Paroxetine and Linezolid Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Paroxetine
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
An increased risk of serotonin syndrome (hypertension, tachycardia, hyperthermia, myoclonus, mental status changes)
Interaction Deep Dive
Concurrent use of linezolid, an MAOI, and PARoxetine is contraindicated. Wait at least 14 days after discontinuing an MAOI intended to treat psychiatric disorders before initiating PARoxetine. Wait at least 14 days after discontinuing PARoxetine before initiating therapy with an MAOI intended to treat psychiatric disorders. Do not initiate PARoxetine in a patient being treated with linezolid. If it is necessary to initiate treatment with an MAOI such as linezolid in a patient taking PARoxetine, discontinue PARoxetine before initiating treatment with linezolid345. 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
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 1.
b) Linezolid may cause serotonin syndrome in patients receiving SSRIs. A 56-year-old woman with a history of depression, chronic hepatitis C infection, hypertension, diabetes, and cervical stenosis was admitted for elective laminectomy. There was evidence of hepatic cirrhosis with an abdominal CT scan. Her medications preoperatively included PARoxetine, interferon-alpha, felodipine, terazosin, lisinopril, insulin, methocarbamol, morphine sulfate, and ibuprofen. The last dose of PARoxetine was administered on postoperative day 14. At that point it was discovered that the patient had an infected surgical site and empiric therapy with vancomycin was initiated. The patient remained febrile, however, and linezolid was substituted for vancomycin. Within 24 hours, the patient developed delirium, hypertension, hostility, anger, and tremors. Serotonin syndrome was diagnosed and linezolid therapy was discontinued. Vancomycin was reinstated and within 48 hours the patient returned to her baseline mental status. The serum half-life of PARoxetine is 21 hours. It is likely that the inhibitory effect of linezolid combined with residual PARoxetine activity produced serotonin syndrome in this patient. This particular patient may have been at increased risk for this syndrome because of her other medications as well as a decreased hepatic clearance. The author suggests that in high-risk patients, a 2-week washout period is advised between the discontinuation of SSRIs and initiation of linezolid 2.
Common questions
Can I take Paroxetine and Linezolid Injection together?
An increased risk of serotonin syndrome (hypertension, tachycardia, hyperthermia, myoclonus, mental status changes) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Paroxetine 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 "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 Paroxetine 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)
- 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
- Wigen C & Goetz M: Serotonin syndrome and linezolid. CID 2002; 34:1651-1652. DOI
- Product Information: PEXEVA(R) oral tablets, paroxetine mesylate oral tablets. Sebela Pharmaceuticals Inc (per FDA), Roswell, GA, 2023.
- Product Information: BRISDELLE(R) oral capsules, paroxetine oral capsules. Sebela Pharmaceuticals Inc (per FDA), Roswell, GA, 2023. DailyMed
- Product Information: PAXIL(R) oral tablets, oral suspension, paroxetine oral tablets, oral suspension. Apotex Corp (per FDA), Weston, FL, 2023. DailyMed
Keep reading about Paroxetine
Keep reading about Linezolid Injection
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist