Acetaminophen And Codeine and Nevirapine: 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
Nevirapine
Acetaminophen And Codeine
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.
Nevirapine can make your codeine work less well. Codeine only relieves pain after your body turns it into morphine. Nevirapine speeds up the liver enzymes that break codeine down, so less of it becomes the active painkiller. That can mean your pain isn't controlled as well as expected.
If you've been taking codeine for a while and your body is used to it, this drop could even bring on withdrawal-type feelings like sweating, chills, or an upset stomach. This is manageable. Don't change anything on your own. Talk with your pharmacist or doctor, who can adjust your dose and keep an eye on how well your pain is controlled.
Effect: Nevirapine, a CYP3A4 inducer, may reduce codeine efficacy via increased CYP3A4-mediated metabolism (shunting toward norcodeine), leaving less codeine for CYP2D6 conversion to morphine, the active analgesic. Net result: reduced morphine exposure, decreased analgesia, and possible withdrawal in physically dependent patients.
- Direction: reduced opioid effect (codeine is a prodrug; less active morphine formed)
- Evidence: theoretical; onset unspecified
- Management: monitor for inadequate analgesia and withdrawal signs; codeine dose may be increased and individualized as needed. If nevirapine is discontinued, anticipate rising morphine levels and consider reducing codeine while monitoring for sedation or respiratory depression.
What happens
Reduced codeine and morphine exposure, reduced opioid efficacy and precipitation of opioid withdrawal
Interaction Deep Dive
When codeine is taken together with CYP3A4 inducers, codeine concentrations may fall while norcodeine concentrations rise, and metabolism through CYP2D6 may be diminished, producing lower morphine levels. This can lead to reduced effectiveness or trigger a withdrawal syndrome in patients who have become physically dependent. Should combined use be required, monitor patients carefully for loss of efficacy or indications of opioid withdrawal syndrome, and raise the codeine dose when needed. When a CYP3A4 inducer is being stopped, consider lowering the codeine dose and watch patients closely for signs of respiratory depression or sedation12.
Why it happens (mechanism)
Induction of CYP3A4-mediated codeine metabolism
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise.
- Watch for signs your codeine isn't working as well, such as poorly controlled pain, or withdrawal symptoms like sweating, chills, aches, or a queasy stomach.
- Your codeine dose may need to be adjusted and individualized by your care team, and they may monitor you more closely while you take these together.
- If your nevirapine is ever stopped, tell your team, because your codeine may then become stronger and they may lower the dose and watch for excess drowsiness or slowed breathing.
Report any changes in pain control or new symptoms to your pharmacist or prescriber.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Nevirapine together?
Nevirapine can lower the amount of active pain relief you get from codeine, which may weaken pain control or trigger withdrawal if you're dependent. Keep taking both as prescribed and tell your pharmacist or doctor so they can adjust your dose and monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Nevirapine 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 Nevirapine interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. Watch for signs your codeine isn't working as well, such as poorly controlled pain, or withdrawal symptoms like sweating, chills, aches, or a queasy stomach. Your codeine dose may need to be adjusted and individualized by your care team, and they may monitor you more closely while you take these together. If your n… 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 Nevirapine 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 Nevirapine
Keep reading about Acetaminophen And Codeine
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major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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