OBJECTIVES : To summarize serious treatment-emergent adverse events (TEAEs) associated with hospitalizations in a completed long-term safety study of diazepam nasal spray for acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) in patients aged ≥6 years.

METHODS : Patients were aged 6–65 years with highly intractable epilepsy and frequent seizure clusters; history of status epilepticus was allowed. Age- and weight-based doses of diazepam nasal spray were administered, with a second dose 4–12 hours later if needed. TEAEs were recorded.

RESULTS : The study enrolled 175 patients. Diazepam nasal spray was administered 4390 times to 163 patients (54.6% female; mean age, 23.1 years [range, 6–65]; 2 with history of status epilepticus); 46 discontinued. Duration on study was ≥12 months in 81.6% of patients, and median duration was 15 months (range, 1.8–40.5); 52.8% averaged ≥2 doses per month.

A total of 134 patients (82.2%) had TEAEs. Fifty patients (30.7%) had serious TEAEs, none treatment related. One patient died (not treatment related). Forty-four patients (27.0%) had serious TEAEs that required/prolonged hospitalization (105 total events); most common (>2% of patients) were seizure 24 (14.7%), status epilepticus and pneumonia 7 (4.3% each), and amnesia 4 (2.5%). Six study-drug treated seizure episodes progressed to status epilepticus, and all 6 resulted in hospitalization. Ten doses of diazepam nasal spray were used in these episodes (including 4 second doses)—0.23% of the 4390 doses given in the study.

CONCLUSIONS : In this long-term safety study of diazepam nasal spray, 27.0% of patients had serious TEAEs requiring/prolonging hospitalization; none were treatment related. Only 0.23% of doses were given for seizures progressing to status epilepticus in this highly intractable population. Overall, healthcare resource utilization related to diazepam nasal spray was very low, given the known safety profile of diazepam.