Acetaminophen And Codeine and Lormetazepam: 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
Lormetazepam
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 lormetazepam is a sedative in the benzodiazepine family. Both slow down the brain and the body. When taken together, they can cause heavy drowsiness, very slow or shallow breathing, low blood pressure, and in serious cases loss of consciousness.
Please don't stop either one on your own. Instead, talk with your doctor or pharmacist. They can decide if you truly need both, keep the doses as low as possible, and watch you closely. Right away, tell them if you feel unusually sleepy, confused, or short of breath.
Interaction: Additive CNS and respiratory depression when codeine (opioid agonist) is combined with lormetazepam (benzodiazepine).
- Direction/effect: Increased risk of hypotension, profound sedation, respiratory depression, coma, and death.
- Mechanism: Pharmacodynamic (additive CNS depression), not a CYP-mediated PK interaction. Note: codeine is a prodrug requiring CYP2D6 activation to morphine, but that is not the driver here.
- Evidence: Theoretical; severity major; onset unspecified.
- Management: Reserve for patients lacking adequate alternatives. Use lowest effective doses and shortest duration. Monitor for sedation and respiratory depression; consider co-prescribing naloxone.
What happens
An increased risk of hypotension, respiratory depression, profound sedation, coma, and death
Interaction Deep Dive
Taking codeine together with benzodiazepines may heighten the likelihood of hypotension, respiratory depression, deep sedation, coma and death. Prescribing both agents at the same time should be limited to patients whose alternative treatment options are insufficient. Keep doses and treatment durations as low as possible. Monitor patients closely for indications of sedation and respiratory depression. When combined use is justified, consider prescribing naloxone for the emergency management of opioid overdose134.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
This combination can be managed, but it needs care. Keep taking both exactly as prescribed unless your care team tells you otherwise.
- Your team may reserve this pairing only for when other options aren't enough, and use the lowest dose for the shortest time that works.
- They may monitor you more closely for sedation and breathing changes.
- Your doctor may consider prescribing naloxone as an emergency rescue medicine.
- Get help right away for severe drowsiness, confusion, very slow or shallow breathing, or fainting.
Bring any questions to your pharmacist or prescriber.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) A study found that the rate of emergency department visits related to nonmedical use between 2004 and 2011 and involving opioid analgesics along with benzodiazepines rose significantly from 11 to 34.2 per 100,000. Deaths from drug overdose attributable to prescribed and above-prescribed doses of both classes of drugs likewise rose significantly from 0.6 to 1.7 per 100,000, and overdose deaths caused by 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 spanning 2004 to 2009, the risk of fatal overdose rose significantly by 2.33 fold in patients receiving opioid analgesics who had a prior 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 daily benzodiazepine doses increased 2.
d) Observational studies have shown that using opioid analgesics together with benzodiazepines raises the risk of drug-related death compared with using opioid analgesics alone. Given the 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 Lormetazepam together?
Codeine and lormetazepam both depress the brain and breathing, so together they raise the risk of dangerous sedation and slowed breathing. Use only if truly 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 Lormetazepam 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 Lormetazepam interaction managed?
This combination can be managed, but it needs care. Keep taking both exactly as prescribed unless your care team tells you otherwise. Your team may reserve this pairing only for when other options aren't enough, and use the lowest dose for the shortest time that works. They may monitor you more closely for sedation and breathing changes. Your doctor may consider prescribing 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 Lormetazepam 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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