Buprenorphine and Remimazolam: 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
Remimazolam
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.
These two medicines both slow down your brain and breathing, and together the effect adds up. Buprenorphine is an opioid used for pain or for treating opioid use disorder, and remimazolam (Byfavo) is a benzodiazepine-type sedative given during medical procedures. When they are in your body at the same time, they can cause heavy sleepiness, slowed or shallow breathing, and in serious cases very deep sedation.
The good news is that this is well understood. If you receive remimazolam for a procedure, your medical team knows you also take buprenorphine and will watch your breathing closely and keep you safe. Always tell every provider about your buprenorphine so they can plan and monitor.
Mechanism: additive CNS depression. Neither agent requires metabolic activation for this pharmacodynamic effect. Combining the partial opioid agonist buprenorphine with the benzodiazepine remimazolam increases risk of respiratory depression, profound sedation, coma, and death.
- Direction: additive PD interaction, enhanced CNS/respiratory depression.
- Evidence: probable; epidemiologic data link concomitant CNS depressants with increased overdose mortality in MAT patients.
- Onset: unspecified; relevant with acute procedural sedation.
- Management: monitor respiratory rate, oxygenation, and mental status; use lowest effective sedative dose; titrate cautiously in a monitored setting. Do not withhold MAT.
What happens
An increased risk of CNS depression and respiratory depression
Interaction Deep Dive
Using buprenorphine together with a benzodiazepine can produce additive depression of the CNS, raising the likelihood of respiratory depression, deep sedation, coma, and fatality. Rather than combining these agents, discontinuing benzodiazepines or other CNS depressants is the preferred approach. Depending on the situation, either observation within a higher level of care or a taper may be warranted. For some patients, it may be suitable to slowly wean them off a prescribed benzodiazepine or other CNS depressant, or to reduce the dose to the lowest amount that remains effective. When simultaneous use cannot be avoided, watch for respiratory depression and proceed with caution during management1. A Swedish epidemiological investigation found that individuals undergoing medication-assisted treatment (MAT) based on methadone or buprenorphine, when combined with benzodiazepines or other CNS depressants (for instance, agents used to treat insomnia), face a heightened risk of death. Analysis of pooled nationwide death certificate records spanning 2010 to 2014 showed that most overdose fatalities involving buprenorphine and methadone also involved the concurrent use of a CNS depressant. Whether the risk of fatal overdose associated with concurrent CNS depressant drugs varied between buprenorphine and methadone remains unknown 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
This combination is manageable when your care team plans for it.
- Keep taking buprenorphine as prescribed and tell any team giving you remimazolam that you take it. Do not stop your buprenorphine on your own.
- Because remimazolam is usually given for procedures, your team can monitor your breathing and alertness closely in a supervised setting and use the lowest effective dose.
- For ongoing anxiety or sleep problems, ask your prescriber whether a non-sedating alternative might be a better fit.
- Get help right away for extreme drowsiness, confusion, or slow/shallow breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) A Swedish epidemiological study reported that patients receiving methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, drugs used to treat insomnia) have an increased risk of death. From July 1, 2005 to December 31, 2012, investigators analyzed the risk of fatal overdose, non-overdose related mortality, and all-cause mortality during periods when CNS depressants were prescribed compared with periods without CNS depressant therapy in MAT prescribed 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 MAT and benzodiazepine treatment; however, these data were not considered statistically significant. Although the results also demonstrated a raised risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods when MAT and non-benzodiazepines were coadministered, only the data for fatal overdose and all-cause mortality reached statistical significance; 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 with the non-benzodiazepine cohort because they did not adjust for the indication of use for the drugs 3.
b) According to a study of aggregate nationwide death certificate data from 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone and other CNS depressants were often reported as contributors in those deaths. Concurrent alprazolam use was reported in 18.1% of cases, followed by oxycodone (10.1%), cocaine (9.6%), heroin (9%), and diazepam (6.6%). The FDA reported 322 drug overdose deaths in 2014 involving buprenorphine. Of 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 absolute number of methadone-involved deaths was 10 times the number of buprenorphine-involved deaths, though confounding factors and differences in drug utilization were not accounted for. Whether the risk of overdose death with concomitant CNS depressant drugs differed between buprenorphine and methadone is unknown 3.
Common questions
Can I take Buprenorphine and Remimazolam together?
Buprenorphine and remimazolam both depress the brain and breathing, so together they raise the risk of dangerous sedation and slowed breathing; this is safely handled with close monitoring and lowest effective dosing, and you should never stop your buprenorphine on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Remimazolam 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 Remimazolam interaction managed?
This combination is manageable when your care team plans for it. Keep taking buprenorphine as prescribed and tell any team giving you remimazolam that you take it. Do not stop your buprenorphine on your own. Because remimazolam is usually given for procedures, your team can monitor your breathing and alertness closely in a supervised setting and use the lowest effective dose. For ongoing anxiety o… 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 Remimazolam 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 Remimazolam
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