Acetaminophen And Codeine and Vonoprazan: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jun 30, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Acetaminophen And Codeine
Vonoprazan
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 your body turns into morphine to relieve pain. Vonoprazan (Voquezna), a stomach acid reducer, may slow down one of the liver pathways that handles codeine. That can let more codeine and morphine build up in your body, which could make you more drowsy or slow your breathing more than expected.
This concern is theoretical, meaning it is based on how the drugs work rather than lots of real-world reports. Still, opioids deserve care. The good news is your care team can manage this easily by watching how you respond and adjusting your codeine dose if needed. Let them know if you feel unusually sleepy or short of breath.
Effect: Vonoprazan may inhibit CYP3A4-mediated metabolism of codeine, increasing exposure to codeine and its active metabolite morphine (formed via CYP2D6). Increased opioid exposure raises the risk of sedation and potentially fatal respiratory depression.
- Direction: increased opioid effect (codeine is a prodrug, but the CYP3A4 pathway here is a clearance route, so inhibition raises parent and morphine levels).
- Onset: unspecified. Evidence: theoretical. Severity: major.
- Management: monitor for respiratory depression and sedation; consider codeine dose reduction until stable effects seen. If vonoprazan is stopped, monitor for opioid withdrawal and consider increasing codeine dose.
What happens
Increased codeine and morphine exposure
Interaction Deep Dive
Taking codeine together with CYP3A4 inhibitors has led to elevated levels of both codeine and morphine, potentially intensifying or extending adverse effects and possibly producing fatal respiratory depression. This risk is especially notable when an inhibitor is introduced after a patient has reached a stable codeine dose. When such combined use is required, monitor the patient closely for sedation and respiratory depression, and weigh reducing the codeine dose until stable drug effects are seen. Conversely, if a CYP3A4 inhibitor is being withdrawn, watch for signs of opioid withdrawal in the patient and consider raising the codeine dose until stable drug effects have been observed12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated codeine metabolism
How to manage this interaction
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. Because this combination can raise opioid levels, your team may:
- Watch you more closely for excess drowsiness or slowed breathing.
- Adjust your codeine dose, which may need to be individualized until your response is stable.
- Watch for signs of withdrawal and possibly adjust codeine if the vonoprazan is later stopped.
Call your pharmacist or prescriber right away if you notice unusual sleepiness, confusion, very slow or shallow breathing, or trouble waking up. Ask them before making any changes.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Vonoprazan together?
Vonoprazan may increase codeine and morphine levels, raising the risk of sedation and slowed breathing, so watch for drowsiness or breathing changes and let your care team adjust and monitor as needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Vonoprazan 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 Vonoprazan interaction managed?
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. Because this combination can raise opioid levels, your team may: Watch you more closely for excess drowsiness or slowed breathing. Adjust your codeine dose, which may need to be individualized until your response is stable. Watch for signs of withdrawal and possibly adjust codeine if the vonoprazan is later… 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 Vonoprazan 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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