fluoxetine and linezolid

Linezolid is a reversible monoamine oxidase inhibitor and fluoxetine is a selective serotonin reuptake inhibitor. Both increase serotonin concentration at the synaptic cleft. Linezolid inhibits monoamine oxidase type A, the enzyme responsible for serotonin breakdown, while fluoxetine blocks serotonin reuptake. The combined effect leads to profound serotonin accumulation in the central nervous system, resulting in excessive serotonergic activity.

Co-prescription can precipitate serotonin syndrome, a potentially life-threatening condition. Clinical features include mental status changes such as agitation and confusion, autonomic instability with tachycardia, hypertension and diaphoresis, neuromuscular hyperactivity with clonus and hyperreflexia, and hyperthermia. Severity ranges from mild to fatal; onset is usually within hours to days of the interaction, and even single doses have been implicated.

Avoid concomitant use. If linezolid is essential for a severe infection, stop fluoxetine and allow a washout period of at least 5 to 6 weeks due to its long half-life and active metabolite. If urgent co-administration is unavoidable, monitor closely in a hospital setting for signs of serotonin syndrome and be prepared for supportive care including benzodiazepines, active cooling and discontinuation of both agents. Consult current formularies and specialist guidance.

This interaction is well established. Linezolid's prescribing information lists serotonergic drugs as contraindicated, and numerous case reports describe serotonin syndrome with this combination.