Etofenamate 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
Etofenamate
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.
Here's what's going on. Amitriptyline (Elavil) is a tricyclic antidepressant, and etofenamate is an anti-inflammatory pain medicine (an NSAID). When these two are used together, they can raise your risk of bleeding. In rare cases this includes serious bleeding, such as bleeding in the brain, especially in the first month of using them together.
Please don't panic, and don't stop either medicine on your own. Many people take combinations like this safely with a little extra care. The best next step is to check in with your pharmacist or doctor so they can watch for any warning signs and keep you safe.
Interaction: Concurrent use of amitriptyline (a tricyclic antidepressant) and etofenamate (an NSAID) is associated with an increased risk of bleeding, including intracranial hemorrhage, reported within 30 days of concomitant use.
- Direction: Additive bleeding risk (pharmacodynamic).
- Mechanism: Unknown; not a clear CYP or transporter interaction. Neither agent is a prodrug relevant here.
- Evidence: Established. Onset: unspecified.
- Magnitude: Not quantified.
Management: Use caution if coadministered. Monitor for signs and symptoms of bleeding (bruising, GI bleeding, neurologic changes). Consider dose review and closer monitoring individualized by the care team.
What happens
An increased risk of bleeding
Interaction Deep Dive
Coadministering NSAIDs with tricyclic antidepressants warrants caution, since it may raise the likelihood of bleeding, such as intracranial hemorrhage occurring within 30 days of combined use1. Should these agents be used together, watch the patient for indications of heightened bleeding.
Why it happens (mechanism)
Unknown
How to manage this interaction
The good news: your care team can manage this by keeping a closer eye on you. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Your team may monitor you more closely for signs of bleeding.
- Your doses may be adjusted and individualized by your care team.
- Watch for and report: unusual bruising, nosebleeds, blood in stool or urine, black/tarry stools, or vomiting blood.
- Seek urgent care for severe headache, confusion, weakness, or trouble speaking, which can signal serious bleeding.
Bring this up with your pharmacist or doctor so they can tailor your plan.
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, led to a heightened risk of intracranial hemorrhage within 30 days of concurrent use when compared with antidepressant use by itself. No meaningful difference was found among the antidepressant drug classes regarding this elevated risk; nevertheless, a greater risk was observed in male patients relative to female patients 1.
Common questions
Can I take Etofenamate and Amitriptyline together?
Taking amitriptyline with the NSAID etofenamate can increase your risk of bleeding, so keep taking both as prescribed but ask your pharmacist or doctor to monitor you and watch for bruising or bleeding. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Etofenamate 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 Etofenamate and Amitriptyline interaction managed?
The good news: your care team can manage this by keeping a closer eye on you. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Your team may monitor you more closely for signs of bleeding. Your doses may be adjusted and individualized by your care team. Watch for and report: unusual bruising, nosebleeds, blood in stool or urine, black/tarry stools, or vo… 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 Etofenamate 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 Etofenamate
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