Acetaminophen And Codeine and Magnesium Oxybate: 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
Magnesium Oxybate
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.
These two medicines both slow down your brain and body. The codeine in your pain medicine is an opioid, and Xywav (magnesium oxybate) is a strong sleep medicine. Taken together, they can add up and slow your breathing too much. That can lead to very deep sleepiness, low blood pressure, fainting, or in rare cases, breathing that stops.
This warning is based on how these drugs work rather than lots of real-world reports, but it is taken seriously because the risk is severe. Please don't stop either medicine on your own. Talk with your pharmacist or doctor so they can adjust things safely and keep you protected.
Additive CNS and respiratory depression from combining an opioid-containing product (acetaminophen/codeine) with an oxybate (Xywav, magnesium oxybate and mixed oxybate salts).
- Mechanism: pharmacodynamic additive CNS depression; no prodrug consideration alters direction here.
- Direction: increased sedation, respiratory depression, hypotension, obtundation, syncope, potentially fatal.
- Evidence: theoretical; severity major; onset unspecified.
- Management: combination not recommended. If required, consider dose reduction or discontinuation of one or more agents. For short-term/perioperative opioid use, consider interrupting oxybate. Monitor mental status and respiration; strongly consider prescribing naloxone.
What happens
An increased risk of CNS depression and clinically significant respiratory depression, obtundation, hypotension, profound sedation, syncope, and death
Interaction Deep Dive
Taking sodium oxybate or mixed oxybate salts together with other CNS depressants raises the likelihood of cumulative CNS depression along with clinically meaningful respiratory depression, obtundation, hypotension, deep sedation, syncope, and death. Nonetheless, when combining these CNS depressants with an oxybate cannot be avoided, clinicians should weigh reducing the dose of or stopping one or more of the CNS depressants (oxybates included). Furthermore, should short-term opioid administration be needed (for instance, post- or perioperatively), pausing oxybate therapy should be weighed123. When concurrent use is unavoidable, watch for alterations in mental status and respiratory depression, proceed with caution, and give strong consideration to prescribing naloxone for the emergency management of opioid overdose4.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Keep taking both exactly as prescribed unless your care team tells you otherwise, but raise this combination with them promptly.
- Your team may lower the dose of one medicine or pause one of them, since using both is generally not recommended.
- If you need the opioid only briefly (like after surgery), your team may temporarily interrupt the oxybate.
- They may monitor you more closely for heavy sedation or slowed breathing.
- Ask whether naloxone (a rescue medicine for opioid overdose) is right for you to keep on hand.
Get emergency help for very slow breathing, extreme drowsiness, fainting, or trouble waking up.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Magnesium Oxybate together?
Combining codeine with Xywav can dangerously add up to slow your breathing and heart, so this pairing is generally avoided. Do not stop either drug on your own; ask your pharmacist or doctor to manage it and consider having naloxone available. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Magnesium Oxybate 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 Magnesium Oxybate interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise, but raise this combination with them promptly. Your team may lower the dose of one medicine or pause one of them, since using both is generally not recommended. If you need the opioid only briefly (like after surgery), your team may temporarily interrupt the oxybate. They may monitor you more closely for heavy sedati… 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 Magnesium Oxybate 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 (4)
- Product Information: XYWAV(R) oral solution, calcium, magnesium, potassium, sodium oxybates oral solution. Jazz Pharmaceuticals Inc (per manufacturer), Palo Alto, CA, 2023. DailyMed
- Product Information: XYREM(R) oral solution, sodium oxybate oral solution. Jazz Pharmaceuticals Inc (per manufacturer), Palo Alto, CA, 2023. DailyMed
- Product Information: LUMRYZ(TM) oral extended-release suspension, sodium oxybate extended-release suspension. Avadel CNS Phamaceuticals LLC (per FDA), Chesterfield, MO, 2024. DailyMed
- Product Information: SUBUTEX(R) sublingual tablets, buprenorphine sublingual tablets. Indivior Inc (per FDA), North Chesterfield, VA, 2021. DailyMed
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