Voxelotor 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
Voxelotor
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 your body has to break down. Voxelotor (Oxbryta) can slow one of the enzymes that handles codeine, so more of it (and its active form, morphine) can build up in your body. That could make the codeine side effects stronger, like heavy drowsiness or very slow, shallow breathing.
This is based on how these drugs are expected to behave, not on lots of real-world reports, but breathing problems are serious, so it's worth taking seriously. Please don't stop or change either medicine on your own. Talk with your pharmacist or doctor. They can adjust your dose and watch you more closely so you stay safe and comfortable.
Effect: Voxelotor inhibits CYP3A4, reducing codeine clearance and increasing codeine and active metabolite (morphine) exposure. Note codeine is a prodrug, but morphine formation occurs mainly via CYP2D6; CYP3A4 inhibition raises parent codeine and overall opioid exposure, increasing risk of sedation and respiratory depression.
- Direction: increased opioid effect
- Onset: unspecified
- Evidence: theoretical
- Severity: major
Management: Monitor for respiratory depression and sedation, especially when voxelotor is added to stable codeine therapy. Consider codeine dose reduction until stable effects are seen. If voxelotor is discontinued, monitor for opioid withdrawal and consider increasing codeine dose accordingly. Acetaminophen component is unaffected.
What happens
Increased codeine and morphine exposure
Interaction Deep Dive
Taking codeine together with CYP3A4 inhibitors has led to elevated levels of both codeine and morphine, which may intensify or extend adverse reactions and carries the risk of respiratory depression that can be fatal, especially in cases where an inhibitor is introduced once a stable codeine dose has already been reached. When combined use cannot be avoided, patients should be watched closely for sedation and respiratory depression, and reducing the codeine dose should be considered until drug effects have stabilized. Conversely, when a CYP3A4 inhibitor is being withdrawn, watch for indications of opioid withdrawal and consider raising the codeine dose until stable drug effects are seen12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated codeine metabolism
How to manage this interaction
The good news: your care team can manage this by tailoring your dose and keeping a closer eye on you.
- Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Your team may reduce your codeine dose for a while and watch for signs of too much opioid, like unusual drowsiness or slow, shallow breathing.
- Tell someone right away if you feel very sleepy, confused, or hard to wake.
- If voxelotor is ever stopped, your codeine dose may need to be increased again, so watch for withdrawal symptoms and report them.
Bring both medicines up with your pharmacist or doctor so they can individualize your plan.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Voxelotor and Acetaminophen And Codeine together?
Voxelotor can raise codeine levels and increase the risk of heavy sedation and slow breathing. Keep taking both as prescribed, but ask your pharmacist or doctor to adjust the dose and monitor you more closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Voxelotor 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 Voxelotor and Acetaminophen And Codeine interaction managed?
The good news: your care team can manage this by tailoring your dose and keeping a closer eye on you. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Your team may reduce your codeine dose for a while and watch for signs of too much opioid, like unusual drowsiness or slow, shallow breathing. Tell someone right away if you feel very sleepy, confused, or… 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 Voxelotor 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)
- 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 Voxelotor
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