Acetaminophen and Diflunisal: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 10, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Diflunisal
Acetaminophen
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.
What happens
An increased risk of acetaminophen toxicity (hepatotoxicity)
Interaction Deep Dive
Concomitant diflunisal and acetaminophen administration results in a 50% increase in plasma concentrations of acetaminophen2. Since significantly elevated acetaminophen plasma levels have been associated with hepatotoxicity, the combination should be used with caution.
Why it happens (mechanism)
Unknown
Literature reports
1 report — tap to read
a) Coadministration of acetaminophen and diflunisal led to an approximately 50% increase in acetaminophen plasma concentrations in normal volunteers 1. Concurrent acetaminophen caused no alterations in diflunisal concentrations.
Common questions
Can I take Acetaminophen and Diflunisal together?
An increased risk of acetaminophen toxicity (hepatotoxicity) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen and Diflunisal interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Acetaminophen or Diflunisal 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 anything you'd monitor while I'm on both?
References (2)
Keep reading about Diflunisal
Keep reading about Acetaminophen
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.
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