Delorazepam 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
Delorazepam
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 delorazepam is a benzodiazepine (a calming, sedative-type medicine). Both slow down your brain and breathing. When you take them together, those effects can add up. That can mean heavy drowsiness, low blood pressure, and dangerously slow or shallow breathing. In serious cases this can lead to coma or even death.
This warning is based on how these drug types work rather than on studies of these two exact drugs, but it is taken seriously. Please don't stop either medicine on your own. Your care team can manage this safely by using the lowest doses for the shortest time and watching you closely. Ask your pharmacist or doctor if you have questions.
Effect: Additive CNS and respiratory depression from combining codeine (opioid agonist) with delorazepam (long-acting benzodiazepine). Risk includes hypotension, profound sedation, respiratory depression, coma, and death.
- Mechanism: Pharmacodynamic additive CNS depression (opioid mu-receptor plus GABA-A potentiation). Not primarily a PK interaction.
- Evidence: Theoretical / class-based; severity rated major.
- Onset: Unspecified; expect with peak concentrations.
- 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.
What happens
An increased risk of hypotension, respiratory depression, profound sedation, coma, and death
Interaction Deep Dive
Concomitant use of codeine with benzodiazepines can increase the risk of hypotension, respiratory depression, profound sedation, coma and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation. If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose134.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
If both are prescribed together, your care team is choosing this deliberately and can keep it safe.
- Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Do not adjust doses yourself.
- Your team may use the lowest doses for the shortest time needed, and monitor you more closely for sedation or slowed breathing.
- Ask whether a naloxone rescue kit is right for you, and make sure someone at home knows how to use it.
- Get urgent help for severe drowsiness, confusion, very slow or shallow breathing, or fainting.
- Avoid alcohol or other sedatives, and raise any concerns with your pharmacist or prescriber.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) One study found that between 2004 and 2011, the rate of emergency department visits related to nonmedical use and involving opioid analgesics together with benzodiazepines rose significantly from 11 to 34.2 per 100,000. Drug overdose deaths attributable to prescribed and higher than 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) In a prospective cohort study, the rate of overdose deaths involving the dispensing of both opioid analgesics and benzodiazepines was 10 times greater than that 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 death compared with using opioid analgesics alone. Given the 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 Delorazepam and Acetaminophen And Codeine together?
Codeine and delorazepam both depress the brain and breathing, so combining them raises the risk of heavy sedation and slowed breathing. Take both only as prescribed, use the lowest doses, and ask about naloxone and warning signs. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Delorazepam 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 Delorazepam and Acetaminophen And Codeine interaction managed?
If both are prescribed together, your care team is choosing this deliberately and can keep it safe. Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Do not adjust doses yourself. Your team may use the lowest doses for the shortest time needed, and monitor you more closely for sedation or slowed breathing. Ask whether a naloxone rescue kit is right for you, and m… 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 Delorazepam 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
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