Duloxetine and Linezolid Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Duloxetine
No brand names on recordLinezolid 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
An increased risk of CNS toxicity or serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes)
Interaction Deep Dive
Concurrent administration or overlapping therapy with DULoxetine and an MAOI may result in CNS toxicity or serotonin syndrome, a hyperserotonergic state characterized by symptoms such as restlessness, myoclonus, changes in mental status, hyperreflexia, diaphoresis, shivering, and tremor. There have been spontaneous reports of serotonin syndrome associated with concomitant use of linezolid and serotonergic agents, including one case report involving DULoxetine5. Concurrent use of DULoxetine and linezolid is contraindicated. Do not initiate DULoxetine in a patient who is being treated with linezolid. If it is necessary to initiate treatment with linezolid in a patient taking DULoxetine, discontinue DULoxetine before initiating. The patient should be monitored for symptoms of serotonin syndrome for 5 days or until 24 hours after the last dose of linezolid or whichever comes first. Therapy with DULoxetine may be resumed 24 hours after the last dose of linezolid 3. 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 2.
Why it happens (mechanism)
Inhibition of monoamine oxidase-mediated serotonin metabolism
Literature reports
2 reports — 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 2.
b) Serotonin syndrome was induced in a 55-year-old woman maintained on DULoxetine 60 mg/day for recurrent depression, following the addition of intravenous linezolid 600 mg every 12 hours to her treatment regimen. The patient was initially admitted to an inpatient oncology center for pain management and treatment of an infected dehiscing abdominal wound. Due to persistence of vancomycin-resistant enterococcus in wound cultures, linezolid was added to the existing regimen. Approximately 3 hours after the first dose of linezolid, the patient demonstrated mental status changes, including confusion, restlessness, agitation, and abnormal movements. Additional symptoms occurring over the following hours included new-onset dense insomnia, disorientation, nonsensical speech, involuntary movements of the extremities, continued agitation, and roving eye movements. Laboratory data were noncontributory; a low-grade fever (38 degrees Celsius) was present. DULoxetine was discontinued and the patient improved throughout the day, returning to baseline mental and physical status by late afternoon. Linezolid was then discontinued, and 2 days later the patient chose to resume DULoxetine at a 30 mg/day dose. DULoxetine was tolerated without incident for the remainder of her hospital stay. A week later, the patient died from malignancy-associated sepsis and renal failure 5.
Common questions
Can I take Duloxetine and Linezolid Injection together?
An increased risk of CNS toxicity or serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Duloxetine and Linezolid Injection interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
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 Duloxetine or Linezolid Injection 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 (5)
- Product Information: ZYVOX(R) IV injection, oral tablets, oral suspension, linezolid IV injection, oral tablets, oral suspension. Pharmacia and Upjohn Company, New York, NY, 2008.
- 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: DRIZALMA SPRINKLE(TM) oral delayed-release capsules, duloxetine oral delayed-release capsules. Sun Pharmaceuticals Industries Inc (per FDA), Cranbury, NJ, 2023. DailyMed
- Boyer EW & Shannon M: The serotonin syndrome. N Eng J Med 2005; 352(11):1112-1120. PubMed
- Strouse TB, Kerrihard TN, Forscher CA, et al: Serotonin syndrome precipitated by linezolid in a medically ill patient on duloxetine. J Clin Psychopharmacol 2006; 26(6):681-683. DOI
Keep reading about Duloxetine
Keep reading about Linezolid Injection
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