Acetaminophen And Codeine and Meprobamate: 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
Meprobamate
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 can slow you down too much when taken together. Your pain medicine contains codeine, an opioid, and acetaminophen (Tylenol). Meprobamate is a calming medicine that also relaxes the brain. Both of them slow down your breathing and your alertness. When you take them at the same time, those effects can stack up and become dangerous.
This could cause heavy drowsiness, very slow or shallow breathing, low blood pressure, or in serious cases, hard-to-wake sleep. Please don't stop either medicine on your own. Talk with your pharmacist or doctor. They can adjust doses, watch you more closely, or find a safer plan for you.
Additive CNS and respiratory depression from combining codeine (an opioid; note it is a prodrug activated by CYP2D6, but the concern here is pharmacodynamic, not metabolic) with meprobamate, a sedative-hypnotic carbamate.
- Mechanism: additive PD depression of the CNS and respiratory drive; no PK interaction implied.
- Risk: hypotension, profound sedation, respiratory depression, coma, death.
- Evidence: theoretical, but severity rated major (opioid + CNS depressant class effect).
- Management: avoid if possible; reserve for patients lacking alternatives. Use lowest effective doses and shortest duration. Monitor sedation and respiratory status; 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. Studies have linked the joint use of opioid analgesics and benzodiazepines to higher rates of both emergency department visits and fatal overdose2. When codeine is taken together with CNS depressants, the likelihood of hypotension, respiratory depression, profound sedation, coma, and death rises. Prescribe these agents together only for patients whose alternative treatment options prove inadequate. Keep both the doses and the treatment periods to the smallest amount necessary. Monitor patients carefully for indications of sedation and respiratory depression. Should concurrent use be justified, consider providing naloxone so that opioid overdose can be treated on an emergency basis341.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Keep taking both only as prescribed and do not stop either one on your own. This combination is best avoided when possible, so your care team may look for a safer alternative.
- If both are truly needed, the team typically uses the lowest dose and shortest duration of the codeine product or the meprobamate.
- Your dose may need to be adjusted and individualized, and your team may monitor you more closely for heavy sedation or slowed breathing.
- Your prescriber may also consider giving you naloxone for emergencies.
- Call for help right away if you notice extreme drowsiness, confusion, or slow, shallow breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) In one study, 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. Drug overdose deaths attributable to prescribed doses and doses exceeding those prescribed for 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 the dispensing of both opioid analgesics and benzodiazepines was 10 times greater than the rate with dispensing of opioid analgesics alone (7 versus 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 without a 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 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 concurrently with opioid analgesics 34.
Common questions
Can I take Acetaminophen And Codeine and Meprobamate together?
Combining acetaminophen-codeine with meprobamate stacks their sedative effects and can dangerously slow breathing; avoid this combo if you can, and let your pharmacist or doctor tailor doses and monitoring if both are truly needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Meprobamate 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 Meprobamate interaction managed?
Keep taking both only as prescribed and do not stop either one on your own. This combination is best avoided when possible, so your care team may look for a safer alternative. If both are truly needed, the team typically uses the lowest dose and shortest duration of the codeine product or the meprobamate. Your dose may need to be adjusted and individualized, and your team may monitor you more clos… 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 Meprobamate 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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