Dexketoprofen 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
Dexketoprofen
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 dexketoprofen (an anti-inflammatory pain reliever, a type of 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.
The good news is that this is very manageable. Many people take medicines like these safely under a doctor's watch. Please keep taking both exactly as prescribed, and let your care team know right away if you notice things like unusual bruising, blood in your stool, dark or tarry stools, a bad headache, or any bleeding that won't stop. Your pharmacist or doctor can help you weigh the safest option.
Effect: Increased bleeding risk with concurrent tricyclic antidepressant (amitriptyline) and NSAID (dexketoprofen), including reports of intracranial hemorrhage within 30 days of combined use.
Direction/mechanism: Additive bleeding tendency; precise mechanism unknown. TCAs may impair platelet function and NSAIDs inhibit platelet aggregation plus cause GI mucosal injury. Neither agent's effect here depends on prodrug activation.
- Severity: Major
- Evidence: Established
- Onset: Unspecified
Management: Use caution when coadministering. Monitor for signs of increased bleeding (GI bleeding, bruising, neurologic changes suggesting intracranial hemorrhage). Consider gastroprotection or alternative analgesia in higher-risk patients.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs are administered together with tricyclic antidepressants, since combining them may raise the likelihood of bleeding, such as intracranial hemorrhage occurring within 30 days of concurrent use1. During concomitant therapy with these two drug classes, watch the patient for indications of heightened bleeding.
Why it happens (mechanism)
Unknown
How to manage this interaction
This combination can be managed with care from your team. Keep taking both medicines as prescribed unless your prescriber tells you otherwise.
- Your care team may monitor you more closely for signs of bleeding while you use both.
- They may consider a different pain reliever or add stomach protection, especially if you have other bleeding risks (older age, ulcers, blood thinners, alcohol use).
- Watch for warning signs: black or tarry stools, blood in vomit or urine, unusual bruising, a sudden severe headache, weakness, or trouble speaking, and get help right away for these.
Ask your pharmacist or doctor before adding any over-the-counter NSAID like ibuprofen or naproxen.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) 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 concurrent use when compared with antidepressant use by itself. No significant difference was observed between the antidepressant drug classes with respect to the elevated risk; nonetheless, an increased risk was associated with male patients relative to female patients 1.
Common questions
Can I take Dexketoprofen and Amitriptyline together?
Taking amitriptyline with the NSAID dexketoprofen raises your bleeding risk, so watch for unusual bleeding or bruising and check with your pharmacist or doctor before combining them or adding other NSAIDs. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Dexketoprofen 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 Dexketoprofen and Amitriptyline interaction managed?
This combination can be managed with care from your team. Keep taking both medicines as prescribed unless your prescriber tells you otherwise. Your care team may monitor you more closely for signs of bleeding while you use both. They may consider a different pain reliever or add stomach protection, especially if you have other bleeding risks (older age, ulcers, blood thinners, alcohol use). Watch… 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 Dexketoprofen 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 Dexketoprofen
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