Buprenorphine and Suvorexant: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Buprenorphine
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 slow down your body. Buprenorphine is a strong opioid used for pain or for treating opioid use disorder, and suvorexant (Belsomra) is a sleep medicine. When you take them together, their calming effects can add up. This can make you very sleepy and, more seriously, can slow your breathing.
The most dangerous concern is slowed or stopped breathing, especially at higher doses. The good news is your care team can manage this. They may adjust your doses, watch you more closely, or suggest a different sleep aid. Please don't stop either medicine on your own, just talk with your pharmacist or doctor about the safest plan for you.
Mechanism: Additive CNS depression. Neither drug is a prodrug; this is a pharmacodynamic interaction, not a metabolic one. Buprenorphine (opioid partial agonist) plus suvorexant (orexin receptor antagonist) can produce additive sedation and respiratory depression.
Effect / direction: Increased risk of profound sedation, respiratory depression, coma, and death.
- Evidence: Probable; epidemiologic overdose-death data support the opioid + CNS depressant risk.
- Severity: Major. Onset unspecified.
- Management: Avoid concurrent use where possible; use lowest effective dose and shortest duration; consider alternative insomnia therapy; monitor for respiratory depression and oversedation. Do not withhold MAT.
What happens
An increased risk of respiratory depression and CNS depression
Interaction Deep Dive
When buprenorphine is given together with a CNS depressant, the combined effect on the CNS can be additive, raising the likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing CNS depressants is favored rather than using them at the same time. For certain patients, it may be suitable to observe them in a higher level of care or to taper. For others, an appropriate approach may involve gradually withdrawing a patient from a prescribed CNS depressant or reducing it to the lowest dose that remains effective. When concurrent use cannot be avoided, exercise caution in monitoring and management, and weigh alternative therapies for treating anxiety or insomnia2. A Swedish epidemiological study found that patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) who also took benzodiazepines or other CNS depressants (for instance, medications used for insomnia) face a greater risk of death. Analysis of aggregated national death certificate records covering 2010 to 2014 showed that most overdose fatalities involving buprenorphine and methadone also involved concurrent CNS depressant use. Whether buprenorphine and methadone differed in the risk of overdose death when combined with CNS depressant drugs remains unknown 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
What your care team may do:
- Prefer avoiding the combination when possible, or use the lowest effective dose of the sleep medicine for the shortest time.
- Consider an alternative treatment for insomnia.
- Monitor you more closely for heavy sedation or slowed breathing, sometimes tapering one medicine rather than stopping abruptly.
What you should do: Keep taking both as prescribed unless told otherwise. Tell your pharmacist or prescriber about all sedating medicines, alcohol, and other opioids. Get help right away for severe drowsiness, confusion, or slow/shallow breathing. If you are on buprenorphine for opioid use disorder, do not stop it on your own.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) A Swedish epidemiological study found that patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) taken together with benzodiazepines or other CNS depressants (for example, medications used for insomnia) have an increased risk of death. From July 1, 2005 to December 31, 2012, investigators examined the risk of fatal overdose, non-overdose related mortality, and all-cause mortality by comparing periods when CNS depressants were prescribed with periods without CNS depressant therapy in MAT patients (aged 18 to 50). The findings showed a raised risk of all-cause mortality (adjusted hazard ratio (HR) 1.44; 95% CI, 0.93 to 2.23) and non-overdose related mortality (HR 1.74; 95% CI 1.00 to 3.01) with combined MAT and benzodiazepine treatment; however, these figures were not regarded as statistically significant. Although the results also indicated a raised risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods of coadministration of MAT and non-benzodiazepines, only the figures for fatal overdose and all-cause mortality were considered statistically significant; HR 2.34 (95% CI, 1.37 to 3.99) and HR 1.33 (95% CI, 1.12 to 2.45), respectively. The authors did not compare the benzodiazepine cohort against the non-benzodiazepine cohort because they did not adjust for the indication for which the drugs were used 3.
b) Based on a study of pooled nationwide death certificate data covering 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone along with other CNS depressants were often cited as contributors in those deaths. Concurrent use of ALPRAZolam was noted in 18.1% of cases, followed by oxyCODONE (10.1%), cocaine (9.6%), heroin (9%), and diazePAM (6.6%). The FDA documented 322 drug overdose deaths in 2014 that involved buprenorphine. Among these 322 deaths, 32.9% involved ALPRAZolam, 17.4% involved clonazePAM, 11.2% involved diazePAM, 11.2% involved heroin, and 9.9% involved fentaNYL. The total number of methadone-involved deaths was 10 times that of buprenorphine-involved deaths, though confounding factors and differences in drug utilization were not taken into account. Whether the risk of overdose death with concurrent CNS depressant drugs differed between buprenorphine and methadone is not known 3.
Common questions
Can I take Buprenorphine and Suvorexant together?
Taking buprenorphine with suvorexant adds up their sedating effects and can dangerously slow your breathing, so use the combination only under close guidance from your care team and never stop either drug on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Suvorexant 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 Buprenorphine and Suvorexant interaction managed?
What your care team may do: Prefer avoiding the combination when possible, or use the lowest effective dose of the sleep medicine for the shortest time. Consider an alternative treatment for insomnia. Monitor you more closely for heavy sedation or slowed breathing, sometimes tapering one medicine rather than stopping abruptly. What you should do: Keep taking both as prescribed unless told otherwis… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Buprenorphine or Suvorexant 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 (3)
- Product Information: BRIXADI(TM) subcutaneous extended-release injection, buprenorphine subcutaneous extended-release injection. Braeburn Inc (per FDA), Plymouth Meeting, PA, 2023. DailyMed
- Product Information: SUBUTEX(R) sublingual tablets, buprenorphine sublingual tablets. Indivior Inc (per FDA), North Chesterfield, VA, 2021. DailyMed
- US Food and Drug Administration (FDA): Drug Safety Communications: FDA urges caution about withholding opioid addiction medications from patients taking benzodiazepines or CNS depressants: careful medication management can reduce risks. US Food and Drug Administration (FDA). Silver Spring, MD. 2017.
Keep reading about Buprenorphine
Keep reading about Suvorexant
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