Bufexamac 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
Bufexamac
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 bufexamac (an anti-inflammatory medicine in the NSAID family). When these two are taken together, they can raise your risk of bleeding. This can range from easier bruising or stomach bleeding to, rarely, more serious bleeding.
The good news is that this is very manageable. Your care team can keep an eye on you and adjust things if needed. Please keep taking both medicines as prescribed and let your pharmacist or doctor know if you notice unusual bruising, black or bloody stools, vomiting that looks like coffee grounds, or a bad headache that won't go away.
Effect: Concurrent use of amitriptyline (TCA) and bufexamac (NSAID) is associated with an increased risk of bleeding, including intracranial hemorrhage, notably within 30 days of combined use.
- Direction: Additive/synergistic bleeding risk (increased effect).
- Mechanism: Unknown; likely additive effects on platelet function/serotonin-mediated hemostasis plus NSAID GI mucosal and antiplatelet effects.
- Evidence: Established. Onset: unspecified.
- Management: Use caution; monitor for signs/symptoms of bleeding (GI bleed, bruising, neurologic changes). Consider GI protection or alternative analgesia per patient risk.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs and tricyclic antidepressants are used together, because the combination may raise the likelihood of bleeding, such as intracranial hemorrhage, within 30 days of joint use1. If these two agents are administered at the same time, watch the patient for indications of heightened bleeding.
Why it happens (mechanism)
Unknown
How to manage this interaction
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. Because this combination can increase bleeding risk, your care team will usually manage it with closer monitoring and, if appropriate, tailoring your treatment.
- Your team may monitor you more closely for any signs of bleeding.
- Watch for and report: unusual bruising, black or tarry stools, blood in vomit or urine, or a severe, persistent headache.
- Ask your pharmacist whether a different pain option or added stomach protection makes sense for you.
Bring an updated list of all your medicines to each visit so your team can adjust and individualize your plan.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) Using 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 than antidepressant use by itself. No meaningful difference in the elevated risk was found among the antidepressant drug classes; however, an increased risk was seen in male patients relative to female patients 1.
Common questions
Can I take Bufexamac and Amitriptyline together?
Taking amitriptyline with bufexamac can raise your bleeding risk, so watch for signs like unusual bruising or dark stools and stay in touch with your care team, who can monitor you and adjust treatment as needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Bufexamac 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 Bufexamac and Amitriptyline interaction managed?
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. Because this combination can increase bleeding risk, your care team will usually manage it with closer monitoring and, if appropriate, tailoring your treatment. Your team may monitor you more closely for any signs of bleeding. Watch for and report: unusual bruising, black or tarry stools, blood in vomit or urine,… 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 Bufexamac 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 Bufexamac
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