Acetaminophen And Codeine and Thiopental: 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
Thiopental
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.
Both of these medicines slow down your brain and breathing. Acetaminophen with codeine is a pain reliever that contains an opioid (codeine). Thiopental is a strong sedative used to make you sleepy, often before or during a procedure. When you take both, their calming effects can add up.
Together they can make you very drowsy, lower your blood pressure, and slow your breathing more than either one alone. In serious cases that can be dangerous. The good news is your care team knows about this and can manage it by using the lowest doses needed and watching you closely. Never adjust either medicine on your own. If you feel unusually sleepy or short of breath, tell your doctor or pharmacist right away.
Effect: Additive CNS and respiratory depression when codeine (an opioid analgesic) is combined with thiopental (a barbiturate anesthetic/CNS depressant).
- Mechanism: Pharmacodynamic additive CNS depression, not a metabolic/prodrug issue. Both agents independently depress central respiratory drive and consciousness.
- Direction: Increased sedation, hypotension, respiratory depression, risk of coma and death.
- Onset: Unspecified; effect expected during overlapping exposure.
- Evidence: Theoretical, but severity rated major given opioid + CNS depressant class data.
- Management: Reserve concomitant use for when alternatives are inadequate; use lowest effective dose and shortest duration; consider dose reduction of one agent; monitor closely for sedation and respiratory depression; consider prescribing naloxone.
What happens
An increased risk of respiratory and CNS depression
Interaction Deep Dive
Do not combine opioid-based cough preparations with CNS depressants. Taking opioid analgesics together with benzodiazepines has been linked to higher rates of both emergency department visits and fatal overdose2. When codeine is used alongside CNS depressants, patients face a greater risk of hypotension, respiratory depression, profound sedation, coma, and death. Prescribing these agents together should be limited to patients for whom other treatment options prove insufficient. Keep both doses and treatment durations at the lowest level necessary. Monitor patients closely for indications of sedation and respiratory depression. Should concurrent use be justified, consider prescribing naloxone to allow emergency management of opioid overdose341.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Keep taking both exactly as prescribed and do not stop or change either one on your own. Your care team may take steps to keep this combination safe:
- Using the lowest dose and shortest duration needed to reach your treatment goals.
- Possibly lowering the dose of the codeine product or the sedative, individualized by your team.
- Monitoring you more closely for excess drowsiness, low blood pressure, and slowed breathing.
- In some cases, prescribing naloxone for emergency use.
Ask your pharmacist or prescriber before adding any other sedating medicine, alcohol, or sleep aid, and report unusual sleepiness or trouble breathing promptly.
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 took place between 2004 and 2011 and that 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 likewise increased 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 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 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 grew as the daily doses of benzodiazepines increased 2.
d) Observational studies have shown that using opioid analgesics and benzodiazepines together increases 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 concurrently with opioid analgesics 34.
Common questions
Can I take Acetaminophen And Codeine and Thiopental together?
Combining acetaminophen/codeine with thiopental adds up their sedative effects and can dangerously slow breathing, so this pairing should only be used when needed, at the lowest dose, with close monitoring by your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Thiopental 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 Thiopental interaction managed?
Keep taking both exactly as prescribed and do not stop or change either one on your own. Your care team may take steps to keep this combination safe: Using the lowest dose and shortest duration needed to reach your treatment goals. Possibly lowering the dose of the codeine product or the sedative, individualized by your team. Monitoring you more closely for excess drowsiness, low blood pressure, a… 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 Thiopental 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 Thiopental
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