CriticalSelective serotonin reuptake inhibitors×Oxazolidinone antibiotic
Updated · Methodology
Mechanism
Fluoxetine (SSRI) raises synaptic serotonin. Linezolid reversibly inhibits MAO. The pair is notable because fluoxetine's active metabolite, norfluoxetine, persists for up to 5 weeks – the serotonergic effect outlasts dosing.
Symptoms
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.
Management
The combination is not prescribed. Stop fluoxetine at least 5 weeks before planned linezolid. For acute antibiotic need, use vancomycin or daptomycin. If linezolid is still required, monitor for serotonin syndrome during therapy plus 5 weeks after fluoxetine discontinuation.
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Sources
- FDA: Zyvox (linezolid) prescribing information (2018)– ; DailyMed setid 6e70e63b-bfd5-478d-a8ee-8ba22c9efabd
- AEMPS: Ficha técnica de Zyvoxid 2 mg/ml solución para perfusión (linezolid) (2026)– AEMPS, CIMA, nº registro 64106, secciones 4.3 y 4.4
- FDA: Prozac (fluoxetine) prescribing information (2026)– FDA label, DailyMed setid c88f33ed-6dfb-4c5e-bc01-d8e36dd97299, version 59, revised 01/2026, section 7.7 Drugs Metabolized by CYP2D6