Amprenavir 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
Amprenavir
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.
Your pain medicine contains codeine, and amprenavir (an HIV medicine) can slow down one of the liver pathways that handles codeine. That can let more codeine, and the morphine your body makes from it, build up. The main worry is too much sedation and slowed breathing, which in rare cases can be dangerous, especially soon after the two are combined.
This warning is based on how these drugs work rather than lots of real-world reports, so please do not panic. The important thing is that your care team can manage this well by watching how sleepy you feel and adjusting your codeine dose if needed. Let them know if you feel unusually drowsy or your breathing feels slow.
Effect: Amprenavir inhibits CYP3A4, reducing codeine clearance and increasing exposure to codeine and its active metabolite morphine. This raises the risk of sedation and potentially fatal respiratory depression.
- Direction: increased opioid effect (codeine is bioactivated mainly via CYP2D6 to morphine; CYP3A4 is a competing/clearance pathway, so its inhibition raises overall opioid exposure).
- Evidence: theoretical; magnitude not quantified.
- Onset: unspecified; highest risk when inhibitor is added to a stable codeine dose.
- Management: monitor for respiratory depression and sedation; consider codeine dose reduction until stable effects are seen. If amprenavir is stopped, monitor for opioid withdrawal and consider increasing 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
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. This is something your team can handle with a few simple steps.
- Your codeine dose may need to be adjusted and individualized by your care team, and they may monitor you more closely for drowsiness and slow breathing, especially when starting or after any change.
- If the HIV medicine is ever stopped, your team may watch for withdrawal signs and adjust codeine as needed.
- Call your pharmacist or prescriber right away if you feel very sleepy, confused, or your breathing seems slow or shallow.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Amprenavir and Acetaminophen And Codeine together?
Amprenavir can raise codeine and morphine levels, increasing the risk of heavy sedation and slowed breathing, so keep taking both as prescribed but tell your care team so they can adjust the codeine dose and watch you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amprenavir 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 Amprenavir and Acetaminophen And Codeine interaction managed?
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. This is something your team can handle with a few simple steps. Your codeine dose may need to be adjusted and individualized by your care team, and they may monitor you more closely for drowsiness and slow breathing, especially when starting or after any change. If the HIV medicine is ever stopped, your tea… 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 Amprenavir 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 Amprenavir
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