Morphine × Phenazepam

Phenazepam is a benzodiazepine. The morphine SmPC warns that with benzodiazepines and related sedatives morphine can cause sedation, respiratory depression, coma and death because of additive central nervous system depression (morphine SmPC). The US Food and Drug Administration (FDA) puts this risk in the boxed warning of the morphine label and cites observational studies: with benzodiazepines, the risk of drug-related death is higher than with opioids alone (morphine FDA label). Phenazepam is not authorised in Spain or the US and has no centralised EU authorisation, so these agencies have no label for it.

Severe drowsiness, reduced alertness, confusion, slow and shallow breathing, low blood pressure; in severe cases coma and death (morphine labels). The patient and caregivers are taught in advance to recognise these signs (morphine labels).

The combination is not prohibited, but the morphine SmPC allows morphine with benzodiazepines only for patients who have no other treatment options. Both drugs are then given at the lowest effective dose for the shortest possible time, and the patient is closely watched for respiratory depression and sedation (morphine SmPC). The morphine label approved by the US Food and Drug Administration (FDA) adds: in a patient already on morphine, start the benzodiazepine at a lower dose than usual; when morphine is added to a benzodiazepine, lower the starting dose of morphine. Explain the risk and the signs of respiratory depression to the patient and caregivers, advise against driving until the effect of the combination is known, and if the combination is warranted consider prescribing naloxone, the opioid antidote (morphine FDA label). Older patients and patients with chronic kidney or liver disease receive a lower morphine dose (morphine SmPC).