Abstracts

Respiratory depression is rare following administration of rectal diazepam. In 4 studies involving more than 500 patients treated with diazepam rectal gel, no episodes of respiratory depression were reported. However, the possibility of respiratory depression as a consequence of home administration of diazepam rectal gel remains a concern among clinicians and caregivers.
All respiratory adverse events (those termed respiratory depression, hypoventilation, dyspnea, or apnea) spontaneously reported to Xcel Pharmaceuticals, which markets diazepam rectal gel, were reviewed to evaluate the incidence of respiratory depression and the possible association of each of these adverse events with the administration of diazepam rectal gel.
As of Feb 1, 2003, over 1.3 million diazepam rectal gel syringes were prescribed, and it is estimated that over 1 million doses have been given. Reports of respiratory adverse events were filed for 6 patients. Two subjects had a prior history of respiratory depression and apnea associated with their seizures, which also occurred with rectal diazepam gel use. One patient became unresponsive and had shallow breathing without cyanosis, which spontaneously resolved prior to arrival in the emergency department. One consumer-filed report observed only that the patient had difficulty breathing that started a few minutes after diazepam rectal gel administration, and was attended to by emergency personnel with full recovery. Two subjects had more serious respiratory adverse events. One required respiratory support following administration of a total of 20 mg diazepam rectal gel, a dose well in excess of that recommended for his age and weight. The other was hospitalized for respiratory distress secondary to an anaphylactic reaction following diazepam rectal gel administration. The patient tested positive for opiates, which were not prescribed. The patient[rsquo]s history was remarkable for a similar reaction, also involving opiates, which resulted in cardiorespiratory arrest. It is unknown whether benzodiazepines were administered prior to the first event.
Reports of respiratory depression with diazepam rectal gel are very rare. In the majority of cases, other factors were also involved. While relying on reported adverse events may underestimate the total number of respiratory adverse events, the extreme rarity of these reports, even with widespread clinical use, is reassuring. Respiratory depression can also occur with seizures, and in one recent study of the prehospital treatment of seizures (Alldredge et al, [italic]NEJM[/italic] 2001;345:631-637) was as common in the placebo group as in the IV benzodiazepine-treated group. When used as recommended, diazepam rectal gel has an extremely low rate of respiratory depression.
[Supported by: Xcel Pharmaceuticals]