Flunitrazepam 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
Flunitrazepam
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 flunitrazepam is a benzodiazepine (a sedative). Both slow down your brain and body. Taken together, they can add up and make you very drowsy, slow your breathing, drop your blood pressure, and in serious cases cause coma or death.
This warning is based on how these types of drugs work together rather than on a specific study, but it is taken seriously because breathing problems can be dangerous. The good news is that your care team can manage this. Keep taking both exactly as prescribed, and call your doctor or pharmacist right away if you feel unusually sleepy, confused, or short of breath.
Additive CNS and respiratory depression from combining codeine (opioid agonist) with flunitrazepam (benzodiazepine). This is a pharmacodynamic interaction, not a CYP-based PK effect; note codeine is a prodrug bioactivated by CYP2D6 to morphine, but that is not the mechanism here.
- Direction: synergistic sedation, respiratory depression, hypotension, coma, death.
- Evidence: theoretical/class-based; severity major; onset unspecified.
- Management: reserve for patients lacking adequate alternatives; use lowest effective dose and shortest duration; monitor closely for sedation and respiratory depression; consider co-prescribing naloxone.
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 your prescriber has you on both, it is usually because the benefit is judged to outweigh the risk. Here is how a care team typically handles this:
- Prescribing the lowest effective doses for the shortest time needed.
- Watching you more closely for heavy sedation, slow or shallow breathing, and low blood pressure.
- Sometimes providing naloxone at home for emergency use.
Keep taking both as prescribed, do not add alcohol or other sedatives, and ask your pharmacist or doctor before making any changes. Get emergency help for very slow breathing or unresponsiveness.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) One study found that the rate of emergency department visits related to nonmedical use between 2004 and 2011 that involved opioid analgesics together with benzodiazepines rose significantly from 11 to 34.2 per 100,000. Deaths from drug overdose attributable to 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 that 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 patients taking opioid analgesics who had no history of a benzodiazepine prescription. The risk of drug overdose deaths grew as daily doses of benzodiazepines increased 2.
d) Observational studies have shown that using opioid analgesics and benzodiazepines together increases the risk of drug-related death 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 concomitantly with opioid analgesics 34.
Common questions
Can I take Flunitrazepam and Acetaminophen And Codeine together?
Combining codeine with flunitrazepam adds up their sedating effects and can dangerously slow breathing, so use only if truly needed, at the lowest dose, and stay alert for excessive drowsiness or breathing trouble. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Flunitrazepam 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 Flunitrazepam and Acetaminophen And Codeine interaction managed?
If your prescriber has you on both, it is usually because the benefit is judged to outweigh the risk. Here is how a care team typically handles this: Prescribing the lowest effective doses for the shortest time needed. Watching you more closely for heavy sedation, slow or shallow breathing, and low blood pressure. Sometimes providing naloxone at home for emergency use. Keep taking both as prescrib… 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 Flunitrazepam 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
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