Nimesulide Beta Cyclodextrin 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 Beta Cyclodextrin
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 (a tricyclic antidepressant) along with nimesulide, an anti-inflammatory pain medicine (an NSAID). Taken together, these two can raise your chance of bleeding. In rare cases this can include serious bleeding, such as bleeding in the brain.
The good news is that this is manageable. Your care team can keep an eye on you and watch for warning signs. Please tell your doctor or pharmacist right away if you notice things like unusual bruising, black or bloody stools, vomit that looks like coffee grounds, a severe headache, or bleeding that won't stop. Keep taking both as prescribed unless your provider tells you otherwise.
Effect: Increased bleeding risk, including reports of intracranial hemorrhage, with concomitant NSAID (nimesulide) and tricyclic antidepressant (amitriptyline) use.
- Direction: Additive/synergistic increase in bleeding tendency.
- Mechanism: Unknown; neither agent requires bioactivation relevant here. NSAIDs impair platelet function and gastric mucosa; TCAs may contribute via serotonergic effects on platelet aggregation.
- Evidence: Established. Onset: Unspecified (bleeding events reported within 30 days).
- Severity: Major.
Management: Use with caution. Monitor for signs of GI or other bleeding. Individualize therapy; consider gastroprotection or alternatives per clinical judgment.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution if NSAIDs are administered together with tricyclic antidepressants, since combined use can raise the likelihood of bleeding, such as intracranial hemorrhage occurring within 30 days of using both agents together1. Should NSAIDs and tricyclic antidepressants be used at the same time, watch the patient for indications of heightened bleeding.
Why it happens (mechanism)
Unknown
How to manage this interaction
Both medicines can be used together when needed, but your care team will take extra care to keep you safe.
- Keep taking both as prescribed unless your prescriber tells you to change something.
- Your team may monitor you more closely for signs of bleeding, and your treatment may be adjusted and individualized to your needs.
- Watch for and promptly report: unusual bruising, nosebleeds or bleeding that won't stop, black or bloody stools, vomit that looks like coffee grounds, or a sudden severe headache.
Ask your pharmacist or doctor whether a stomach-protecting medicine or a different pain option makes sense for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) The combined use of NSAIDs with antidepressants, including tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors, and MAOIs, led to a heightened risk of intracranial hemorrhage within 30 days of the concurrent use when compared to antidepressant use by itself. No significant difference was found among the various antidepressant drug classes with respect to this heightened risk; nevertheless, male patients showed an increased risk relative to female patients 1.
Common questions
Can I take Nimesulide Beta Cyclodextrin and Amitriptyline together?
Combining amitriptyline with the NSAID nimesulide can increase your bleeding risk, so keep taking both as prescribed while your care team monitors you, and report any signs of unusual bleeding right away. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Nimesulide Beta Cyclodextrin 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 Beta Cyclodextrin and Amitriptyline interaction managed?
Both medicines can be used together when needed, but your care team will take extra care to keep you safe. Keep taking both as prescribed unless your prescriber tells you to change something. Your team may monitor you more closely for signs of bleeding, and your treatment may be adjusted and individualized to your needs. Watch for and promptly report: unusual bruising, nosebleeds or bleeding that… 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 Beta Cyclodextrin 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 Beta Cyclodextrin
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