Acetaminophen And Codeine and Promazine: 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
Promazine
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.
These two medicines can both slow you down in the same way. Codeine (an opioid pain reliever combined with acetaminophen) and promazine (a phenothiazine that treats agitation and can cause drowsiness) both calm the brain. When taken together, that calming effect can add up. This may make you very sleepy, lower your blood pressure, and in serious cases slow your breathing too much.
The good news is your care team can manage this. Don't stop either medicine on your own. Talk with your pharmacist or doctor, who may use the lowest doses needed and keep a closer eye on you. Watch for heavy drowsiness, confusion, or slow or shallow breathing, and get help right away if those happen.
Mechanism: additive CNS depression. Codeine is an opioid analgesic (a CYP2D6-activated prodrug for morphine, but the relevant concern here is pharmacodynamic, not metabolic) and promazine is a sedating phenothiazine. Combined use potentiates sedation, hypotension, respiratory depression, and in extreme cases coma or death.
- Direction: increased combined CNS/respiratory depressant effect (PD additive).
- Onset: unspecified.
- Evidence: theoretical, but severity rated major.
- Management: reserve concomitant use for when alternatives are inadequate; use lowest effective dose and shortest duration; consider reducing dose of either agent; monitor closely for sedation and respiratory depression; consider prescribing naloxone.
What happens
An increased risk of respiratory and CNS depression
Interaction Deep Dive
Do not combine opioid-based cough remedy formulations with CNS depressants. When opioid analgesics are taken together with benzodiazepines, higher rates of emergency department visits and fatal overdose have been reported2. Taking codeine alongside CNS depressants can raise the likelihood of hypotension, respiratory depression, profound sedation, coma and death. Prescribing these agents together should be limited to patients in whom other treatment options prove inadequate. Keep both the doses and treatment durations at the lowest level necessary. Monitor patients carefully for indications of sedation and respiratory depression. Should concurrent use be justified, consider prescribing naloxone to allow for emergency management of opioid overdose341.
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 generally reserved for when other options aren't enough.
- Your team may prescribe the lowest dose and shortest duration needed, and may lower the dose of the codeine product or the promazine.
- They may monitor you more closely for heavy sedation and slowed breathing.
- In some cases they may prescribe naloxone as an emergency backup.
Ask your pharmacist or prescriber before adding alcohol, sleep aids, or other sedating medicines. Seek help right away for severe drowsiness, confusion, or slow, shallow breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) In one study, emergency department visits related to nonmedical use that occurred between 2004 and 2011 and involved both opioid analgesics and benzodiazepines rose significantly, from 11 to 34.2 per 100,000. Deaths from drug overdose 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 seen 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 was significantly increased by 2.33 fold among patients taking opioid analgesics who had a history of a benzodiazepine prescription, and increased 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 rose as daily benzodiazepine doses increased 2.
d) Observational studies have shown that using opioid analgesics together with benzodiazepines 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 together with opioid analgesics 34.
Common questions
Can I take Acetaminophen And Codeine and Promazine together?
Taking codeine (with acetaminophen) together with promazine can add up to dangerous drowsiness, low blood pressure, and slowed breathing, so use only under close medical supervision at the lowest doses. Never stop either drug on your own; talk with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Promazine 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 Promazine interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. This combination is generally reserved for when other options aren't enough. Your team may prescribe the lowest dose and shortest duration needed, and may lower the dose of the codeine product or the promazine. They may monitor you more closely for heavy sedation and slowed breathing. In some cases they may prescribe… 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 Promazine 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 Promazine
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