Mephobarbital 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
Mephobarbital
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.
Your pain medicine contains codeine, an opioid, and you also take mephobarbital, a barbiturate. Both of these slow down your brain and your breathing. When they are taken together, that calming effect can stack up. This can make you very sleepy, slow your breathing too much, drop your blood pressure, and in serious cases it can be dangerous.
This warning is based on how these drugs work rather than on lots of studies, but the risk is taken seriously because both are strong sedatives. Please don't stop or change either medicine on your own. Talk with your pharmacist or doctor. Your care team can manage this by using the lowest doses needed and watching you closely.
Effect: Additive CNS and respiratory depression from combining codeine (opioid analgesic, in the acetaminophen/codeine product) with mephobarbital (a barbiturate CNS depressant).
Mechanism: Pharmacodynamic additive CNS depression, not a pharmacokinetic interaction. Both agents depress central respiratory drive and consciousness.
- Direction: Increased sedation, hypotension, respiratory depression; risk of coma and death.
- Onset: Unspecified; expect with concurrent dosing.
- Evidence: Theoretical, but rated major given known opioid plus sedative fatality data.
- Management: Avoid if possible; reserve for inadequate alternatives. Use lowest effective doses and shortest duration, consider reducing dose of either agent, monitor for sedation and respiratory depression, and consider prescribing naloxone.
What happens
An increased risk of respiratory and CNS depression
Interaction Deep Dive
Do not combine opioid formulations intended for cough with CNS depressants. When opioid analgesics are taken together with benzodiazepines, the rates of emergency department visits and fatal overdose rise2. Taking codeine alongside CNS depressants heightens the likelihood of hypotension, respiratory depression, profound sedation, coma, and death. Prescribing these agents together should be limited to patients whose alternative treatment options are inadequate. Keep both the dosage and the length of therapy to the lowest amount necessary. Monitor patients closely for indications of sedation and respiratory depression. Should combined use be justified, think about prescribing naloxone to treat opioid overdose in an emergency341.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
The safest approach is often to avoid this combination, so your care team may look at whether an alternative is available. If you do need both, here is what a care team typically does:
- Uses the lowest dose and shortest duration that works.
- May lower the dose of the codeine product or the mephobarbital, individualized to you.
- Watches you closely for heavy sedation or slowed breathing.
- May prescribe naloxone to keep on hand for emergencies.
Keep taking both exactly as prescribed for now. Tell your pharmacist or prescriber that you take these together, and report any unusual drowsiness, confusion, or slow or shallow breathing right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) In one study, the frequency of emergency department visits related to nonmedical use that occurred between 2004 and 2011 and involved opioid analgesics together with benzodiazepines rose significantly from 11 to 34.2 per 100,000. Deaths from drug overdose attributed 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 attributed 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 with the 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 receiving opioid analgesics who had a prior 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 grew 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 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 Mephobarbital and Acetaminophen And Codeine together?
Combining the codeine in your pain medicine with mephobarbital adds up their sedating effects and can dangerously slow breathing, so use this pairing only under close medical supervision. Do not stop or change either drug on your own; talk with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Mephobarbital 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 Mephobarbital and Acetaminophen And Codeine interaction managed?
The safest approach is often to avoid this combination, so your care team may look at whether an alternative is available. If you do need both, here is what a care team typically does: Uses the lowest dose and shortest duration that works. May lower the dose of the codeine product or the mephobarbital, individualized to you. Watches you closely for heavy sedation or slowed breathing. May prescribe… 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 Mephobarbital 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 Mephobarbital
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