Celecoxib 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
Celecoxib
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 celecoxib (Celebrex), an anti-inflammatory pain reliever. When these two are taken together, they can raise your risk of bleeding. In rare cases this has included serious bleeding, even in the brain, within the first month of taking them together.
This doesn't mean you can't use both, but it's something your care team will want to keep an eye on. Watch for things like unusual bruising, nosebleeds, blood in your stool or urine, or a bad headache that won't go away. Please don't stop either medicine on your own, just check in with your pharmacist or doctor so they can guide you safely.
Effect: Concurrent use of the NSAID celecoxib and the TCA amitriptyline is associated with an increased risk of bleeding, including intracranial hemorrhage, reported within 30 days of combined use.
Mechanism: Unknown, though additive antiplatelet/hemostatic effects are plausible (NSAID prostaglandin/platelet effects plus TCA effects on platelet serotonin). Neither agent is a prodrug relevant here.
- Severity: Major; evidence: established; onset: unspecified.
- Management: Use with caution. Monitor for signs of bleeding (bruising, GI bleed, epistaxis, neurologic changes). Consider gastroprotection and reassess necessity/duration; individualize per patient risk.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs and tricyclic antidepressants are administered together, because this combination can raise the likelihood of bleeding, including intracranial hemorrhage occurring within 30 days of using them concurrently1. During concurrent therapy with 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 with some added attention.
- Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise.
- Your team may monitor you more closely for bleeding, especially in the first month.
- Watch for warning signs: unusual bruising, nosebleeds, black or bloody stools, blood in urine, vomiting that looks like coffee grounds, or a sudden severe headache.
- Tell your prescriber if you also take other blood thinners, aspirin, or other NSAIDs.
If you notice any bleeding signs, contact your care team promptly, and call emergency services for a severe or sudden headache.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) Taking NSAIDs together with antidepressants, such as tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors, and MAOIs, was associated with a higher risk of intracranial hemorrhage within 30 days of combined use when compared to using an antidepressant by itself. No significant difference in this elevated risk was observed among the various antidepressant drug classes; nevertheless, the risk was higher in male patients than in female patients 1.
Common questions
Can I take Celecoxib and Amitriptyline together?
Taking amitriptyline with celecoxib can raise your bleeding risk, so watch for signs of bleeding and stay in touch with your care team, but don't stop either medicine on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Celecoxib 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 Celecoxib and Amitriptyline interaction managed?
Your care team can manage this combination safely with some added attention. Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Your team may monitor you more closely for bleeding, especially in the first month. Watch for warning signs: unusual bruising, nosebleeds, black or bloody stools, blood in urine, vomiting that looks like coffee grounds, or a sudden severe… 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 Celecoxib 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 Celecoxib
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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.
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