Amitriptyline and Proquazone: 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
Proquazone
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 proquazone (an anti-inflammatory pain medicine, in the NSAID family). 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 can't take both. It just means your care team will want to keep an eye on you. Watch for things like unusual bruising, blood in your stool or urine, nosebleeds that won't stop, or a bad headache. Keep taking both as prescribed, and reach out to your pharmacist or doctor with any questions.
Effect: Increased bleeding risk, including intracranial hemorrhage, reported within 30 days of concomitant NSAID (proquazone) and TCA (amitriptyline) use.
Direction: Additive/synergistic bleeding risk, not a classic CYP prodrug interaction. Neither agent requires bioactivation that would reverse this. TCAs may affect platelet serotonin, and NSAIDs impair platelet aggregation and gastric mucosal protection.
- Mechanism: Unknown/undefined; likely additive antiplatelet and mucosal effects
- Severity: Major; evidence: established; onset: unspecified
- Management: Monitor for signs of bleeding (GI, mucocutaneous, neurologic). Individualize therapy; consider gastroprotection or alternatives per clinical judgment.
What happens
An increased risk of bleeding
Interaction Deep Dive
Coadministering NSAIDs with tricyclic antidepressants warrants caution, since the combination may raise the risk of bleeding, such as intracranial hemorrhage occurring within 30 days of concurrent use1. Watch the patient for indications of heightened bleeding whenever these two drug classes are administered together.
Why it happens (mechanism)
Unknown
How to manage this interaction
Your care team can manage this safely with attention and monitoring.
- Keep taking both exactly as prescribed unless your doctor tells you otherwise.
- Your team may monitor you more closely for signs of bleeding, and your doses may be adjusted and individualized to your situation.
- Watch for and report: unusual bruising, black or bloody stools, blood in urine, prolonged nosebleeds, coughing or vomiting blood, or a sudden severe headache.
- Ask your pharmacist before adding other pain relievers, aspirin, or blood thinners.
Bring any bleeding concerns to your pharmacist or prescriber promptly.
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 the concurrent use when compared with antidepressant use by itself. No significant difference in the increased risk was found among the antidepressant drug classes; nevertheless, an increased risk was observed in male patients compared with female patients 1.
Common questions
Can I take Amitriptyline and Proquazone together?
Taking amitriptyline with proquazone can raise your risk of bleeding, so keep taking both as prescribed but watch for bruising or bleeding and report anything unusual to your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Proquazone 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 Proquazone interaction managed?
Your care team can manage this safely with attention and monitoring. Keep taking both exactly as prescribed unless your doctor tells you otherwise. Your team may monitor you more closely for signs of bleeding, and your doses may be adjusted and individualized to your situation. Watch for and report: unusual bruising, black or bloody stools, blood in urine, prolonged nosebleeds, coughing or vomitin… 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 Proquazone 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 Proquazone
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist