Acetaminophen and Codeine Interaction
Drug interaction information between Acetaminophen and Codeine.
Acetaminophen and Codeine have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Acetaminophen and Codeine. Major interactions are generally avoided, moderate ones may need monitoring or a dose adjustment, and minor ones are usually low-risk. This page shows the documented mechanism and guidance. Label-documented interactions are not a complete safety review, so always confirm your own medications with a pharmacist or doctor. Educational information, not medical advice.
How They Interact
These two drugs work in different ways to help stop pain better than they would on their own. One works on the brain's pain centers while the other works on different pain signals in the body.
What To Do
Make sure you do not take other medicines that contain acetaminophen to avoid hurting your liver.
FDA Label Information
Drug Interactions Anticoagulants Chronic oral acetaminophen use at a dose of 4000 mg/day has been shown to cause an increase in international normalized ratio (INR) in some patients who have been stabilized on sodium warfarin as an anticoagulant. As no studies have been performed evaluating the short term use of acetaminophen and codeine phosphate tablets in patients on oral anticoagulants, more frequent assessment of INR may be appropriate in such circumstances. The concomitant use of acetaminophen and codeine phosphate tablets and CYP2D6 inhibitors (e.g., paroxetine, fluoxetine,...
Acetaminophen Also Interacts With
- Dapsone Topical moderate
- Lidocaine Topical moderate
- Acetaminophen/Oxycodone minor
- Carbamazepine minor
- Cidofovir minor
Codeine Also Interacts With
- Bupropion minor
- Fluoxetine minor
- Trazodone minor
- Tramadol minor
- Cyclobenzaprine minor
Frequently Asked Questions
Can I take Acetaminophen and Codeine together?
This is a minor interaction. Make sure you do not take other medicines that contain acetaminophen to avoid hurting your liver.
How serious is the interaction between Acetaminophen and Codeine?
This interaction is classified as "minor" severity by the FDA. Minor interactions are unlikely to cause significant problems but should still be mentioned to your healthcare provider.
Why do Acetaminophen and Codeine interact?
These two drugs work in different ways to help stop pain better than they would on their own. One works on the brain's pain centers while the other works on different pain signals in the body.
Understanding the Acetaminophen and Codeine Interaction
FDA-approved prescribing information for these two drugs flags their combination as a minor-severity interaction. Acetaminophen belongs to the Analgesic / Antipyretic class and Codeine belongs to the Opioid Analgesic class - two categories that can collide when co-prescribed. The mechanism described in FDA labeling is: These two drugs work in different ways to help stop pain better than they would on their own. Severity tiers matter: major flags generally advise avoidance, moderate flags often require monitoring or dose adjustment, and minor flags may only call for awareness.
Context around a specific patient determines real-world impact. Acetaminophen has 23 total documented interactions on file in this dataset, and Codeine has 27. Each additional medication compounds the interaction surface, which is why pharmacists run full-profile checks rather than evaluating one pair at a time. FDA-derived guidance for this pair is: Make sure you do not take other medicines that contain acetaminophen to avoid hurting your liver. Timing of doses, renal and hepatic function, age, and other concurrent prescriptions all shape whether a labeled interaction matters clinically.
An interaction flag is not a verdict. A large share of labeled interactions are managed routinely in clinical practice, the fix may be as simple as spacing doses or adding a monitoring test. Others require the prescriber to choose a different medication entirely. This page surfaces FDA-sourced labeling and openFDA data for educational purposes only; it is not medical advice and cannot account for your full clinical picture. Never start, stop, or adjust either Acetaminophen or Codeine based on a web page, speak with your prescriber or pharmacist before making any change.
Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. Always consult your healthcare provider about drug interactions.
Read our methodology - how this data is sourced, computed, and verified.