Acetaminophen And Codeine and Lorazepam: 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
Lorazepam
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 slow down your brain and breathing. Codeine is an opioid pain reliever (combined here with acetaminophen, or Tylenol), and lorazepam (Ativan) is a benzodiazepine used for anxiety or sleep. When taken together, their calming effects add up. This can make you very drowsy, lower your blood pressure, and in serious cases slow your breathing dangerously, which can lead to coma or even death.
Please don't stop either medicine on your own. Doctors do sometimes prescribe them together when needed. The key is using the lowest dose for the shortest time and watching closely. Talk with your pharmacist or doctor about how to take these safely.
Mechanism: Additive CNS depression from an opioid (codeine) plus a benzodiazepine (lorazepam). Neither is a prodrug consideration relevant here; the concern is pharmacodynamic, not enzymatic.
Effect / direction: Increased risk of hypotension, respiratory depression, profound sedation, coma, and death.
- Evidence: Theoretical, but severity rated major (FDA class warning for opioid/benzodiazepine coadministration).
- Onset: Unspecified; can occur early in therapy.
- Management: Reserve for patients lacking adequate alternatives. Use lowest effective doses and shortest durations. Monitor closely 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 low blood pressure, respiratory depression, deep sedation, coma, and death. Prescribing both agents concurrently should be limited to patients whose alternative treatment options prove insufficient. Keep doses and treatment lengths at the lowest levels necessary. Monitor patients carefully for indications of sedation and respiratory depression. When combined use is justified, consider prescribing naloxone to allow 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. Your team can manage this combination safely.
- Your doctor may prescribe the lowest doses for the shortest time needed.
- They may monitor you more closely for heavy drowsiness or slowed breathing.
- Your care team may consider prescribing naloxone for emergencies, and can show you and your family how to use it.
- Avoid alcohol and other sedatives, and tell your prescriber if you feel very sleepy, confused, or short of breath.
Ask your pharmacist or doctor before making any changes.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) In one study, emergency department visits related to nonmedical use that occurred between 2004 and 2011 and involved opioid analgesics along with benzodiazepines rose significantly from 11 to 34.2 per 100,000. Deaths from drug overdose attributable to prescribed as well as 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) 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 dispensing of opioid analgesics on their own (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 death from drug overdose 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. Owing to comparable pharmacological properties, a similar risk can reasonably be anticipated when other CNS depressant drugs are used together with opioid analgesics 34.
Common questions
Can I take Acetaminophen And Codeine and Lorazepam together?
Taking codeine (with acetaminophen) and lorazepam together adds up their sedating effects and can dangerously slow breathing. Use the lowest doses for the shortest time, watch for heavy drowsiness or slow breathing, and keep your care team involved. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Lorazepam 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 Lorazepam interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. Your team can manage this combination safely. Your doctor may prescribe the lowest doses for the shortest time needed. They may monitor you more closely for heavy drowsiness or slowed breathing. Your care team may consider prescribing naloxone for emergencies, and can show you and your family how to use it. Avoid alc… 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Acetaminophen And Codeine or Lorazepam 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 Lorazepam
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