Diazepam × Morphine

Morphine and diazepam act on different receptors (μ-opioid and GABA-A) but both depress the central nervous system and the medullary respiratory centre. Effects are additive – risk of fatal respiratory depression rises several-fold. FDA expanded the boxed warning to all opioid + benzodiazepine pairs in 2016.

Drowsiness, slowed and shallow breathing (respiratory rate below 12/min), cyanosis of lips and nail beds. Severe cases progress to respiratory arrest and death. Symptoms are easy to miss, so the patient and family are warned in advance.

Avoid where possible. In palliative care and cancer pain, use minimal doses of both with continuous respiratory rate and saturation monitoring. Provide the patient and family with naloxone (opioid antidote) and train them in its use. Alternative anxiolytics without respiratory depression: gabapentin, pregabalin, hydroxyzine.