Zopiclone 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
Zopiclone
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're also taking zopiclone, a sleep medicine. Both of these calm down your brain and slow your breathing. When you take them together, those effects can add up. This can make you very drowsy, slow your breathing too much, drop your blood pressure, and in serious cases it can be dangerous.
The good news is your care team can manage this. They may use the lowest doses for the shortest time and watch you closely. Please don't stop or change either medicine on your own. Just talk with your pharmacist or doctor about the safest plan for you.
Additive CNS depression. Codeine (an opioid; also a CYP2D6 prodrug converted to morphine) combined with zopiclone (a non-benzodiazepine sedative-hypnotic) produces overlapping pharmacodynamic CNS and respiratory depression.
- Direction: additive/potentiated sedation, respiratory depression, hypotension; risk of coma and death.
- Onset: unspecified.
- Evidence: theoretical, but severity rated major; opioid plus sedative-hypnotic combinations carry documented overdose risk.
- Management: avoid if possible; reserve for patients lacking adequate alternatives. Use lowest effective dose and shortest duration. Consider dose reduction of either agent, monitor for sedation and respiratory depression, and consider prescribing naloxone.
What happens
An increased risk of respiratory and CNS depression
Interaction Deep Dive
Do not combine opioid-based cough preparations with CNS depressants. Taking opioid analgesics together with benzodiazepines has been linked to a rise in emergency department visits as well as fatal overdoses2. When codeine is used alongside CNS depressants, there is a heightened likelihood of hypotension, respiratory depression, profound sedation, coma, and death. Prescribing these agents together should be limited to patients whose alternative treatment options are insufficient. Keep both the doses and the treatment duration to the lowest amount needed. Monitor patients carefully for indications of sedation and respiratory depression. When such combined use is justified, naloxone may be prescribed for emergency management of opioid overdose341.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Both medicines slow the brain and breathing, so your care team's goal is to keep you safe if you must use them together.
- Keep taking both as prescribed unless your prescriber tells you otherwise.
- Your team may use the lowest dose and shortest duration needed, and may adjust and individualize your doses.
- They may monitor you more closely for heavy drowsiness, confusion, or slowed breathing.
- In some cases they may prescribe naloxone as an emergency backup.
- Tell your pharmacist or doctor about any other sleep aids, alcohol, or sedatives, and report unusual sleepiness or breathing changes right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) In one study, 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. Drug overdose deaths resulting from 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 associated with the dispensing of both opioid analgesics and benzodiazepines was 10 times greater than the rate seen with the dispensing of opioid analgesics by themselves (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 who had no history of a benzodiazepine prescription. The risk of drug overdose deaths grew as the daily benzodiazepine dose increased 2.
d) Observational studies have shown that using opioid analgesics together with benzodiazepines raises the risk of drug-related mortality when compared with using opioid analgesics alone. Given their 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 Zopiclone and Acetaminophen And Codeine together?
Taking codeine (in your acetaminophen-codeine pain medicine) with zopiclone can add up to dangerous drowsiness and slowed breathing, so use them together only under your care team's guidance at the lowest doses. 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 Zopiclone 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 Zopiclone and Acetaminophen And Codeine interaction managed?
Both medicines slow the brain and breathing, so your care team's goal is to keep you safe if you must use them together. Keep taking both as prescribed unless your prescriber tells you otherwise. Your team may use the lowest dose and shortest duration needed, and may adjust and individualize your doses. They may monitor you more closely for heavy drowsiness, confusion, or slowed breathing. In some… 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 Zopiclone 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 Zopiclone
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