Nimesulide and Amitriptyline: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Amitriptyline
Nimesulide
No brand names on record
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.
You've been prescribed amitriptyline (Elavil), a tricyclic antidepressant, along with nimesulide, an anti-inflammatory pain reliever (an NSAID). When these two are taken together, they can raise your risk of bleeding. That can mean easier bruising, stomach or gut bleeding, or, rarely, more serious bleeding.
This doesn't mean you can't take both, but it's something your care team will keep an eye on. Please keep taking both as prescribed and let your pharmacist or doctor know if you notice unusual bruising, black or bloody stools, vomiting that looks like coffee grounds, or a sudden bad headache. Your team can manage this safely with a little extra watchfulness.
Effect: Increased bleeding risk, including reports of intracranial hemorrhage within 30 days of concomitant NSAID plus TCA use.
- Direction: Additive/pharmacodynamic increase in bleeding tendency (neither agent's magnitude is quantified).
- Mechanism: Unknown; likely additive effects on platelet function and GI mucosa (NSAID) combined with serotonergic reuptake effects of the TCA.
- Evidence: Established. Onset: unspecified.
- Severity: Major.
Management: Use caution with coadministration. Monitor for signs of bleeding (GI bleed, bruising, neurologic changes suggesting ICH). Dose and duration of the NSAID should be individualized by the care team; consider gastroprotection or an alternative analgesic where appropriate.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs are combined with tricyclic antidepressants, since this combination may heighten the risk of bleeding, such as intracranial hemorrhage occurring within 30 days of using both agents together1. During concurrent administration of NSAIDs and tricyclic antidepressants, watch the patient for indications of heightened bleeding.
Why it happens (mechanism)
Unknown
How to manage this interaction
Your care team can manage this combination safely. Typical steps include:
- Closer monitoring for any signs of bleeding while you take both drugs.
- Individualized dosing of the NSAID (nimesulide) tailored by your prescriber, sometimes using the lowest effective dose for the shortest time needed.
- Considering an alternative pain reliever if the risk is a concern for you.
What you should do: keep taking both medications as prescribed, and promptly tell your pharmacist or doctor if you notice unusual bruising, black or bloody stools, blood in vomit, or a sudden severe headache. Don't stop either medicine on your own first talk with your care team.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) The joint use of NSAIDs and antidepressants, including tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors, and MAOIs, produced a heightened risk of intracranial hemorrhage within 30 days of combined use when compared with antidepressant use by itself. No meaningful difference was observed among the antidepressant drug classes with respect to this increased risk; however, an elevated risk was linked to male patients as opposed to female patients 1..
Common questions
Can I take Nimesulide and Amitriptyline together?
Taking amitriptyline with the NSAID nimesulide can raise your bleeding risk, so keep taking both as prescribed but watch for unusual bruising or bleeding and report it to your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Nimesulide and Amitriptyline interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Nimesulide and Amitriptyline interaction managed?
Your care team can manage this combination safely. Typical steps include: Closer monitoring for any signs of bleeding while you take both drugs. Individualized dosing of the NSAID (nimesulide) tailored by your prescriber, sometimes using the lowest effective dose for the shortest time needed. Considering an alternative pain reliever if the risk is a concern for you. What you should do: keep taking… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Nimesulide or Amitriptyline 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 (1)
- Shin JY, Park MJ, Lee SH, et al: Risk of intracranial haemorrhage in antidepressant users with concurrent use of non-steroidal anti-inflammatory drugs: nationwide propensity score matched study. BMJ 2015; 351:h3517. PubMed
Keep reading about Amitriptyline
Keep reading about Nimesulide
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