Effectiveness and safety of benzodiazepine seizure cluster rescue therapy may be affected by concomitant use of benzodiazepines. Diazepam nasal spray (Valtoco^®) is indicated for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years.

Patients and caregivers were trained to administer diazepam nasal spray 5, 10, 15, or 20 mg (age- and weight-based), with a second dose, if needed, 4 to 12 hours later. This analysis evaluated diazepam nasal spray utilization and safety in patients with and without concomitant use of benzodiazepines, including alprazolam, clobazam, clonazepam, clorazepate, diazepam, lorazepam, and midazolam.

Of 175 patients enrolled, 158 received diazepam nasal spray (aged 6–65 years). Of those, 119 (75.3%) used benzodiazepines as part of their antiseizure drug regimen; 39 (24.7%) did not. Duration of diazepam nasal spray exposure was ≥12 months for 75.6% of those with concomitant benzodiazepines and 66.7% of those without. Percentage of seizure episodes using a single dose of diazepam nasal spray (proxy for effectiveness) was 90.5% for those with concomitant benzodiazepines and 92.4% for those without. Rates of treatment-emergent adverse events (TEAEs) were 79.8% for those with concomitant benzodiazepines, and 61.5% for those without. Serious TEAEs were higher among the patients using concomitant benzodiazepines (30.3% vs 23.1%); none were treatment related. Retention rate was 84.1% with concomitant benzodiazepines and 76.9% without.

In this long-term safety study, effects of diazepam nasal spray were similar whether or not patients used other benzodiazepines. In most cases, the number of doses used for seizure activity was independent of the presence of concomitant benzodiazepines, and no difference in retention rate was seen. Safety was consistent with what is expected for diazepam.