Amiodarone and Acetaminophen And Codeine: 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
Amiodarone
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 Tylenol with codeine and amiodarone can interact. Amiodarone slows down one of the liver enzymes that helps clear codeine from your body. That means codeine (and the morphine your body makes from it) can build up higher than expected.
The main worry is too much of the opioid effect: heavy drowsiness, feeling very sedated, or breathing that becomes slow or shallow. This is based mostly on how these drugs work rather than lots of real-world reports, but it is worth taking seriously. Please don't stop either medicine on your own. Let your pharmacist or doctor know you take both, so they can watch you closely and tailor your dose safely.
Effect: Amiodarone (CYP3A4 inhibitor) may inhibit CYP3A4-mediated metabolism of codeine, increasing codeine and active morphine exposure (PK effect).
- Direction: Increased opioid exposure and pharmacodynamic effect (sedation, respiratory depression).
- Evidence: Theoretical; magnitude not quantified.
- Onset: Unspecified; risk is highest when the inhibitor is added to an established codeine dose.
- Management: Monitor for respiratory depression and sedation. Codeine dose may need to be reduced and individualized until stable effects are seen. If amiodarone is discontinued, monitor for opioid withdrawal and reassess codeine dosing.
Note amiodarone's long half-life means CYP3A4 inhibition can persist for weeks after stopping.
What happens
Increased codeine and morphine exposure
Interaction Deep Dive
Concomitant use of codeine with CYP3A4 inhibitors has resulted in increased codeine and morphine concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dose of codeine is achieved. If concomitant use is needed, closely monitor patients for respiratory depression and sedation, and consider dose reduction of codeine until stable drug effects have been observed. If a CYP3A4 inhibitor is being discontinued, monitor patients for signs of opioid withdrawal, and consider increasing dose of codeine until stable drug effects have been observed12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated codeine metabolism
How to manage this interaction
Keep taking both exactly as prescribed unless your care team tells you otherwise, then let your pharmacist or prescriber know you use them together.
- Your team may monitor you more closely for excess sedation and slow or shallow breathing, especially soon after amiodarone is started or a dose changes.
- Your codeine dose may need to be adjusted and individualized until stable, steady effects are seen.
- If amiodarone is ever stopped, your team may watch for opioid withdrawal and reassess your codeine dose.
- Seek help right away for extreme drowsiness, confusion, or breathing that feels slow or difficult.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Amiodarone and Acetaminophen And Codeine together?
Amiodarone can raise codeine and morphine levels, increasing the risk of heavy sedation and slowed breathing, so tell your care team you take both and watch for excess drowsiness. They can manage this by monitoring you and tailoring your codeine dose. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amiodarone and Acetaminophen And Codeine 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 Amiodarone and Acetaminophen And Codeine interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise, then let your pharmacist or prescriber know you use them together. Your team may monitor you more closely for excess sedation and slow or shallow breathing, especially soon after amiodarone is started or a dose changes. Your codeine dose may need to be adjusted and individualized until stable, steady effects are seen… 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Amiodarone or Acetaminophen And Codeine 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 (2)
- 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 Amiodarone
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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