Abstracts

Spontaneous reporting programs for adverse events (AEs), such as the Food and Drug Administration[rsquo]s MedWatch program, provide one method to evaluate the safety of a drug in a large population over time. Diazepam rectal gel (Diastat) has a favorable safety record in clinical trials. This analysis was conducted to assess the safety of diazepam rectal gel, as reflected by the number and nature of spontaneously reported AEs.
The total number of diazepam rectal gel treatments prescribed to date was used to estimate the total number of doses administered. Spontaneous reports of AEs were obtained from Xcel Pharmaceuticals, which markets the drug. The AEs were categorized and reviewed, and compared to the number of prescribed treatments.
As of February 2003, 1,327,000 treatments have been prescribed. It is therefore estimated that more than 1 million doses of diazepam rectal gel have been administered. A total of 40 reports (35 original and 5 follow-up reports) describing 63 adverse events coinciding with diazepam rectal gel use were spontaneously filed with the manufacturer. These events included convulsion/drug ineffective (8 patients), gastrointestinal AEs (7), emotional/cognitive AEs (6), respiratory AEs (6), somnolence (4), death (3; causes unknown), hypotension/vasodilation (2), pain (2), rash or anaphylactic reaction (2), abnormal vision, infection, a positive drug screen in a health professional who had administered the drug, reaction unevaluable, and rectal hemorrhage (1 patient each). Only 6 patients reported a respiratory AE (hypoventilation, dyspnea, respiratory depression, or apnea). In 1 of these patients, the respiratory AE was clearly secondary to an anaphylactoid reaction and the presence of opiates. The remaining 54 AEs were pharmacologic extensions of benzodiazepines as a class (including the emotional/cognitive AEs, hypotension/vasodilation, and somnolence), or were secondary to other factors.
Because spontaneous reports are not collected in a systematic way, they cannot be used to calculate the incidence of any particular AE. Additionally, some reported events have a doubtful relationship to the drug, or are known complications of seizures. However, the scarcity of spontaneously reported AEs (63) relative to the large number of treatments ([gt]1 million) suggests that serious adverse reactions to diazepam rectal gel are very rare.