Piroxicam 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
Piroxicam
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) along with piroxicam (an anti-inflammatory pain reliever, or NSAID). Taking these two together can raise your risk of bleeding. NSAIDs like piroxicam can irritate the stomach and affect how well your blood clots, and combining them with a tricyclic can add to that risk.
Watch for warning signs like unusual bruising, black or bloody stools, vomiting that looks like coffee grounds, or a sudden bad headache. This is manageable. Your care team knows about this combination and can watch you closely. Please don't stop either medicine on your own, but do talk with your pharmacist or doctor about it.
Effect: Increased bleeding risk (including reports of intracranial hemorrhage within 30 days of concomitant use) when combining an NSAID (piroxicam) with a tricyclic antidepressant (amitriptyline).
- Direction: Additive/synergistic bleeding risk, not a straightforward CYP prodrug issue; mechanism on file is unknown.
- Evidence: Established. Severity: Major. Onset: Unspecified.
- Contributing factors: Piroxicam is a long half-life NSAID with antiplatelet and GI mucosal effects; caution in patients with GI, cerebrovascular, or bleeding risk.
- Management: Monitor for signs of bleeding (GI, bruising, neurologic changes). Dose and choice may need individualized adjustment by the care team.
What happens
An increased risk of bleeding
Interaction Deep Dive
Concurrent use of NSAIDs together with tricyclic antidepressants warrants caution, since the combination can elevate the risk of bleeding, with intracranial hemorrhage reported within 30 days of taking them together1. If these two agents are administered 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 is used with caution and monitoring.
- Your care team may monitor you more closely for signs of bleeding.
- They may adjust and individualize your medications, or consider an alternative, based on your personal risk.
- Report right away: black or bloody stools, coffee-ground vomit, unusual bruising, or a sudden severe headache.
- Ask your pharmacist before adding other pain relievers or blood thinners, since these can add to the risk.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) The combined use of NSAIDs with antidepressants, including tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors, and MAOIs, produced a heightened risk of intracranial hemorrhage within 30 days of the combined use when compared with antidepressant use by itself. No meaningful distinction was found among the antidepressant drug classes with respect to the elevated risk; nevertheless, a greater risk was seen in male patients as compared with female patients 1..
Common questions
Can I take Piroxicam and Amitriptyline together?
Combining amitriptyline with piroxicam can increase your bleeding risk, so keep taking both as prescribed but watch for signs of bleeding and stay in touch with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Piroxicam 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 Piroxicam and Amitriptyline interaction managed?
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This combination is used with caution and monitoring. Your care team may monitor you more closely for signs of bleeding. They may adjust and individualize your medications, or consider an alternative, based on your personal risk. Report right away: black or bloody stools, coffee-ground vomit, unusual bruising, or… 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 Piroxicam 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 Piroxicam
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