Linezolid × venlafaxine

Venlafaxine is a serotonin–norepinephrine reuptake inhibitor (SNRI). Linezolid reversibly inhibits MAO. Combined action raises both serotonin and norepinephrine, risking serotonin syndrome.

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, dilated pupils. Autonomic features: profuse sweating, tachycardia, hypertension, fever above 38.5 °C. Severe cases progress to seizures, rhabdomyolysis, disseminated intravascular coagulation, and death. First signs appear within hours of concurrent dosing.

The combination is not prescribed. Stop venlafaxine at least 1 week before linezolid. For acute antibiotic need, use vancomycin or daptomycin. After completing linezolid, venlafaxine may resume 24 hours later.