Linezolid × Morphine

Besides its antibacterial action, linezolid is a reversible, non-selective inhibitor of monoamine oxidase (MAO), so it belongs to the MAO inhibitors (linezolid SmPC). The US Food and Drug Administration (FDA) morphine labels warn that MAO inhibitors may potentiate the effects of morphine, including respiratory depression, coma and confusion, and that MAO inhibitor interactions with opioids may present as serotonin syndrome or opioid toxicity. The linezolid SmPC also reports serotonin syndrome when linezolid was combined with serotonergic drugs, including opioids.

Increasing drowsiness, confusion, slow and shallow breathing, up to coma (FDA morphine labels). Signs of serotonin syndrome: agitation, high fever, heavy sweating, tremor, muscle jerks and rigidity, exaggerated reflexes, impaired thinking and coordination (linezolid labels).

The combination is contraindicated. Spanish SmPCs for oral morphine contraindicate morphine with monoamine oxidase (MAO) inhibitors and within two weeks of stopping them, and the linezolid SmPC classes linezolid as an MAO inhibitor. The US Food and Drug Administration (FDA) morphine labels set the same 14-day ban and name linezolid among MAO inhibitors. The linezolid SmPC contraindicates its use with serotonergic drugs, opioids included, unless the combination is absolutely necessary. If it cannot be avoided, the patient is closely watched for signs of serotonin syndrome: cognitive dysfunction, high fever, exaggerated reflexes, poor coordination; if they appear, stopping one or both drugs is considered (linezolid SmPC).