Droperidol 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
Droperidol
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 pain medicine Tylenol with codeine and droperidol can both slow down your brain and breathing. When you take them together, those calming effects add up. This can make you very sleepy, lower your blood pressure, and in serious cases slow your breathing too much.
This warning is based on how these medicines work rather than a lot of real-world cases, but it is taken seriously because the combination can be dangerous. The good news is your care team can manage this safely by using the lowest doses needed and keeping a close eye on you. Please do not stop or change either medicine on your own. Talk with your doctor or pharmacist about how to use them together safely.
Effect: Additive CNS and respiratory depression from combining codeine (opioid) with droperidol (CNS depressant). Both drugs independently depress the CNS; combined use raises the risk of profound sedation, hypotension, respiratory depression, coma, and death.
Mechanism: Pharmacodynamic (additive), not a metabolic interaction. Direction: increased combined depressant effect.
Evidence: Theoretical; severity rated major.
- Reserve concomitant use for patients without adequate alternatives.
- Use lowest effective dose and shortest duration; consider reducing either agent's dose.
- 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
Keep taking both exactly as prescribed unless your care team tells you otherwise. This combination can be used when needed, but it is managed carefully.
Your care team typically will:
- Use the lowest dose and shortest duration that works.
- Possibly lower the dose of the codeine product or the droperidol.
- Monitor you closely for heavy sedation, slowed breathing, or low blood pressure.
- Sometimes prescribe naloxone as a safety backup.
Tell your doctor or pharmacist right away if you feel unusually drowsy, confused, dizzy, or notice slow or shallow breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) A study found that the rate of emergency department visits related to nonmedical use that occurred between 2004 and 2011 and involved 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 drug classes likewise rose 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 involving the dispensing of both opioid analgesics and benzodiazepines was 10 times greater than the rate 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 among patients receiving opioid analgesics who had a history of a benzodiazepine prescription and rose by 3.86 fold among those with a current benzodiazepine prescription, when compared with patients taking opioid analgesics who had no history of a benzodiazepine prescription. The risk of drug overdose deaths increased 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 the similar pharmacological properties, it is reasonable to anticipate a comparable risk when other CNS depressant drugs are used concomitantly with opioid analgesics 34.
Common questions
Can I take Droperidol and Acetaminophen And Codeine together?
Combining Tylenol with codeine and droperidol adds up their sedating effects and can dangerously slow breathing, so use only when necessary at the lowest dose with close monitoring. Never adjust either medicine yourself; check with your doctor or pharmacist. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Droperidol 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 Droperidol and Acetaminophen And Codeine interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. This combination can be used when needed, but it is managed carefully. Your care team typically will: Use the lowest dose and shortest duration that works. Possibly lower the dose of the codeine product or the droperidol. Monitor you closely for heavy sedation, slowed breathing, or low blood pressure. Sometimes presc… 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 Droperidol 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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