Flufenamic 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
Flufenamic 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're taking amitriptyline (a tricyclic antidepressant) along with flufenamic acid, which is an anti-inflammatory pain reliever (an NSAID). When these two are used together, there can be a higher chance of bleeding. This can range from easier bruising or stomach bleeding to, rarely, more serious bleeding.
Please don't stop either medicine on your own. This combination is often used safely with a little extra care. Your care team can watch you more closely and adjust things if needed. Just let your pharmacist or doctor know about any unusual bruising, black or bloody stools, vomit that looks like coffee grounds, or a bad headache that won't go away.
Effect: Increased bleeding risk when a tricyclic antidepressant (amitriptyline) is combined with an NSAID (flufenamic acid), including reports of intracranial hemorrhage within 30 days of concomitant use.
- Mechanism: Unknown; likely additive antiplatelet/hemostatic effects plus NSAID-related GI mucosal injury. Neither agent's activation is enzyme-dependent in a way that changes direction here.
- Direction: Additive, increases bleeding risk.
- Evidence/severity: Established, rated major; onset unspecified.
- Management: Use with caution; monitor for signs of bleeding (GI bleed, bruising, neurologic changes). Consider gastroprotection and reassess if risk factors are present.
What happens
An increased risk of bleeding
Interaction Deep Dive
The combination of NSAIDs with tricyclic antidepressants warrants caution, since it may heighten the risk of bleeding, such as intracranial hemorrhage occurring within 30 days of using both together1. Watch for indications of heightened bleeding in patients receiving these two agents at the same time.
Why it happens (mechanism)
Unknown
How to manage this interaction
This combination can usually be managed with a little extra attention from your care team.
- Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
- Your team may monitor you more closely for any signs of bleeding, and your treatment may be adjusted and individualized to fit you.
- Watch for and report: unusual bruising, black or bloody stools, pink or red urine, vomiting that looks like coffee grounds, or a severe or unusual headache.
- Ask your pharmacist before adding other pain relievers, aspirin, or blood thinners.
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, encompassing tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors, and MAOIs, was associated with a greater risk of intracranial hemorrhage within 30 days of joint administration when compared with using an antidepressant by itself. No meaningful difference was observed among the various antidepressant drug classes with respect to this heightened risk; nevertheless, the risk was greater in male patients than in female patients 1..
Common questions
Can I take Flufenamic Acid and Amitriptyline together?
Using amitriptyline with the NSAID flufenamic acid can raise your bleeding risk, so keep taking both as prescribed but watch for signs of bleeding and report anything unusual to your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Flufenamic 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 Flufenamic Acid and Amitriptyline interaction managed?
This combination can usually be managed with a little extra attention from your care team. Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Your team may monitor you more closely for any signs of bleeding, and your treatment may be adjusted and individualized to fit you. Watch for and report: unusual bruising, black or bloody stools, pink or red urine, vomiting th… 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 Flufenamic 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 Flufenamic Acid
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