Linezolid × Sertraline

Linezolid is an oxazolidinone antibiotic that also reversibly inhibits monoamine oxidase (MAO). Sertraline, a selective serotonin reuptake inhibitor (SSRI), raises synaptic serotonin. Combined action sharply amplifies serotonergic transmission. The FDA carries a boxed warning for this combination.

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 sertraline at least 2 weeks before starting linezolid (washout). If urgent antibiotic therapy is needed, use vancomycin, daptomycin, or ceftaroline based on susceptibility. If serotonin syndrome has already developed, stop both drugs immediately, start cyproheptadine, and admit for intensive supportive care.