Fosamprenavir and Acetaminophen And Codeine: 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
Fosamprenavir
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.
What's going on: Your pain medicine (Tylenol with codeine) relies on your body to break the codeine down. Fosamprenavir (Lexiva), an HIV medicine, slows down one of the liver enzymes (called CYP3A4) that handles codeine. When that pathway is slowed, more codeine and morphine can build up in your body.
That means the opioid effects could feel stronger or last longer, including extra drowsiness and, in serious cases, dangerously slow breathing. This is expected based on how the drugs work, though it hasn't been heavily studied. The good news is your care team can manage this safely by adjusting your dose and watching you closely. Never stop or change either medicine on your own. Just check in with your pharmacist or doctor.
Mechanism: Fosamprenavir inhibits CYP3A4, a pathway involved in codeine metabolism. Reduced CYP3A4 clearance increases codeine and its active metabolite morphine exposure (opioid effect is increased, not reduced).
- Direction: Higher codeine/morphine concentrations, heightened/prolonged opioid effects.
- Risk: Excessive sedation and potentially fatal respiratory depression, especially when the inhibitor is added to a stable codeine regimen.
- Evidence: Theoretical; severity rated major. Onset unspecified.
- Management: Monitor for respiratory depression and sedation; consider codeine dose reduction until stable effects seen. If fosamprenavir is discontinued, 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
You can usually take both, with the right precautions. Keep taking both medicines exactly as prescribed unless your care team tells you otherwise.
- Your team may lower your codeine dose and individualize it until they see how you respond.
- They may monitor you more closely for excessive drowsiness or slowed, shallow breathing, especially right after starting fosamprenavir.
- If fosamprenavir is later stopped, they may watch for withdrawal signs and adjust your codeine dose back up.
Tell your pharmacist or doctor right away if you feel unusually sleepy, confused, or notice slow or difficult breathing. Ask them to review the pair before any changes.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Fosamprenavir and Acetaminophen And Codeine together?
Fosamprenavir can slow codeine breakdown and raise codeine/morphine levels, increasing the risk of heavy sedation and dangerously slow breathing; keep taking both as prescribed and have your care team adjust the codeine dose and monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Fosamprenavir 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 Fosamprenavir and Acetaminophen And Codeine interaction managed?
You can usually take both, with the right precautions. Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. Your team may lower your codeine dose and individualize it until they see how you respond. They may monitor you more closely for excessive drowsiness or slowed, shallow breathing, especially right after starting fosamprenavir. If fosamprenavir is later… 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 Fosamprenavir 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 Fosamprenavir
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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