Acetaminophen And Codeine and Atazanavir: 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
Atazanavir
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, plus acetaminophen (Tylenol). Atazanavir (Reyataz), an HIV medicine, can slow down one of the liver enzymes that handles codeine. When codeine builds up, more of it turns into morphine in your body. That can make you more sleepy or slow your breathing more than expected.
This is based mostly on how these drugs work in theory, not lots of real cases, but breathing problems are serious enough to take seriously. Please don't stop either medicine on your own. Your care team can manage this safely by adjusting your codeine dose and watching how you respond. Call your doctor right away if you feel very drowsy or your breathing feels slow.
Effect: Atazanavir, a potent CYP3A4 inhibitor, may reduce codeine metabolism, increasing exposure to codeine and its active metabolite morphine (via O-demethylation). Codeine is a prodrug, so higher parent levels can translate to greater opioid effect.
- Direction: increased opioid effect, risk of sedation and respiratory depression.
- Onset: unspecified; risk highest when inhibitor added to a stable codeine dose.
- Evidence: theoretical.
- Management: monitor for respiratory depression and sedation; consider codeine dose reduction until stable effects observed. On atazanavir discontinuation, monitor for opioid withdrawal and consider dose increase.
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
The goal is to keep you comfortable and safe while treating both conditions.
- Keep taking both medicines as prescribed unless your care team tells you otherwise.
- Your codeine dose may need to be adjusted and individualized by your care team, and they may monitor you more closely for excess drowsiness or slowed breathing.
- If the HIV medicine (atazanavir) is ever stopped, tell your team, since your codeine dose may need to be raised again and they will watch for signs of withdrawal.
- Contact your pharmacist or prescriber about any unusual sleepiness, confusion, or slow or shallow breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Atazanavir together?
Atazanavir can raise codeine and morphine levels, increasing sedation and breathing risks, so your care team may lower your codeine dose and watch you more closely. Keep taking both as prescribed and report any heavy drowsiness or slow breathing right away. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Atazanavir 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 Atazanavir interaction managed?
The goal is to keep you comfortable and safe while treating both conditions. Keep taking both medicines as prescribed unless your care team tells you otherwise. Your codeine dose may need to be adjusted and individualized by your care team, and they may monitor you more closely for excess drowsiness or slowed breathing. If the HIV medicine (atazanavir) is ever stopped, tell your team, since your c… 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 Atazanavir 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 Atazanavir
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.
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