Acetaminophen And Codeine and Triazolam: 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
Triazolam
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 you're also taking triazolam (Halcion), a sleep medicine in the benzodiazepine family. Both of these slow down your brain and your breathing. When taken together, those calming effects can add up, and that can make you very drowsy, lower your blood pressure, or slow your breathing more than is safe. In rare cases this can become serious.
The good news is that this is very manageable. Please don't stop either medicine on your own. Talk with your pharmacist or doctor so they can make sure your doses are as low as needed and keep an eye on how you're feeling.
Mechanism: additive CNS and respiratory depression from combining an opioid (codeine) with a benzodiazepine (triazolam). This is a pharmacodynamic interaction, not a metabolic one; neither drug's clearance drives the effect here.
- Direction: increased sedative and respiratory-depressant effect.
- Risk: hypotension, respiratory depression, profound sedation, coma, death.
- Severity/evidence: major; substantiation theoretical. Onset unspecified.
- Management: reserve co-prescribing for patients lacking adequate alternatives; 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
Using 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 prove insufficient. Keep doses and treatment durations to the lowest amount necessary. Monitor patients carefully for indications of sedation and respiratory depression. When combined use is justified, consider prescribing naloxone for emergency management of opioid overdose134.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
This combination can be used when needed, but your care team will take steps to keep it safe.
- Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise.
- Your team may keep doses low and durations short, tailored to you.
- They may monitor you more closely for heavy drowsiness, slowed breathing, or confusion.
- Your prescriber might discuss keeping naloxone on hand for emergencies.
- Avoid alcohol and other sedating substances, and ask your pharmacist before adding new medicines.
Call for help right away if you notice slow or shallow breathing, extreme sleepiness, or trouble waking.
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 involving both opioid analgesics and 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 dispensing of both opioid analgesics and benzodiazepines was 10 times greater than 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 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 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 Triazolam together?
Taking codeine and triazolam together adds up their sedating effects and can dangerously slow breathing, so use both only as prescribed at the lowest needed doses and watch for excessive drowsiness or slowed breathing. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Triazolam 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 Triazolam interaction managed?
This combination can be used when needed, but your care team will take steps to keep it safe. Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Your team may keep doses low and durations short, tailored to you. They may monitor you more closely for heavy drowsiness, slowed breathing, or confusion. Your prescriber might discuss keeping naloxone on hand for emergen… 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 Triazolam 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 Triazolam
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