Tolfenamic Acid 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
Tolfenamic 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.
Taking these two together can raise your risk of bleeding. Amitriptyline (Elavil) is a tricyclic antidepressant, and tolfenamic acid is an anti-inflammatory painkiller (an NSAID). Both can make it a little easier for your body to bleed, and using them together adds those effects up. In rare cases this includes serious bleeding, such as in the brain, most often in the first month of using them together.
The good news is that this is very manageable. Keep taking both exactly as prescribed, and let your doctor or pharmacist know so they can watch you more closely. Please don't stop either medicine on your own.
Effect: Additive bleeding risk when a tricyclic antidepressant (amitriptyline) is combined with an NSAID (tolfenamic acid), including reports of intracranial hemorrhage within 30 days of concomitant use.
- Direction: Increased bleeding risk (PD, additive).
- Mechanism: Unknown; neither agent is a prodrug requiring activation here.
- Severity/Evidence: Major; established.
- Onset: Unspecified (heightened risk noted early, within ~30 days).
- Management: Use caution with coadministration. Monitor for signs of bleeding (bruising, GI bleeding, melena, neurologic changes suggesting intracranial hemorrhage). Consider gastroprotection or an alternative analgesic per clinical judgment.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs are given together with tricyclic antidepressants, since combined use may heighten the risk of bleeding, including intracranial hemorrhage occurring within 30 days of the concurrent administration1. If a patient is receiving both an NSAID and a tricyclic antidepressant at the same time, watch for indications of increased bleeding.
Why it happens (mechanism)
Unknown
How to manage this interaction
This interaction can be managed with awareness and monitoring. Keep taking both medications as prescribed unless your care team tells you otherwise.
- Tell your pharmacist and prescriber that you take both, so they can monitor you more closely for bleeding.
- Watch for warning signs: unusual bruising, black or bloody stools, vomiting that looks like coffee grounds, or nosebleeds that won't stop.
- Seek emergency care for sudden severe headache, weakness, confusion, or trouble speaking, which can signal bleeding in the brain.
- Your team may choose a different pain reliever or add stomach protection if appropriate.
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, produced a heightened risk of intracranial hemorrhage within 30 days of concurrent use when compared to antidepressant use by itself. No significant difference in the elevated risk was observed among the various antidepressant drug classes; nevertheless, an increased risk was seen in male patients relative to female patients 1.
Common questions
Can I take Tolfenamic Acid and Amitriptyline together?
Combining amitriptyline with the NSAID tolfenamic acid raises bleeding risk, so keep taking both as prescribed but tell your care team so they can monitor you and watch for signs of bleeding. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Tolfenamic Acid 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 Tolfenamic Acid and Amitriptyline interaction managed?
This interaction can be managed with awareness and monitoring. Keep taking both medications as prescribed unless your care team tells you otherwise. Tell your pharmacist and prescriber that you take both, so they can monitor you more closely for bleeding. Watch for warning signs: unusual bruising, black or bloody stools, vomiting that looks like coffee grounds, or nosebleeds that won't stop. Seek… 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 Tolfenamic Acid 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 Tolfenamic Acid
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist