Amitriptyline and Dipyrone: 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
Dipyrone
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 dipyrone (a pain and fever medicine that works like an NSAID). When these two are used together, the main concern is a higher chance of bleeding. In rare cases this can include serious bleeding, such as inside the head, especially in the first month of using them together.
The good news is that this is manageable. Your care team can keep an eye on you and watch for warning signs. Please don't stop either medicine on your own. Just check in with your pharmacist or doctor so they can make sure this combination is right for you.
Effect: Increased bleeding risk, including reports of intracranial hemorrhage within 30 days of concomitant use.
- Drugs: Amitriptyline (TCA) + dipyrone (metamizole, non-opioid analgesic/antipyretic often grouped with NSAIDs).
- Direction: Additive/pharmacodynamic increase in bleeding tendency. Neither agent is a prodrug relevant here; mechanism on file is unknown.
- Evidence: Established. Severity: Major. Onset: Unspecified (bleeding events reported within ~30 days).
Management: Use caution with coadministration. Monitor for signs and symptoms of bleeding (bruising, GI bleeding, neurologic changes). Individualize therapy and consider alternatives if bleeding risk is elevated.
What happens
An increased risk of bleeding
Interaction Deep Dive
Caution is warranted when NSAIDs are combined with tricyclic antidepressants, because such concurrent use may raise the risk of bleeding, including intracranial hemorrhage occurring within 30 days of coadministration1. Patients receiving both NSAIDs and tricyclic antidepressants at the same time should be watched 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 managed with attention and monitoring.
- Your care team may monitor you more closely for signs of bleeding, and your treatment may be adjusted and individualized if needed.
- Watch for and report unusual bruising, black or bloody stools, vomiting blood, nosebleeds that won't stop, or a severe headache with confusion or weakness (these can signal serious bleeding).
- Tell your pharmacist about any other blood thinners, aspirin, or NSAIDs you take.
Raise any bleeding concerns with your pharmacist or doctor right away.
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 the concurrent use when compared with the use of antidepressants alone. No significant difference in the elevated risk was found among the antidepressant drug classes; however, an increased risk was observed in male patients relative to female patients 1.
Common questions
Can I take Amitriptyline and Dipyrone together?
Combining amitriptyline with dipyrone can raise your bleeding risk, so watch for unusual bruising or bleeding and check in with your care team, but don't stop either medicine on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Dipyrone 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 Dipyrone interaction managed?
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This combination can be managed with attention and monitoring. Your care team may monitor you more closely for signs of bleeding, and your treatment may be adjusted and individualized if needed. Watch for and report unusual bruising, black or bloody stools, vomiting blood, nosebleeds that won't stop, or a severe h… 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 Dipyrone 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 Dipyrone
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