Acetaminophen And Codeine and Mobocertinib: 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
Mobocertinib
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.
Let me explain what's going on here. Codeine is a prodrug, meaning your body has to convert it into an active painkiller (morphine) before it works. Mobocertinib can speed up the enzyme (called CYP3A4) that handles codeine. When that enzyme runs faster, more of your codeine gets shunted down a path that makes less morphine, so your pain relief may not work as well.
If you've been taking codeine for a while, you might even feel withdrawal-like symptoms, such as chills, aches, sweating, or a runny nose. This is manageable. Don't change either medicine on your own. Talk with your pharmacist or doctor so they can watch how you're doing and adjust your dose if needed.
Mechanism: Mobocertinib is a CYP3A4 inducer; codeine is a prodrug requiring O-demethylation (CYP2D6) to morphine, its active metabolite. Enhanced CYP3A4 activity increases N-demethylation to norcodeine, diverting substrate away from the CYP2D6 pathway and reducing morphine formation.
Effect / direction: Reduced codeine and morphine exposure, diminished analgesia, and possible opioid withdrawal in physically dependent patients.
- Evidence: Theoretical; magnitude unquantified.
- Onset: Unspecified.
- Management: Monitor for reduced efficacy and withdrawal; codeine dose may need upward titration individualized by the team. If mobocertinib is discontinued, consider codeine dose reduction and watch 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 together with CYP3A4 inducers, codeine concentrations may fall while norcodeine concentrations rise, and metabolism through CYP2D6 may decline, lowering morphine levels as a result. This can diminish therapeutic effect or precipitate a withdrawal syndrome in patients who have become physically dependent. Should combined use be necessary, monitor patients carefully for reduced efficacy or indications of opioid withdrawal syndrome, and raise the codeine dose as required. When a CYP3A4 inducer is being stopped, consider lowering the codeine dose and watch patients closely for signs of sedation or respiratory depression12.
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 handled with monitoring and dose tailoring.
- Watch for less pain relief or withdrawal-type symptoms (sweating, chills, body aches, runny nose, restlessness), and report them.
- Your team may adjust and individualize your codeine dose and monitor you more closely while you take both.
- If mobocertinib is ever stopped, tell your prescriber, since your codeine dose may need to be lowered and you may be watched for extra sedation or slowed breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Mobocertinib together?
Mobocertinib can speed up how your body processes codeine, which may weaken pain relief and, if you're dependent, trigger withdrawal. Keep taking both as prescribed and let your care team monitor you and adjust your codeine dose as needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Mobocertinib 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 Mobocertinib interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This interaction can usually be handled with monitoring and dose tailoring. Watch for less pain relief or withdrawal-type symptoms (sweating, chills, body aches, runny nose, restlessness), and report them. Your team may adjust and individualize your codeine dose and monitor you more closely while you take both. If… 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 Mobocertinib 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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