Acetaminophen And Codeine and Voriconazole: 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
Voriconazole
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 pill contains codeine, and voriconazole is an antifungal medicine. Voriconazole slows down one of the liver pathways (called CYP3A4) that helps clear codeine from your body. When that pathway is blocked, more codeine (and the morphine your body makes from it) can build up.
That means the codeine can hit harder or last longer, which could cause too much sleepiness or slowed, shallow breathing. This matters most if the antifungal is added after you have been on a steady codeine dose. The good news: your care team can manage this by watching you closely and adjusting your codeine dose if needed. Please talk with your pharmacist or doctor before changing anything.
Effect: Voriconazole (strong CYP3A4 inhibitor) inhibits CYP3A4-mediated codeine metabolism, increasing codeine and its active metabolite morphine exposure. This is a PD-relevant increase in opioid effect (codeine is a prodrug, but the affected pathway here is 3A4-mediated clearance, not 2D6 activation, so inhibition raises parent and active-metabolite levels).
- Direction: increased opioid exposure and effect
- Risk: respiratory depression, sedation; greatest when inhibitor added to a stable codeine regimen
- Evidence: theoretical; severity: major; onset unspecified
- Management: monitor for sedation/respiratory depression; consider codeine dose reduction until stable effects seen. On voriconazole discontinuation, watch for withdrawal and consider dose increase.
What happens
Increased codeine and morphine exposure
Interaction Deep Dive
When codeine is taken together with CYP3A4 inhibitors, elevated levels of both codeine and morphine have been observed. This may intensify or extend adverse effects and carries the risk of respiratory depression that can be fatal, a hazard that is especially pronounced when an inhibitor is introduced after the patient has already reached a stable codeine dose. Should combined use be necessary, watch patients carefully for sedation and respiratory depression, and weigh lowering the codeine dose until the drug's effects have stabilized. Conversely, when a CYP3A4 inhibitor is being withdrawn, observe patients for indications of opioid withdrawal and consider raising the codeine dose until stable drug effects are seen12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated codeine metabolism
How to manage this interaction
Keep taking both exactly as prescribed unless your care team tells you otherwise. Because voriconazole can raise codeine levels, your team may:
- Watch you more closely for heavy drowsiness or slow, shallow breathing, especially in the first days after adding the antifungal.
- Adjust and individualize your codeine dose, sometimes lowering it until your response is steady.
- Watch for opioid withdrawal signs and possibly raise the codeine dose back up if voriconazole is stopped.
Call your pharmacist or prescriber right away if you feel unusually sleepy, confused, or notice your breathing slowing down. These are things the team can manage by tailoring the dose and monitoring you.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Voriconazole together?
Voriconazole can raise codeine and morphine levels, increasing sedation and the risk of slowed breathing, so your care team may lower your codeine dose and monitor you closely. Do not change either medicine on your own; contact your pharmacist or doctor with any excess drowsiness or breathing changes. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Voriconazole 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 Voriconazole interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. Because voriconazole can raise codeine levels, your team may: Watch you more closely for heavy drowsiness or slow, shallow breathing, especially in the first days after adding the antifungal. Adjust and individualize your codeine dose, sometimes lowering it until your response is steady. Watch for opioid withdrawal s… 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 Voriconazole 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 Voriconazole
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist