Valdecoxib 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
Valdecoxib
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) and valdecoxib (an anti-inflammatory pain medicine, an NSAID). When these two are taken together, they can raise your risk of bleeding. In rare cases this can include serious bleeding, such as bleeding in the brain, especially in the first month of using them together.
Please don't stop either medicine on your own. This is something your care team can manage. Let your pharmacist or doctor know you take both, and watch for warning signs like easy bruising, blood in your stool or urine, unusual headaches, or bleeding that won't stop. Report anything like that right away.
Effect: Increased bleeding risk with concurrent tricyclic antidepressant (amitriptyline) and NSAID (valdecoxib), including reports of intracranial hemorrhage within 30 days of combined use.
- Direction: Additive bleeding risk (PD interaction); both drugs contribute independently.
- Mechanism: Unknown/not fully characterized. Neither is a relevant prodrug in this context.
- Severity/Evidence: Major; established. Onset unspecified.
- Management: Use caution when coadministering. Monitor for signs of bleeding (GI bleed, bruising, neurologic changes suggesting ICH). Individualize therapy and consider closer follow-up in higher-risk patients.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs are given together with tricyclic antidepressants, since combined use may raise the likelihood of bleeding, such as intracranial hemorrhage occurring within 30 days of taking both agents together1. 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
How to manage this interaction
Keep taking both medications as prescribed unless your doctor or pharmacist tells you otherwise. This combination is used with caution, and your care team can manage it.
- Tell your pharmacist and prescriber that you take both amitriptyline and valdecoxib.
- Your team may monitor you more closely for signs of bleeding, and your therapy may be adjusted and individualized to your situation.
- Watch for and promptly report: unusual bruising, black or bloody stools, blood in urine, coughing or vomiting blood, or a sudden severe headache.
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, encompassing tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors, and MAOIs, led to a heightened risk of intracranial hemorrhage within 30 days of concurrent use when compared to the use of an antidepressant on its own. No meaningful difference was found among the various antidepressant drug classes with respect to this elevated risk; nevertheless, male patients carried an increased risk relative to female patients 1.
Common questions
Can I take Valdecoxib and Amitriptyline together?
Taking amitriptyline with valdecoxib can add up to a higher bleeding risk, so keep taking both as prescribed but tell your care team and report any unusual bleeding or bruising right away. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Valdecoxib 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 Valdecoxib and Amitriptyline interaction managed?
Keep taking both medications as prescribed unless your doctor or pharmacist tells you otherwise. This combination is used with caution, and your care team can manage it. Tell your pharmacist and prescriber that you take both amitriptyline and valdecoxib. Your team may monitor you more closely for signs of bleeding, and your therapy may be adjusted and individualized to your situation. Watch for an… 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 Valdecoxib 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 Valdecoxib
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:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist