Temazepam 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
Temazepam
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 medicine Tylenol with Codeine contains codeine, an opioid pain reliever. Temazepam (Restoril) is a benzodiazepine used for sleep. Both of these slow down your brain and breathing. When taken together, those calming effects can add up. That means more drowsiness, and in some cases dangerously slow breathing, very low blood pressure, or being hard to wake up.
The good news is your care team can manage this. If both are truly needed, they'll usually use the lowest doses for the shortest time and watch you closely. Please don't stop or change either medicine on your own. Just talk with your pharmacist or doctor, and tell them 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 (temazepam). This is a pharmacodynamic interaction, not a CYP-based PK one. Codeine is a prodrug activated via CYP2D6, but that is not the driver here; the concern is overlapping depressant effects.
- Effect/direction: Increased risk of hypotension, profound sedation, respiratory depression, coma, death.
- Severity: Major. Evidence: Theoretical/class-based. Onset: Unspecified.
- Management: Reserve co-prescribing for when alternatives are inadequate. Use lowest effective doses, shortest duration. 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 together with benzodiazepines can 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 other treatment choices are insufficient. Keep the doses and the length of therapy to the lowest amount necessary, and monitor patients closely for indications of sedation and respiratory depression. When combined use is justified, consider providing naloxone so that opioid overdose can be treated as an emergency134.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
If your care team decides you need both medicines, they can manage this combination safely.
- Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Do not stop suddenly on your own.
- Your team will usually prescribe the lowest doses for the shortest time needed.
- They may monitor you more closely for heavy drowsiness or slowed breathing.
- Your doctor may also consider prescribing naloxone as a safety backup.
- Call your prescriber or pharmacist right away if you notice unusual sleepiness, confusion, slow or shallow breathing, or feeling faint.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) One study found that emergency department visits related to nonmedical use that took place between 2004 and 2011 and involved both opioid analgesics and benzodiazepines rose significantly from 11 to 34.2 per 100,000. Deaths from drug overdose 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 caused by 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 seen 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 together with benzodiazepines raises the risk of drug-related mortality compared with 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 Temazepam and Acetaminophen And Codeine together?
Combining codeine (in Tylenol with Codeine) with temazepam adds up their sedating effects and can dangerously slow breathing. Use only if truly needed, at the lowest dose for the shortest time, and tell your care team about extreme drowsiness or slow breathing. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Temazepam 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 Temazepam and Acetaminophen And Codeine interaction managed?
If your care team decides you need both medicines, they can manage this combination safely. Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Do not stop suddenly on your own. Your team will usually prescribe the lowest doses for the shortest time needed. They may monitor you more closely for heavy drowsiness or slowed breathing. Your doctor may also consider pre… 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 Temazepam 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
Keep reading about Acetaminophen And Codeine
Keep reading about Temazepam
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