Flurazepam 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
Flurazepam
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 here contains codeine, which is an opioid, and it also has acetaminophen (Tylenol). Flurazepam is a benzodiazepine used to help with sleep. Both of these drugs slow down your brain and nervous system. When taken together, that slowing effect can add up.
This can mean heavy drowsiness, slowed or shallow breathing, low blood pressure, and in rare, serious cases it can become life-threatening. The good news is your care team can manage this. Please keep taking both exactly as prescribed, and tell your doctor or pharmacist right away if you feel unusually sleepy, foggy, or short of breath.
Additive CNS depression between codeine (an opioid) and flurazepam (a benzodiazepine). This is a pharmacodynamic interaction, not a metabolic one, so both agents' sedative and respiratory-depressant effects compound.
- Direction: increased opioid/benzodiazepine effect (hypotension, respiratory depression, profound sedation, coma, death).
- Evidence: theoretical; severity: major; onset unspecified.
- Management: reserve concurrent use for patients without adequate alternatives; limit dose and duration to the minimum required; monitor closely for sedation and respiratory depression; consider prescribing naloxone.
Note codeine is a prodrug (CYP2D6-activated to morphine), but that does not alter this additive PD interaction.
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
Your care team can manage this combination safely with some precautions.
- Keep taking both as prescribed unless your doctor tells you otherwise. Do not stop or change doses on your own.
- Your team may keep your dose and treatment length as low as possible and may monitor you more closely for drowsiness and breathing changes.
- Your prescriber may also consider giving you naloxone to have on hand as an emergency backup.
- Avoid alcohol and other sedating medicines unless cleared by your care team.
Call your pharmacist or prescriber if you notice heavy sedation, confusion, or slowed breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) In one study, the rate of emergency department visits linked 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 associated with the dispensing of both opioid analgesics and benzodiazepines was 10 times greater than the rate associated with dispensing of opioid analgesics alone (7 vs 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 those 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 relative to using opioid analgesics alone. Given their comparable pharmacological properties, it is reasonable to anticipate a similar risk when other CNS depressant drugs are used concurrently with opioid analgesics 34.
Common questions
Can I take Flurazepam and Acetaminophen And Codeine together?
Combining this codeine/acetaminophen product with flurazepam adds up their sedating effects and can slow breathing, so use both only as prescribed at the lowest effective dose and watch closely for excessive drowsiness or breathing trouble. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Flurazepam 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 Flurazepam and Acetaminophen And Codeine interaction managed?
Your care team can manage this combination safely with some precautions. Keep taking both as prescribed unless your doctor tells you otherwise. Do not stop or change doses on your own. Your team may keep your dose and treatment length as low as possible and may monitor you more closely for drowsiness and breathing changes. Your prescriber may also consider giving you naloxone to have on hand as an… 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 Flurazepam 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 Flurazepam
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