Drug Interaction Report

Amitriptyline and Aspirin: Interaction Details

A pharmacist-reviewed analysis of the Amitriptyline and Aspirin interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Amitriptyline

Elavil
+

Aspirin

Acuprin® Anacin Aspirin Regimen Anacin® Aspirin Regimen Ascriptin® Aspergum Aspergum® Aspi-Cor Aspidrox®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Jul 11, 2026
Editorial policy · Data sources
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
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.

Of 525 documented Amitriptyline interactions, 421 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
established
Severity
Major

What happens

An increased risk of bleeding

Interaction Deep Dive

Exercise caution when NSAIDs are given together with tricyclic antidepressants, because such combined use can raise the likelihood of bleeding, including intracranial hemorrhage occurring within 30 days of concurrent administration1. If a patient receives both an NSAID and a tricyclic antidepressant at the same time, watch for indications of heightened bleeding.

Why it happens (mechanism)

Unknown

Literature reports

1 report — tap to read

a) The combined use of NSAIDs and antidepressants, such as tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors, and MAOIs, led to a higher risk of intracranial hemorrhage within 30 days of the combined use when compared with using an antidepressant by itself. No significant difference in the heightened risk was found among the antidepressant drug classes; however, male patients had an increased risk compared with female patients 1.

Common questions

Can I take Amitriptyline and Aspirin together?

An increased risk of bleeding Always confirm with your pharmacist or prescriber before making any change.

How serious is the Amitriptyline and Aspirin 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 strong is the evidence for this interaction?

The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.

Questions for your pharmacist

  • Does my dose of Amitriptyline or Aspirin 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)

  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
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Amitriptyline

Keep reading about Amitriptyline

All Amitriptyline interactions (525)
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Aspirin

Keep reading about Aspirin

All Aspirin interactions (465) Aspirin drug information
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Beyond drug–drug

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:

Amitriptyline + 1,4-butanediol Activated Charcoal American Hellebore Arsenic Beer Cesium Ephedra Gamma-hydroxybutyrate (ghb) + 288 more
Aspirin + Activated Charcoal Asarabacca Beer Danshen Piracetam Siberian Cocklebur Wine Aconite + 234 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.