Acetaminophen And Codeine and Tazemetostat: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jun 30, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Acetaminophen And Codeine
Tazemetostat
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. Tazemetostat (Tazverik) is a cancer medicine that can speed up how your body breaks down certain other drugs. Codeine is a bit unusual: your body has to turn it on to give pain relief. When tazemetostat speeds up that pathway, less codeine may be left working the way it should, so your pain medicine could feel weaker than expected.
The acetaminophen part isn't the main concern here. The good news is your care team can handle this. If your pain isn't well controlled, don't stop or change anything on your own. Just let your doctor or pharmacist know so they can adjust your plan.
Mechanism: Tazemetostat is a CYP3A inducer. It reduced midazolam AUC by 40% and Cmax by 21% in a clinical DDI study, indicating meaningful CYP3A induction.
Direction for this pair: Codeine undergoes CYP3A4-mediated N-demethylation (to norcodeine) alongside CYP2D6 activation to morphine. Increased CYP3A metabolism may shift or reduce active analgesic exposure, potentially reducing analgesic efficacy. Acetaminophen is not a significant CYP3A substrate.
- Evidence: probable; onset unspecified.
- Management: monitor for inadequate analgesia; opioid dose may need individualized adjustment by the care team; consider alternative analgesia if pain control is poor.
What happens
Reduced CYP3A substrate exposure and reduced efficacy of CYP3A substrate
Interaction Deep Dive
Taking tazemetostat alongside CYP3A substrates can lower the exposure of those substrates, which may diminish their effectiveness. When patients received tazemetostat 800 mg twice daily together with oral midazolam (a sensitive CYP3A substrate) in a drug interaction study, the AUC and Cmax of midazolam fell by 40% and 21%, respectively1.
Why it happens (mechanism)
Induction of CYP3A-substrate metabolism by tazemetostat
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. This combination can make the codeine pain relief work less well for some people.
- Watch how well your pain is controlled and let your prescriber or pharmacist know if it isn't.
- Your pain medicine dose may need to be adjusted and individualized by your care team.
- Your team may monitor you more closely or consider a different pain option if needed.
- Don't increase your acetaminophen-codeine on your own, as too much acetaminophen can harm the liver.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a drug interaction study, giving tazemetostat 800 mg twice daily together with oral midazolam (a sensitive CYP3A substrate) in patients reduced midazolam AUC by 40% and Cmax by 21% 1.
Common questions
Can I take Acetaminophen And Codeine and Tazemetostat together?
Tazemetostat can speed up how your body handles codeine, which may make pain relief weaker; if your pain isn't well controlled, tell your doctor or pharmacist so they can adjust your plan. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Tazemetostat 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 Tazemetostat interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This combination can make the codeine pain relief work less well for some people. Watch how well your pain is controlled and let your prescriber or pharmacist know if it isn't. Your pain medicine dose may need to be adjusted and individualized by your care team. Your team may monitor you more closely or consider a… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Acetaminophen And Codeine or Tazemetostat 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 (1)
- Product Information: TAZVERIK(R) oral tablets, tazemetostat oral tablets. Epizyme Inc (per FDA), Cambridge, MA, 2024. DailyMed
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