Acetaminophen And Codeine and Apalutamide: 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
Apalutamide
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 is what is going on. Codeine is a "prodrug," which means your body has to convert it into the active pain reliever (morphine) before it can work. Apalutamide (Erleada) speeds up the liver enzymes that break codeine down, so more of it gets sent down the wrong path and less becomes morphine.
The likely result is that your codeine works less well for pain. If you have been taking codeine regularly, you could even feel early withdrawal symptoms like restlessness, sweating, or an upset stomach. The good news is your care team can manage this by watching how you respond and tailoring your dose. Please keep taking both as prescribed and talk with your pharmacist or doctor about pain control.
Mechanism: Apalutamide is a strong CYP3A4 inducer. Codeine is metabolized by CYP3A4 (to norcodeine) and CYP2D6 (to morphine, the active analgesic metabolite). Induction shifts codeine toward the CYP3A4 pathway, lowering morphine formation.
- Direction: Reduced codeine and morphine exposure, reduced analgesic efficacy, and possible opioid withdrawal in physically dependent patients.
- Evidence: Theoretical; magnitude not quantified.
- Onset: Unspecified (enzyme induction is typically gradual over days to weeks).
- Management: Monitor for reduced efficacy and withdrawal signs; the codeine dose may need to be increased and individualized. If apalutamide is later stopped, anticipate reduced clearance and monitor for sedation or respiratory depression, considering a codeine dose reduction.
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 medications as prescribed unless your prescriber tells you otherwise. This combination can be managed with monitoring and dose tailoring.
- Watch for less pain relief than usual and for early withdrawal signs (restlessness, sweating, chills, muscle aches, nausea) if you have been on codeine a while.
- Your care team may adjust and individualize your codeine dose and monitor you more closely while you are on apalutamide.
- If apalutamide is ever stopped, tell your team, since your codeine dose may need to be lowered to avoid excess sedation or slowed breathing.
- Report any changes to your pharmacist or prescriber rather than adjusting doses yourself.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Apalutamide together?
Apalutamide can make your codeine work less well and may trigger opioid withdrawal if you take it regularly; your care team can manage this by monitoring you and adjusting your codeine dose, so keep taking both as prescribed and report any drop in pain relief or withdrawal symptoms. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Apalutamide 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 Apalutamide interaction managed?
Keep taking both medications as prescribed unless your prescriber tells you otherwise. This combination can be managed with monitoring and dose tailoring. Watch for less pain relief than usual and for early withdrawal signs (restlessness, sweating, chills, muscle aches, nausea) if you have been on codeine a while. Your care team may adjust and individualize your codeine dose and monitor you more c… 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 Apalutamide 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 Apalutamide
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major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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