Propyphenazone 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
Propyphenazone
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.
Amitriptyline (Elavil) is a tricyclic antidepressant, and propyphenazone is a pain and fever reliever in the same family as NSAIDs. When these two are taken together, the concern is 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.
This does not mean you should stop either medicine. It just means your care team may want to watch you more closely. Please tell your pharmacist or doctor if you notice unusual bruising, black or bloody stools, nosebleeds, or a bad headache. They can help you use both safely.
Interaction: Concomitant amitriptyline (TCA) and propyphenazone (NSAID-type analgesic) is associated with an increased bleeding risk, including intracranial hemorrhage within 30 days of combined use.
- Direction: Additive/synergistic bleeding risk (neither drug is a prodrug; interpretation is unchanged).
- Mechanism: Unknown; likely additive effects on platelet function/serotonin-mediated hemostasis plus NSAID GI mucosal risk.
- Evidence: Established. Severity: Major. Onset: Unspecified.
- Management: Monitor for signs of bleeding (GI, mucocutaneous, neurologic). Consider GI protection and reassess need for combined therapy per care team.
What happens
An increased risk of bleeding
Interaction Deep Dive
Concurrent administration of NSAIDs with tricyclic antidepressants warrants caution, since this combination may elevate the likelihood of bleeding events, such as intracranial hemorrhage occurring within 30 days of using both agents together1. Patients receiving these two drug classes at the same time should be watched for indications of heightened bleeding.
Why it happens (mechanism)
Unknown
How to manage this interaction
If you have been prescribed both, keep taking them as directed unless your prescriber tells you otherwise. The main step your care team takes here is closer monitoring for signs of bleeding.
- Watch for and report: unusual bruising, nosebleeds, bleeding gums, black or bloody stools, vomiting that looks like coffee grounds, or a sudden severe headache.
- Ask your pharmacist or doctor whether stomach protection or an alternative pain reliever is appropriate for you.
- Your team may adjust and individualize your plan and monitor you more closely while you use both.
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, led to a higher risk of intracranial hemorrhage within 30 days of concurrent use when compared with antidepressant use by itself. No significant difference was found between the antidepressant drug classes with respect to the elevated risk; however, an increased risk was observed in male patients relative to female patients 1.
Common questions
Can I take Propyphenazone and Amitriptyline together?
Taking amitriptyline with propyphenazone can raise your bleeding risk, so keep taking both as prescribed but watch for signs of bleeding and check with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Propyphenazone 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 Propyphenazone and Amitriptyline interaction managed?
If you have been prescribed both, keep taking them as directed unless your prescriber tells you otherwise. The main step your care team takes here is closer monitoring for signs of bleeding. Watch for and report: unusual bruising, nosebleeds, bleeding gums, black or bloody stools, vomiting that looks like coffee grounds, or a sudden severe headache. Ask your pharmacist or doctor whether stomach pr… 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 Propyphenazone 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 Propyphenazone
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