Acetaminophen And Codeine and Ivacaftor: 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
Ivacaftor
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.
What's going on: Codeine is a pain medicine that your body has to process. One pathway that helps break codeine down is a liver enzyme called CYP3A4. Ivacaftor (Kalydeco) can slow that enzyme down. When it does, more codeine (and the morphine your body makes from it) can build up in your system.
That can mean stronger opioid effects, like extra drowsiness or slowed breathing, especially if the ivacaftor is added after you've been on a steady codeine dose. This warning is based on how the drugs work rather than lots of real-world cases, but breathing changes are serious. The good news is your care team can manage this by adjusting your dose and watching you more closely. Never stop or change either medicine on your own. Talk with your pharmacist or doctor.
Mechanism: Ivacaftor is a weak CYP3A4 inhibitor. Codeine undergoes CYP3A4-mediated N-demethylation; inhibition shifts metabolism, potentially increasing codeine and its active metabolite morphine (CYP2D6-derived) exposure.
Direction/effect: Increased codeine and morphine concentrations, raising risk of sedation and potentially fatal respiratory depression, most notably when the inhibitor is added to a stable codeine regimen.
- Evidence: Theoretical; magnitude and onset unspecified.
- Monitoring: Respiratory depression, sedation, opioid excess.
- Management: If combined, consider codeine dose reduction until stable effects observed; on inhibitor discontinuation, monitor for withdrawal and consider increasing codeine dose.
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, potentially intensifying or extending adverse reactions and possibly producing respiratory depression that can be fatal, especially when the 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 think about lowering the codeine dose until the drug effects have stabilized. 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 seen12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated codeine metabolism
How to manage this interaction
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This can be managed with tailoring and monitoring.
- Your care team may reduce the codeine dose and individualize it, especially if ivacaftor is started while you're already on codeine.
- They may watch you more closely for excess sedation and slowed or shallow breathing.
- If ivacaftor is ever stopped, your team may watch for signs of opioid withdrawal and adjust the codeine dose again.
Tell your pharmacist or doctor right away if you feel unusually drowsy, confused, or notice slow or difficult breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Ivacaftor together?
Combining ivacaftor with codeine may raise codeine and morphine levels, increasing the risk of excess sedation and slowed breathing; keep taking both as prescribed and let your care team adjust the codeine dose and monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Ivacaftor 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 Ivacaftor interaction managed?
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This can be managed with tailoring and monitoring. Your care team may reduce the codeine dose and individualize it, especially if ivacaftor is started while you're already on codeine. They may watch you more closely for excess sedation and slowed or shallow breathing. If ivacaftor is ever stopped, your team may wa… 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 Ivacaftor 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 Ivacaftor
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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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