Palbociclib and Acetaminophen And Codeine: 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
Palbociclib
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 the short version: Palbociclib (Ibrance) can slow down one of the liver enzymes (called CYP3A4) that helps process codeine. When that enzyme is slowed, more codeine and its active form, morphine, can build up in your body. That means the opioid effects, like drowsiness and slowed breathing, could become stronger or last longer.
This is a caution based on how these drugs work, not on lots of real-world cases, but because slowed breathing can be serious, it's worth taking seriously. Please don't stop or change either medicine on your own. Your doctor or pharmacist can manage this by adjusting your dose and watching you more closely.
Effect: Increased codeine and morphine exposure via palbociclib inhibition of CYP3A4-mediated codeine metabolism.
Direction/mechanism: Codeine relies on CYP2D6 for conversion to morphine and CYP3A4 for clearance. Reduced CYP3A4 activity raises parent codeine (and downstream morphine) concentrations, increasing opioid effect.
- Evidence: Theoretical; severity rated major.
- Risk: Enhanced or prolonged sedation and potentially fatal respiratory depression, especially when the inhibitor is added to a stable codeine regimen.
- Management: Monitor closely for sedation and respiratory depression; consider codeine dose reduction until stable effects seen. If palbociclib is discontinued, monitor for withdrawal and consider increasing codeine dose.
What happens
Increased codeine and morphine exposure
Interaction Deep Dive
When codeine is taken together with CYP3A4 inhibitors, elevated levels of both codeine and morphine have been observed. This can intensify or extend adverse effects and carries the risk of respiratory depression that may be fatal, especially in situations where an inhibitor is introduced once a stable codeine dose has already been established. Should combined use be required, keep a close watch on patients for sedation and respiratory depression, and weigh reducing the codeine dose until the drug's effects have stabilized. Conversely, when a CYP3A4 inhibitor is being withdrawn, watch for indications of opioid withdrawal in patients, and consider raising the codeine dose until stable drug effects are seen12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated codeine metabolism
How to manage this interaction
Keep taking both as prescribed unless your care team tells you otherwise. This combination can be used safely with the right oversight.
- Your team may monitor you more closely for excess sleepiness or slowed, shallow breathing, especially soon after starting both together.
- Your codeine dose may need to be adjusted and individualized by your care team until your response is steady.
- If palbociclib is ever stopped, tell your team, as your codeine dose may need review to avoid withdrawal or reduced pain relief.
Call your prescriber or pharmacist right away if you notice unusual drowsiness, confusion, or trouble breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Palbociclib and Acetaminophen And Codeine together?
Palbociclib can raise codeine and morphine levels, increasing the risk of heavy sedation and slowed breathing, so watch for those signs and let your care team adjust and monitor your codeine dose. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Palbociclib 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 Palbociclib and Acetaminophen And Codeine interaction managed?
Keep taking both as prescribed unless your care team tells you otherwise. This combination can be used safely with the right oversight. Your team may monitor you more closely for excess sleepiness or slowed, shallow breathing, especially soon after starting both together. Your codeine dose may need to be adjusted and individualized by your care team until your response is steady. If palbociclib is… 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 Palbociclib 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 Palbociclib
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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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