Acetaminophen And Codeine and Letermovir: 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
Letermovir
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. Your pain medicine contains codeine, which your body turns into morphine to relieve pain. Letermovir (Prevymis) can slow down one of the enzymes that handles codeine, so more of it may build up and turn into morphine. That can mean stronger opioid effects, like heavy drowsiness or slowed, shallow breathing.
This concern is based mostly on how these drugs work, not on lots of real-world cases, but breathing problems can be serious, so it's worth taking seriously. Please don't stop either medicine on your own. Talk with your pharmacist or doctor. They can watch you more closely and adjust your codeine dose if needed to keep you safe.
Mechanism: Letermovir is a moderate CYP3A4 inhibitor. Codeine undergoes CYP3A4-mediated N-demethylation; inhibition can shift metabolism and increase codeine and its active metabolite morphine exposure, raising opioid effect.
- Direction: Increased codeine/morphine concentrations, potentiated opioid effect.
- Risk: Excess sedation and potentially fatal respiratory depression, especially when the inhibitor is added to a stable codeine regimen.
- Evidence: Theoretical; onset unspecified.
- Management: Monitor closely for sedation and respiratory depression; consider codeine dose reduction until stable effects observed. On letermovir discontinuation, monitor for withdrawal and consider increasing codeine dose.
What happens
Increased codeine and morphine exposure
Interaction Deep Dive
When codeine is taken together with CYP3A4 inhibitors, elevated levels of both codeine and morphine have been observed. This can intensify or extend adverse effects and may lead to respiratory depression that is potentially fatal, especially if the inhibitor is introduced once a patient has already reached a stable codeine dose. Should combined use be required, monitor patients closely for sedation and respiratory depression, and weigh reducing the codeine dose until steady drug effects are seen. Conversely, when a CYP3A4 inhibitor is being withdrawn, watch patients for indications of opioid withdrawal, and consider raising the codeine dose until stable drug effects are confirmed12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated codeine metabolism
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. This combination can be managed with attention and tailoring.
- Your team may monitor you more closely for excessive drowsiness or slow, shallow breathing.
- Your codeine dose may need to be adjusted and individualized by your care team until your response is steady.
- If letermovir is later stopped, your team may watch for opioid withdrawal and may adjust codeine again.
- Get help right away for very slow breathing, hard-to-wake sleepiness, or confusion.
Raise any new sedation 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 Letermovir together?
Letermovir can raise codeine and morphine levels, increasing the risk of heavy sedation and dangerously slowed breathing. Keep taking both as prescribed, watch for excessive drowsiness or slow breathing, and let your care team adjust and monitor your codeine dose. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Letermovir 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 Letermovir interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This combination can be managed with attention and tailoring. Your team may monitor you more closely for excessive drowsiness or slow, shallow breathing. Your codeine dose may need to be adjusted and individualized by your care team until your response is steady. If letermovir is later stopped, your team may watch… 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 Letermovir 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
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