Amitriptyline and Parecoxib: 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
Parecoxib
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 parecoxib (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 in the brain, usually within the first month of using them together.
This doesn't mean you can't take both, but it's something your care team keeps an eye on. Watch for things like easy bruising, unusual bleeding, blood in your stool or urine, or a bad new headache, and let your doctor know. Please keep taking both exactly as prescribed and talk with your pharmacist or doctor about any concerns.
Effect: Concomitant use of the tricyclic antidepressant amitriptyline and the NSAID parecoxib is associated with an increased bleeding risk, including intracranial hemorrhage, reported within 30 days of combined use.
- Direction: Additive bleeding risk (increased effect).
- Mechanism: Unknown; neither drug is a prodrug relevant here. Contributions may include TCA-related effects on platelet serotonin and NSAID effects on platelet aggregation/GI mucosa.
- Onset: Unspecified; events reported within 30 days.
- Evidence: Established. Severity major.
- Management: Use caution; monitor for signs/symptoms of bleeding (GI, mucocutaneous, neurologic). Individualize therapy per patient bleeding risk.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs and tricyclic antidepressants are administered together, since the combination may heighten bleeding risk, such as intracranial hemorrhage occurring within 30 days of joint use1. During concurrent therapy with these two drug classes, watch the patient for indications of elevated bleeding.
Why it happens (mechanism)
Unknown
How to manage this interaction
Your care team can manage this combination safely, usually by watching you more closely rather than stopping either drug.
- Keep taking both as prescribed unless your doctor tells you otherwise.
- Your team may monitor you more closely for signs of bleeding, and your treatment may be adjusted and individualized based on your personal risk.
- Tell your doctor or pharmacist right away about unusual bruising, bleeding gums, nosebleeds, blood in stool or urine, black stools, vomiting blood, or a sudden severe headache.
- Mention any other blood thinners, aspirin, or other NSAIDs you take.
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, led to a higher risk of intracranial hemorrhage within 30 days of concurrent use when compared to using an antidepressant on its own. No significant difference in the elevated risk was observed among the different antidepressant drug classes; however, the risk was increased in male patients compared with female patients 1.
Common questions
Can I take Amitriptyline and Parecoxib together?
Taking amitriptyline and parecoxib together can increase your bleeding risk, so keep taking both as prescribed but watch for any unusual bleeding and report it to your care team promptly. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Parecoxib 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 Parecoxib interaction managed?
Your care team can manage this combination safely, usually by watching you more closely rather than stopping either drug. Keep taking both as prescribed unless your doctor tells you otherwise. Your team may monitor you more closely for signs of bleeding, and your treatment may be adjusted and individualized based on your personal risk. Tell your doctor or pharmacist right away about unusual bruisi… 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 Parecoxib 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 Parecoxib
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