Efavirenz 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
Efavirenz
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, which your body has to turn into its active, pain-relieving form (partly with an enzyme called CYP3A4). Efavirenz speeds that enzyme up. Because of this, codeine can get cleared faster before it does its job, so you may get less pain relief than expected.
If you have been taking codeine for a while and depend on it, the faster clearance could even bring on withdrawal-type feelings like restlessness, sweating, or achiness. The good news is this is manageable. Keep taking both as prescribed and let your pharmacist or doctor know if your pain isn't controlled, so they can adjust your plan.
Effect: Efavirenz (CYP3A4 inducer) increases codeine metabolism, shunting more toward norcodeine and reducing available substrate for CYP2D6 conversion to morphine. Net result: reduced codeine/morphine exposure, decreased analgesia, and possible opioid withdrawal in physically dependent patients.
- Direction: reduced active opioid effect (codeine is a prodrug requiring bioactivation)
- Evidence: theoretical; magnitude unspecified
- Onset: unspecified
Management: If co-prescribed, monitor for reduced efficacy and withdrawal signs; codeine dose may be increased and individualized. If efavirenz is later discontinued, anticipate the reverse (consider dose reduction, monitor for sedation/respiratory depression).
What happens
Reduced codeine and morphine exposure, reduced opioid efficacy and precipitation of opioid withdrawal
Interaction Deep Dive
Concomitant use of codeine with CYP3A4 inducers may result in reduced codeine levels, greater norcodeine levels, and less metabolism via CYP2D6 with resultant lower morphine levels, resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If concomitant use is needed, closely monitor patients for decreased efficacy or signs of opioid withdrawal syndrome, and consider increasing the dose of codeine as necessary. If a CYP3A4 inducer is being discontinued, consider codeine dose reduction and closely monitor patients 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. This interaction is manageable with monitoring and tailoring.
- Watch for poor pain control or withdrawal-type symptoms (restlessness, sweating, chills, aches, stomach upset) and report them.
- Your team may monitor you more closely and adjust the codeine dose to fit your response.
- Important: if efavirenz is ever stopped, your codeine dose may need lowering, since the previously reduced effect can rebound. Do not change doses on your own.
Bring any concerns about pain or side effects to your pharmacist or prescriber.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Efavirenz and Acetaminophen And Codeine together?
Efavirenz can speed up how your body breaks down codeine, so your pain medicine may work less well or cause withdrawal feelings; keep taking both as prescribed and tell your care team if your pain isn't controlled so they can adjust the dose. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Efavirenz 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 Efavirenz and Acetaminophen And Codeine interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This interaction is manageable with monitoring and tailoring. Watch for poor pain control or withdrawal-type symptoms (restlessness, sweating, chills, aches, stomach upset) and report them. Your team may monitor you more closely and adjust the codeine dose to fit your response. Important: if efavirenz is ever stopp… 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 Efavirenz 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 Efavirenz
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