Amitriptyline and Tiaprofenic Acid: 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
Tiaprofenic Acid
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 tiaprofenic acid (an anti-inflammatory pain reliever, an NSAID). Taken together, these two can raise your risk of bleeding. This can range from easier bruising or stomach bleeding to, more rarely, bleeding in the brain.
This doesn't mean you can't take both, but it's worth being aware of. Watch for signs like unusual bruising, black or bloody stools, vomiting that looks like coffee grounds, or a sudden severe headache. Please talk with your pharmacist or doctor so they can keep an eye on things and make sure this combination is right for you.
Effect: Concurrent use of an NSAID (tiaprofenic acid) and a tricyclic antidepressant (amitriptyline) is associated with an increased risk of bleeding, including intracranial hemorrhage within 30 days of combined use.
- Direction: Additive bleeding risk (increased effect).
- Mechanism: Unknown; NSAIDs impair platelet function and cause GI mucosal injury, and TCAs may further affect platelet serotonin/hemostasis.
- Onset: Unspecified.
- Evidence: Established.
- Management: Use caution; monitor for signs of bleeding (GI, bruising, neurologic changes). Consider gastroprotection or an alternative analgesic if risk is high.
What happens
An increased risk of bleeding
Interaction Deep Dive
Caution is warranted when NSAIDs are given together with tricyclic antidepressants, because the combination may raise the risk of bleeding, such as intracranial hemorrhage occurring within 30 days of concurrent use1. Patients receiving both an NSAID and a tricyclic antidepressant at the same time should be watched for indications of heightened bleeding.
Why it happens (mechanism)
Unknown
How to manage this interaction
Keep taking both medications as prescribed unless your care team tells you otherwise. Because this combination can raise bleeding risk, here's how it's typically handled:
- Your team may monitor you more closely for signs of bleeding.
- They may consider a stomach-protecting medication or a different pain reliever if your risk is high.
Tell your pharmacist or doctor right away if you notice unusual bruising, blood in stool or urine, black stools, vomit that looks like coffee grounds, or a sudden severe headache. Also mention any other blood thinners, aspirin, or NSAIDs you take.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) The combined use of NSAIDs and antidepressants, including tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors, and MAOIs, was associated with a heightened risk of intracranial hemorrhage within 30 days of concurrent use when compared with the use of antidepressants alone. No significant difference was observed among the antidepressant drug classes with respect to this elevated risk; nonetheless, male patients carried an increased risk relative to female patients 1.
Common questions
Can I take Amitriptyline and Tiaprofenic Acid together?
Taking amitriptyline with tiaprofenic acid can increase your bleeding risk, so keep taking both as prescribed but watch for signs of bleeding and check with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Tiaprofenic Acid 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 Amitriptyline and Tiaprofenic Acid interaction managed?
Keep taking both medications as prescribed unless your care team tells you otherwise. Because this combination can raise bleeding risk, here's how it's typically handled: Your team may monitor you more closely for signs of bleeding. They may consider a stomach-protecting medication or a different pain reliever if your risk is high. Tell your pharmacist or doctor right away if you notice unusual br… 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 Amitriptyline or Tiaprofenic Acid 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 Tiaprofenic Acid
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