Amitriptyline and Rofecoxib: 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
Rofecoxib
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) along with rofecoxib (an anti-inflammatory pain reliever). When these two are taken together, there's a higher chance of bleeding. This can range from bruising more easily or stomach bleeding to, rarely, more serious bleeding.
The good news is that this is very manageable. Your care team can keep an eye on you and adjust things as needed. Please keep taking both medicines as prescribed unless your doctor tells you otherwise, and let them know right away if you notice unusual bruising, black or bloody stools, blood in your vomit, or a bad headache that won't go away.
Effect: Increased bleeding risk (including reports of intracranial hemorrhage within 30 days of concomitant use) when a tricyclic antidepressant (amitriptyline) is combined with an NSAID (rofecoxib).
- Direction: Additive/pharmacodynamic increase in bleeding tendency.
- Mechanism: Unknown per record; neither agent is a prodrug relevant to this effect.
- Severity/Evidence: Major; evidence considered established. Onset unspecified.
- Management: Use caution. Monitor for signs and symptoms of bleeding (GI bleeding, bruising, neurologic changes suggesting intracranial hemorrhage). Individualize therapy and consider closer follow-up.
What happens
An increased risk of bleeding
Interaction Deep Dive
Concurrent administration of NSAIDs with tricyclic antidepressants warrants caution, since the combination may raise the likelihood of bleeding, such as intracranial hemorrhage occurring within 30 days of combined use1. During simultaneous use of NSAIDs and tricyclic antidepressants, watch the patient for indications of heightened bleeding.
Why it happens (mechanism)
Unknown
How to manage this interaction
Your care team can manage this combination safely with attention and monitoring.
- Keep taking both as prescribed unless your prescriber advises a change.
- Your team may monitor you more closely for any signs of bleeding, and your treatment may be adjusted and individualized to you.
- Watch for: unusual or easy bruising, black/tarry or bloody stools, blood in vomit or urine, or a sudden severe headache.
- Get urgent care for a severe headache, confusion, or weakness, which could signal serious bleeding.
Bring up any concerns with your pharmacist or doctor, especially if you also take other blood thinners or aspirin.
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 greater 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 Rofecoxib together?
Taking amitriptyline with rofecoxib can raise your bleeding risk, so watch for signs like unusual bruising, bloody or black stools, or a severe headache, and report them promptly. Keep taking both as prescribed and let your care team monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Rofecoxib 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 Rofecoxib interaction managed?
Your care team can manage this combination safely with attention and monitoring. Keep taking both as prescribed unless your prescriber advises a change. Your team may monitor you more closely for any signs of bleeding, and your treatment may be adjusted and individualized to you. Watch for: unusual or easy bruising, black/tarry or bloody stools, blood in vomit or urine, or a sudden severe headache… 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 Rofecoxib 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 Rofecoxib
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