Acetaminophen And Codeine and Propofol: 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
Propofol
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 slow down your brain and breathing. The codeine in your acetaminophen and codeine pain medicine is an opioid, and it can make you very sleepy and slow your breathing. Propofol is a strong sedative used to put people to sleep for procedures. When they are used together, those calming effects add up, which can lead to too much sleepiness, very slow or shallow breathing, low blood pressure, and in serious cases dangerous problems.
The good news: Propofol is almost always given in a monitored setting like a hospital or surgery center, where your care team watches your breathing closely. Always tell them about your codeine so they can keep you safe.
Effect: Additive CNS and respiratory depression when codeine (opioid analgesic in the acetaminophen/codeine product) is combined with propofol (a sedative-hypnotic).
- Mechanism: Pharmacodynamic additive CNS depression; no primary CYP interaction driving this. Codeine's opioid effect plus propofol's GABA-mediated sedation compound respiratory drive suppression, sedation, and hypotension.
- Direction/magnitude: Increased risk of profound sedation, respiratory depression, hypotension, coma, death. Evidence is theoretical but rated major.
- Management: Reserve concurrent use for when alternatives are inadequate; use lowest effective doses; monitor sedation, respiratory rate, SpO2, and hemodynamics; have naloxone available.
What happens
An increased risk of respiratory and CNS depression
Interaction Deep Dive
Do not combine opioid cough preparations with agents that depress the CNS. When opioid analgesics are taken together with benzodiazepines, higher rates of both emergency department visits and lethal overdose have been reported2. Taking codeine alongside CNS depressants heightens the likelihood of hypotension, respiratory depression, profound sedation, coma, and death. Prescribing these medications together should be limited to patients whose alternative treatment options are insufficient. Keep both the dose and the length of therapy to the lowest amount necessary. Monitor patients carefully for indications of sedation and respiratory depression. Should concurrent use be justified, consider prescribing naloxone as an emergency intervention for opioid overdose341.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
This combination should be used carefully and usually only when necessary. Propofol is typically given in a monitored medical setting, which is the safest place for this pairing.
- Keep taking your acetaminophen and codeine exactly as prescribed, and do not stop or change it on your own.
- Tell every provider, especially before any procedure or surgery, that you take codeine.
- Your care team may use the lowest dose and shortest duration needed, and monitor you closely for heavy sedation and slow breathing.
- Watch for extreme drowsiness, confusion, or slow/shallow breathing and get help right away.
Ask your pharmacist or doctor whether keeping naloxone on hand makes sense for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) In one study, the frequency of emergency department visits related to nonmedical use between 2004 and 2011 that involved opioid analgesics together with benzodiazepines rose significantly from 11 to 34.2 per 100,000. Drug overdose deaths attributable to both prescribed and above-prescribed doses of both drug classes likewise rose significantly from 0.6 to 1.7 per 100,000, and overdose deaths attributable to benzodiazepines increased significantly from 18% to 31% 2.
b) In a prospective cohort study, the rate of overdose deaths associated with dispensing of both opioid analgesics and benzodiazepines was 10 times greater than that with 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 taking 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 relative to using opioid analgesics alone. Owing to comparable pharmacological properties, it is reasonable to anticipate a similar risk when other CNS depressant drugs are used concurrently with opioid analgesics 34.
Common questions
Can I take Acetaminophen And Codeine and Propofol together?
Combining codeine with propofol adds up their sedating effects and can dangerously slow breathing, so it should only be done under close medical monitoring. Always tell your care team you take codeine before any procedure. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Propofol 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 Propofol interaction managed?
This combination should be used carefully and usually only when necessary. Propofol is typically given in a monitored medical setting, which is the safest place for this pairing. Keep taking your acetaminophen and codeine exactly as prescribed, and do not stop or change it on your own. Tell every provider, especially before any procedure or surgery, that you take codeine. Your care team may use th… 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 Propofol 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 Propofol
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