Acetaminophen And Codeine and Quazepam: 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
Quazepam
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 both slow down your brain and body. Your pain pill contains codeine, an opioid, and quazepam (Doral) is a sleep and calming medicine in the benzodiazepine family. When you take them together, their calming effects add up. That can make you very sleepy, drop your blood pressure, and (most seriously) slow your breathing. In rare, severe cases this can be life threatening.
The good news: your care team can manage this. They may use the lowest doses for the shortest time and watch you closely. Please don't stop either medicine on your own. Tell your doctor or pharmacist if you feel unusually drowsy, dizzy, confused, or short of breath.
Effect: Additive CNS depression from combining codeine (opioid) with quazepam (benzodiazepine), increasing risk of hypotension, respiratory depression, profound sedation, coma, and death.
Mechanism: Pharmacodynamic additive CNS and respiratory depression. Codeine is a prodrug activated to morphine via CYP2D6, but this is a PD, not PK, interaction. No prodrug caveat alters the direction here.
Evidence/severity: Theoretical basis, rated major. Onset unspecified.
- Reserve concurrent use for when alternatives are inadequate
- Use lowest effective doses and shortest durations
- Monitor for sedation and respiratory depression
- Consider prescribing naloxone
What happens
An increased risk of hypotension, respiratory depression, profound sedation, coma, and death
Interaction Deep Dive
Taking codeine together with benzodiazepines can heighten the likelihood of respiratory depression, profound sedation, hypotension, coma and death. Prescribing both agents concurrently should be reserved for patients in whom other treatment options prove insufficient. Keep doses and treatment durations at the lowest levels necessary. Monitor patients carefully for indications of sedation and respiratory depression. When combined use is justified, consider providing naloxone for the emergency management of opioid overdose134.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
This combination can be managed, but it needs care. Providers usually reserve using both together for when other options aren't enough.
- Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
- Your team may use the lowest doses for the shortest time and monitor you more closely.
- Ask whether having naloxone (a rescue medicine for opioid overdose) at home is right for you.
- Get help right away for very slow or shallow breathing, extreme drowsiness, confusion, or fainting.
Bring this up with your pharmacist or doctor so your dose can be adjusted and individualized for you.
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 took place between 2004 and 2011 and involved opioid analgesics together with benzodiazepines rose significantly from 11 to 34.2 per 100,000. Deaths from drug overdose attributable to prescribed and greater than prescribed doses of both drug classes likewise increased 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 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 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 compared with using opioid analgesics alone. Given their similar pharmacological properties, it is reasonable to anticipate a comparable risk when other CNS depressant drugs are used concomitantly with opioid analgesics 34.
Common questions
Can I take Acetaminophen And Codeine and Quazepam together?
Taking codeine and quazepam together adds up their sedating effects and can dangerously slow breathing, so use both only under close medical supervision at the lowest effective doses and know the signs of oversedation. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Quazepam 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 Quazepam interaction managed?
This combination can be managed, but it needs care. Providers usually reserve using both together for when other options aren't enough. Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Your team may use the lowest doses for the shortest time and monitor you more closely. Ask whether having naloxone (a rescue medicine for opioid overdose) at home is right for you.… 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 Quazepam 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 Quazepam
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