Acetaminophen And Codeine and Darunavir: 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
Darunavir
No brand names on record
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. Codeine is a pain medicine, and darunavir is an HIV medicine. Codeine is broken down by two liver pathways in your body. Darunavir can slow those pathways down, so more codeine (and the morphine your body makes from it) can build up. That could mean stronger or longer-lasting effects like heavy drowsiness, and in serious cases, dangerously slow breathing.
This concern is based mostly on how these drugs work in theory, not lots of real-world reports. Please don't stop either medicine on your own. Talk with your pharmacist or doctor. They can adjust your dose and watch you more closely so you stay safe and comfortable.
Effect: Increased codeine and morphine exposure via darunavir inhibition of CYP3A4 and CYP2D6.
Mechanism/direction: Codeine is metabolized by CYP3A4 (to norcodeine) and CYP2D6 (to active morphine). Darunavir inhibits both, raising parent and active metabolite exposure and enhancing opioid effect.
- Risk: Enhanced/prolonged sedation and potentially fatal respiratory depression, especially when the inhibitor is added to a stable codeine dose.
- Evidence/onset: Theoretical; onset unspecified.
- Management: If coadministered, monitor for respiratory depression and sedation; consider codeine dose reduction. If darunavir is stopped, monitor for withdrawal and reassess codeine dose.
What happens
Increased codeine and morphine exposure
Interaction Deep Dive
Concomitant use of codeine with CYP3A4 inhibitors, such as darunavir, may result in increased codeine and morphine exposure, 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. Coadministration of darunavir (CYP2D6 inhibitor) with codeine (CYP2D6 substrate) may increase or prolong their therapeutic effect and can be associated with adverse events. Careful monitoring of therapeutic effects and adverse reactions associated with CYP3A4-metabolized narcotic analgesics (including potentially fatal respiratory depression) is recommended with coadministration 34.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of codeine; inhibition of CYP2D6 substrate metabolism of codeine
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. This combination can be used with the right precautions.
- Your team may lower your codeine dose and individualize it while watching how you respond.
- Expect closer monitoring for heavy drowsiness or slow, shallow breathing, especially soon after darunavir is started.
- If darunavir is later stopped, tell your team, since your codeine dose may need to be revisited to avoid withdrawal.
Call for help right away if you notice extreme sleepiness, confusion, or slowed breathing. Raise any concerns with your pharmacist or prescriber.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Darunavir together?
Darunavir can raise codeine and morphine levels, increasing the risk of oversedation and dangerously slow breathing. Don't change anything yourself; your care team can adjust the codeine dose and monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Darunavir 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 Darunavir interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This combination can be used with the right precautions. Your team may lower your codeine dose and individualize it while watching how you respond. Expect closer monitoring for heavy drowsiness or slow, shallow breathing, especially soon after darunavir is started. If darunavir is later stopped, tell your team, sin… 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 Darunavir 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 (4)
- 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
- Product Information: PREZCOBIX® PED oral tablets for suspension, darunavir cobicistat oral tablets for suspension. Janssen Products, LP (per FDA), Horsham, PA, 2026. DailyMed
- Product Information: PREZCOBIX® oral tablets, darunavir cobicistat oral tablets. Janssen Products, LP (per FDA), Horsham, PA, 2026. DailyMed
Keep reading about Acetaminophen And Codeine
Keep reading about Darunavir
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