Oxymorphone and Acetaminophen And Codeine: 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
Oxymorphone
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.
These are both opioid pain medicines. One combines acetaminophen with codeine, and the other is oxymorphone. Taking them together means you have two opioids in your body at once, and their effects add up. That can make you very drowsy and, more importantly, can slow your breathing down more than either would alone. There is also a small, mostly theoretical chance of a reaction called serotonin syndrome, which can cause things like agitation, sweating, shivering, or a fast heartbeat.
The good news: your care team can manage this by using the lowest doses needed and watching you closely. Never change either medicine on your own. If you feel unusually sleepy or your breathing feels slow, get help right away.
Effect: Additive CNS and respiratory depression from concurrent opioids (codeine plus oxymorphone), with a theoretical additive serotonergic risk (serotonin syndrome). Note codeine is a CYP2D6 prodrug requiring activation to morphine; the concern here is pharmacodynamic additivity, not a metabolic issue.
- Direction/magnitude: Increased sedation and respiratory depression; magnitude dose-dependent. Onset unspecified.
- Evidence: Theoretical, but severity rated major.
- Management: Reserve concurrent use for when alternatives are inadequate; use lowest effective dose and shortest duration. Consider reducing the oxymorphone or the CNS depressant dose. Monitor for sedation, respiratory depression, and serotonin syndrome; discontinue oxymorphone if serotonin syndrome is suspected. Consider prescribing naloxone.
What happens
Increased risk of respiratory and CNS depression and an increased risk of serotonin syndrome
Interaction Deep Dive
Limit the combined use of oxyMORphone with CNS depressants to those patients for whom other options prove insufficient. When such combined use cannot be avoided, employ the smallest dose over the briefest period needed to meet the therapeutic objectives. A reduced dose of either oxyMORphone or the CNS depressant should be considered, alongside careful observation for sedation, respiratory depression, and any indication of serotonin syndrome. Should serotonin syndrome be suspected, oxyMORphone should be stopped12. Patients and their caregivers should be made aware of this possible interaction and taught to recognize the signs and symptoms of respiratory depression (sedation included). Where combined use is justified, consider prescribing naloxone to allow emergency management of opioid overdose2.
Why it happens (mechanism)
Additive CNS depression; additive serotonergic effects
How to manage this interaction
Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Here is how care teams typically handle two opioids together:
- They reserve this combination for when other options are not enough, and use the lowest dose for the shortest time needed.
- Your dose of one or both medicines may be adjusted and individualized by your care team, and they may monitor you more closely for drowsiness and slowed breathing.
- They may prescribe naloxone for emergency use, and teach you and your caregivers the warning signs of an overdose.
Call your pharmacist or prescriber if you notice heavy sedation, slow breathing, confusion, sweating, shivering, or a racing heart.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Oxymorphone and Acetaminophen And Codeine together?
Combining these two opioids adds up their sedating and breathing-slowing effects, so use only under your care team's direction at the lowest effective doses, and know the warning signs of over-sedation. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Oxymorphone 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 Oxymorphone and Acetaminophen And Codeine interaction managed?
Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Here is how care teams typically handle two opioids together: They reserve this combination for when other options are not enough, and use the lowest dose for the shortest time needed. Your dose of one or both medicines may be adjusted and individualized by your care team, and they may monitor you more closely for d… 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 Oxymorphone 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: OPANA(R) oral tablets, oxymorphone HCl oral tablets. Endo Pharmaceuticals Inc (per FDA), Malvern, PA, 2019. DailyMed
- Product Information: OPANA(R) ER oral extended-release tablets, oxymorphone HCl oral extended-release tablets. Endo Pharmaceuticals Inc (per FDA), Malvern, PA, 2023. DailyMed
Keep reading about Acetaminophen And Codeine
Keep reading about Oxymorphone
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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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