Acetaminophen And Codeine and Pipotiazine: 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
Pipotiazine
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.
You've been given two medicines that can each make you sleepy and slow your breathing. One contains codeine, an opioid pain reliever (mixed with acetaminophen), and the other is pipotiazine, an antipsychotic that also calms the brain. Taken together, these effects can add up. That can lead to being overly drowsy, having very slow or shallow breathing, low blood pressure, or being hard to wake up.
This is a serious combination, but it can be managed. Your care team may use the lowest possible dose for the shortest time and watch you closely. Please don't stop or change either medicine on your own. Talk with your pharmacist or doctor about how to take them safely.
Effect: Additive CNS and respiratory depression from combining codeine (opioid, in an acetaminophen/codeine product) with pipotiazine (a phenothiazine antipsychotic and CNS depressant).
- Mechanism: Pharmacodynamic additivity, not a metabolic interaction. Both agents depress the CNS and can potentiate sedation, hypotension, respiratory depression, coma, and death.
- Direction/magnitude: Increased depressant effect; magnitude not quantified.
- Evidence: Theoretical, but severity rated major (extrapolated from opioid plus benzodiazepine overdose data).
- Onset: Unspecified.
- Management: Reserve for patients lacking alternatives; use lowest effective doses and shortest duration; monitor 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 cough preparations with CNS depressants. Taking opioid analgesics together with benzodiazepines has been linked to higher rates of both emergency department visits and fatal overdose2. When codeine is used alongside CNS depressants, there is a greater likelihood of hypotension, respiratory depression, profound sedation, coma and death. Prescribing these agents together should be limited to patients whose alternative treatment options prove inadequate. Keep both dosage and duration at the minimum needed, and monitor patients carefully for indications of sedation and respiratory depression. Should concurrent use be justified, prescribing naloxone for emergency management of opioid overdose may be considered341.
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. Because both can slow breathing and cause heavy sedation, your team will manage this carefully.
- They may use the lowest effective dose of the codeine product and/or the pipotiazine for the shortest time needed.
- They will watch you closely for excess sleepiness, slow or shallow breathing, confusion, or dizziness.
- Your team may consider prescribing naloxone for emergency use, and will show you and your family how to use it.
Call your prescriber or pharmacist right away if you feel unusually drowsy or have trouble breathing, and avoid alcohol or other sedatives.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) One study found that 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 attributed to prescribed and above-prescribed doses of both drug classes likewise 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 that involved the dispensing of both opioid analgesics and benzodiazepines was 10 times greater than dispensing of opioid analgesics alone (7 versus 0.7 per 10,000 person years) 2.
c) In a cohort study drawing on 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 increases the risk of drug-related mortality compared with using opioid analgesics alone. Given 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 Pipotiazine together?
Combining acetaminophen/codeine with pipotiazine adds up their sedating effects and can dangerously slow breathing, so use it only when necessary at the lowest dose 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 Pipotiazine 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 Pipotiazine interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. Because both can slow breathing and cause heavy sedation, your team will manage this carefully. They may use the lowest effective dose of the codeine product and/or the pipotiazine for the shortest time needed. They will watch you closely for excess sleepiness, slow or shallow breathing, confusion, or dizziness. Your… 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 Pipotiazine 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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