Acetaminophen And Codeine and Nitrous Oxide: 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
Nitrous Oxide
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 nitrous oxide is a sedating gas often used for procedures or dental work. Both of these can slow down your brain and your breathing. When you take them together, that slowing effect can add up.
This means you could feel very drowsy, breathe too slowly or shallowly, or have your blood pressure drop. In serious cases this can be dangerous. The good news is your care team knows how to handle this. They can use the lowest dose needed, keep the time short, and watch you closely. Always tell your dentist or doctor you take acetaminophen with codeine before any procedure.
Effect: Additive CNS and respiratory depression from combining codeine (opioid) with nitrous oxide (inhaled CNS depressant/anesthetic). Both agents produce PD-level sedation and respiratory drive suppression; the effect is additive, not PK-mediated.
- Direction: Increased risk of hypotension, profound sedation, respiratory depression, and rarely coma or death.
- Onset: Unspecified; expect during concurrent exposure.
- Evidence: Theoretical, but severity rated major.
- Management: Reserve concurrent use for when alternatives are inadequate. Use lowest effective codeine and/or nitrous oxide dose, shortest duration. Monitor sedation and respiratory status; consider naloxone availability.
What happens
An increased risk of respiratory and CNS depression
Interaction Deep Dive
Do not combine opioid cough preparations with CNS depressants. Taking opioid analgesics together with benzodiazepines has been linked to higher numbers of emergency department visits and deaths from overdose2. When codeine is used alongside CNS depressants, the likelihood of hypotension, respiratory depression, profound sedation, coma, and death rises. Prescribing these agents together should be limited to patients whose alternative treatment options prove inadequate. Keep both the dose and the length of therapy as low as possible. Monitor patients carefully for indications of sedation and respiratory depression. Should combined use be justified, think about prescribing naloxone to treat opioid overdose in an emergency341.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Keep taking your medications exactly as prescribed, and do not stop anything on your own. The main goal here is to avoid unnecessary overlap of two sedating agents.
- Tell your dentist, surgeon, or doctor that you take acetaminophen with codeine before any procedure that uses nitrous oxide.
- Your care team may use the lowest dose and shortest duration of either drug, and the dose may be adjusted and individualized for you.
- They may monitor you more closely for heavy drowsiness, slow or shallow breathing, or low blood pressure.
- In some cases, your team may discuss having naloxone available.
Ask your pharmacist if you are unsure about any of your sedating medicines.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) A study found that 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 and above-prescribed doses of both drug classes also 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 with the 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 in patients receiving 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 grew as daily benzodiazepine doses 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 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 Acetaminophen And Codeine and Nitrous Oxide together?
Codeine and nitrous oxide both depress the brain and breathing, so combining them adds up and can be dangerous. Tell your care team you take acetaminophen with codeine before any nitrous oxide procedure so they can use the lowest dose and watch you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Nitrous Oxide 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 Nitrous Oxide interaction managed?
Keep taking your medications exactly as prescribed, and do not stop anything on your own. The main goal here is to avoid unnecessary overlap of two sedating agents. Tell your dentist, surgeon, or doctor that you take acetaminophen with codeine before any procedure that uses nitrous oxide. Your care team may use the lowest dose and shortest duration of either drug, and the dose may be adjusted and… 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 Nitrous Oxide 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 Nitrous Oxide
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist