An Open‐Label Study of Repeated Use of Diazepam Rectal Gel (Diastat) for Episodes of Acute Breakthrough Seizures and Clusters: Safety, Efficacy, and Tolerance

Summary: Purpose: To assess safety of diazepam rectal gel (DZPRG) for control of acute seizures in epilepsy patients and to evaluate tolerance with repeated use of DZPRG at intervals of ≤5 days. Methods: Subjects were persons with epilepsy, age 2 years or older, with seizure clusters or prolonged seizures. Onset of a treatable episode was defined; caregivers were trained to administer DZPRG and to monitor respiration, seizures, and adverse effects (AEs). DZPRG was dispensed in a single‐use, prefilled syringe; dosage was determined by age and weight. Maximal use was ≤5‐day intervals, ≥5 times/month. After use, caregivers returned data booklets and syringe. Caregivers and physicians completed global ratings yearly. Results: In 149 subjects treated, 77% of 1,578 administrations resulted in seizure freedom for the next 12 h. One hundred twenty‐five received two or more treatments (two to 78; median, 8), 0.03–4.3/month (median, 0.4). To evaluate tolerance, subjects with two or more episodes were divided into low (two to seven episodes) and high use (eight to 78 episodes treated). There was no difference in proportion seizure free 12 h after the first administration versus last administration, for either infrequent or frequent administration. Sedation occurred in 17%, attributed to DZPRG in 9%. No respiratory depression was attributable to DZPRG. Three subjects withdrew because of AEs attributable to (agitation) or possibly attributable to DZPRG (chest pain, rash). Five subjects withdrew because of AEs unrelated to DZPRG. Caregiver and physician global ratings were highly positive at both 12 and 24 months. Conclusions: DZPRG is safe and effective in children and adults with epilepsy with breakthrough seizures. Neither tolerance nor significant medication‐related AEs were seen with repeated DZPRG administration at intervals ≤5 days.