Linezolid Injection and Trazodone: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Trazodone
Linezolid Injection
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased risk of serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes)
Interaction Deep Dive
Concurrent use of linezolid, an MAOI, and traZODone is contraindicated due to the potential for serotonin syndrome. Wait at least 14 days after discontinuing an MAOI before initiating traZODone. Serotonin syndrome is a potentially life-threatening condition. Serotonin syndrome signs and symptoms may include mental status changes (eg, agitation, hallucinations, delirium, and coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (eg, nausea, vomiting, diarrhea). If it is necessary to initiate treatment with linezolid in a patient receiving traZODone, discontinue traZODone before initiating linezolid and inform patients of the increased risk for serotonin syndrome and monitor for symptoms2. In a retrospective cohort study in older adults, serotonin syndrome occurred in less than 0.5% of patients who were taking a concurrent antidepressant and linezolid. In the propensity score-matched cohort, there was no difference in the risk of serotonin syndrome in patients taking concomitant antidepressants and linezolid compared with patients not taking antidepressants. There was also no difference in the rate of altered mental status or confusion, hospitalization, or death from any cause between groups 1.
Why it happens (mechanism)
Additive serotonergic effects
Literature reports
1 report — tap to read
a) In a retrospective cohort study in older adults who were prescribed oral linezolid 600 mg twice daily (N=1134), serotonin syndrome occurred in fewer than 6 patients (less than 0.5%) who were taking a concomitant antidepressant (n=215). In the propensity score-matched cohort (n=332), there was no difference in the risk of clinically significant serotonin syndrome in patients taking concomitant antidepressants and linezolid compared with patients taking linezolid without antidepressants (adjusted risk difference, -1.2%; 95% CI, -2.9% to 0.5%). There was also no difference in the rate of altered mental status or confusion, hospitalization, or death from any cause between groups. Patients were aged 66 years or older, and of those taking an antidepressant, 47.9% were taking an SSRI, 16.7% were taking an SNRI, 7% were taking a tricyclic antidepressant, 3.3% were taking a norepinephrine and dopamine reuptake inhibitor, and none were taking an MAOI 1.
Common questions
Can I take Linezolid Injection and Trazodone together?
Increased risk of serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Linezolid Injection and Trazodone interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Linezolid Injection or Trazodone need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (2)
- Bai AD, McKenna S, Wise H, et al: Association of linezolid with risk of serotonin syndrome in patients receiving antidepressants. JAMA Netw Open 2022; 5(12):e2247426. DOI
- Product Information: Trazodone HCl oral tablets, trazodone HCl oral tablets. Rising Pharma Holdings, Inc (per DailyMed), East Brunswick, NJ, 2025. DailyMed
Keep reading about Trazodone
Keep reading about Linezolid Injection
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