Acetaminophen And Codeine and Acepromazine: 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
Acepromazine
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.
Your medicine acetaminophen with codeine is an opioid pain reliever, and acepromazine is a sedative. Both of them can slow down your brain and your breathing. When you take them together, those calming effects can stack up. That means you could feel very drowsy, dizzy, or lightheaded, and in serious cases your breathing could slow down too much.
This warning is based mostly on how these drugs work rather than lots of studies, but the risk is taken seriously. The good news is your care team can manage this. Please don't stop either medicine on your own. Instead, talk with your doctor or pharmacist so they can guide you safely.
Effect: Additive CNS and respiratory depression from combining codeine (opioid agonist) with acepromazine (a phenothiazine with sedative properties).
- Mechanism: Additive pharmacodynamic CNS depression; not a metabolic (PK) interaction.
- Direction: Increased sedation, hypotension, respiratory depression, and in extremes coma or death.
- Onset: Unspecified.
- Evidence: Theoretical, but rated major given opioid overdose data with CNS depressants.
- Management: Reserve concurrent use for when alternatives are inadequate; use lowest effective dose and shortest duration; consider dose reduction of one agent; monitor closely for sedation and respiratory depression; consider prescribing naloxone.
What happens
An increased risk of respiratory and CNS depression
Interaction Deep Dive
Avoid concomitant use of opioid cough medication formulations and CNS depressants. Concomitant use of opioid analgesics with benzodiazepines has been associated with increased rates of emergency department visits and fatal overdose2. Concomitant use of codeine with CNS depressants can increase the risk of hypotension, respiratory depression, profound sedation, coma and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation. If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose 341.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
The main concern is that both drugs cause sedation and can slow breathing, so the effects add together.
- Keep taking both as prescribed unless your care team tells you otherwise.
- Your team may reserve this combination for when other options aren't enough, and may use the lowest dose for the shortest time needed.
- The dose of one or both may be adjusted and individualized by your care team, and they may monitor you more closely for heavy drowsiness or slowed breathing.
- Ask whether naloxone (an emergency rescue medicine) is appropriate for you.
Call your doctor or pharmacist right away if you feel unusually sleepy, confused, or short of breath.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) One study found that emergency department visits related to nonmedical use occurring between 2004 and 2011 that involved opioid analgesics and benzodiazepines rose significantly, from 11 to 34.2 per 100,000. Deaths from drug overdose attributable to both prescribed and above-prescribed doses of these two drug classes likewise rose significantly, from 0.6 to 1.7 per 100,000, while overdose deaths attributable to benzodiazepines rose significantly from 18% to 31% 2.
b) In a prospective cohort study, the rate of overdose deaths involving the dispensing of both opioid analgesics and benzodiazepines was 10 times greater than with the 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 among patients receiving opioid analgesics who had a history of a benzodiazepine prescription, and by 3.86 fold among those with a current benzodiazepine prescription, relative to patients taking opioid analgesics who had no history of a benzodiazepine prescription. The risk of overdose death grew 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 the comparable pharmacological properties, it is reasonable to anticipate a similar risk when other CNS depressant drugs are used concomitantly with opioid analgesics 34.
Common questions
Can I take Acetaminophen And Codeine and Acepromazine together?
Combining acetaminophen/codeine with acepromazine can add up to dangerous drowsiness and slowed breathing, so use it only when needed, at the lowest dose, and under close monitoring by your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Acepromazine 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 Acepromazine interaction managed?
The main concern is that both drugs cause sedation and can slow breathing, so the effects add together. Keep taking both as prescribed unless your care team tells you otherwise. Your team may reserve this combination for when other options aren't enough, and may use the lowest dose for the shortest time needed. The dose of one or both may be adjusted and individualized by your care team, and they… 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 Acepromazine 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
Keep reading about Acetaminophen And Codeine
Keep reading about Acepromazine
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