Acetaminophen And Codeine and Ivosidenib: 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
Ivosidenib
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. Codeine is a "prodrug," meaning your body has to change it into morphine before it can relieve pain. Ivosidenib (Tibsovo) can speed up the liver enzyme that handles codeine, so your body makes less of the active pain-relieving form. That can mean your pain medicine works less well, and if your body is used to the codeine, you could feel withdrawal symptoms like sweating, chills, a runny nose, or feeling anxious.
Good news: this is a manageable situation. Keep taking both exactly as prescribed and let your care team know if your pain isn't controlled or you feel off. They can adjust your dose and watch you more closely.
Mechanism: Ivosidenib is a CYP3A4 inducer. Codeine is a prodrug requiring O-demethylation (CYP2D6) to morphine, its active metabolite. Increased CYP3A4 activity shunts codeine toward N-demethylation (norcodeine), reducing substrate available for CYP2D6 conversion and lowering morphine exposure.
- Direction: reduced codeine/morphine exposure, reduced analgesic efficacy; risk of withdrawal in physically dependent patients.
- Evidence: theoretical; magnitude/onset unspecified.
- Management: monitor for loss of efficacy or withdrawal; codeine dose may be increased and individualized. If ivosidenib is discontinued, anticipate rising opioid levels, consider dose reduction, and monitor for sedation/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 CYP2D6-mediated metabolism may diminish, producing lower morphine levels. This can lead to reduced effectiveness or trigger a withdrawal syndrome in patients who have become physically dependent. Should this combination be necessary, watch patients carefully for loss of efficacy or indications of opioid withdrawal syndrome, and consider raising the codeine dose when required. When a CYP3A4 inducer is being withdrawn, a reduction in the codeine dose should be considered, along with close observation for signs of sedation or respiratory depression12.
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. Because ivosidenib can lower the amount of active pain reliever your body makes from codeine, your care team will watch how well your pain is controlled.
- Tell your team if your pain relief drops off or you notice withdrawal signs (sweating, chills, runny nose, cramps, restlessness).
- Your codeine dose may be adjusted and individualized, and your team may monitor you more closely.
- If ivosidenib is ever stopped, mention it, because your codeine dose may need to be lowered to avoid too much sedation.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Ivosidenib together?
Ivosidenib can weaken codeine's pain relief and may trigger opioid withdrawal in dependent patients; keep taking both as prescribed and tell your care team if your pain returns or you feel withdrawal, so they can adjust and monitor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Ivosidenib 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 Ivosidenib interaction managed?
Keep taking both medications as prescribed unless your prescriber tells you otherwise. Because ivosidenib can lower the amount of active pain reliever your body makes from codeine, your care team will watch how well your pain is controlled. Tell your team if your pain relief drops off or you notice withdrawal signs (sweating, chills, runny nose, cramps, restlessness). Your codeine dose may be adju… 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 Ivosidenib 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 Ivosidenib
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist