Prochlorperazine 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
Prochlorperazine
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, and you also take prochlorperazine for nausea. Both of these can slow down your brain and breathing, so taking them together can make you more sleepy, foggy, or short of breath than either alone.
On top of that, both drugs can slow your gut and bladder. That means more constipation and trouble urinating, and in rare cases the gut can nearly stop moving (a serious blockage). This concern is based on how the drugs work rather than lots of real cases, but it is worth taking seriously. Please don't change anything on your own. Your care team can manage this safely by adjusting doses and watching you closely.
Effect: Additive CNS/respiratory depression plus additive reduction in GI motility, raising the risk of sedation, respiratory depression, severe constipation, urinary retention, and paralytic ileus.
Mechanism: Additive CNS depression; additive anticholinergic/antidopaminergic effects on gastric motility. Codeine is a prodrug activated via CYP2D6, but this is a pharmacodynamic (not metabolic) interaction.
- Direction: Increased combined depressant and GI-slowing effect.
- Evidence: Theoretical; severity major; onset unspecified.
- Management: Reserve for when alternatives are inadequate; use lowest effective dose, shortest duration. Consider lower-dose codeine or CNS depressant. Monitor sedation, respiratory status, urinary retention, and bowel function. Consider prescribing naloxone.
What happens
Increased risk of paralytic ileus and an increased risk of respiratory and CNS depression
Interaction Deep Dive
Do not use opioid cough preparations together with CNS depressants2. Combining codeine with CNS depressants should be limited to those patients in whom other options are insufficient. When such combined use cannot be avoided, employ the smallest effective dose for the briefest time needed to meet therapeutic objectives. In addition, giving codeine alongside anticholinergics can heighten the likelihood of urinary retention and/or severe constipation, potentially resulting in paralytic ileus. A reduced dose of either codeine or the CNS depressant should be considered, with careful surveillance for urinary retention, decreased gastric motility, sedation, and respiratory depression. Should concurrent use be justified, prescribing naloxone for the emergency management of opioid overdose is worth considering 134.
Why it happens (mechanism)
Additive effects on gastric motility; additive CNS depression
How to manage this interaction
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. This combination can be used when needed, but your team will typically manage it carefully.
- Your team may use the lowest dose for the shortest time needed, and may lower the dose of one medicine.
- They may monitor you more closely for heavy drowsiness, slowed or shallow breathing, trouble urinating, and constipation.
- Because an opioid is involved, your prescriber may consider giving you naloxone to have on hand.
Call your pharmacist or doctor if you notice unusual sleepiness, breathing changes, no bowel movements, or difficulty urinating.
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, 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 attributed to prescribed and above-prescribed doses of both drug classes also 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 involving the dispensing of both opioid analgesics and benzodiazepines was 10 times greater than that seen 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 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 patients taking opioid analgesics who had no history of a benzodiazepine prescription. The risk of drug overdose deaths grew 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 compared with using opioid analgesics alone. Given their comparable pharmacological properties, a similar risk can reasonably be anticipated when other CNS depressant drugs are used together with opioid analgesics 34.
Common questions
Can I take Prochlorperazine and Acetaminophen And Codeine together?
Taking codeine (in your acetaminophen/codeine) with prochlorperazine can add up to more drowsiness, slowed breathing, and a slowed gut, so use both only as prescribed and watch for these effects. Contact your pharmacist or doctor with any concerns. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Prochlorperazine 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 Prochlorperazine and Acetaminophen And Codeine interaction managed?
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. This combination can be used when needed, but your team will typically manage it carefully. Your team may use the lowest dose for the shortest time needed, and may lower the dose of one medicine. They may monitor you more closely for heavy drowsiness, slowed or shallow breathing, trouble urinating, and cons… 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 Prochlorperazine 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
Keep reading about Acetaminophen And Codeine
Keep reading about Prochlorperazine
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist