Adagrasib 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
Adagrasib
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, which only works well after your body turns it into morphine using a liver enzyme called CYP2D6. Adagrasib (Krazati) slows that enzyme down. That means your body may make less morphine, so the codeine may not relieve your pain as well, and if you take codeine regularly you could even feel mild withdrawal.
This concern is theoretical, based on how the drugs work rather than lots of real-world reports. Please don't change anything on your own. Your care team can manage this by watching how well your pain is controlled and adjusting your dose if needed.
Effect: Adagrasib inhibits CYP2D6, reducing conversion of codeine (a prodrug) to its active metabolite morphine. Expected result: increased parent codeine exposure and reduced morphine formation, leading to diminished analgesia and possible opioid withdrawal in dependent patients.
- Direction: reduced active-drug effect (prodrug activation blocked)
- Evidence: theoretical; magnitude unspecified
- Onset: unspecified
Management: Monitor for inadequate analgesia and withdrawal; the codeine dose may need to be individualized upward while on adagrasib. When adagrasib is discontinued, CYP2D6 activity recovers, so reduce codeine dose and monitor for sedation and respiratory depression.
What happens
Increased codeine exposure and reduced active metabolite (morphine) exposure
Interaction Deep Dive
Concomitant use of codeine and a CYP2D6 inhibitor may reduce plasma concentrations of morphine, the active metabolite of codeine, thus potentially leading to reduced efficacy and withdrawal symptoms. If concomitant use is necessary, monitor patients for withdrawal symptoms and consider increasing the codeine dose. Once the CYP2D6 inhibitor is discontinued, consider reducing the codeine dose and monitor for signs and symptoms of respiratory depression and sedation312.
Why it happens (mechanism)
Inhibition of CYP2D6-mediated codeine metabolism
How to manage this interaction
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise.
- What your team may do: watch whether your pain is well controlled and check for withdrawal symptoms. Your codeine dose may need to be adjusted and individualized by your care team while you are on adagrasib.
- When adagrasib is stopped: your team may lower the codeine dose again and watch for excess sedation or slowed breathing, since codeine can become more effective once the enzyme recovers.
- What to raise: tell your pharmacist or prescriber if your pain isn't controlled or you feel shaky, restless, or unwell.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Adagrasib and Acetaminophen And Codeine together?
Adagrasib can blunt codeine's pain relief by blocking its conversion to morphine, so tell your care team if your pain isn't controlled; they can adjust your dose and monitor you, including when the adagrasib is stopped. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Adagrasib 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 Adagrasib and Acetaminophen And Codeine interaction managed?
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. What your team may do: watch whether your pain is well controlled and check for withdrawal symptoms. Your codeine dose may need to be adjusted and individualized by your care team while you are on adagrasib. When adagrasib is stopped: your team may lower the codeine dose again and watch for excess sedation… 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 Adagrasib 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 (3)
- 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
- Product Information: codeine sulfate oral tablets, codeine sulfate oral tablets. West-Ward Pharmaceuticals Corp. (per FDA), Eatontown, NJ, 2017. DailyMed
Keep reading about Acetaminophen And Codeine
Keep reading about Adagrasib
These medications also interact with supplements
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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