Fepradinol 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
Fepradinol
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 fepradinol (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.
This doesn't mean you should stop either one. It just means your care team will want to keep an eye on you. Watch for things like unusual bruising, nosebleeds, blood in your stool or urine, or a bad headache that won't go away, and tell your doctor or pharmacist right away if you notice them. Your team can manage this safely.
Effect: Increased bleeding risk, including intracranial hemorrhage, reported within 30 days of concomitant use of an NSAID (fepradinol) and a tricyclic antidepressant (amitriptyline).
Direction/mechanism: Additive bleeding risk; precise mechanism unknown. TCAs may impair platelet function via serotonin effects, and NSAIDs inhibit platelet aggregation and irritate GI mucosa. Neither drug is a prodrug relevant here.
- Severity: Major; evidence: established; onset: unspecified (events noted within 30 days).
- Management: Monitor for signs/symptoms of bleeding (GI, mucocutaneous, neurologic). Consider gastroprotection or alternative analgesia if risk is high; individualize per patient risk factors.
What happens
An increased risk of bleeding
Interaction Deep Dive
Concurrent administration of NSAIDs with tricyclic antidepressants warrants caution, since it can elevate the likelihood of bleeding, such as intracranial hemorrhage occurring within 30 days of combined use1. Patients receiving both an NSAID and a tricyclic antidepressant at the same time should be observed for indications of heightened bleeding.
Why it happens (mechanism)
Unknown
How to manage this interaction
If both amitriptyline and fepradinol are prescribed, keep taking them as directed unless your prescriber tells you otherwise. Because the combination can raise bleeding risk, your care team will typically manage this by watching you more closely.
- Watch for and report unusual bruising, nosebleeds, bleeding gums, black or bloody stools, pink or red urine, vomiting blood, or a severe headache.
- Ask your pharmacist or doctor whether a stomach-protecting medicine or a different pain option makes sense for you.
- Mention any other blood thinners, aspirin, or additional NSAIDs you take.
Your team can tailor your treatment and monitoring to keep you safe.
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 heightened risk of intracranial hemorrhage within 30 days of concurrent use when compared to using an antidepressant on its own. No meaningful difference was observed among the various antidepressant drug classes with respect to this elevated risk; however, an increased risk was seen in male patients relative to female patients 1.
Common questions
Can I take Fepradinol and Amitriptyline together?
Taking amitriptyline with the NSAID fepradinol can increase your risk of bleeding, so keep taking both as prescribed but watch for signs of bleeding and report them to your doctor or pharmacist. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Fepradinol 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 Fepradinol and Amitriptyline interaction managed?
If both amitriptyline and fepradinol are prescribed, keep taking them as directed unless your prescriber tells you otherwise. Because the combination can raise bleeding risk, your care team will typically manage this by watching you more closely. Watch for and report unusual bruising, nosebleeds, bleeding gums, black or bloody stools, pink or red urine, vomiting blood, or a severe headache. Ask yo… 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 Fepradinol 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 Fepradinol
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