Amitriptyline and Clonixin: 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
Clonixin
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) and clonixin (an anti-inflammatory pain reliever, or NSAID). When these two are taken together, they can raise your risk of bleeding. This can range from easier bruising or stomach bleeding to, rarely, bleeding in the brain, especially in the first month of using them together.
The good news is that this is very manageable. Your care team can watch you more closely and adjust things if needed. Please don't stop either medicine on your own. Instead, tell your pharmacist or doctor about any unusual bruising, black or bloody stools, or bad headaches so they can help right away.
Effect: Increased bleeding risk (including intracranial hemorrhage) with concurrent NSAID (clonixin) and TCA (amitriptyline) use, reported within 30 days of coadministration.
- Direction: Additive/pharmacodynamic increase in bleeding tendency (neither is a prodrug relevant here).
- Mechanism: Unknown; likely combined effects on platelet function and mucosal integrity.
- Evidence: Established.
- Onset: Unspecified.
- Management: Monitor for signs of bleeding (GI bleed, bruising, neurologic changes). Consider gastroprotection or alternative analgesia in higher-risk patients; individualize per patient bleeding risk.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs and tricyclic antidepressants are used together, because the combination can raise the likelihood of bleeding, such as intracranial hemorrhage occurring within 30 days of concurrent use1. If these two drug classes are administered at the same time, watch the patient for indications of heightened bleeding.
Why it happens (mechanism)
Unknown
How to manage this interaction
Both medicines can usually be continued, but your care team will take steps to keep you safe.
- Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise.
- Your team may monitor you more closely for signs of bleeding, and the plan may be adjusted and individualized for you.
- Watch for and report: unusual bruising, black or bloody stools, blood in urine or vomit, or a sudden severe headache.
- Ask your pharmacist before adding other pain relievers or blood thinners, since these can add to the risk.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) The combined use of NSAIDs with antidepressants, including tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors, and MAOIs, was associated with a higher risk of intracranial hemorrhage within 30 days of using them together when compared to using an antidepressant on its own. No significant difference was found among the antidepressant drug classes with respect to this increased risk; nevertheless, an increased risk was observed in male patients relative to female patients 1.
Common questions
Can I take Amitriptyline and Clonixin together?
Taking amitriptyline with the NSAID clonixin can raise your bleeding risk, so keep both as prescribed but tell your care team right away about any unusual bruising, bloody stools, or severe headache. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Clonixin 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 Amitriptyline and Clonixin interaction managed?
Both medicines can usually be continued, but your care team will take steps to keep you safe. Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Your team may monitor you more closely for signs of bleeding, and the plan may be adjusted and individualized for you. Watch for and report: unusual bruising, black or bloody stools, blood in urine or vomit, or a sudden s… 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 Amitriptyline or Clonixin 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 Clonixin
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