Acetaminophen And Codeine and Sodium 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
Sodium 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 breathing, so taking them together can be dangerous. The codeine in your acetaminophen-codeine is an opioid pain reliever, and sodium oxybate (Xyrem, Xywav, or Lumryz) is a strong sleep medicine. Each one alone can make you very drowsy and slow your breathing. Put together, that effect adds up and can lead to extreme sleepiness, very low blood pressure, fainting, dangerously slow breathing, and in the worst cases, death.
This is a serious combination, but your care team can manage it. Please don't stop either medicine on your own. Talk with your doctor or pharmacist so they can decide the safest plan for you.
Additive CNS and respiratory depression. Combining sodium oxybate (Xyrem/Xywav/Lumryz) with acetaminophen-codeine (an opioid) produces pharmacodynamic additive depression of the CNS and respiratory drive.
- Direction/effect: increased risk of respiratory depression, obtundation, hypotension, profound sedation, syncope, and death.
- Mechanism: PD additive CNS depression (not a PK/enzyme interaction).
- Evidence: theoretical; severity major; onset unspecified.
- Management: combination not recommended. If required, reduce dose or discontinue one or more agents. For short-term/perioperative opioid use, interrupt 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 additive CNS depression along with clinically meaningful respiratory depression, obtundation, hypotension, profound sedation, syncope, and death. When combining these CNS depressants with an oxybate cannot be avoided, clinicians should weigh lowering the dose or stopping one or more of the CNS depressants (oxybates included). Furthermore, should an opioid be needed for a brief period (for instance, post- or perioperatively), pausing oxybate therapy should be weighed123. Where 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 treatment of opioid overdose4.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Keep taking both medicines exactly as prescribed until your care team advises otherwise, but flag this pairing to them promptly. This combination is generally not recommended because the depressant effects add up.
- Your team may lower the dose of one medicine, or stop one, to reduce risk.
- If you need the opioid only briefly (for example after surgery), they may pause the oxybate during that time.
- If both are truly needed, expect closer monitoring for excessive sleepiness and slowed breathing.
- Ask whether you should have naloxone on hand for emergencies.
Call for help right away if breathing becomes slow, or you feel faint or hard to wake.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Sodium Oxybate together?
Acetaminophen-codeine and sodium oxybate both depress the brain and breathing, and using them together can be life-threatening; the combination is not recommended, so talk to your doctor or pharmacist before combining them. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Sodium 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 Sodium Oxybate interaction managed?
Keep taking both medicines exactly as prescribed until your care team advises otherwise, but flag this pairing to them promptly. This combination is generally not recommended because the depressant effects add up. Your team may lower the dose of one medicine, or stop one, to reduce risk. If you need the opioid only briefly (for example after surgery), they may pause the oxybate during that time. I… 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 Sodium 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
Keep reading about Acetaminophen And Codeine
Keep reading about Sodium Oxybate
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.
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