Acetaminophen And Codeine and Larotrectinib: 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
Larotrectinib
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.
You're taking a pain medicine that combines acetaminophen with codeine, along with larotrectinib (a cancer medicine). Codeine has to be broken down by your body in a couple of steps, and larotrectinib can slow one of those steps down. This can let more codeine and its stronger form (morphine) build up in your blood.
When that happens, you could feel more of codeine's effects, like being very sleepy or having slow, shallow breathing. That breathing effect can be serious. The good news is this is a possible (theoretical) concern your care team can plan for. Keep taking both as prescribed, and let your pharmacist or doctor know if you feel unusually drowsy or short of breath.
Effect: Larotrectinib is a CYP3A4 inhibitor that may reduce codeine clearance, increasing codeine and its active metabolite morphine exposure.
- Direction: Increased opioid effect; risk of excess sedation and potentially fatal respiratory depression.
- Evidence: Theoretical; based on the known effect of CYP3A4 inhibitors on codeine.
- Onset: Unspecified; highest concern when the inhibitor is added to a stable codeine dose.
- Management: Monitor for respiratory depression and sedation. Consider codeine dose reduction until stable effects are seen. If larotrectinib is later stopped, monitor for opioid withdrawal and consider increasing the 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, potentially intensifying or extending adverse reactions and raising the risk of respiratory depression that may be fatal. This concern is heightened when an inhibitor is introduced after a patient has already reached a stable codeine dose. Should combined therapy be required, monitor patients carefully for sedation and respiratory depression, and consider lowering the codeine dose until stable drug effects are confirmed. Conversely, when a CYP3A4 inhibitor is withdrawn, watch for indications of opioid withdrawal and consider raising the codeine dose until stable drug effects have been established12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated codeine metabolism
How to manage this interaction
Both medicines can usually be used together with the right precautions. Your care team may take steps such as:
- Watching you more closely for excess drowsiness or slow, shallow breathing, especially soon after larotrectinib is started.
- Adjusting your codeine dose (it may need to be individualized) until your response is steady.
- Watching for signs of opioid withdrawal and possibly adjusting your codeine dose again if larotrectinib is ever stopped.
What you should do: Keep taking both exactly as prescribed. Don't change doses on your own. Tell your pharmacist or doctor right away if you feel unusually sleepy, confused, or short of breath.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Larotrectinib together?
Larotrectinib can raise codeine and morphine levels, which may increase sedation and serious breathing problems; keep taking both as prescribed and watch for unusual drowsiness or shortness of breath, reporting it to your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Larotrectinib 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 Larotrectinib interaction managed?
Both medicines can usually be used together with the right precautions. Your care team may take steps such as: Watching you more closely for excess drowsiness or slow, shallow breathing, especially soon after larotrectinib is started. Adjusting your codeine dose (it may need to be individualized) until your response is steady. Watching for signs of opioid withdrawal and possibly adjusting your cod… 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 Larotrectinib 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 Larotrectinib
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