Suvorexant 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
Suvorexant
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.
Both of these medicines can slow down your brain and your breathing. Codeine is an opioid pain reliever (combined here with acetaminophen), and suvorexant (Belsomra) is a sleep medicine. When you take them together, those calming effects can stack up. That can make you very drowsy, slow your breathing, drop your blood pressure, and in serious cases it can be dangerous.
This is a real safety concern, so please don't combine them on your own. The good news is your care team can manage this. They may choose different medicines, use the lowest doses for the shortest time, and watch you closely. Please talk with your doctor or pharmacist before taking both.
Effect: Additive CNS and respiratory depression from combining codeine (an opioid) plus acetaminophen with the orexin-receptor antagonist suvorexant. Codeine is a prodrug activated by CYP2D6 to morphine, but this is a pharmacodynamic interaction, not a metabolic one, so the direction is additive sedative/respiratory depressant effect.
- Direction: Increased sedation, respiratory depression, hypotension; risk of profound sedation, coma, death.
- Onset: Unspecified.
- Evidence: Theoretical; class effect extrapolated from opioid plus CNS depressant data.
- Management: Avoid if possible; reserve for inadequate alternatives; use lowest dose/shortest duration; monitor for sedation and respiratory depression; consider prescribing naloxone.
What happens
An increased risk of respiratory and CNS depression
Interaction Deep Dive
Do not combine opioid-based cough preparations with agents that depress the CNS. When opioid analgesics are taken together with benzodiazepines, higher rates of emergency department visits and fatal overdose have been reported2. Taking codeine alongside CNS depressants raises the likelihood of hypotension, respiratory depression, profound sedation, coma, and death. Prescribing both classes together should be limited to patients who lack adequate alternative treatment options. Keep both the dose and the length of therapy to the smallest amount necessary. Monitor patients carefully for indications of sedation and respiratory depression. Should combined use be justified, naloxone may be prescribed for the emergency management of opioid overdose341.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
This combination can add up to too much sedation and slowed breathing, so your care team takes it seriously.
- Keep taking both only as prescribed, and don't start, stop, or change doses on your own.
- Your team may choose an alternative, or use the lowest dose for the shortest time if both are truly needed.
- The dose may need to be adjusted and individualized, and your team may monitor you more closely for drowsiness and breathing changes.
- Your prescriber may also consider a naloxone prescription for emergencies.
- Get help right away if you notice extreme sleepiness, confusion, or slow/shallow breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) In a study, the rate of nonmedical use-related emergency department visits taking place between 2004 and 2011 and involving opioid analgesics together with benzodiazepines rose significantly from 11 to 34.2 per 100,000. Drug overdose deaths attributable to prescribed and greater 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 seen with dispensing of opioid analgesics alone (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 in patients taking opioid analgesics who had a history of a benzodiazepine prescription and rose by 3.86 fold in those with a current benzodiazepine prescription, compared with those taking opioid analgesics who had no history of a benzodiazepine prescription. The risk of drug overdose deaths increased as daily benzodiazepine doses increased 2.
d) Observational studies have shown that concurrent use of opioid analgesics and benzodiazepines raises the risk of drug-related mortality compared with use of opioid analgesics alone. Owing to comparable pharmacological properties, it is reasonable to anticipate a similar risk with the concurrent use of other CNS depressant drugs together with opioid analgesics 34.
Common questions
Can I take Suvorexant and Acetaminophen And Codeine together?
Combining codeine/acetaminophen with suvorexant can dangerously stack sedation and slow your breathing, so this pairing should generally be avoided. Talk with your doctor or pharmacist before taking both together. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Suvorexant 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 Suvorexant and Acetaminophen And Codeine interaction managed?
This combination can add up to too much sedation and slowed breathing, so your care team takes it seriously. Keep taking both only as prescribed, and don't start, stop, or change doses on your own. Your team may choose an alternative, or use the lowest dose for the shortest time if both are truly needed. The dose may need to be adjusted and individualized, and your team may monitor you more closel… 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 Suvorexant 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 Suvorexant
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist