Acetaminophen And Codeine and Posaconazole: 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
Posaconazole
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.
Here's what's going on. Posaconazole (Noxafil) is an antifungal that slows down a liver enzyme called CYP3A4. That enzyme helps your body clear codeine. When posaconazole slows it down, more codeine (and the morphine your body makes from it) can build up in your blood.
That means the pain medicine's effects, including drowsiness and slowed breathing, could become stronger or last longer. This matters most if the antifungal is started after you're already settled on your codeine dose. Please don't change anything on your own. Your care team can manage this safely by adjusting your dose and watching you a bit more closely, so let your pharmacist or doctor know you take both.
Mechanism: Posaconazole is a potent CYP3A4 inhibitor. Codeine is metabolized via CYP3A4 (to norcodeine) and CYP2D6 (to morphine). Inhibiting CYP3A4 shifts metabolism, increasing exposure to codeine and its active metabolite morphine.
- Direction: Increased opioid effect (opioid, not prodrug-attenuated here).
- Risk: Enhanced/prolonged opioid adverse effects, including sedation and potentially fatal respiratory depression, especially when the inhibitor is added to a stable codeine regimen.
- Evidence: Theoretical; onset unspecified.
- Management: If co-use is needed, monitor for sedation and respiratory depression and consider codeine dose reduction. On posaconazole discontinuation, monitor for withdrawal and consider increasing the codeine dose to stable effect.
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, an effect that may intensify or extend adverse reactions and carries the risk of potentially fatal respiratory depression, especially in cases where the inhibitor is introduced after the patient has reached a stable codeine dose. When these agents must be used together, monitor patients carefully for sedation and respiratory depression, and weigh reducing the codeine dose until steady drug effects are seen. Conversely, when a CYP3A4 inhibitor is being withdrawn, watch for indications of opioid withdrawal and consider raising the codeine dose until stable drug effects are established12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated codeine metabolism
How to manage this interaction
Keep taking both as prescribed unless your care team tells you otherwise. This combination can be managed.
- Your team may lower your codeine dose while you are on posaconazole and adjust it once your response is stable.
- They may monitor you more closely for excess drowsiness, confusion, or slow or shallow breathing.
- If posaconazole is later stopped, your codeine dose may need to be increased again, so watch for signs of opioid withdrawal.
Get help right away for very slow breathing, extreme sleepiness, or trouble waking. Tell your pharmacist or prescriber that you take both so they can tailor your plan.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Posaconazole together?
Posaconazole can raise codeine and morphine levels, increasing sedation and the risk of dangerous slowed breathing. Keep taking both as prescribed and ask your pharmacist or doctor about dose adjustments and closer monitoring. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Posaconazole 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 Posaconazole interaction managed?
Keep taking both as prescribed unless your care team tells you otherwise. This combination can be managed. Your team may lower your codeine dose while you are on posaconazole and adjust it once your response is stable. They may monitor you more closely for excess drowsiness, confusion, or slow or shallow breathing. If posaconazole is later stopped, your codeine dose may need to be increased again,… 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 Posaconazole 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 Posaconazole
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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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