Acetaminophen And Codeine and Alprazolam: 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
Alprazolam
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, which is an opioid, and Xanax (alprazolam) is a benzodiazepine. Both slow down your brain and nervous system. When you take them together, those calming effects add up. This can make you very drowsy, slow your breathing, drop your blood pressure, and in serious cases it can be life-threatening.
The good news is that this is manageable. Your care team can decide if you really need both, keep the doses and length of treatment as low as possible, and watch you closely. Please don't stop or change either medicine on your own. Talk with your doctor or pharmacist, and let them know right away if you feel unusually sleepy or short of breath.
Mechanism: additive CNS and respiratory depression from combining an opioid (codeine) with a benzodiazepine (alprazolam). Neither drug's effect here depends on prodrug activation of the other; this is a pharmacodynamic, not pharmacokinetic, interaction.
Effect / direction: increased risk of hypotension, respiratory depression, profound sedation, coma, and death.
- Severity: major; evidence: theoretical/additive-effect based; onset: unspecified.
- Management: reserve concurrent use for patients lacking adequate alternatives; use lowest effective doses and shortest duration; 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
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 medicines are prescribed together, your care team is watching for this and can manage it.
- Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise.
- Your team may use the lowest doses for the shortest time needed and monitor you more closely.
- They may consider prescribing naloxone to have on hand for emergencies.
- Ask whether a non-opioid pain option or a different anxiety approach is possible.
Get help right away if you notice extreme drowsiness, confusion, very slow or shallow breathing, or you can't be easily woken.
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 occurring between 2004 and 2011 and involving both opioid analgesics and benzodiazepines rose significantly from 11 to 34.2 per 100,000. Drug overdose deaths attributable to prescribed and above-prescribed doses of both drug classes also rose significantly from 0.6 to 1.7 per 100,000, while overdose deaths due 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 associated with dispensing 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 increased significantly by 2.33 fold in patients taking opioid analgesics who had a history of a benzodiazepine prescription, and increased by 3.86 fold in those with a current benzodiazepine prescription, compared with patients taking opioid analgesics without any 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 increases the risk of drug-related mortality relative to using opioid analgesics alone. Given their comparable pharmacological properties, 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 Alprazolam together?
Codeine and Xanax both depress the brain and breathing, so combining them can cause dangerous sedation and slowed breathing. Use only if truly needed, at the lowest doses, and stay in close contact with your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Alprazolam 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 Alprazolam interaction managed?
If both medicines are prescribed together, your care team is watching for this and can manage it. Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Your team may use the lowest doses for the shortest time needed and monitor you more closely. They may consider prescribing naloxone to have on hand for emergencies. Ask whether a non-opioid pain option or a different… 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 Alprazolam 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 Alprazolam
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