Acetaminophen And Codeine and Loprazolam: 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
Loprazolam
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 both calm your brain and body, so taking them together can be risky. Your pain medicine contains codeine (an opioid) plus acetaminophen (Tylenol). Loprazolam is a benzodiazepine used for sleep or anxiety. Both slow down your central nervous system.
When combined, they can add up and cause very deep sleepiness, slowed or shallow breathing, low blood pressure, and in serious cases coma or death. Warning signs include being hard to wake, confusion, or breathing that seems slow. The good news: your care team can manage this safely by using the lowest doses for the shortest time and watching you closely. Never stop or change either medicine on your own, talk with your doctor or pharmacist first.
Mechanism: Additive CNS and respiratory depression from combining an opioid (codeine, in the acetaminophen/codeine product) with a benzodiazepine (loprazolam). Note: codeine is a prodrug activated to morphine via CYP2D6, but this interaction is pharmacodynamic (additive), not metabolic.
- Effect: Increased risk of hypotension, respiratory depression, profound sedation, coma, and death.
- Direction: Enhanced CNS depressant effect of both agents.
- Evidence: Theoretical, but severity rated major (opioid + benzodiazepine class warning).
- Management: Reserve co-prescribing for patients lacking adequate alternatives. Use minimum effective doses and durations. Monitor for sedation and respiratory depression. Consider prescribing naloxone.
What happens
An increased risk of hypotension, respiratory depression, profound sedation, coma, and death
Interaction Deep Dive
Taking codeine alongside benzodiazepines may heighten the likelihood of profound sedation, respiratory depression, hypotension, coma and death. Prescribing both agents together should be limited to patients whose alternative treatments are insufficient. Restrict doses and treatment length to the minimum necessary, and monitor patients carefully for indications of sedation and respiratory depression. When combined use is justified, consider prescribing naloxone to treat opioid overdose on an emergency basis134.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
This combination can be used when needed, but it should be handled carefully by your care team. Doctors typically reserve using an opioid and a benzodiazepine together for when other options are not enough.
- Doses and durations may be kept as low and as short as possible, individualized by your care team.
- Your team may monitor you more closely for heavy drowsiness or slowed breathing.
- Your prescriber may also provide naloxone as an emergency rescue medicine.
What you should do: Keep taking both exactly as prescribed unless told otherwise. Tell your pharmacist or doctor if you feel very sleepy, confused, or notice slow breathing, and make sure they know you take both.
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 related to nonmedical use between 2004 and 2011 involving both opioid analgesics and 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 attributable to benzodiazepines rose significantly from 18% to 31% 2.
b) A prospective cohort study reported that the rate of overdose deaths associated with the dispensing of both opioid analgesics and benzodiazepines was 10 times greater than with 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 among patients receiving 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 the 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 relative to using opioid analgesics alone. Given comparable pharmacological characteristics, 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 Loprazolam together?
Combining codeine (with acetaminophen) and loprazolam adds up their sedating effects and can dangerously slow breathing, so use only when necessary, at the lowest dose, with close monitoring and possibly naloxone on hand. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Loprazolam 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 Loprazolam interaction managed?
This combination can be used when needed, but it should be handled carefully by your care team. Doctors typically reserve using an opioid and a benzodiazepine together for when other options are not enough. Doses and durations may be kept as low and as short as possible, individualized by your care team. Your team may monitor you more closely for heavy drowsiness or slowed breathing. Your prescrib… 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 Loprazolam 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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