Sulindac 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
Sulindac
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 sulindac (an anti-inflammatory pain reliever, or NSAID). Taken together, these two can raise your risk of bleeding. NSAIDs like sulindac can irritate the stomach lining and affect how well your blood clots, and combining them with an antidepressant like amitriptyline appears to increase that bleeding risk a bit more.
The good news is this is very manageable. Watch for things like unusual bruising, black or bloody stools, vomit that looks like coffee grounds, or a bad headache that won't go away. Don't stop either medicine on your own. Just let your pharmacist or doctor know you take both so they can keep an eye on you.
Effect: Increased bleeding risk (including reports of intracranial hemorrhage within 30 days of concomitant use) when a tricyclic antidepressant (amitriptyline) is combined with an NSAID (sulindac).
- Direction: Additive/pharmacodynamic increase in bleeding tendency, not a prodrug-mediated effect.
- Mechanism: Unknown; likely additive hemostatic effects (NSAID platelet/GI effects plus TCA contribution).
- Evidence: Established. Severity: Major. Onset: Unspecified.
- Management: Use with caution. Monitor for signs of bleeding (GI bleed, bruising, neurologic changes). Consider GI protection and reassess NSAID need in higher-risk patients.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs and tricyclic antidepressants are administered together, since the combination can heighten the risk of bleeding, such as intracranial hemorrhage occurring within 30 days of using them together1. Patients receiving both NSAIDs and tricyclic antidepressants at the same time should be monitored for indications of increased bleeding.
Why it happens (mechanism)
Unknown
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. This combination is used, but it calls for closer attention.
- Your care team may monitor you more closely for signs of bleeding and may individualize your therapy (for example, reassessing how much or how long you need the NSAID).
- Watch for and promptly report: unusual bruising, black or tarry stools, blood in vomit or stool, pink or brown urine, or a severe/sudden headache.
- Tell every prescriber and your pharmacist that you take both drugs, and mention any other blood thinners, aspirin, or other NSAIDs.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) Simultaneous administration of NSAIDs and antidepressants, encompassing tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors, and MAOIs, led to a heightened risk of intracranial hemorrhage within 30 days of combined use when compared with taking antidepressants by themselves. No meaningful difference was observed between the antidepressant drug classes with respect to the elevated risk; nevertheless, the increased risk was greater in male patients than in female patients 1.
Common questions
Can I take Sulindac and Amitriptyline together?
Taking amitriptyline with sulindac can raise your bleeding risk, so keep taking both as prescribed but watch for signs of bleeding and let your pharmacist or doctor know you use both. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sulindac 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 Sulindac and Amitriptyline interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This combination is used, but it calls for closer attention. Your care team may monitor you more closely for signs of bleeding and may individualize your therapy (for example, reassessing how much or how long you need the NSAID). Watch for and promptly report: unusual bruising, black or tarry stools, blood in vomit… 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 Sulindac 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 Sulindac
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