Amitriptyline and Phenylbutazone: 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
Phenylbutazone
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.
These two medicines together can raise your risk of bleeding. Amitriptyline (Elavil) is a tricyclic antidepressant, and phenylbutazone is an NSAID (an anti-inflammatory pain reliever). When taken together, they can make bleeding more likely, and in rare cases this can include serious bleeding in the brain, especially in the first month of using them together.
The good news is that this is very manageable. Please don't stop either medicine on your own. Instead, talk with your pharmacist or doctor so they can keep an eye on you. Watch for things like unusual bruising, black or bloody stools, vomiting blood, or a bad headache, and get help right away if those happen.
Effect: Increased bleeding risk, including intracranial hemorrhage, reported within 30 days of concurrent use of an NSAID (phenylbutazone) and a TCA (amitriptyline).
- Direction: Additive bleeding risk from combined use.
- Mechanism: Unknown; likely reflects additive effects on hemostasis (NSAID platelet/GI effects plus serotonergic effects of the TCA).
- Evidence: Established. Onset: unspecified.
- Management: Use with caution. Monitor for signs of bleeding (GI bleed, bruising, neurologic changes). Dosing and choice of therapy may be individualized by the care team; consider alternative analgesia where appropriate.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs and tricyclic antidepressants are used together, since combined use may raise the risk of bleeding, including intracranial hemorrhage occurring within 30 days of concurrent administration1. If these two agents are taken at the same time, watch the patient for any indications of heightened bleeding.
Why it happens (mechanism)
Unknown
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. This combination can be managed with closer attention.
- Your care team may monitor you more closely for signs of bleeding, and your therapy may be adjusted and individualized based on your needs.
- Watch for warning signs: unusual bruising, blood in urine or stool, black stools, vomiting blood, nosebleeds that won't stop, or a sudden severe headache.
- Get emergency help for a severe headache, confusion, or weakness, which could signal bleeding in the brain.
- Ask your pharmacist whether a different pain reliever might be a safer option for you.
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 higher risk of intracranial hemorrhage within 30 days of concurrent use when compared with using an antidepressant alone. No significant difference was found among the various antidepressant drug classes with respect to this elevated risk; however, an increased risk was observed in male patients relative to female patients 1.
Common questions
Can I take Amitriptyline and Phenylbutazone together?
Taking amitriptyline with the NSAID phenylbutazone raises your risk of bleeding, so stay alert for bleeding signs and check with your pharmacist or doctor about the safest plan. 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 Phenylbutazone 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 Phenylbutazone interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This combination can be managed with closer attention. Your care team may monitor you more closely for signs of bleeding, and your therapy may be adjusted and individualized based on your needs. Watch for warning signs: unusual bruising, blood in urine or stool, black stools, vomiting blood, nosebleeds that won't s… 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 Phenylbutazone 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 Phenylbutazone
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