Amitriptyline and Aceclofenac: 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
Aceclofenac
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've been prescribed amitriptyline (a tricyclic antidepressant) and aceclofenac (an anti-inflammatory pain reliever, an NSAID). Taken together, these two can raise your risk of bleeding. NSAIDs can irritate the stomach lining and affect how well your blood clots, and adding a tricyclic appears to nudge that risk higher, including rare but serious bleeding.
Please don't stop either medicine on your own. Just be alert for warning signs like unusual bruising, black or bloody stools, vomit that looks like coffee grounds, or a sudden severe headache. Your care team can manage this well, so let your pharmacist or doctor know you take both.
Effect: Increased bleeding risk with concurrent NSAID (aceclofenac) and TCA (amitriptyline), including reports of intracranial hemorrhage within 30 days of combined use.
- Mechanism: Unknown; NSAIDs contribute via COX-mediated antiplatelet effect and GI mucosal injury. Neither agent requires bioactivation relevant here, so this is an additive PD interaction rather than a prodrug issue.
- Direction/magnitude: Additive bleeding risk; magnitude not precisely quantified.
- Onset: Unspecified.
- Evidence: Established.
- Management: Use caution; monitor for GI and other bleeding signs (melena, hematemesis, bruising, neurologic changes). Consider gastroprotection or an alternative analgesic if risk is high.
What happens
An increased risk of bleeding
Interaction Deep Dive
Caution is warranted when NSAIDs are given together with tricyclic antidepressants, since combined use can raise the likelihood of bleeding, including intracranial hemorrhage occurring within 30 days of concurrent administration1. Should these two agents be used at the same time, watch the patient for indications of heightened bleeding.
Why it happens (mechanism)
Unknown
How to manage this interaction
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This combination can be used safely with the right precautions.
- Your care team may monitor you more closely for signs of bleeding.
- They may consider a stomach-protecting medicine or a different pain option if your bleeding risk is higher.
- Watch for and promptly report: black or tarry stools, blood in vomit or stool, easy bruising, or a sudden severe headache.
- Tell your pharmacist and doctor you take both, and mention any history of ulcers or bleeding.
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 with antidepressant use by itself. No significant difference in the elevated risk was observed among the antidepressant drug classes; nevertheless, an increased risk was linked to male patients relative to female patients 1.
Common questions
Can I take Amitriptyline and Aceclofenac together?
Taking amitriptyline with aceclofenac can increase your bleeding risk, so watch for signs like black stools, unusual bruising, or a severe headache and keep your care team informed. Don't stop either drug on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Aceclofenac 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 Aceclofenac interaction managed?
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This combination can be used safely with the right precautions. Your care team may monitor you more closely for signs of bleeding. They may consider a stomach-protecting medicine or a different pain option if your bleeding risk is higher. Watch for and promptly report: black or tarry stools, blood in vomit or stoo… 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 Aceclofenac 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 Aceclofenac
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