Pranoprofen 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
Pranoprofen
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.
Taking amitriptyline (Elavil) with pranoprofen (an NSAID pain reliever) can raise your risk of bleeding. Both types of medicine can make it a little harder for your blood to clot normally, so putting them together adds up. In rare cases this bleeding can be serious, including bleeding in the brain, usually noticed within the first month of using them together.
Please don't stop either medicine on your own. This is something your care team handles all the time. Watch for warning signs like unusual bruising, blood in your stool or urine, black tarry stools, nosebleeds that won't stop, or a sudden bad headache, and let your pharmacist or doctor know right away if any show up.
Effect: Additive bleeding risk when the NSAID pranoprofen is combined with the tricyclic antidepressant amitriptyline, including reports of intracranial hemorrhage within 30 days of concurrent use.
- Direction: Increased bleeding risk (pharmacodynamic, additive). Neither agent's dose flips the risk.
- Mechanism: Unknown/not fully characterized; likely additive antiplatelet and mucosal effects.
- Evidence: Established. Severity: Major. Onset: Unspecified.
- Management: Use caution. Monitor for signs of GI, mucosal, and CNS bleeding. Assess for other risk factors (age, anticoagulants, GI history). Dose and duration may be individualized by the care team; consider gastroprotection or an alternative analgesic if risk is high.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs and tricyclic antidepressants are administered together, since this combination may heighten the risk of bleeding, such as intracranial hemorrhage occurring within 30 days of using both agents at the same time1. Watch the patient for indications of heightened bleeding whenever these two drug classes are used concurrently.
Why it happens (mechanism)
Unknown
How to manage this interaction
The main goal here is watching for bleeding, not stopping your medicines. Keep taking both amitriptyline and pranoprofen exactly as prescribed unless your prescriber tells you otherwise.
- Your care team may monitor you more closely and tailor your dose or how long you use the NSAID to your situation.
- Tell them about any other blood thinners, aspirin, or a history of stomach ulcers, since these add to the risk.
- Report right away: unusual bruising, black or bloody stools, blood in urine or vomit, nosebleeds that won't stop, or a sudden severe headache.
Ask your pharmacist whether a different pain reliever or a stomach-protecting medicine might be right for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) Taking NSAIDs together with antidepressants, such as tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors, and MAOIs, led to a greater risk of intracranial hemorrhage within 30 days of combined use when compared with using antidepressants by themselves. No meaningful difference was found among the various antidepressant drug classes with respect to this heightened risk; nonetheless, male patients had an increased risk relative to female patients 1.
Common questions
Can I take Pranoprofen and Amitriptyline together?
Combining amitriptyline with the NSAID pranoprofen adds up to a higher bleeding risk, so keep taking both as prescribed but watch for bleeding signs and check in with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Pranoprofen 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 Pranoprofen and Amitriptyline interaction managed?
The main goal here is watching for bleeding, not stopping your medicines. Keep taking both amitriptyline and pranoprofen exactly as prescribed unless your prescriber tells you otherwise. Your care team may monitor you more closely and tailor your dose or how long you use the NSAID to your situation. Tell them about any other blood thinners, aspirin, or a history of stomach ulcers, since these add… 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 Pranoprofen 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 Pranoprofen
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