Acetaminophen And Codeine and Nitrazepam: 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
Nitrazepam
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 nitrazepam is a benzodiazepine used for sleep or anxiety. Both of these slow down your brain and breathing. When you take them together, those calming effects add up. That can make you very drowsy, lower your blood pressure, and in serious cases slow your breathing dangerously.
This does not mean you cannot use both. It means your care team wants to keep the doses low, use them for as short a time as possible, and watch you closely. Please do not start, stop, or change either medicine on your own. Talk with your doctor or pharmacist, and ask them about warning signs to watch for.
Additive CNS and respiratory depression from combining codeine (opioid agonist) with nitrazepam (benzodiazepine). Risk includes hypotension, profound sedation, respiratory depression, coma, and death.
- Mechanism: additive pharmacodynamic CNS depression (not a CYP or transporter interaction). Note codeine is a prodrug activated to morphine via CYP2D6, but that is not the concern here.
- Direction/magnitude: increased sedative/respiratory-depressant effect; magnitude not quantified.
- Evidence: theoretical; severity rated major.
- Management: reserve for patients lacking adequate alternatives; use lowest effective dose and shortest duration; 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 may raise the likelihood of hypotension, respiratory depression, deep sedation, coma, and death. Prescribing these agents together should be limited to patients for whom other treatment options are insufficient. Keep both the doses and the length of therapy to the lowest amount necessary. Monitor patients carefully for indications of sedation and respiratory depression. When combined use is justified, consider prescribing naloxone to treat opioid overdose in emergencies134.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Keep taking both exactly as prescribed unless your care team tells you otherwise. Because these medicines add to each other's sedating effects, your team manages this by tailoring how much and how long you take them.
- Doses may be kept low and durations short, individualized by your care team.
- Your team may monitor you more closely for heavy drowsiness, slow or shallow breathing, confusion, or feeling faint.
- Your prescriber may consider giving you naloxone to keep on hand for emergencies.
Ask your pharmacist or doctor which warning signs matter most and avoid alcohol or other sedatives while on both.
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 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 doses and doses exceeding what was prescribed 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 dispensing of opioid analgesics alone (7 versus 0.7 per 10,000 person years) 2.
c) In a cohort study drawing on 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 patients taking opioid analgesics who had no history of a benzodiazepine prescription. The risk of drug overdose deaths increased 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 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 Acetaminophen And Codeine and Nitrazepam together?
Codeine and nitrazepam both depress the brain and breathing, so together they raise the risk of heavy sedation, slowed breathing, and low blood pressure. Use only as prescribed, at the lowest dose for the shortest time, and ask your care team about warning signs and possibly keeping naloxone on hand. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Nitrazepam 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 Nitrazepam interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. Because these medicines add to each other's sedating effects, your team manages this by tailoring how much and how long you take them. Doses may be kept low and durations short, individualized by your care team. Your team may monitor you more closely for heavy drowsiness, slow or shallow breathing, confusion, or feel… 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 Nitrazepam 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 Nitrazepam
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