Amitriptyline and Indomethacin: 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
Indomethacin
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 indomethacin (Indocin), an anti-inflammatory pain reliever. Taken together, these two can raise your chance of bleeding. In rare cases this has included bleeding in the brain, especially in the first month of using both.
This doesn't mean something bad will happen, but it's worth knowing. Watch for signs like easy bruising, unusual bleeding, black or bloody stools, or a bad headache that won't go away. Please keep taking both as prescribed and talk with your pharmacist or doctor so they can keep an eye on you and adjust things if needed.
Effect: Concurrent NSAID (indomethacin) and TCA (amitriptyline) use is associated with an increased bleeding risk, including intracranial hemorrhage within 30 days of starting combined therapy.
- Direction: Additive/synergistic increase in bleeding risk (not a clear PK interaction).
- Mechanism: Unknown; likely additive effects on platelet function and mucosal/vascular integrity.
- Evidence: Established. Severity: Major. Onset: Unspecified.
- Management: Use with caution; monitor for GI bleeding, bruising, and neurologic changes suggesting ICH. Consider GI protection or alternative analgesia if risk is high.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution if NSAIDs and tricyclic antidepressants are used together, since combined use may raise the likelihood of bleeding, such as intracranial hemorrhage occurring within 30 days of concurrent administration1. 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
Your care team can manage this combination safely with a few sensible steps:
- Keep taking both exactly as prescribed unless your doctor tells you otherwise.
- Your team may monitor you more closely for signs of bleeding, particularly in the first month.
- Watch for and report: unusual bruising, nosebleeds, black or bloody stools, vomiting that looks like coffee grounds, or a severe or persistent headache.
Ask your pharmacist or prescriber whether a stomach-protecting medicine or a different pain reliever might be right for you, especially if you have other bleeding risks.
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, led to a higher risk of intracranial hemorrhage within 30 days of combined use when compared to using antidepressants by themselves. No significant difference in the increased risk was found among the various antidepressant drug classes; nevertheless, male patients had a greater risk than female patients 1.
Common questions
Can I take Amitriptyline and Indomethacin together?
Taking amitriptyline with indomethacin can raise your risk of bleeding, so keep both as prescribed but watch for bruising, stomach bleeding, or bad headaches and report them to your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Indomethacin 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 Indomethacin interaction managed?
Your care team can manage this combination safely with a few sensible steps: Keep taking both exactly as prescribed unless your doctor tells you otherwise. Your team may monitor you more closely for signs of bleeding, particularly in the first month. Watch for and report: unusual bruising, nosebleeds, black or bloody stools, vomiting that looks like coffee grounds, or a severe or persistent headac… 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 Indomethacin 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 Indomethacin
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.
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