Acetaminophen And Codeine and Sulpiride: 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
Sulpiride
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 two medicines can both make you sleepy and slow down your breathing, so taking them together adds those effects up. Codeine is an opioid pain reliever, and sulpiride is a medicine that can also calm the nervous system. Combined, they can cause heavy drowsiness, low blood pressure, and dangerously slow breathing.
This warning is mostly based on theory and on what we know about opioids plus other calming drugs, not on a lot of direct studies. Still, it is worth taking seriously. Please don't stop either medicine on your own. Talk with your pharmacist or doctor so they can make sure the doses are safe and watch you closely.
Mechanism: additive CNS and respiratory depression. Codeine (an opioid; note it is a prodrug activated by CYP2D6 to morphine, but this is a pharmacodynamic, not pharmacokinetic, interaction) combined with sulpiride's sedative CNS effects produces summative depression. The acetaminophen component is not implicated.
Direction/effect: increased risk of hypotension, profound sedation, respiratory depression, coma, death.
- Evidence: theoretical; extrapolated from opioid plus CNS-depressant (e.g., benzodiazepine) data.
- Onset: unspecified.
- Management: reserve co-use for when alternatives are inadequate; use lowest effective dose and shortest duration; consider dose reduction of either agent; monitor sedation and respiratory status; consider naloxone.
What happens
An increased risk of respiratory and CNS depression
Interaction Deep Dive
Do not combine opioid cough medication products with CNS depressants. Taking opioid analgesics together with benzodiazepines has been linked to higher rates of emergency department visits and fatal overdose2. When codeine is used alongside CNS depressants, the likelihood of hypotension, respiratory depression, profound sedation, coma, and death rises. Prescribing these agents together should be limited to patients who lack adequate alternative treatment options. Keep both doses and treatment durations to the minimum needed. Monitor patients carefully for indications of sedation and respiratory depression. Where concurrent use is justified, consider prescribing naloxone to allow emergency management of opioid overdose 341.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Your care team can manage this safely. Typically they will:
- Reserve using both together for when other options aren't enough.
- Use the lowest dose and shortest duration needed, and they may lower the dose of the codeine product or the sulpiride.
- Monitor you more closely for heavy drowsiness, slowed breathing, or low blood pressure.
- Sometimes prescribe naloxone as an emergency rescue medicine.
Keep taking both exactly as prescribed unless told otherwise. Tell your pharmacist or prescriber right away if you feel unusually sleepy, confused, dizzy, or short of breath, and make sure they know you take both.
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 related to nonmedical use, occurring between 2004 and 2011 and involving both opioid analgesics and benzodiazepines, rose significantly from 11 to 34.2 per 100,000. Drug overdose deaths attributable to prescribed and above-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 involving the dispensing of both opioid analgesics and benzodiazepines was 10 times greater than that associated with the dispensing of opioid analgesics alone (7 versus 0.7 per 10,000 person years) 2.
c) In a cohort study based on data from 2004 to 2009, the risk of fatal overdose was significantly elevated by 2.33 fold among patients taking opioid analgesics who had a history of a benzodiazepine prescription, and by 3.86 fold among those with a current benzodiazepine prescription, compared with patients taking opioid analgesics who had no 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 death compared with using opioid analgesics alone. Given comparable pharmacological properties, a similar risk can reasonably be anticipated when other CNS depressant drugs are used concurrently with opioid analgesics 34.
Common questions
Can I take Acetaminophen And Codeine and Sulpiride together?
Taking a codeine product with sulpiride adds up their sedating effects and can dangerously slow breathing, so use them together only under your care team's guidance with the lowest doses and close monitoring. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Sulpiride 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 Sulpiride interaction managed?
Your care team can manage this safely. Typically they will: Reserve using both together for when other options aren't enough. Use the lowest dose and shortest duration needed, and they may lower the dose of the codeine product or the sulpiride. Monitor you more closely for heavy drowsiness, slowed breathing, or low blood pressure. Sometimes prescribe naloxone as an emergency rescue medicine. Keep… 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 Sulpiride 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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