Alprazolam × Morphine

Alprazolam and morphine act on different receptors (GABA-A and mu-opioid), 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 alprazolam and morphine 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 (alprazolam and morphine labels). The patient and caregivers are taught in advance to recognise these signs (alprazolam and morphine labels).

The combination is not prohibited, but the alprazolam and morphine 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 (alprazolam and morphine labels). The alprazolam and morphine labels approved by the US Food and Drug Administration (FDA) add: in a patient already on morphine, start alprazolam at a lower dose than usual; when morphine is added to alprazolam, 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). Alprazolam is given for no longer than 2–4 weeks, at a lower dose in older or debilitated patients and in chronic respiratory insufficiency, and it is contraindicated in severe respiratory insufficiency and sleep apnoea syndrome (alprazolam SmPC); morphine is also given at a lower dose to older patients and in chronic kidney or liver disease (morphine SmPC).