Drug Interaction Report

Etravirine 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

Capital® & Codeine Codrix® Empracet® (#3, #4) Papa-deine® (#3, #4) Phenaphen® with Codeine (#2, #3, #4) Proval® #3 Tylenol with Codeine Tylenol® with Codeine (#3, #4)
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Etravirine

Intelence
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Updated Jul 1, 2026
LinkedIn
Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
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.

Of 81 documented Etravirine interactions, 70 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
At a glance + Prodrug involved Effects may be weaker Theoretical
The Bottom Line
Etravirine may weaken codeine's pain relief and could trigger withdrawal, so tell your care team if your pain isn't controlled; they can adjust the dose and monitor you.

Your pain medicine here contains codeine, which your body has to turn into its active pain-relieving form. Etravirine (Intelence) speeds up one of the liver enzymes that handles codeine, so less of it may get converted the way it needs to. That can mean less pain relief than expected. If your body is used to the codeine, you might even feel early withdrawal-type symptoms like restlessness, sweating, or an upset stomach.

The good news is this is manageable. Keep taking both medicines as prescribed, and let your care team know if your pain isn't controlled. They can adjust your dose and watch you closely.

Effect: Etravirine, a CYP3A4 inducer, may reduce codeine exposure. Codeine is a prodrug; induction shunts metabolism toward norcodeine and away from CYP2D6-mediated conversion to morphine (the active analgesic), lowering morphine levels and analgesic efficacy. In physically dependent patients this can precipitate opioid withdrawal.

  • Direction: reduced opioid effect (prodrug activation impaired).
  • Evidence: theoretical; magnitude not quantified.
  • Onset: unspecified.
  • Management: monitor for reduced efficacy and withdrawal; codeine dose may be increased and individualized. If etravirine is stopped, consider codeine dose reduction and monitor for sedation/respiratory depression.
Onset
unspecified
Evidence
theoretical
Severity
Major

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 exactly as prescribed unless your prescriber tells you otherwise. Because etravirine can lower how well codeine works, your care team may:

  • Watch you more closely for poor pain control or signs of withdrawal (restlessness, sweating, chills, stomach upset).
  • Adjust and individualize your codeine dose if needed.
  • Be extra careful if etravirine is later stopped, since your codeine may then feel stronger; they may lower the dose and watch for excess sedation.

Tell your pharmacist or prescriber if your pain isn't controlled or you feel unwell.

Management is individual — confirm any change with your pharmacist or prescriber.

Common questions

Can I take Etravirine and Acetaminophen And Codeine together?

Etravirine may weaken codeine's pain relief and could trigger withdrawal, so tell your care team if your pain isn't controlled; they can adjust the dose and monitor you. Always confirm with your pharmacist or prescriber before making any change.

How serious is the Etravirine 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 Etravirine and Acetaminophen And Codeine interaction managed?

Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Because etravirine can lower how well codeine works, your care team may: Watch you more closely for poor pain control or signs of withdrawal (restlessness, sweating, chills, stomach upset). Adjust and individualize your codeine dose if needed. Be extra careful if etravirine is later stopped, since your cod… 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 Etravirine 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)

  1. Product Information: Codeine sulfate oral solution, codeine sulfate oral solution. Hikma Pharmaceuticals USA Inc(per FDA), Berkeley Heights, NJ, 2023. DailyMed
  2. 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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Beyond drug–drug

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.