Diazepam × Morphine

Morphine and diazepam act on different receptors (mu-opioid and GABA-A), but both depress the central nervous system and the respiratory centre, and the effects add up. The labels of both drugs warn that together they can cause profound sedation, respiratory depression, coma and death. The US Food and Drug Administration (FDA) puts this risk in the boxed warning of the morphine and diazepam labels and cites observational studies: with benzodiazepines, the risk of drug-related death is higher than with opioids alone (FDA labels).

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

The combination is not prohibited, but the morphine and diazepam labels allow it 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 and diazepam labels). The morphine and diazepam labels approved by the US Food and Drug Administration (FDA) add: in a patient already on morphine, start diazepam at a lower dose than usual and titrate to response; when morphine is added to diazepam, 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 (FDA labels). Diazepam is contraindicated in severe respiratory insufficiency and sleep apnoea syndrome, its dose is reduced in chronic respiratory insufficiency, and older patients start at 2–2.5 mg (diazepam SmPC); morphine is also given at a lower dose to older patients and in chronic kidney or liver disease (morphine SmPC).