Acetaminophen And Codeine and Ethylmorphine: 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
Ethylmorphine
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 your medicines are opioids. Your acetaminophen with codeine is a pain reliever, and ethylmorphine is another opioid often used for cough or pain. When two opioids are taken together, their calming effects add up. That can make you very drowsy and, more importantly, slow your breathing too much. There is also a smaller, more theoretical concern about a reaction called serotonin syndrome (things like shakiness, agitation, fast heart rate, or sweating).
The good news is this is very manageable. Please don't stop either medicine on your own. Talk with your pharmacist or doctor so they can tailor your doses and keep a close eye on how you feel.
Effect: Additive CNS and respiratory depression from two concurrent opioids (codeine plus ethylmorphine), with a theoretical additive serotonergic risk (serotonin syndrome).
- Mechanism: Additive mu-opioid CNS depression; additive serotonergic activity.
- Direction: Increased sedation and respiratory depression (PD additivity).
- Evidence: Theoretical; severity rated major.
- Management: Avoid combining opioid cough formulations with other CNS depressants; reserve for when alternatives are inadequate. Use lowest effective dose, shortest duration. Consider lower codeine or ethylmorphine dosing. Monitor for sedation, respiratory depression, and serotonin syndrome, especially at initiation/titration. Consider prescribing naloxone. Discontinue codeine if serotonin syndrome is suspected.
What happens
Increased risk of respiratory and CNS depression and an increased risk of serotonin syndrome
Interaction Deep Dive
Avoid concomitant use of opioid cough medication formulations and CNS depressants2. Reserve the concomitant use of non-cough codeine products and CNS depressants to patients for whom alternatives are inadequate. If concomitant use is necessary, use the lowest dose and shortest duration necessary to achieve treatment goals. Consider using a lower dose of codeine or the CNS depressant and closely monitor for sedation, respiratory depression, and signs and symptoms of serotonin syndrome. Additionally, concomitant use of opioids with serotonergic drugs has resulted in serotonin syndrome. If concomitant use is needed, carefully observe the patient, particularly during treatment initiation and dose adjustments. Consider prescribing naloxone for the emergency treatment of opioid overdose. Discontinue codeine if serotonin syndrome is suspected 134.
Why it happens (mechanism)
Additive CNS depression; additive serotonergic effects
How to manage this interaction
Your care team can manage this safely.
- Keep taking both as prescribed unless your prescriber tells you otherwise. Do not stop or change doses on your own.
- Your team may use the lowest dose for the shortest time needed, and may adjust and individualize either opioid dose.
- They may monitor you more closely for heavy drowsiness, slow or shallow breathing, and signs of serotonin syndrome (agitation, fast heart rate, sweating, shivering, muscle twitching).
- Ask whether naloxone (a rescue medicine for opioid overdose) is right for you.
- Get help right away if breathing slows or you can't stay awake.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
5 reports — tap to read
a) One study found that the rate of emergency department visits related to nonmedical use taking place between 2004 and 2011 and involving opioid analgesics together with benzodiazepines rose significantly from 11 to 34.2 per 100,000. Deaths from drug overdose attributable to prescribed and above-prescribed doses of both classes of drugs likewise rose significantly from 0.6 to 1.7 per 100,000, and overdose deaths caused by benzodiazepines rose significantly from 18% to 31% 2.
b) In a prospective cohort study, the rate of overdose deaths involving dispensing of both opioid analgesics and benzodiazepines was 10 times greater than dispensing of opioid analgesics on their own (7 versus 0.7 per 10,000 person years) 2.
c) In a cohort study using data spanning 2004 to 2009, the risk of fatal overdose rose significantly by 2.33 fold among patients using opioid analgesics who had a history of a benzodiazepine prescription and rose by 3.86 fold in those with a current benzodiazepine prescription, when compared with patients taking opioid analgesics who had no history of a benzodiazepine prescription. The risk of death from drug overdose rose as daily benzodiazepine doses increased 2.
d) Observational studies have shown that using opioid analgesics together with benzodiazepines raises the risk of drug-related death compared with using opioid analgesics alone. Given their comparable pharmacological characteristics, it is reasonable to anticipate a similar risk when other CNS depressant drugs are combined with opioid analgesics 34.
e) Instances of serotonin syndrome, a condition that can be life-threatening, have been reported when opioids are used concurrently with serotonergic drugs 34.
Common questions
Can I take Acetaminophen And Codeine and Ethylmorphine together?
Taking two opioids together (codeine and ethylmorphine) adds up their sedating effects and can dangerously slow breathing, with a smaller theoretical risk of serotonin syndrome. Don't change anything yourself; ask your pharmacist or doctor to tailor the doses and monitor you, and ask about naloxone. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Ethylmorphine 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 Ethylmorphine interaction managed?
Your care team can manage this safely. Keep taking both as prescribed unless your prescriber tells you otherwise. Do not stop or change doses on your own. Your team may use the lowest dose for the shortest time needed, and may adjust and individualize either opioid dose. They may monitor you more closely for heavy drowsiness, slow or shallow breathing, and signs of serotonin syndrome (agitation, f… 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 Ethylmorphine 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: CARISOPRODOL, ASPIRIN, CODEINE PHOSPHATE oral tablets, carisoprodol, aspirin, codeine phosphate oral tablets. Ingenus Pharmaceuticals LLC (per DailyMed), Orlando, FL, 2021. DailyMed
- US Food and Drug Administration (FDA): Drug Safety Communications: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. US Food and Drug Administration (FDA). Silver Spring, MD. 2016.
- 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
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