Benperidol 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
Benperidol
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 contains codeine, an opioid, along with acetaminophen (Tylenol). Benperidol is an antipsychotic that also calms the brain. Both can slow down your breathing and make you very sleepy. Taken together, those calming effects add up, and that can lead to dangerously slow breathing, extreme drowsiness, low blood pressure, or worse.
This does not mean the combination can never be used, but it deserves care. The good news is your care team can manage this by keeping doses as low as possible, using them only as long as needed, and watching you closely. Please talk with your pharmacist or doctor before changing anything, and get help right away if you feel very drowsy or short of breath.
Effect: Additive CNS and respiratory depression when codeine (an opioid analgesic) is combined with benperidol (a butyrophenone antipsychotic/CNS depressant).
Mechanism: Pharmacodynamic additive CNS depression, not a metabolic interaction. Risk includes hypotension, profound sedation, respiratory depression, coma, and death.
- Direction: Increased combined sedative/respiratory-depressant effect.
- Evidence: Theoretical; severity rated major. Onset unspecified.
- Management: Reserve concomitant use for when alternatives are inadequate. Use lowest effective doses and shortest duration. Consider lowering the codeine or benperidol 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 is used only when needed, so your team will aim for the lowest doses for the shortest time.
- Your team may adjust and individualize the codeine or benperidol dose, and may monitor you more closely for heavy sedation or slowed breathing.
- Ask your pharmacist or prescriber whether a naloxone rescue kit is right for you.
- Get emergency help for very slow or shallow breathing, extreme sleepiness, confusion, or fainting.
- Avoid adding alcohol or other sedating medicines without checking first.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) One study found that the rate of emergency department visits linked to nonmedical use and involving both opioid analgesics and benzodiazepines rose significantly between 2004 and 2011, going from 11 to 34.2 per 100,000. Drug overdose deaths attributed to prescribed and greater than prescribed doses of both drug classes likewise 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 associated with dispensing both opioid analgesics and benzodiazepines was 10 times greater than with dispensing opioid analgesics alone (7 versus 0.7 per 10,000 person years) 2.
c) In a cohort study using data spanning 2004 to 2009, the risk of fatal overdose rose significantly by 2.33 fold among patients taking 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 taking opioid analgesics without any 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 relative to using opioid analgesics alone. Given comparable pharmacological properties, it is reasonable to anticipate a similar risk when other CNS depressant drugs are used together with opioid analgesics 34.
Common questions
Can I take Benperidol and Acetaminophen And Codeine together?
Combining codeine with benperidol adds up their sedating effects and can dangerously slow breathing, so use the lowest doses for the shortest time and watch closely for heavy drowsiness or trouble breathing. Talk with your pharmacist or doctor before making any changes. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Benperidol 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 Benperidol and Acetaminophen And Codeine interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. This combination is used only when needed, so your team will aim for the lowest doses for the shortest time. Your team may adjust and individualize the codeine or benperidol dose, and may monitor you more closely for heavy sedation or slowed breathing. Ask your pharmacist or prescriber whether a naloxone rescue kit i… 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 Benperidol 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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