Halothane 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
Halothane
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.
These two medicines both slow down your brain and breathing, and using them together makes that effect stronger. The codeine in your pain medicine is an opioid, and halothane is an anesthetic gas used during surgery. Both can cause deep sleepiness and slower breathing. Stacked together, they can lower your blood pressure and make breathing dangerously slow.
The good news is that this is very manageable. Your surgical and anesthesia team knows about this and will plan for it. Always tell your care team every medicine you take, including your acetaminophen and codeine, so they can keep you safe.
Mechanism: additive CNS and respiratory depression. Codeine is an opioid prodrug activated via CYP2D6 to morphine; halothane is a volatile anesthetic with intrinsic CNS-depressant activity. This is a pharmacodynamic (additive), not pharmacokinetic, interaction.
- Direction: increased sedation, hypotension, respiratory depression, potential coma or death.
- Severity/evidence: major; theoretical/mechanistic basis.
- Onset: unspecified (perioperative).
- Management: avoid unless necessary; use lowest effective opioid dose and shortest duration; reduce doses of one or both agents; monitor sedation, SpO2, respiratory rate, and BP. Consider naloxone availability.
What happens
An increased risk of respiratory and CNS depression
Interaction Deep Dive
Avoid concomitant use of opioid cough medication formulations and CNS depressants. Concomitant use of opioid analgesics with benzodiazepines has been associated with increased rates of emergency department visits and fatal overdose2. Concomitant use of codeine with CNS depressants 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 overdose 341.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
This is something your care team handles routinely, especially around surgery. Keep taking your acetaminophen and codeine exactly as prescribed, and make sure your surgeon, anesthesiologist, and pharmacist have your full medication list.
- Your team may lower the dose of one or both medicines and individualize it to you.
- They will monitor you closely for heavy sedation, slow breathing, and low blood pressure.
- They generally use the lowest dose for the shortest time when both are needed.
- Naloxone may be kept available as a safety measure.
Ask your prescriber or pharmacist before any planned procedure so they can plan ahead.
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 along 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 increased significantly from 0.6 to 1.7 per 100,000, and overdose deaths attributable to benzodiazepines increased 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 seen 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 increased as daily doses of benzodiazepines increased 2.
d) Observational studies have shown that using opioid analgesics together with benzodiazepines 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 concomitantly with opioid analgesics 34.
Common questions
Can I take Halothane and Acetaminophen And Codeine together?
Codeine and halothane both depress breathing and the central nervous system, so combining them raises the risk of dangerous sedation and slow breathing; your surgical team manages this by limiting doses and monitoring you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Halothane 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 Halothane and Acetaminophen And Codeine interaction managed?
This is something your care team handles routinely, especially around surgery. Keep taking your acetaminophen and codeine exactly as prescribed, and make sure your surgeon, anesthesiologist, and pharmacist have your full medication list. Your team may lower the dose of one or both medicines and individualize it to you. They will monitor you closely for heavy sedation, slow breathing, and low blood… 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 Halothane 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
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