Buprenorphine and Prazepam: 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
Prazepam
No brand names on record
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.
Buprenorphine (used for pain or opioid use disorder) and prazepam (a benzodiazepine used for anxiety) both slow down your brain and your breathing. When you take them together, those calming effects add up. This can make you very drowsy, and in serious cases it can slow your breathing dangerously, which can lead to coma or even death.
This does not mean these drugs can never be used together. Sometimes they are, but it takes care. Please don't stop or change either medicine on your own. Talk with your doctor or pharmacist so they can find the safest plan for you and watch you closely.
Additive CNS and respiratory depression from combining buprenorphine (partial opioid agonist) with prazepam (a benzodiazepine). This is a pharmacodynamic interaction, not enzyme-mediated; neither agent's activation is at issue here.
- Direction: increased CNS depression, sedation, respiratory depression, risk of coma and death.
- Evidence: probable; supported by epidemiologic overdose data.
- Severity: major. Onset unspecified.
- Management: Prefer avoiding concurrent use; consider tapering the benzodiazepine to lowest effective dose or an alternative anxiolytic/hypnotic. If co-prescribed, monitor mental status and respiratory status closely. Do not withhold MAT solely due to benzodiazepine use.
What happens
An increased risk of CNS depression and respiratory depression
Interaction Deep Dive
Taking buprenorphine together with a benzodiazepine can produce additive depression of the central nervous system and raise the likelihood of respiratory depression, deep sedation, coma, and death. Rather than using them together, discontinuing benzodiazepines or other CNS depressants is the preferred approach. Depending on the situation, it may be suitable to observe the patient in a higher level of care or to institute a taper. For other patients, it may be appropriate to gradually withdraw a prescribed benzodiazepine or other CNS depressant, or to reduce it to the lowest effective dose. When concurrent use cannot be avoided, watch for respiratory depression and proceed with caution in management1. 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 example, agents used to treat insomnia) faced a heightened risk of death. Based on an analysis of pooled nationwide death certificate data spanning 2010 to 2014, most overdose deaths involving buprenorphine and methadone also involved concurrent use of a CNS depressant. Whether the risk of fatal overdose with concomitant CNS depressant drugs varied between buprenorphine and methadone is not known 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Your care team can manage this combination safely with the right precautions.
- Keep taking both as prescribed unless your prescriber tells you otherwise, and never adjust doses on your own.
- Your team may prefer to lower the prazepam dose to the lowest that works, gradually taper it, or consider a different option for anxiety or sleep.
- They may monitor you more closely for extreme drowsiness or slowed breathing, sometimes in a higher level of care.
- Get emergency help for very slow or shallow breathing, trouble waking up, or severe confusion.
If you take both, ask your pharmacist whether having naloxone on hand is right for you.
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 that treat insomnia) have an increased risk of death. From July 1, 2005 to December 31, 2012, the risk of fatal overdose, non-overdose related mortality, and all-cause mortality was analyzed in MAT prescribed patients (aged 18 to 50), comparing periods of prescribed CNS depressants with periods without CNS depressant therapy. The findings showed an increased 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, this data was not deemed statistically significant. Although the results showed an increased risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods of coadministration of MAT and non-benzodiazepines, 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. A comparison between the benzodiazepine cohort and the non-benzodiazepine cohort was not performed because the authors 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 cited as contributors to 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 taken into account. 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 Prazepam together?
Taking buprenorphine and prazepam together adds up their sedating effects and can dangerously slow breathing, so use both only under close supervision and never change your doses on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Prazepam 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 Prazepam interaction managed?
Your care team can manage this combination safely with the right precautions. Keep taking both as prescribed unless your prescriber tells you otherwise, and never adjust doses on your own. Your team may prefer to lower the prazepam dose to the lowest that works, gradually taper it, or consider a different option for anxiety or sleep. They may monitor you more closely for extreme drowsiness or slow… 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 Prazepam 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 Prazepam
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