Amitriptyline and Tolmetin: 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
Tolmetin
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.
Taking these two together can raise your chance of bleeding. Amitriptyline (Elavil) is an antidepressant, and tolmetin (Tolectin) is an anti-inflammatory pain reliever, similar to ibuprofen. Each one on its own can nudge your bleeding risk up a little, and together the effect can add up. In rare cases this includes serious bleeding, such as in the brain, especially in the first month of using both.
Please don't stop either medicine on your own. Watch for warning signs like easy bruising, black or bloody stools, throwing up something that looks like coffee grounds, or a bad headache that won't go away. Your doctor and pharmacist can manage this safely, so keep them in the loop.
Effect: Increased bleeding risk with concurrent amitriptyline (TCA) and tolmetin (NSAID), including reports of intracranial hemorrhage within 30 days of combined use.
- Direction: Additive/synergistic bleeding risk (PD interaction). NSAIDs impair platelet function and irritate GI mucosa; TCAs are associated with increased bleeding tendency. Neither is a prodrug relevant here.
- Mechanism: Not fully established (listed unknown), likely additive hemostatic effects.
- Evidence: Established. Severity: Major. Onset: Unspecified.
- Management: Use caution; monitor for GI and other bleeding (melena, hematemesis, bruising, neuro changes). Consider GI protection or alternative analgesia if risk is high.
What happens
An increased risk of bleeding
Interaction Deep Dive
Coadministration of tricyclic antidepressants with NSAIDs warrants caution, because the combination may heighten the likelihood of bleeding events, such as intracranial hemorrhage, occurring within 30 days of using both agents together1. Watch for indications of increased bleeding in any patient receiving these two drug classes at the same time.
Why it happens (mechanism)
Unknown
How to manage this interaction
Keep taking both exactly as prescribed unless your care team tells you otherwise. This combination is used, but with extra attention to bleeding.
- Your team may monitor you more closely for signs of bleeding, especially in the first month.
- They may consider a different pain reliever or add stomach protection, depending on your situation. Any changes should be individualized by your care team.
- Call your doctor right away if you notice black or bloody stools, vomit that looks like coffee grounds, unusual bruising, or a severe headache.
- Tell your pharmacist about 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 with antidepressants, including tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors, and MAOIs, produced a higher risk of intracranial hemorrhage within 30 days of concurrent use when compared to using antidepressants alone. No significant difference in the elevated risk was found among the different antidepressant drug classes; however, an increased risk was observed in male patients relative to female patients 1.
Common questions
Can I take Amitriptyline and Tolmetin together?
Using amitriptyline and tolmetin together raises your bleeding risk, so keep both as prescribed but watch for signs of bleeding and check with your doctor or pharmacist. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Tolmetin 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 Tolmetin interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. This combination is used, but with extra attention to bleeding. Your team may monitor you more closely for signs of bleeding, especially in the first month. They may consider a different pain reliever or add stomach protection, depending on your situation. Any changes should be individualized by your care team. Call… 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 Tolmetin 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 Tolmetin
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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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