Acetaminophen And Codeine and Dronedarone: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jun 30, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Acetaminophen And Codeine
Dronedarone
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 has two parts: acetaminophen (like Tylenol) and codeine. Codeine is a prodrug, meaning your body has to convert it into morphine before it works well for pain. Dronedarone (Multaq) is a heart rhythm medicine that can slow down two of the liver enzymes that handle codeine.
Because of this, codeine may build up in your body, and the morphine your body makes from it could go either up or down. That means you might get too much (more drowsiness, slowed breathing) or not enough (less pain relief). This is a theoretical concern, so please don't stop either medicine. Just talk with your pharmacist or doctor so they can watch you and adjust your dose if needed.
Effect: Dronedarone inhibits both CYP3A4 and CYP2D6, the enzymes governing codeine disposition. Since codeine is a prodrug requiring CYP2D6 for conversion to morphine (its active metabolite), the net effect is unpredictable.
- Direction: Increased parent codeine exposure; morphine levels may rise or fall.
- Clinical result: Either reduced analgesia/withdrawal or increased opioid toxicity (respiratory depression, sedation).
- Evidence: Theoretical; onset unspecified.
- Severity: Major.
Management: If used together, monitor for withdrawal, sedation, and respiratory depression. Codeine dose may be adjusted and individualized by the care team.
What happens
Increased codeine exposure and increased or reduced active metabolite (morphine) exposure
Interaction Deep Dive
Concomitant use of codeine with a CYP3A4 inhibitor that is also a CYP2D6 inhibitor may either increase the codeine exposure and may either increase or reduce plasma concentrations of morphine, the active metabolite of codeine, thus potentially leading to reduced efficacy and withdrawal symptoms or an increased risk of adverse effects such as respiratory depression and sedation. If concomitant use is necessary, monitor patients for withdrawal symptoms, respiratory depression and sedation, and consider adjusting the codeine dose as needed123.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated codeine metabolism; inhibition of CYP2D6-mediated codeine metabolism
How to manage this interaction
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. Because the effect can go in either direction, your team can manage this safely by watching you.
- Your codeine dose may be adjusted and individualized by your prescriber if needed.
- Your team may monitor you more closely for signs of too much opioid (unusual drowsiness, very slow or shallow breathing, confusion) or too little (return of pain, withdrawal feelings like restlessness or nausea).
- Tell your pharmacist or doctor about any of these symptoms.
Do not start or stop either drug on your own.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Dronedarone together?
Dronedarone can change how your body handles the codeine in your pain medicine, possibly making it stronger or weaker, so ask your pharmacist or doctor to monitor you and adjust the dose if needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Dronedarone 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 Acetaminophen And Codeine and Dronedarone interaction managed?
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. Because the effect can go in either direction, your team can manage this safely by watching you. Your codeine dose may be adjusted and individualized by your prescriber if needed. Your team may monitor you more closely for signs of too much opioid (unusual drowsiness, very slow or shallow breathing, confusi… 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 Dronedarone 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 (3)
- Product Information: CARISOPRODOL, ASPIRIN, CODEINE PHOSPHATE oral tablets, carisoprodol, aspirin, codeine phosphate oral tablets. Ingenus Pharmaceuticals LLC (per DailyMed), Orlando, FL, 2021. DailyMed
- Product Information: Codeine sulfate oral solution, codeine sulfate oral solution. Hikma Pharmaceuticals USA Inc(per FDA), Berkeley Heights, NJ, 2023. DailyMed
- Product Information: Codeine sulfate oral tablets, codeine sulfate oral tablets. Hikma Pharmaceuticals USA Inc. (per FDA), Berkeley Heights, NJ, 2023. DailyMed
Keep reading about Acetaminophen And Codeine
Keep reading about Dronedarone
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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