Floctafenine 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
Floctafenine
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 floctafenine (an anti-inflammatory pain reliever, or NSAID). When these two are taken together, they can add up to a higher chance 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.
Please don't stop either medicine on your own. This combination can be used safely when your care team keeps an eye on you. Watch for things like unusual bruising, black or bloody stools, blood in your urine, nosebleeds that won't stop, or a sudden bad headache, and tell your pharmacist or doctor right away if you notice them.
Effect: Additive increased bleeding risk when a tricyclic antidepressant (amitriptyline) is combined with an NSAID (floctafenine), including reports of intracranial hemorrhage within 30 days of concomitant use.
Mechanism: Not fully established; likely additive/pharmacodynamic. TCAs can impair platelet function and NSAIDs inhibit platelet aggregation plus cause GI mucosal injury. Neither agent's activity here depends on prodrug activation.
- Direction/magnitude: Increased bleeding risk; magnitude not quantified.
- Onset: Unspecified; ICH reported within 30 days.
- Evidence: Established.
- Management: Monitor for signs of bleeding (GI, mucocutaneous, neurologic). Consider gastroprotection and reassess if higher-risk patient.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution if NSAIDs and tricyclic antidepressants are administered together, because the combination may raise the likelihood of bleeding events, such as intracranial hemorrhage occurring within 30 days of concurrent use1. Should these two drug classes be used at the same time, watch the patient for indications of heightened bleeding.
Why it happens (mechanism)
Unknown
How to manage this interaction
This combination can be managed. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Your care team may monitor you more closely for signs of bleeding while you use both drugs.
- Watch for warning signs: unusual bruising, black or bloody stools, vomiting blood, blood in urine, prolonged nosebleeds, or a sudden severe headache.
- Tell your pharmacist about any other blood thinners, aspirin, or other NSAIDs you take, since these add to the risk.
- Report any bleeding symptoms to your pharmacist or doctor promptly; the plan may be individualized by your care team.
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, produced a heightened risk of intracranial hemorrhage within 30 days of concurrent use when compared with using an antidepressant on its own. No meaningful difference in this elevated risk was found among the antidepressant drug classes; nevertheless, the risk was greater in male patients than in female patients 1.
Common questions
Can I take Floctafenine and Amitriptyline together?
Taking amitriptyline with floctafenine can raise your risk of bleeding, so watch for bleeding signs and keep in touch with your care team, who can monitor you and adjust the plan if needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Floctafenine 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 Floctafenine and Amitriptyline interaction managed?
This combination can be managed. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Your care team may monitor you more closely for signs of bleeding while you use both drugs. Watch for warning signs: unusual bruising, black or bloody stools, vomiting blood, blood in urine, prolonged nosebleeds, or a sudden severe headache. Tell your pharmacist about any o… 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 Floctafenine 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 Floctafenine
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