Acetaminophen And Codeine and Lumacaftor: 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
Lumacaftor
No brand names on record
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 here contains codeine. Codeine is a bit unusual: it doesn't do much until your body changes it into morphine, which is what actually relieves pain. Lumacaftor can speed up the liver enzyme that handles codeine, and that can leave you with less active pain relief.
If you take both, you might notice the codeine working less well. And if your body has gotten used to the opioid, you could feel withdrawal-type symptoms like restlessness, sweating, or a runny nose. The good news: this is manageable. Don't change anything on your own, but tell your doctor or pharmacist so they can watch you closely and adjust your dose if needed.
Effect: Lumacaftor is a CYP3A4 inducer and may reduce codeine exposure. Codeine is a prodrug; increased CYP3A4 activity shunts codeine toward norcodeine, leaving less available for CYP2D6-mediated conversion to morphine (the active analgesic moiety).
- Direction: Reduced morphine exposure, decreased analgesic efficacy, and possible opioid withdrawal in physically dependent patients.
- Evidence: Theoretical; magnitude and onset unspecified.
- Management: If co-administered, monitor for reduced efficacy and withdrawal; consider increasing codeine dose as needed. If lumacaftor is discontinued, consider codeine dose reduction and monitor for sedation/respiratory depression.
What happens
Reduced codeine and morphine exposure, reduced opioid efficacy and precipitation of opioid withdrawal
Interaction Deep Dive
When codeine is taken alongside CYP3A4 inducers, codeine concentrations may fall while norcodeine concentrations rise, and CYP2D6-mediated metabolism may diminish, producing lower morphine levels. This can lead to diminished efficacy or trigger a withdrawal syndrome in patients who have developed physical dependence. Should concurrent use be required, watch patients carefully for reduced efficacy or indications of opioid withdrawal syndrome, and consider raising the codeine dose as needed. When a CYP3A4 inducer is being withdrawn, consider lowering the codeine dose and monitor patients closely for signs of respiratory depression or sedation12.
Why it happens (mechanism)
Induction of CYP3A4-mediated codeine metabolism
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. This interaction can usually be managed with monitoring and dose tailoring.
- Watch for the pain medicine not working as well, or signs of withdrawal (restlessness, sweating, runny nose, aches, stomach upset).
- Your care team may adjust and individualize your codeine dose and monitor you more closely while you are on both.
- If lumacaftor is ever stopped, tell your team so they can consider lowering the codeine dose and watch for excess sedation or slowed breathing.
Report any changes to your pharmacist or prescriber rather than adjusting doses yourself.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Lumacaftor together?
Lumacaftor may speed up codeine breakdown and lower its pain-relieving effect, which can also trigger opioid withdrawal in dependent patients. Keep taking both as prescribed and ask your care team to monitor and adjust your dose as needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Lumacaftor 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 Lumacaftor interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This interaction can usually be managed with monitoring and dose tailoring. Watch for the pain medicine not working as well, or signs of withdrawal (restlessness, sweating, runny nose, aches, stomach upset). Your care team may adjust and individualize your codeine dose and monitor you more closely while you are on… 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 Lumacaftor 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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