Crizotinib 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
Crizotinib
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, and crizotinib (Xalkori) can slow down one of the liver enzymes that helps your body process codeine. Because of this, more codeine and its active form (morphine) can build up in your system. That can make the drowsiness, slowed breathing, and other opioid side effects stronger or longer-lasting.
This is a theoretical concern, meaning it is based on how these drugs work rather than lots of real-world reports, but it is taken seriously because breathing problems from opioids can be dangerous. The good news is your care team can manage this. Please don't stop either medicine on your own. Just talk with your doctor or pharmacist, especially if you feel unusually sleepy or short of breath.
Effect: Crizotinib inhibits CYP3A4, reducing codeine clearance and increasing exposure to codeine and its active metabolite morphine (formed via CYP2D6). Predicted PK increase raises risk of enhanced/prolonged opioid effects, including potentially fatal respiratory depression.
- Direction: Increased opioid effect (CYP3A4 inhibition).
- Onset: Unspecified; highest concern when inhibitor added to a stable codeine regimen.
- Evidence: Theoretical.
- Severity: Major.
Management: Monitor for sedation and respiratory depression; consider codeine dose reduction until stable effects are seen. If crizotinib is discontinued, monitor for opioid withdrawal and consider increasing the codeine dose.
What happens
Increased codeine and morphine exposure
Interaction Deep Dive
Concomitant use of codeine with CYP3A4 inhibitors has resulted in increased codeine and morphine concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dose of codeine is achieved. If concomitant use is needed, closely monitor patients for respiratory depression and sedation, and consider dose reduction of codeine until stable drug effects have been observed. If a CYP3A4 inhibitor is being discontinued, monitor patients for signs of opioid withdrawal, and consider increasing dose of codeine until stable drug effects have been observed12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated codeine metabolism
How to manage this interaction
Your care team can safely manage this combination when it is needed. Typically they will:
- Watch you more closely for excess sedation and slowed or shallow breathing.
- Possibly lower your codeine dose, adjusted and individualized to you, until your response is stable.
- If crizotinib is ever stopped, watch for withdrawal signs and possibly adjust your codeine dose back up.
What you can do: Keep taking both medicines exactly as prescribed. Tell your pharmacist or doctor right away if you feel very drowsy, confused, or notice breathing that is slow, shallow, or hard. Do not change doses on your own.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Crizotinib and Acetaminophen And Codeine together?
Crizotinib can raise codeine and morphine levels, increasing the risk of heavy sedation and dangerous breathing problems, so your care team may lower your codeine dose and monitor you more closely. Keep taking both as prescribed and report unusual drowsiness or breathing changes. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Crizotinib 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 Crizotinib and Acetaminophen And Codeine interaction managed?
Your care team can safely manage this combination when it is needed. Typically they will: Watch you more closely for excess sedation and slowed or shallow breathing. Possibly lower your codeine dose, adjusted and individualized to you, until your response is stable. If crizotinib is ever stopped, watch for withdrawal signs and possibly adjust your codeine dose back up. What you can do: Keep taking… 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 Crizotinib 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 Crizotinib
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