Respiratory depression rare with rectal diazepam

Rectal diazepam is associated with an extremely low rate of respiratory depression or death, according to an analysis of adverse events reported in the US over seven years.The adverse events related to a rectal diazepam gel (not available in Australia) and were reported to MedWatch, the Food and Drug Administration's adverse event reporting program. The authors say that concern over rectal diazepam's potential to cause respiratory depression is based on the association between IV diazepam and respiratory depression and the relatively high doses given rectally for prolonged seizures.Over 2 million doses of the rectal gel have been prescribed in the US, the authors say. They identified nine cases of respiratory depression from the MedWatch program, and each case occurred in the context of prolonged seizures. Where the outcome was reported, respiratory depression was followed by full recovery to the patient's baseline status. There were also three deaths reported over the period, which also occurred in the context of prolonged seizures. Respiratory depression was not a presenting symptom in any of the deaths.The authors discuss the pharmacokinetic differences between IV and rectal diazepam that make respiratory depression less likely with the rectal route. They say, "IV diazepam produces a rapid spike in plasma diazepam concentrations, sometimes precipitating respiratory depression. Because diazepam is highly lipid soluble, it is rapidly absorbed via the rectal route (therapeutic levels are reached within 15 minutes). However, in contrast to IV administration, rectal administration does not produce the marked spike in plasma diazepam levels following administration."The authors raise the possibility that patients' ictal events may have been an underlying factor in those reported to experience respiratory depression. They describe the results of a recent study where seizure patients treated with placebo had a higher rate of respiratory depression than those treated with a benzodiazepine.Reference...