Dexibuprofen 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
Dexibuprofen
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're taking amitriptyline (Elavil) for mood, sleep, or nerve pain, along with dexibuprofen, an anti-inflammatory pain reliever much like ibuprofen. Used together, these two can raise your risk of bleeding. In rare cases this can include serious bleeding, even bleeding in the brain, especially in the first weeks of taking them together.
This does not mean you have to stop either one. It just means your care team wants to keep an eye on you. Watch for things like unusual bruising, nosebleeds, black or bloody stools, or bleeding that won't stop. Please talk with your pharmacist or doctor about the safest plan for you, and don't change anything on your own.
Effect: Increased bleeding risk, including reports of intracranial hemorrhage within 30 days of starting concurrent use.
Mechanism: Not fully established. NSAIDs (dexibuprofen) inhibit platelet aggregation and cause GI mucosal injury; TCAs (amitriptyline) may contribute additive bleeding tendency. Neither is a prodrug relevant to this effect; this is a pharmacodynamic, not a PK, concern.
- Direction: Additive bleeding risk (increased effect on hemostasis).
- Onset: Unspecified; risk noted within 30 days.
- Evidence: Established.
- Management: Use with caution; monitor for signs/symptoms of bleeding (GI, mucocutaneous, neurologic). Consider gastroprotection or an alternative analgesic where appropriate.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise care when NSAIDs are combined with tricyclic antidepressants, because this combination can raise the likelihood of bleeding, such as intracranial hemorrhage occurring within 30 days of using both agents together1. If a patient receives NSAIDs alongside tricyclic antidepressants, watch for indications of heightened bleeding.
Why it happens (mechanism)
Unknown
How to manage this interaction
Your care team can manage this safely. Keep taking both medications as prescribed unless your prescriber tells you otherwise.
- Your team may monitor you more closely for signs of bleeding.
- They may consider a different pain reliever or add stomach protection if you need long-term NSAID use.
- Report right away: unusual bruising, nosebleeds, blood in stool or urine, black tarry stools, vomiting blood, or a severe or sudden headache.
Ask your pharmacist before adding any over-the-counter NSAIDs (like ibuprofen or naproxen), since they add to the same risk. Talk with your prescriber about the safest pain plan for you.
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 higher risk of intracranial hemorrhage within 30 days of concurrent use when compared with using an antidepressant by itself. No meaningful difference was found among the antidepressant drug classes with respect to this elevated risk; nevertheless, the increased risk was greater in male patients than in female patients 1..
Common questions
Can I take Dexibuprofen and Amitriptyline together?
Taking amitriptyline with dexibuprofen can raise your bleeding risk, so watch for unusual bruising or bleeding and check with your pharmacist or doctor about the safest pain relief plan. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Dexibuprofen 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 Dexibuprofen and Amitriptyline interaction managed?
Your care team can manage this safely. Keep taking both medications as prescribed unless your prescriber tells you otherwise. Your team may monitor you more closely for signs of bleeding. They may consider a different pain reliever or add stomach protection if you need long-term NSAID use. Report right away: unusual bruising, nosebleeds, blood in stool or urine, black tarry stools, vomiting blood,… 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 Dexibuprofen 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 Dexibuprofen
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