Acetaminophen And Codeine and Lesinurad: 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
Lesinurad
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.
Here's what's going on. Codeine is a medicine that your body has to turn on to relieve pain. It gets changed into morphine, which does the actual pain relief. Lesinurad can speed up one of the enzymes (called CYP3A4) that handles codeine. When that enzyme works faster, less of your codeine gets turned into morphine, so the pain relief may be weaker.
If you've been taking codeine for a while, this can also make you feel withdrawal symptoms, like feeling shaky, sweaty, or achy. This is based on theory more than real-world reports, so please don't change anything on your own. Your care team can adjust and watch this closely.
Mechanism: Lesinurad is a CYP3A4 inducer. Codeine is a prodrug requiring metabolism (partly via CYP3A4 to norcodeine, and via CYP2D6 to morphine, the active analgesic).
- Direction: Induction shunts codeine toward norcodeine and reduces available substrate for CYP2D6-mediated morphine formation, lowering morphine exposure and analgesic efficacy.
- Risk: Reduced opioid effect; possible withdrawal in physically dependent patients.
- Evidence: Theoretical; onset unspecified.
- Management: Monitor for reduced efficacy or withdrawal; codeine dose may be increased and individualized. On lesinurad discontinuation, anticipate rising opioid effect, 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 metabolism through CYP2D6 may diminish, lowering morphine levels. This can reduce effectiveness or trigger a withdrawal syndrome in patients who have become physically dependent. Should combined use be necessary, monitor patients carefully for reduced efficacy or indications of opioid withdrawal syndrome, and consider raising the codeine dose when required. When a CYP3A4 inducer is being withdrawn, consider lowering the codeine dose and watch patients closely 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 medicines as prescribed unless your care team tells you otherwise. This interaction can be managed.
- Watch for signs your pain control is weaker than usual, or symptoms of opioid withdrawal (restlessness, sweating, chills, body aches, stomach upset).
- Report these to your pharmacist or prescriber. Your codeine dose may need to be adjusted and individualized by your care team, and they may monitor you more closely.
- If lesinurad is ever stopped, tell your team, because your codeine effect could increase. They may lower your dose and watch for extra drowsiness or slowed breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Lesinurad together?
Lesinurad may weaken codeine's pain relief and could trigger opioid withdrawal in dependent patients. Don't change anything yourself; report weaker pain control or withdrawal symptoms so your care team can adjust and monitor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Lesinurad 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 Lesinurad interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This interaction can be managed. Watch for signs your pain control is weaker than usual, or symptoms of opioid withdrawal (restlessness, sweating, chills, body aches, stomach upset). Report these to your pharmacist or prescriber. Your codeine dose may need to be adjusted and individualized by your care team, and th… 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 Lesinurad 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 Lesinurad
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