Morphine × Phenazepam

Phenazepam is a long-acting benzodiazepine with an active metabolite persisting for several days. Morphine and phenazepam together depress the CNS and respiratory centre. Effects are additive – risk of fatal respiratory depression rises. FDA boxed warning applies to all opioid + benzodiazepine pairs since 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 the combination. In palliative care for cancer pain, minimal doses of both with saturation monitoring and naloxone available. For long-term anxiolytic support, choose gabapentinoids or hydroxyzine.