Acetaminophen And Codeine and Thiopropazate: 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
Thiopropazate
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 thiopropazate is an older antipsychotic. Both can slow down your brain and body. When taken together, they can add up and cause heavy drowsiness, slowed or shallow breathing, low blood pressure, and in serious cases loss of consciousness.
This concern is based mostly on how these drug types work rather than firm studies, but the risk is treated seriously. The good news is your care team can manage this. If you have been prescribed both, please talk with your pharmacist or doctor before making any changes, and never adjust doses on your own.
Effect: Additive CNS and respiratory depression from combining codeine (opioid analgesic) with thiopropazate (phenothiazine antipsychotic, itself sedating). Risk includes hypotension, profound sedation, respiratory depression, coma, and death.
- Mechanism: Pharmacodynamic (additive CNS depression), not primarily PK-driven.
- Direction: Enhanced sedative/respiratory-depressant effect.
- Onset: Unspecified; evidence is theoretical.
- Management: Avoid if possible; reserve for patients without adequate alternatives. Use lowest effective dose and shortest duration. Consider dose reduction 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 cough medication products with CNS depressants. Taking opioid analgesics together with benzodiazepines has been linked to a higher frequency 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 medications together should be limited to patients for whom other treatment options prove insufficient. Keep both the dose and the length of therapy to the lowest amount necessary. Monitor patients carefully for indications of sedation and respiratory depression. Should concurrent use be justified, consider providing naloxone for emergency management of opioid overdose341.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Your care team can manage this safely if both drugs are truly needed.
- Keep taking both exactly as prescribed unless your doctor or pharmacist tells you otherwise. Do not stop or change doses on your own.
- Your team may prescribe the lowest effective dose for the shortest time, and the dose may be adjusted and individualized for you.
- They may monitor you more closely for excessive drowsiness, confusion, or slow/shallow breathing.
- Your prescriber may also consider providing naloxone as a safety measure.
Get help right away for very slow breathing, extreme sleepiness, or someone you cannot wake.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) A study found that the rate of emergency department visits related to nonmedical use between 2004 and 2011 that involved 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 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 associated with the dispensing of both opioid analgesics and benzodiazepines was 10 times greater than that associated with dispensing opioid analgesics alone (7 versus 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 comparable pharmacological properties, it is reasonable to anticipate a similar risk when other CNS depressant drugs are used concomitantly with opioid analgesics 34.
Common questions
Can I take Acetaminophen And Codeine and Thiopropazate together?
Combining codeine with thiopropazate can add up to dangerous drowsiness and slowed breathing, so this pairing is usually avoided; if both are needed, your care team will use the lowest dose, monitor you closely, and may provide naloxone. Talk with your pharmacist or doctor before making any changes. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Thiopropazate 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 Thiopropazate interaction managed?
Your care team can manage this safely if both drugs are truly needed. Keep taking both exactly as prescribed unless your doctor or pharmacist tells you otherwise. Do not stop or change doses on your own. Your team may prescribe the lowest effective dose for the shortest time, and the dose may be adjusted and individualized for you. They may monitor you more closely for excessive drowsiness, confus… 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 Thiopropazate 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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