Acetaminophen And Codeine and Idelalisib: 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
Idelalisib
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 contains codeine, which your body turns into morphine to relieve pain. Idelalisib (Zydelig) can slow down the liver enzyme (CYP3A4) that normally clears codeine. This can let codeine and morphine build up higher than usual.
Too much of these can cause heavy drowsiness and slowed, shallow breathing, which can be dangerous. This is most likely to be a concern if idelalisib is added after you are already settled on a codeine dose. The good news is your care team can manage this by adjusting your dose and watching you more closely. Keep taking both as prescribed, and call your doctor right away if you feel very sleepy or short of breath.
Effect: Idelalisib is a strong CYP3A4 inhibitor and may reduce codeine metabolism, increasing exposure to codeine and its active metabolite morphine (formed via CYP2D6). Higher opioid concentrations raise the risk of sedation and potentially fatal respiratory depression.
- Direction: increased opioid effect and toxicity
- Onset: unspecified; risk highest when inhibitor is added to a stable codeine regimen
- Evidence: theoretical
- Management: monitor closely for respiratory depression and sedation; consider codeine dose reduction until stable effects observed. On idelalisib discontinuation, watch for opioid withdrawal and consider a codeine dose increase.
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, a situation that may intensify or extend adverse reactions and carries the risk of respiratory depression that can be fatal, especially in cases where an inhibitor is introduced after a patient has already reached a stable codeine dose. When these agents must be used together, watch patients carefully for sedation and respiratory depression, and weigh reducing the codeine dose until drug effects are seen to be stable. 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 are established12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated codeine metabolism
How to manage this interaction
If both medicines are needed, your care team can manage this safely.
- Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise.
- Your codeine dose may be adjusted and individualized, and your team may monitor you more closely for excess sleepiness and slowed breathing.
- Extra caution is warranted when idelalisib is first started while you are already on a steady codeine dose.
- If idelalisib is stopped, tell your team, as your codeine may need adjusting to avoid withdrawal or reduced pain relief.
- Get help right away for very slow or shallow breathing, extreme drowsiness, or confusion.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Idelalisib together?
Idelalisib can raise codeine and morphine levels, increasing the risk of heavy sedation and dangerous breathing problems. Keep taking both as prescribed and let your care team adjust the dose and monitor you, especially when idelalisib is started or stopped. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Idelalisib 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 Idelalisib interaction managed?
If both medicines are needed, your care team can manage this safely. Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Your codeine dose may be adjusted and individualized, and your team may monitor you more closely for excess sleepiness and slowed breathing. Extra caution is warranted when idelalisib is first started while you are already on a steady codeine dos… 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 Idelalisib 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 Idelalisib
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