes and no recurrence 10 minutes-6 hours after drug administration.

RESULTS:

Of 175 patients enrolled, 161 (92.0%) received ≥1 MDZ-NS dose, for a total of 1998 SC episodes. Median time spent by patients in the trial was 16.8 months (range = 1-55.7 months). TEAEs were experienced by 40.4% of patients within 2 days of drug administration and 57.1% overall. TEAEs reported by most patients (within 2 days and overall) were nasal discomfort (12.4%) and somnolence (9.3%). One patient each discontinued due to treatment-related nasal discomfort and somnolence. There were no patients with treatment-related respiratory depression, and none with TEAEs indicative of drug abuse or dependence. Treatment success criteria were met in 55% (1108/1998) of SC episodes after administration of a single 5-mg dose and in 80.2% (617/769) with the second dose. Treatment success was consistent over treated episode number.

SIGNIFICANCE:

Repeated, intermittent, acute treatment of patients experiencing SCs with MDZ-NS in the outpatient setting was well tolerated over an extended period, with maintenance of efficacy suggesting lack of development of tolerance.

KEYWORDS:

acute repetitive seizures; acute treatment; benzodiazepine; epilepsy; intranasal; rescue

PMID:
31353457
DOI:
10.1111/epi.16300

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