Fospropofol and Acetaminophen And Codeine: 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
Fospropofol
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.
Your medicine Tylenol with Codeine contains an opioid pain reliever, and fospropofol is a strong sedative used for procedures. Both of these can slow down your breathing and make you very sleepy. When they are used together, those effects can add up, which raises the risk of dangerously slow breathing, very deep sedation, or a big drop in blood pressure.
The good news is that this is very manageable. Fospropofol is almost always given in a monitored setting like a hospital or procedure room, where your team watches your breathing closely. Always tell your care team about every medicine you take so they can keep the doses low and keep you safe.
Effect: Additive CNS and respiratory depression when codeine (opioid analgesic in acetaminophen/codeine) is combined with fospropofol (a sedative-hypnotic prodrug of propofol).
- Mechanism: Pharmacodynamic additive CNS depression; increased risk of hypotension, respiratory depression, profound sedation, coma, and death.
- Direction: Increased depressant effect of both agents (PD, not PK based).
- Evidence: Theoretical, but severity rated major given documented opioid + sedative overdose risk.
- Onset: Unspecified; expect during co-administration.
- Management: Reserve for when alternatives inadequate; use lowest effective doses and shortest duration; monitor sedation and respiratory status; consider naloxone availability.
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
Fospropofol is typically given in a monitored clinical setting, so your team can watch you closely if you have recently taken acetaminophen with codeine. Here is how this is usually handled:
- Keep your team informed: Tell them about all opioids and other medicines you take before any procedure.
- Lowest dose, shortest time: Doses may be adjusted and individualized by your care team, using the smallest amounts needed.
- Close monitoring: Your breathing, blood pressure, and alertness will be watched carefully.
- Safety net: Naloxone may be kept on hand as a precaution.
Do not stop or change either medicine on your own; talk with your pharmacist or prescriber.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) One study found that between 2004 and 2011, the rate of emergency department visits related to nonmedical use that involved both opioid analgesics and benzodiazepines rose significantly from 11 to 34.2 per 100,000. Deaths from drug overdose attributed to prescribed and higher than prescribed doses of both drug classes also rose significantly from 0.6 to 1.7 per 100,000, and overdose deaths attributed 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 that associated 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 using opioid analgesics who had a history of a benzodiazepine prescription and rose by 3.86 fold among those with a current benzodiazepine prescription, compared with those using opioid analgesics without any history of a benzodiazepine prescription. The risk of drug overdose deaths grew as daily doses of benzodiazepines increased 2.
d) Observational studies have shown that using opioid analgesics together with benzodiazepines raises the risk of drug-related mortality when compared with using opioid analgesics alone. Given their similar pharmacological properties, it is reasonable to anticipate a comparable risk when other CNS depressant drugs are used concurrently with opioid analgesics 34.
Common questions
Can I take Fospropofol and Acetaminophen And Codeine together?
Combining acetaminophen/codeine with fospropofol can add up to cause dangerous sedation and slowed breathing, so this pairing should be avoided unless necessary and only under close monitoring. Tell your care team about all your medicines and never adjust doses on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Fospropofol and Acetaminophen And Codeine 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 Fospropofol and Acetaminophen And Codeine interaction managed?
Fospropofol is typically given in a monitored clinical setting, so your team can watch you closely if you have recently taken acetaminophen with codeine. Here is how this is usually handled: Keep your team informed: Tell them about all opioids and other medicines you take before any procedure. Lowest dose, shortest time: Doses may be adjusted and individualized by your care team, using the smalles… 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 Fospropofol or Acetaminophen And Codeine 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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