Chlordiazepoxide 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
Chlordiazepoxide
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 are also taking chlordiazepoxide, a benzodiazepine used for anxiety and other conditions. Both of these drugs slow down your brain and body. When taken together, that calming effect can stack up.
This means you could feel very drowsy, get dizzy from low blood pressure, or, in the worst cases, have your breathing slow down too much. The good news is that your care team knows how to handle this. They can use the lowest doses needed for the shortest time and watch you closely. Never start, stop, or change either medicine on your own. Just talk with your pharmacist or doctor about the best plan for you.
Effect: Combined use of codeine (an opioid) with chlordiazepoxide (a benzodiazepine) produces additive CNS and respiratory depression, increasing risk of hypotension, profound sedation, respiratory depression, coma, and death.
Mechanism: Pharmacodynamic, additive CNS depression (no prodrug reversal relevant here; codeine's analgesic activation via CYP2D6 is not the driver of this PD interaction).
Evidence: Theoretical; severity rated major. Onset unspecified.
- Reserve concurrent use for when alternatives are inadequate.
- Use the minimum effective dose and duration.
- Monitor closely for sedation and respiratory depression.
- Consider prescribing naloxone if co-use is warranted.
What happens
An increased risk of hypotension, respiratory depression, profound sedation, coma, and death
Interaction Deep Dive
Concomitant use of codeine with benzodiazepines can increase the risk of hypotension, respiratory depression, profound sedation, coma and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation. If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose134.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
If both medicines are prescribed together, your care team can manage this safely:
- Keep taking both as prescribed unless your prescriber tells you otherwise.
- Your team may use the lowest doses for the shortest time needed.
- They may monitor you more closely for heavy drowsiness, slowed or shallow breathing, or feeling faint.
- Your prescriber may consider a naloxone rescue kit as a safety net.
Call your pharmacist or doctor if you notice unusual sleepiness, confusion, or trouble breathing, and avoid alcohol, which adds to the effect.
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 took place 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 doses and doses exceeding those prescribed for both drug classes also rose significantly from 0.6 to 1.7 per 100,000, while overdose deaths attributed to benzodiazepines rose significantly from 18% to 31% 2.
b) A prospective cohort study reported that the rate of overdose deaths involving the dispensing of both opioid analgesics and benzodiazepines was 10 times greater than that seen with 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, 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, when compared with patients taking opioid analgesics who had no history of a benzodiazepine prescription. The risk of drug overdose deaths grew as the daily doses of benzodiazepines increased 2.
d) Observational studies have shown that using opioid analgesics together with benzodiazepines raises the risk of drug-related mortality relative to the use of 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 Chlordiazepoxide and Acetaminophen And Codeine together?
Taking codeine (in your acetaminophen/codeine product) with chlordiazepoxide can add up to dangerous drowsiness, low blood pressure, and slowed breathing, so use the lowest doses for the shortest time and watch closely. Talk with your pharmacist or doctor before changing anything. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Chlordiazepoxide 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 Chlordiazepoxide and Acetaminophen And Codeine interaction managed?
If both medicines are prescribed together, your care team can manage this safely: Keep taking both as prescribed unless your prescriber tells you otherwise. Your team may use the lowest doses for the shortest time needed. They may monitor you more closely for heavy drowsiness, slowed or shallow breathing, or feeling faint. Your prescriber may consider a naloxone rescue kit as a safety net. Call yo… 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 Chlordiazepoxide 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
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