Acetaminophen And Codeine and Haloperidol: 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
Haloperidol
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, which is an opioid, plus acetaminophen (Tylenol). Haloperidol is a medicine that can calm the mind but also makes people drowsy. When you take both together, their sleepy, slowing-down effects can add up. This can lead to heavy sedation, very slow or shallow breathing, low blood pressure, and in serious cases it can become dangerous.
The good news is that your care team can manage this. They may use the lowest dose for the shortest time and keep a close eye on you. Please don't stop either medicine on your own. Just talk with your pharmacist or doctor so they can make a plan that keeps you safe.
Effect: Additive CNS and respiratory depression from combining codeine (opioid) with haloperidol (sedating antipsychotic/CNS depressant).
Mechanism: Pharmacodynamic additive CNS depression. Note codeine is a prodrug activated via CYP2D6 to morphine, but the concern here is additive PD sedation, not a metabolic interaction.
- Direction/magnitude: Increased risk of hypotension, profound sedation, respiratory depression, coma, death; magnitude not quantified.
- Onset: Unspecified; Evidence: theoretical, but consistent with opioid plus CNS depressant class data.
- Management: Reserve for patients lacking alternatives; use lowest dose and shortest duration; consider reducing either agent; monitor sedation and respiratory status; 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
This combination is usually reserved for when other options aren't enough, but if your team has prescribed both, they can manage it safely.
- Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise.
- Your team may use the lowest effective dose for the shortest time, and the dose of either medicine may be adjusted and individualized for you.
- They may monitor you more closely for heavy drowsiness, confusion, or slow/shallow breathing.
- Your prescriber may consider giving you naloxone to have on hand as a safety measure.
- Call your care team right away if you feel very sleepy, hard to wake, or short of breath.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) In a study, the rate of nonmedical use-related emergency department visits taking place between 2004 and 2011 that involved opioid analgesics along with benzodiazepines rose significantly from 11 to 34.2 per 100,000. Drug overdose deaths attributable to prescribed and higher than prescribed doses of both drug classes likewise increased 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 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 in patients receiving 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 those taking opioid analgesics who had no history of a benzodiazepine prescription. The risk of drug overdose deaths grew as the daily doses of benzodiazepines 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 Haloperidol together?
Taking codeine (in your acetaminophen/codeine product) with haloperidol can add up to dangerous drowsiness and slowed breathing, so use the lowest dose for the shortest time and let your care team monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Haloperidol 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 Haloperidol interaction managed?
This combination is usually reserved for when other options aren't enough, but if your team has prescribed both, they can manage it safely. Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Your team may use the lowest effective dose for the shortest time, and the dose of either medicine may be adjusted and individualized for you. They may monitor you more closel… 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 Haloperidol 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 Haloperidol
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