Acetaminophen And Codeine and Ribociclib: 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
Ribociclib
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.
These two medicines can add up in a way you should know about. Your pain pill contains codeine, which your body turns into morphine to relieve pain. Ribociclib (Kisqali) slows down the liver enzyme that handles codeine. That can let codeine and morphine build up higher than usual.
When that happens, you may feel very sleepy or drowsy, and in serious cases your breathing can slow down too much. This is more likely if the Kisqali is started after you are already used to your codeine dose. The good news is your care team can manage this by watching you closely and tailoring your dose. Please talk with your pharmacist or doctor before changing anything.
Effect: Ribociclib is a CYP3A4 inhibitor. Codeine is metabolized via CYP3A4 (N-demethylation) and CYP2D6 (O-demethylation to active morphine). Inhibiting CYP3A4 can increase codeine and morphine exposure, raising the risk of sedation and potentially fatal respiratory depression.
- Direction: increased opioid exposure/effect.
- Onset: unspecified; highest risk when inhibitor is added to a stable codeine dose.
- Evidence: theoretical.
- Management: monitor closely for respiratory depression and sedation; consider codeine dose reduction until stable effects observed. On ribociclib discontinuation, 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 elevated levels of both codeine and morphine, which may intensify or extend adverse effects and can produce potentially fatal respiratory depression, especially in cases where an inhibitor is introduced after a patient has reached a stable codeine dose. When the combination cannot be avoided, watch patients carefully for sedation and respiratory depression, and consider lowering the codeine dose until stable drug effects are seen. Conversely, when a CYP3A4 inhibitor is being withdrawn, observe patients for indications of opioid withdrawal, and consider raising the codeine dose 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. This combination can be used safely with the right precautions.
- Your team may monitor you more closely for excess drowsiness, heavy sedation, or slowed or shallow breathing, especially soon after ribociclib is started.
- Your codeine dose may need to be adjusted and individualized by your care team until your response is stable.
- If ribociclib is ever stopped, watch for possible opioid withdrawal, since your codeine may need to be re-adjusted.
- Call your pharmacist or doctor right away if you feel unusually sleepy or notice trouble breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Ribociclib together?
Ribociclib can raise codeine and morphine levels, increasing the risk of excess sedation and dangerously slow breathing, so your care team should monitor you closely and may adjust your codeine dose. Keep taking both as prescribed and report unusual drowsiness or breathing changes. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Ribociclib 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 Ribociclib interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. This combination can be used safely with the right precautions. Your team may monitor you more closely for excess drowsiness, heavy sedation, or slowed or shallow breathing, especially soon after ribociclib is started. Your codeine dose may need to be adjusted and individualized by your care team until your response… 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 Ribociclib 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
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