Acetaminophen And Codeine and Medazepam: 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
Medazepam
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 make each other stronger in a risky way. Your pain medicine contains codeine, an opioid, and medazepam is a benzodiazepine (a calming, sedative-type drug). Both slow down your brain and breathing. Taken together, they can make you very sleepy, lower your blood pressure, and in serious cases slow your breathing dangerously. This is called additive CNS depression.
The good news is that your care team can manage this. They may use the lowest doses for the shortest time, watch you more closely, and sometimes prescribe naloxone as a safety backup. Please don't stop either medicine on your own, but do talk with your pharmacist or doctor.
Additive CNS depression from concurrent codeine (opioid) and medazepam (benzodiazepine). Effect is pharmacodynamic, not a metabolic/enzyme interaction. Neither activation step reverses the direction here; both agents independently depress respiratory and central drive.
- Direction: increased sedation, hypotension, respiratory depression, potential coma/death.
- Onset: unspecified; Evidence: theoretical but consistent class effect (major severity).
- Management: reserve co-prescribing for when alternatives are inadequate; use lowest effective doses and shortest duration; monitor closely for sedation and respiratory depression; consider prescribing naloxone.
Counsel on additive sedation with alcohol and other CNS depressants.
What happens
An increased risk of hypotension, respiratory depression, profound sedation, coma, and death
Interaction Deep Dive
Using codeine together with benzodiazepines can heighten the likelihood of hypotension, respiratory depression, extreme sedation, coma, and death. Combined prescribing of these agents should be limited to patients whose alternative treatment options prove inadequate. Keep both doses and treatment durations to the lowest levels necessary. Monitor patients closely for indications of sedation and respiratory depression. Should concurrent use be justified, consider prescribing naloxone for the emergency management of opioid overdose134.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Keep taking both exactly as prescribed unless your care team tells you otherwise. Because both drugs calm the nervous system, your team manages this by tailoring your treatment.
- They may use the lowest doses for the shortest time needed.
- They may monitor you more closely for heavy drowsiness, slow or shallow breathing, confusion, or feeling faint.
- They may consider prescribing naloxone as an emergency backup.
Tell your pharmacist or doctor if you feel unusually sleepy or short of breath, and avoid alcohol or other sedatives. Ask before making any changes.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) One study found that the rate of emergency department visits linked to nonmedical use and involving both opioid analgesics and benzodiazepines rose significantly between 2004 and 2011, 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 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 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 and benzodiazepines together 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 together with opioid analgesics 34.
Common questions
Can I take Acetaminophen And Codeine and Medazepam together?
Codeine (an opioid) and medazepam (a benzodiazepine) both depress the brain and breathing, so together they raise the risk of heavy sedation, low blood pressure, and slowed breathing. Use only when needed, at the lowest doses, with close monitoring, and talk to your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Medazepam 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 Medazepam interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. Because both drugs calm the nervous system, your team manages this by tailoring your treatment. They may use the lowest doses for the shortest time needed. They may monitor you more closely for heavy drowsiness, slow or shallow breathing, confusion, or feeling faint. They may consider prescribing naloxone as an emerg… 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 Medazepam 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
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