Acetaminophen And Codeine and Thiethylperazine: 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
Thiethylperazine
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 make each other more sedating. The codeine in your acetaminophen-codeine tablets is an opioid, and it can slow your breathing and make you very drowsy. Thiethylperazine is used for nausea and also acts on the brain to calm things down. Taken together, they can add up and cause too much sleepiness, slowed breathing, low blood pressure, or in serious cases even trouble waking up.
The good news is your care team can manage this. Please don't stop either medicine on your own. Talk with your pharmacist or doctor so they can use the lowest helpful dose, keep the time short, and watch you closely.
Mechanism: additive CNS and respiratory depression from an opioid (codeine, a mu-agonist) combined with thiethylperazine, a phenothiazine antiemetic with sedative/CNS-depressant properties. This is a pharmacodynamic (not pharmacokinetic) interaction.
- Direction/effect: increased risk of hypotension, profound sedation, respiratory depression, coma, death.
- Evidence: theoretical; severity rated major.
- Onset: unspecified.
- Management: reserve concomitant use for when alternatives are inadequate; use lowest effective dose and shortest duration; consider lowering the codeine or thiethylperazine dose; monitor closely for sedation and respiratory depression; consider prescribing naloxone.
What happens
An increased risk of respiratory and CNS depression
Interaction Deep Dive
Opioid cough preparations should not be taken together with CNS depressants. Studies have linked the combined use of opioid analgesics and benzodiazepines to higher rates of both emergency department visits and fatal overdose2. When codeine is used alongside CNS depressants, patients face an elevated risk of hypotension, respiratory depression, profound sedation, coma, and death. Prescribing these agents together should be limited to patients in whom other therapeutic options prove inadequate. Keep both the dose and the length of treatment at the lowest level needed. Monitor patients closely for indications of sedation and respiratory depression. Should concurrent use be justified, prescribing naloxone for the 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. This combination is usually reserved for when other options aren't enough, and your team can manage it safely.
- Your prescriber may use the lowest effective dose of the codeine product and/or the thiethylperazine, for the shortest time needed.
- Your team may monitor you more closely for heavy drowsiness or slowed breathing.
- Your prescriber may consider giving you naloxone for emergencies.
- Call your care team or seek help right away if you notice severe sleepiness, slow or shallow breathing, confusion, or trouble waking.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) A study found that emergency department visits related to nonmedical use taking place between 2004 and 2011 and involving 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 the rate 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 taking 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 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 and benzodiazepines together raises the risk of drug-related mortality relative to 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 Thiethylperazine together?
Combining acetaminophen-codeine with thiethylperazine adds up their sedating effects and can dangerously slow breathing, so use it only when necessary, at the lowest dose, and under close monitoring by your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Thiethylperazine 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 Thiethylperazine interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. This combination is usually reserved for when other options aren't enough, and your team can manage it safely. Your prescriber may use the lowest effective dose of the codeine product and/or the thiethylperazine, for the shortest time needed. Your team may monitor you more closely for heavy drowsiness or slowed breat… 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 Thiethylperazine 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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