Chloral Hydrate 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
Chloral Hydrate
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 prescribed acetaminophen with codeine (a pain reliever plus an opioid) along with chloral hydrate (a sedative that helps with sleep). Both of these medicines can slow down your brain and your breathing. When you take them together, those calming effects can stack up. That can lead to feeling very drowsy or confused, breathing too slowly, low blood pressure, and in serious cases it can become dangerous.
The good news is this is very manageable. Your care team can pick the lowest doses that work, keep the treatment short, and watch you closely. Please don't start or stop either medicine on your own, just talk with your pharmacist or doctor about the safest plan for you.
Additive CNS and respiratory depression from combining codeine (opioid agonist) with chloral hydrate (sedative-hypnotic CNS depressant). Effects are pharmacodynamic and additive, not enzyme-mediated, so both drugs' sedating actions compound.
- Direction: increased sedation, hypotension, respiratory depression, risk of coma/death.
- Evidence: theoretical; extrapolated from opioid plus CNS-depressant data (e.g., opioid-benzodiazepine overdose signals).
- Severity/onset: major; onset unspecified.
- Management: avoid where possible; reserve for patients lacking adequate alternatives. Use lowest effective doses and shortest duration; consider reducing 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
Avoid concomitant use of opioid cough medication formulations and CNS depressants. Concomitant use of opioid analgesics with benzodiazepines has been associated with increased rates of emergency department visits and fatal overdose2. Concomitant use of codeine with CNS depressants 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 overdose 341.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Your care team can manage this combination safely with a few common steps:
- They may reserve using both together for when other options aren't enough.
- Doses may be adjusted and individualized, often the lowest dose that works, for the shortest time needed.
- They may monitor you more closely for heavy drowsiness, confusion, or slow breathing.
- They may consider prescribing naloxone as a rescue medicine, just in case.
What you should do: keep taking both exactly as prescribed, don't add alcohol or other sedatives, and tell your pharmacist or doctor right away if you feel unusually sleepy or short of breath.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) In a study, the rate of emergency department visits related to nonmedical use that occurred between 2004 and 2011 and involved opioid analgesics together with benzodiazepines rose significantly from 11 to 34.2 per 100,000. Drug overdose deaths attributable to prescribed and greater 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 that seen with the dispensing of 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 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 those taking opioid analgesics with 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 and benzodiazepines together raises the risk of drug-related mortality relative to using opioid analgesics alone. Given the comparable pharmacological properties, it is reasonable to anticipate a comparable risk when other CNS depressant drugs are used together with opioid analgesics 34.
Common questions
Can I take Chloral Hydrate and Acetaminophen And Codeine together?
Taking acetaminophen with codeine alongside chloral hydrate can add up to dangerous drowsiness and slowed breathing, so use them together only under your care team's guidance at the lowest doses. Watch for excess sedation or breathing trouble and get help right away if they occur. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Chloral Hydrate 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 Chloral Hydrate and Acetaminophen And Codeine interaction managed?
Your care team can manage this combination safely with a few common steps: They may reserve using both together for when other options aren't enough. Doses may be adjusted and individualized, often the lowest dose that works, for the shortest time needed. They may monitor you more closely for heavy drowsiness, confusion, or slow breathing. They may consider prescribing naloxone as a rescue medicin… 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 Chloral Hydrate 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 Chloral Hydrate
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