Methohexital 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
Methohexital
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, so together they can push that too far. Your acetaminophen with codeine is a pain reliever that contains an opioid (codeine). Methohexital (Brevital) is a barbiturate used to help you relax or sleep for a procedure. When you take both, the calming and drowsy effects add up. That can lead to very deep sleepiness, slowed or shallow breathing, low blood pressure, and in serious cases it can become dangerous.
The good news is your care team can manage this. They will use the smallest doses needed and watch you closely. Never start, stop, or change either medicine on your own. Talk with your doctor or pharmacist about how to use them safely.
Additive CNS and respiratory depression from combining codeine (opioid) with methohexital (barbiturate). Both are PD-additive CNS depressants; codeine is a prodrug activated via CYP2D6, but the concern here is pharmacodynamic, not metabolic.
- Effect: increased risk of hypotension, profound sedation, respiratory depression, coma, death.
- Direction: enhanced depressant effect of both agents.
- Onset: unspecified; evidence is theoretical/extrapolated but severity is major.
- Management: avoid if possible; reserve co-use for when alternatives are inadequate. Use lowest effective doses and shortest duration. Monitor sedation, respiratory rate, and hemodynamics. Consider naloxone availability.
What happens
An increased risk of respiratory and CNS depression
Interaction Deep Dive
Do not combine opioid-based cough preparations with agents that depress the CNS. Taking opioid analgesics together with benzodiazepines has been linked to higher rates of emergency department visits as well as fatal overdose2. When codeine is used alongside CNS depressants, the likelihood of hypotension, respiratory depression, profound sedation, coma, and death may rise. Prescribing both drug classes at the same time should be limited to patients in whom other treatment approaches prove insufficient. Keep both dose and treatment duration to the lowest level needed. Monitor patients carefully for indications of sedation and respiratory depression. Should combined use be justified, consider providing naloxone so that opioid overdose can be treated in an emergency341.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Keep taking both exactly as prescribed and let your care team coordinate the timing, since methohexital is usually given for a procedure.
- Your team will generally use the lowest doses for the shortest time needed.
- They may monitor you more closely for heavy sedation, slow or shallow breathing, and low blood pressure.
- They may tailor and adjust the dose of the codeine product or the methohexital to your needs.
- In some cases they may keep naloxone on hand as a safety measure.
Tell your pharmacist or prescriber about all sedating medicines, alcohol, or sleep aids you use, and get help right away if you feel very drowsy or hard to wake.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) A study found that between 2004 and 2011 the rate of emergency department visits related to nonmedical use and involving both opioid analgesics and benzodiazepines rose significantly from 11 to 34.2 per 100,000. Deaths from drug overdose attributable to prescribed and above-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 involving dispensing of both opioid analgesics and benzodiazepines was 10 times greater than 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 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 those taking opioid analgesics without any 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 together with benzodiazepines raises the risk of drug-related mortality relative to using opioid analgesics alone. Given comparable pharmacological characteristics, it is reasonable to anticipate a similar risk when other CNS depressant drugs are used together with opioid analgesics 34.
Common questions
Can I take Methohexital and Acetaminophen And Codeine together?
Codeine and methohexital both depress the brain and breathing, so combining them can cause dangerous sedation and slowed breathing. Only use together under close medical supervision at the lowest effective doses. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Methohexital 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 Methohexital and Acetaminophen And Codeine interaction managed?
Keep taking both exactly as prescribed and let your care team coordinate the timing, since methohexital is usually given for a procedure. Your team will generally use the lowest doses for the shortest time needed. They may monitor you more closely for heavy sedation, slow or shallow breathing, and low blood pressure. They may tailor and adjust the dose of the codeine product or the methohexital to… 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 Methohexital 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 Methohexital
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