Acetaminophen And Codeine and Morphine Sulfate Liposome: 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
Morphine Sulfate Liposome
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.
Both of these medicines are opioids. Your acetaminophen with codeine pill contains codeine, and the other medicine is a long-acting form of morphine. When two opioids are taken together, their calming and slowing effects add up. That can mean very heavy sleepiness, slow or shallow breathing, low blood pressure, and in serious cases, an overdose.
There is also a smaller, more theoretical concern about too much serotonin activity, which can cause things like shakiness, sweating, or a fast heartbeat. The good news is that your care team can manage this by using the lowest dose that works, watching you closely, and adjusting things for you. Do not change either medicine on your own, just talk with your pharmacist or doctor.
Additive CNS and respiratory depression from two concurrent opioids (codeine plus liposomal morphine), with a theoretical additive serotonergic risk.
- Direction/effect: Increased sedation, respiratory depression, hypotension, coma, opioid overdose, and possible serotonin syndrome.
- Mechanism: Additive mu-opioid CNS depression; additive serotonergic activity.
- Evidence: Theoretical; severity rated major. Onset unspecified.
- Management: Reserve combination for when alternatives are inadequate; use lowest effective dose and shortest duration. Monitor closely for sedation, respiratory rate, and serotonin syndrome, especially at initiation and titration. Consider prescribing naloxone. Discontinue if serotonin syndrome is suspected.
What happens
Increased risk of respiratory and CNS depression and an increased risk of serotonin syndrome
Interaction Deep Dive
Taking morphine together with serotonergic CNS depressants can raise the likelihood of respiratory depression, deep sedation, hypotension, coma, opioid overdose, and serotonin syndrome. The combined use of morphine with CNS depressants should be limited to patients for whom other options are insufficient. When such combined use cannot be avoided, employ the smallest dose and briefest duration required to meet therapeutic goals, and monitor carefully for sedation, respiratory depression, and any indications of serotonin syndrome. Watch the patient closely, especially when starting therapy and when adjusting doses. Should serotonin syndrome be suspected, stop morphine1. Because concurrent morphine and CNS depressant use heightens the danger of opioid overdose, consider prescribing naloxone to permit emergency management of opioid overdose2. When beginning a morphine/naltrexone combination, initiate at one-third to one-half of the standard morphine/naltrexone dose3. When starting Morphabond ER(TM), begin with the lowest feasible dose of 15 mg every 12 hours, and think about lowering the dose of the accompanying CNS depressant4.
Why it happens (mechanism)
Additive CNS depression; additive serotonergic effects
How to manage this interaction
Keep taking both exactly as prescribed unless your care team tells you otherwise. When two opioids are combined, teams typically:
- Use the lowest effective dose for the shortest time needed.
- Monitor you more closely, especially when starting or changing a dose.
- Sometimes prescribe naloxone for emergency use, just in case.
Watch for very heavy drowsiness, slow or shallow breathing, confusion, or fainting, and get help right away if these happen. Also mention any agitation, sweating, tremor, or fast heartbeat. Ask your pharmacist or prescriber whether you truly need both, and let them tailor the doses for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
Common questions
Can I take Acetaminophen And Codeine and Morphine Sulfate Liposome together?
Taking codeine and long-acting morphine together stacks two opioids, raising the risk of dangerous sedation, slowed breathing, and overdose, so use the lowest doses possible and let your care team monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Morphine Sulfate Liposome 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 Morphine Sulfate Liposome interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. When two opioids are combined, teams typically: Use the lowest effective dose for the shortest time needed. Monitor you more closely, especially when starting or changing a dose. Sometimes prescribe naloxone for emergency use, just in case. Watch for very heavy drowsiness, slow or shallow breathing, confusion, or fai… 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 Morphine Sulfate Liposome 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 (6)
- Product Information: KADIAN(R) oral extended-release capsules, morphine sulfate oral extended-release capsules. Allergan USA, Inc (per FDA), Irvine, CA, 2016. DailyMed
- Product Information: DURAMORPH intravenous, epidural, intrathecal injection, morphine sulfate intravenous, epidural, intrathecal injection. Hikma Pharmaceuticals USA Inc (Per FDA), Berkeley, NJ, 2023. DailyMed
- Product Information: EMBEDA(R) oral extended-release capsules, morphine sulfate naltrexone HCl oral extended-release capsules. Pfizer Inc. (per FDA), New York, NY, 2016. DailyMed
- Product Information: MORPHABOND(TM) ER oral extended-release tablets, morphine sulfate oral extended-release tablets. Daiichi Sankyo Inc (per FDA), Basking Ridge, NJ, 2018. DailyMed
- Product Information: MS CONTIN(R) oral extended-release tablets, morphine sulfate oral extended-release tablets. Purdue Pharma LP (per FDA), Stamford, CT, 2023. DailyMed
- Product Information: Morphine sulfate oral solution, morphine sulfate oral solution. Hikma Pharmaceuticals USA Inc (per FDA), Berkeley Heights, NJ, 2023. DailyMed
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