Acetaminophen And Codeine and Chlorpromazine: 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
Chlorpromazine
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.
Both of these medicines can slow you down. The codeine in your pain pill is an opioid, and chlorpromazine is a strong medicine often used for mood or nausea. Taken together, they can add up and make you very sleepy, slow your breathing, and slow your gut. That slowed-down gut can cause bad constipation or, rarely, a serious blockage.
The good news is your care team can manage this. They may use the lowest dose for the shortest time and watch you more closely. Please keep taking both exactly as prescribed, and talk with your pharmacist or doctor about any heavy drowsiness, slow breathing, trouble peeing, or constipation.
Additive CNS and GI effects. Codeine (an opioid; note it is a prodrug activated via CYP2D6 to morphine) combined with chlorpromazine produces overlapping sedation and respiratory depression, plus additive slowing of gastric motility (chlorpromazine's anticholinergic activity augments opioid-induced constipation).
- Direction: increased combined depressant and anticholinergic burden.
- Risks: respiratory/CNS depression, urinary retention, reduced motility, paralytic ileus.
- Evidence: theoretical; severity major; onset unspecified.
- Management: reserve for when alternatives are inadequate; use lowest effective dose, shortest duration; consider reducing codeine or chlorpromazine dose; monitor sedation, respiration, retention, motility; consider naloxone access.
What happens
Increased risk of paralytic ileus and an increased risk of respiratory and CNS depression
Interaction Deep Dive
Avoid concomitant use of opioid cough medication formulations and CNS depressants2. Reserve the concomitant use of codeine and CNS depressants to patients for whom alternatives are inadequate. If concomitant use is necessary, use the lowest dose and shortest duration necessary to achieve treatment goals. Additionally, coadministration of codeine with anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Consider using a lower dose of codeine or the CNS depressant and closely monitor for urinary retention, reduced gastric motility, sedation, and respiratory depression. If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose 134.
Why it happens (mechanism)
Additive effects on gastric motility; additive CNS depression
How to manage this interaction
This combination is manageable when your care team plans for it.
- Keep taking both as prescribed unless your prescriber tells you otherwise.
- Your team may use the lowest dose and shortest duration that works, and may adjust the dose of the codeine product or the chlorpromazine.
- They may monitor you more closely for heavy drowsiness, slowed breathing, trouble urinating, and constipation.
- In some cases a prescriber may provide naloxone as a safety measure.
- Call your pharmacist or doctor right away about severe sleepiness, slow or shallow breathing, no bowel movements, or belly pain and swelling.
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 emergency department visits related to nonmedical use occurring between 2004 and 2011 that involved opioid analgesics and 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 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 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 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 without a history of a benzodiazepine prescription. The risk of drug overdose deaths increased as the daily doses of benzodiazepines increased 2.
d) Observational studies have shown that concurrent use of opioid analgesics and benzodiazepines raises the risk of drug-related mortality compared with use of opioid analgesics alone. Given similar pharmacological properties, it is reasonable to anticipate a comparable risk when other CNS depressant drugs are used together with opioid analgesics 34.
Common questions
Can I take Acetaminophen And Codeine and Chlorpromazine together?
Taken together, codeine and chlorpromazine can add up to cause dangerous drowsiness, slowed breathing, and a slowed gut, so use the lowest dose for the shortest time and stay in touch with your care team about any drowsiness, breathing changes, or constipation. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Chlorpromazine 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 Chlorpromazine interaction managed?
This combination is manageable when your care team plans for it. Keep taking both as prescribed unless your prescriber tells you otherwise. Your team may use the lowest dose and shortest duration that works, and may adjust the dose of the codeine product or the chlorpromazine. They may monitor you more closely for heavy drowsiness, slowed breathing, trouble urinating, and constipation. In some cas… 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 Chlorpromazine 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 Chlorpromazine
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