Acetaminophen And Codeine and Amobarbital: 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
Amobarbital
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 two medicines both slow down your brain and body in similar ways. Codeine is an opioid pain reliever, and amobarbital (Amytal) is a barbiturate sedative. When taken together, they can add up and make you very drowsy, slow your breathing, and lower your blood pressure. In serious cases this can be dangerous.
The good news is that this is very manageable. Your care team knows about this combination and can keep you safe by using the lowest doses needed and watching you closely. Please don't stop or change either medicine on your own, just talk with your pharmacist or doctor about how you're feeling on both.
Additive CNS and respiratory depression from combining codeine (opioid analgesic) with amobarbital (barbiturate CNS depressant). This is a pharmacodynamic interaction, not primarily pharmacokinetic; both agents independently depress the CNS and respiratory drive.
- Direction: increased sedation, hypotension, respiratory depression, risk of coma/death.
- Evidence: theoretical/class-based, but severity is major given opioid plus sedative-hypnotic risk.
- Onset: unspecified; expect with overlapping serum levels.
- Management: avoid if possible; if warranted, use lowest effective doses and shortest duration, monitor sedation and respiratory rate, and consider prescribing naloxone.
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
Care teams generally try to avoid using these two together when possible. If both are truly needed, here is what usually happens:
- The dose of codeine and/or amobarbital may be adjusted and individualized to the lowest amount for the shortest time needed.
- Your team may monitor you more closely for excessive drowsiness and slowed breathing.
- A prescriber may consider providing naloxone as an emergency backup.
Keep taking both exactly as prescribed unless told otherwise. Tell your pharmacist or doctor right away if you feel unusually sleepy, confused, or short of breath.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) One study found that emergency department visits related to nonmedical use that occurred between 2004 and 2011 and involved 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 categories 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 opioid analgesics alone (7 versus 0.7 per 10,000 person years) 2.
c) In a cohort study using data from 2004 to 2009, patients taking opioid analgesics who had a history of a benzodiazepine prescription showed a significant 2.33 fold increase in the risk of fatal overdose, and those with a current benzodiazepine prescription showed a 3.86 fold increase, compared with patients taking opioid analgesics without any history of a benzodiazepine prescription. The risk of drug overdose deaths rose as daily benzodiazepine doses 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 Acetaminophen And Codeine and Amobarbital together?
Combining codeine with amobarbital adds up their sedating effects and can dangerously slow breathing, so use together only when necessary at the lowest doses with close monitoring. Talk to your care team before making any changes. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Amobarbital 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 Amobarbital interaction managed?
Care teams generally try to avoid using these two together when possible. If both are truly needed, here is what usually happens: The dose of codeine and/or amobarbital may be adjusted and individualized to the lowest amount for the shortest time needed. Your team may monitor you more closely for excessive drowsiness and slowed breathing. A prescriber may consider providing naloxone as an emergenc… 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 Amobarbital 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 Amobarbital
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