Avacopan 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
Avacopan
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. The other medicine, avacopan (Tavneos), can slow down the liver enzyme (called CYP3A4) that handles codeine. When codeine breaks down more slowly, more of it (and more morphine) can build up in your body.
That extra buildup can make you very drowsy or slow your breathing, which is the part we watch most carefully with opioids. The good news is your care team can manage this by watching you closely and adjusting your codeine dose if needed. Please don't stop or change either medicine on your own. Just check in with your pharmacist or doctor so they can keep you safe.
Effect: Avacopan (a CYP3A4 inhibitor) may reduce codeine clearance, increasing codeine and its active metabolite morphine exposure. Codeine is a prodrug, but this pathway (CYP3A4) governs N-demethylation/clearance rather than the O-demethylation (CYP2D6) that produces morphine, so reduced clearance still raises overall opioid exposure.
- Direction: increased opioid effect; risk of sedation and potentially fatal respiratory depression.
- Onset: unspecified. Evidence: theoretical.
- Management: monitor for respiratory depression and sedation; consider codeine dose reduction until stable effects are seen. If avacopan is discontinued, monitor for opioid withdrawal and consider increasing the codeine dose.
What happens
Increased codeine and morphine exposure
Interaction Deep Dive
Concomitant use of codeine with CYP3A4 inhibitors has resulted in increased codeine and morphine concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dose of codeine is achieved. If concomitant use is needed, closely monitor patients for respiratory depression and sedation, and consider dose reduction of codeine until stable drug effects have been observed. If a CYP3A4 inhibitor is being discontinued, monitor patients for signs of opioid withdrawal, and consider increasing dose of codeine until stable drug effects have been observed12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated codeine metabolism
How to manage this interaction
If you are prescribed both, the goal is safe, ongoing use, not stopping treatment.
- Keep taking both exactly as prescribed unless your care team tells you otherwise.
- Your team may watch you more closely for excessive drowsiness or slowed breathing, and the codeine dose may need to be adjusted and individualized by them.
- If avacopan is ever stopped, your team may watch for signs of opioid withdrawal and adjust the codeine dose again.
- Call your pharmacist or doctor right away if you notice unusual sleepiness, confusion, or trouble breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Avacopan and Acetaminophen And Codeine together?
Avacopan can slow how your body clears codeine, raising codeine and morphine levels and the risk of heavy sedation or slowed breathing. Keep taking both as prescribed and let your care team monitor you and fine-tune the codeine dose. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Avacopan 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 Avacopan and Acetaminophen And Codeine interaction managed?
If you are prescribed both, the goal is safe, ongoing use, not stopping treatment. Keep taking both exactly as prescribed unless your care team tells you otherwise. Your team may watch you more closely for excessive drowsiness or slowed breathing, and the codeine dose may need to be adjusted and individualized by them. If avacopan is ever stopped, your team may watch for signs of opioid withdrawal… 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 Avacopan 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 (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 Avacopan
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