Lonafarnib and Acetaminophen And Codeine: 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
Lonafarnib
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 interact. Lonafarnib (Zokinvy) slows down a liver enzyme that helps your body process codeine. Codeine is turned into morphine in your body, so if it clears more slowly, more can build up. That can lead to too much sleepiness or dangerously slow breathing.
This warning is based on how the drugs work rather than on many real-world reports, but it is taken seriously because breathing problems can be very dangerous. The good news is your care team can manage this by watching you closely and adjusting your codeine dose if needed. Please don't stop or change either medicine on your own, just talk with your pharmacist or doctor.
Mechanism: Lonafarnib is a CYP3A4 inhibitor. Codeine is metabolized in part by CYP3A4 (to inactive norcodeine) and by CYP2D6 (to active morphine). CYP3A4 inhibition shifts metabolism, increasing codeine and morphine exposure.
- Direction: Increased codeine/morphine concentrations, greater/prolonged opioid effect.
- Risk: Sedation and potentially fatal respiratory depression, especially when the inhibitor is added to a stable codeine regimen.
- Evidence: Theoretical; severity rated major.
- Management: Monitor closely for sedation and respiratory depression; consider codeine dose reduction until stable effects seen. On lonafarnib discontinuation, monitor for opioid 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 potentially fatal respiratory depression, especially in cases where the inhibitor is introduced after a patient has already reached a stable codeine dose. Should combined use be necessary, patients should be watched carefully for sedation and respiratory depression, and reducing the codeine dose should be considered until steady drug effects are seen. Conversely, when a CYP3A4 inhibitor is withdrawn, patients should be observed for indications of opioid withdrawal, and raising the codeine dose should be considered until stable drug effects are confirmed12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated codeine metabolism
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. Here is what teams typically do:
- Watch closely for excess sleepiness or slow, shallow breathing, especially soon after lonafarnib is started or a dose changes.
- The codeine dose may be adjusted and individualized by your care team until they see steady, safe effects.
- If lonafarnib is later stopped, they may watch for opioid withdrawal and adjust codeine as needed.
Tell your pharmacist or prescriber right away about severe drowsiness, confusion, or trouble breathing. Bring up any new medicines so your team can plan ahead.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Lonafarnib and Acetaminophen And Codeine together?
Lonafarnib can raise codeine and morphine levels and increase the risk of heavy sedation and slowed breathing, so your care team may adjust your codeine dose and monitor you closely. Never change either medicine on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lonafarnib 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 Lonafarnib and Acetaminophen And Codeine interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. Here is what teams typically do: Watch closely for excess sleepiness or slow, shallow breathing, especially soon after lonafarnib is started or a dose changes. The codeine dose may be adjusted and individualized by your care team until they see steady, safe effects. If lonafarnib is later stopped, they may watch fo… 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 Lonafarnib 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 Lonafarnib
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