Acetaminophen And Codeine and Melperone: 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
Melperone
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 two medicines can add up in a way that slows your breathing and makes you very sleepy. Your pain medicine contains codeine, an opioid, plus acetaminophen (Tylenol). Melperone is a medicine that also calms the brain. When you take both, their sedating effects can stack together. That can lead to deep drowsiness, low blood pressure, and dangerously slow breathing.
The good news is your care team can manage this. They may use the lowest dose for the shortest time, watch you closely, and in some cases suggest having naloxone (a rescue medicine) on hand. Please don't stop either medicine on your own, just talk with your pharmacist or doctor about how you're feeling.
Effect: Additive CNS and respiratory depression when codeine (an opioid analgesic, combined here with acetaminophen) is used with melperone (a butyrophenone with sedative activity).
- Mechanism: Additive pharmacodynamic CNS depression, not a metabolic interaction.
- Direction: Increased sedation, hypotension, respiratory depression, and, in extremes, coma/death.
- Severity/Evidence: Major; evidence is theoretical but the risk class (opioid plus CNS depressant) is well recognized.
- Management: Reserve concomitant use for when alternatives are inadequate. Use lowest effective doses and shortest durations. Monitor for sedation and respiratory depression; consider prescribing naloxone.
What happens
An increased risk of respiratory and CNS depression
Interaction Deep Dive
Do not combine opioid cough medication products with CNS depressants. Taking opioid analgesics alongside benzodiazepines has been linked to a rise in emergency department visits and deadly overdoses2. When codeine is used together with CNS depressants, the likelihood of hypotension, respiratory depression, profound sedation, coma, and death may increase. Prescribing these agents together should be limited to patients whose alternative treatment options prove insufficient. Keep both the dose and the length of therapy as low as possible. Monitor patients carefully for indications of sedation and respiratory depression. Should concurrent use be justified, consider prescribing naloxone to treat opioid overdose as an emergency 341.
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. This combination is used only when other options aren't adequate.
- Your team may prescribe the lowest dose for the shortest time, and may lower the dose of the codeine product or the melperone.
- They may monitor you more closely for heavy sedation or slowed breathing.
- They may consider prescribing naloxone as an emergency rescue medicine.
Call your pharmacist or doctor right away if you notice unusual drowsiness, confusion, very slow or shallow breathing, or dizziness.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) In one study, the rate of emergency department visits related to nonmedical use that took place between 2004 and 2011 and involved opioid analgesics together with benzodiazepines rose significantly from 11 to 34.2 per 100,000. Drug overdose deaths attributable to prescribed and above-prescribed doses of both drug classes likewise increased significantly from 0.6 to 1.7 per 100,000, and overdose deaths attributable to benzodiazepines rose significantly from 18% to 31% 2.
b) In a prospective cohort study, the rate of overdose deaths that involved dispensing of both opioid analgesics and benzodiazepines was 10 times greater than dispensing of opioid analgesics alone (7 vs 0.7 per 10,000 person years) 2.
c) In a cohort study using data from 2004 to 2009, the risk of fatal overdose rose significantly by 2.33 fold in patients receiving opioid analgesics who had a history of a benzodiazepine prescription, and rose by 3.86 fold in those with a current benzodiazepine prescription, compared with patients taking opioid analgesics who had no history of a benzodiazepine prescription. The risk of drug overdose deaths grew as daily benzodiazepine doses increased 2.
d) Observational studies have shown that using opioid analgesics and benzodiazepines together raises the risk of drug-related mortality compared with using opioid analgesics alone. Given their similar pharmacological properties, it is reasonable to anticipate comparable risk when other CNS depressant drugs are used together with opioid analgesics 34.
Common questions
Can I take Acetaminophen And Codeine and Melperone together?
Combining codeine/acetaminophen with melperone can add up to dangerous drowsiness and slowed breathing, so it's used only when needed, at the lowest dose, with close monitoring. Do not stop either medicine on your own; ask your pharmacist or doctor how to use them safely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Melperone 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 Melperone interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. This combination is used only when other options aren't adequate. Your team may prescribe the lowest dose for the shortest time, and may lower the dose of the codeine product or the melperone. They may monitor you more closely for heavy sedation or slowed breathing. They may consider prescribing naloxone as an emerge… 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 Melperone 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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