Acetaminophen And Codeine and Mifepristone: 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
Mifepristone
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.
Here's what's going on. Your pain medicine contains codeine. Codeine is a bit unusual: your body has to break it down to turn some of it into morphine, which is what relieves pain. Mifepristone can slow down one of the liver enzymes (called CYP3A4) that also handles codeine. The concern is that codeine and its morphine may build up more than usual.
Too much opioid can make you very sleepy and, in the worst case, slow your breathing. This is a theoretical concern rather than something proven, but because it can be serious, it's worth watching. Please don't change anything on your own. Your care team can manage this safely by adjusting your dose and keeping a closer eye on you.
Mechanism: Mifepristone inhibits CYP3A4, a pathway involved in codeine metabolism. Reduced CYP3A4 clearance can increase codeine and morphine exposure (AUC/Cmax), potentially prolonging or intensifying opioid effects.
Clinical concern: Additive risk of sedation and potentially fatal respiratory depression, greatest when the inhibitor is added to a stable codeine regimen.
- Direction: Increased opioid exposure/effect
- Onset: Unspecified
- Evidence: Theoretical
- Management: Monitor for respiratory depression and sedation; consider codeine dose reduction until stable effects observed. If mifepristone is discontinued, monitor for withdrawal and consider titrating codeine back up.
What happens
Increased codeine and morphine exposure
Interaction Deep Dive
Taking codeine together with CYP3A4 inhibitors has led to higher levels of both codeine and morphine, a change that can heighten or extend adverse effects and may produce respiratory depression that is potentially fatal, especially when the inhibitor is introduced once a patient has already reached a stable codeine dose. When the two must be given together, watch patients carefully for sedation and respiratory depression, and think about lowering the codeine dose until stable drug effects are seen. Conversely, when a CYP3A4 inhibitor is being stopped, observe patients for indications of opioid withdrawal, and consider raising the codeine dose until stable drug effects are observed12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated codeine metabolism
How to manage this interaction
Keep taking both exactly as prescribed unless your prescriber tells you otherwise. This combination can usually be managed with the right precautions.
- Your care team may reduce the codeine dose and individualize it until they see how you respond.
- They may monitor you more closely for heavy sedation and slowed or shallow breathing, especially soon after mifepristone is started.
- If mifepristone is later stopped, your team may adjust the codeine dose again and watch for withdrawal signs.
- Get urgent help for severe drowsiness, confusion, or trouble breathing.
Ask your pharmacist or doctor before making any changes.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Mifepristone together?
Mifepristone may raise codeine and morphine levels, increasing the risk of excess sedation and slowed breathing. Keep taking both as prescribed, watch for heavy drowsiness or breathing changes, and let your care team adjust and monitor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Mifepristone 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 Mifepristone interaction managed?
Keep taking both exactly as prescribed unless your prescriber tells you otherwise. This combination can usually be managed with the right precautions. Your care team may reduce the codeine dose and individualize it until they see how you respond. They may monitor you more closely for heavy sedation and slowed or shallow breathing, especially soon after mifepristone is started. If mifepristone is l… 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 Mifepristone 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 Mifepristone
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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