Acetaminophen And Codeine and Sulfinpyrazone: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 1, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Acetaminophen And Codeine
Sulfinpyrazone
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.
Your pain medicine contains acetaminophen (the same ingredient as Tylenol) plus codeine. The other medicine, sulfinpyrazone, may speed up how your liver breaks down acetaminophen by about 20%. This matters in two ways. First, the acetaminophen may wear off a little faster, so your pain relief might not last as long. Second, and more importantly, if too much acetaminophen is ever taken, the liver could be more easily harmed.
Please know this concern is based mostly on theory, not on lots of real-world cases. The most important thing is to never take more acetaminophen than directed. Your care team can watch this closely, so talk with your pharmacist or doctor.
Effect: Sulfinpyrazone may increase hepatic metabolism of acetaminophen (~20% increase reported at 800 mg/day), theoretically raising the risk of hepatotoxicity in the setting of acetaminophen overdose and potentially shortening analgesic duration.
- Mechanism: Induction of acetaminophen metabolism, likely shifting more parent drug toward the reactive NAPQI pathway.
- Direction: Faster acetaminophen clearance; greater toxic-metabolite burden if overdosed. Codeine is unaffected here.
- Onset: Delayed. Evidence: Theoretical.
- Management: Avoid combination if possible; if co-administered, monitor LFTs in high-risk patients and reinforce strict acetaminophen dose limits.
What happens
Increased hepatotoxicity in acetaminophen overdose
Interaction Deep Dive
When patients are pretreated with sulfinpyrazone at 800 mg per day, the metabolism of acetaminophen rises by roughly 20%. This may heighten the risk of acetaminophen toxicity in individuals receiving sulfinpyrazone, and it may also reduce how long analgesia lasts1.
Why it happens (mechanism)
Increased hepatic metabolism of acetaminophen
How to manage this interaction
Here is how a care team typically handles this:
- They may avoid using these together when a good alternative exists.
- If both are needed, your doctor may check your liver function more closely, especially if you have higher risk for liver problems.
- Because acetaminophen may not last as long for pain, your team can individualize your pain plan if needed.
What you should do: keep taking both exactly as prescribed, and never exceed the acetaminophen dose on the label. Watch out for hidden acetaminophen in other cold or pain products. Ask your pharmacist or prescriber before making any change.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Sulfinpyrazone together?
Sulfinpyrazone may make acetaminophen break down faster, which can shorten pain relief and, in an overdose, raise the risk of liver harm. Never exceed the acetaminophen dose and let your care team monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Sulfinpyrazone interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How is the Acetaminophen And Codeine and Sulfinpyrazone interaction managed?
Here is how a care team typically handles this: They may avoid using these together when a good alternative exists. If both are needed, your doctor may check your liver function more closely, especially if you have higher risk for liver problems. Because acetaminophen may not last as long for pain, your team can individualize your pain plan if needed. What you should do: keep taking both exactly a… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Acetaminophen And Codeine or Sulfinpyrazone 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 (1)
- Miners JO, Attwood J, & Birkett DJ: Determinants of acetaminophen metabolism: effect of inducers and inhibitors of drug metabolism on acetaminophen's metabolic pathways. Clin Pharmacol Ther 1984; 35:480-486. PubMed
Keep reading about Acetaminophen And Codeine
Keep reading about Sulfinpyrazone
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