Lenacapavir 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
Lenacapavir
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. Lenacapavir (Sunlenca or Yeztugo) is a long-acting HIV medicine that slows down a liver enzyme called CYP3A. That enzyme helps your body break down the codeine part of your acetaminophen-codeine pain medicine. When it works slower, more of the opioid can build up in your body.
That means you could feel stronger opioid effects, like extra drowsiness, or, in serious cases, slowed breathing. Because lenacapavir stays in your body a long time, this can matter for many months after your last dose. Please don't stop either medicine on your own. Your care team can manage this by adjusting your dose and watching you more closely, so let your pharmacist or doctor know you take both.
Mechanism: Lenacapavir is a moderate CYP3A inhibitor. Codeine and its metabolites undergo CYP3A metabolism, so inhibition may increase opioid exposure (AUC/Cmax) and the risk of opioid-mediated adverse effects.
- Direction: Increased opioid exposure and effect (enhanced sedation, respiratory depression risk).
- Evidence: Theoretical; based on lenacapavir's CYP3A inhibition profile.
- Onset: Unspecified; note lenacapavir's prolonged half-life means the effect can persist up to ~9 months after the last dose.
- Management: Monitor for therapeutic effect and opioid toxicity, especially sedation and respiratory depression. Dose may need individualization by the care team.
What happens
Increased CYP3A substrate exposure and an increased risk of CYP3A substrate-mediated adverse reactions
Interaction Deep Dive
When lenacapavir, which acts as a moderate inhibitor of CYP3A, is given alongside medications that undergo CYP3A metabolism, including narcotic analgesics, the exposure to those narcotic analgesics may rise. For drugs that are chiefly metabolized by CYP3A and are begun within 9 months of the final lenacapavir dose, lenacapavir can elevate their exposure, and this may raise the likelihood of adverse reactions as well12. Consequently, when narcotic analgesics metabolized by CYP3A are used together with lenacapavir, close observation of both the intended therapeutic effects and any adverse reactions, including respiratory depression that could be fatal, is advised1.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism by lenacapavir
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. This interaction can usually be managed.
- Your team may monitor you more closely for opioid side effects such as excess drowsiness, confusion, or slowed breathing.
- Your opioid dose may need to be adjusted and individualized by your prescriber.
- Remember this can matter for months after your last lenacapavir dose, so mention it any time a new pain medicine is started.
Get help right away if you notice very slow or shallow breathing, extreme sleepiness, or trouble waking up. Talk with your pharmacist or doctor about the safest plan.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Lenacapavir and Acetaminophen And Codeine together?
Lenacapavir can raise the levels of the codeine in your pain medicine, increasing opioid side effects like heavy drowsiness and slowed breathing, and this can last for months after the last lenacapavir dose. Keep taking both as prescribed and let your care team monitor and adjust your dose. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lenacapavir 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 Lenacapavir and Acetaminophen And Codeine interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This interaction can usually be managed. Your team may monitor you more closely for opioid side effects such as excess drowsiness, confusion, or slowed breathing. Your opioid dose may need to be adjusted and individualized by your prescriber. Remember this can matter for months after your last lenacapavir dose, so… 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 Lenacapavir 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: SUNLENCA(R) oral tablets, subcutaneous injection, lenacapavir oral tablets, subcutaneous injection. Gilead Sciences Inc (per FDA), Foster City, CA, 2024. DailyMed
- Product Information: YEZTUGO(R) oral tablets, subcutaneous injection, lenacapavir oral tablets, subcutaneous injection. Gilead Sciences Inc (per manufacturer), Foster City, CA, 2025. DailyMed
Keep reading about Acetaminophen And Codeine
Keep reading about Lenacapavir
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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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