Long-Term Safety of Midazolam Nasal Spray for Acute Repetitive Seizures

woman using nasal spray
woman using nasal spray
Midazolam nasal spray, a novel benzodiazepine formulation, may be a safe, long-term treatment option for acute seizure episodes.
The following article is part of conference coverage from the American Epilepsy Society’s Annual Meeting in New Orleans, LA. The Neurology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from AES 2018.

NEW ORLEANS — Midazolam nasal spray, a novel benzodiazepine formulation, may be a safe, long-term outpatient rescue treatment option for seizure clusters. The results of the open-label ARTEMIS-2 trial (ClinicalTrials.gov Identifier: NCT01529034), the extension of the ARTEMIS-1, were presented at the 72nd Annual Meeting of the American Epilepsy Society, held November 30-December 4, 2018 in New Orleans, LA.

Researchers included 161 patients from the ARTEMIS-1 trial to evaluate the efficacy and safety of midazolam nasal spray an an outpatient option for patients with seizure cluster episodes being treated repeatedly with midazolam nasal spray. This poster reports the safety results, while another reports the efficacy results.

Data collection included clinical exams, caregiver records, laboratory tests, the Columbia-Suicide Severity Rating Scale, the Brief Smell Identification Test, and adverse event records. Caregivers administered 5 mg of the nasal spray as a rescue treatment at the onset of a seizure, and another 5 mg could be used if needed.

Of the 1998 episodes analyzed, there were 843 total treatment-emergent adverse events reported. Of these, 40.4% of the patients reported treatment-emergent adverse events within 2 days of midazolam administration for each treated episode; only 45 events overall were categorized as serious. No deaths were reported and the adverse event profile was deemed comparable to the established pharmacology of midazolam and the intranasal route of administration.

The most common treatment emergent adverse events were nasal discomfort (12.4%) and somnolence (9.3%), with 2 patients discontinuing use due to these events.

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Episodes of status epilepticus, convulsion, upper gastrointestinal hemorrhage, dysesthesia, and acute central respiratory depression occurred in 4 patients but were deemed unrelated to the treatment. There appeared to be no olfactory toxicity or negative changes in laboratory tests or clinical exams.

In conclusion, this extension study indicates that midazolam nasal spray shows long-term safety and “potentially offers caregivers a novel and reliable means of rescue treatment for patients experiencing [seizure clusters].”

This research was supported by Proximagen, LCC.

For more coverage of AES 2018, click here.


Meng TC, Sequeira DJ, Van Ess PJ, Pullman WE. Long-term safety experience of Nayzilam™ (USL261; midazolam nasal spray) in subjects with seizure clusters: safety results from the open-label, phase 3 extension of the ARTEMIS-1 study. Presented at: 72nd Annual Meeting of the American Epilepsy Society; November 30-December 4, 2018; New Orleans, LA. Poster 2.235.