Buprenorphine and Diazepam: 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
Diazepam
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 brain and breathing. Buprenorphine (like Suboxone or Belbuca) is an opioid, and diazepam (Valium) is a benzodiazepine used for anxiety, seizures, or muscle spasms. When you take them together, their calming effects add up. That can make you very sleepy or slow your breathing more than either one alone, and in serious cases this can be life-threatening.
The good news is your care team can manage this safely. Please don't stop either medicine on your own, especially your buprenorphine, since that treats a serious condition. Instead, talk with your pharmacist or doctor so they can review your doses, watch you more closely, or explore other options for anxiety or sleep.
Effect: Additive CNS and respiratory depression, with risk of profound sedation, coma, and death. Neither agent is a prodrug; this is a pharmacodynamic (not metabolic) interaction.
- Mechanism: Additive CNS depression (opioid partial agonist plus benzodiazepine).
- Evidence: Probable; supported by epidemiologic MAT/overdose data. Severity major.
- Management: Avoid combination where possible. Consider tapering the benzodiazepine to the lowest effective dose or an alternative for anxiety/insomnia. If used concomitantly, monitor mental status and respiratory rate closely and manage cautiously. Do NOT withhold MAT (buprenorphine) solely due to benzodiazepine use, as untreated OUD carries greater mortality risk.
What happens
An increased risk of CNS depression and respiratory depression
Interaction Deep Dive
When buprenorphine is given together with a benzodiazepine, the effect on the CNS can be additive, raising the likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing benzodiazepines or other CNS depressants is favored rather than using them at the same time. Depending on the situation, it may be suitable to observe the patient in a higher level of care or to implement a taper. In other situations, slowly weaning a patient off a prescribed benzodiazepine or other CNS depressant, or reducing to the smallest effective dose, may be appropriate. Should combined use be required, watch for respiratory depression and proceed with caution1. A Swedish epidemiological study found that patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) who also received benzodiazepines or other CNS depressants (for example, medications used for insomnia) face a heightened risk of death. Drawing on pooled nationwide death certificate data spanning 2010 to 2014, one study determined that most overdose deaths involving buprenorphine and methadone also involved concurrent CNS depressant use. Whether the overdose death risk associated with concurrent CNS depressant drugs varied between buprenorphine and methadone is not known 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise, and never stop your buprenorphine on your own.
Here is what your team may do to keep you safe:
- Review whether the diazepam can be lowered to the smallest helpful dose or slowly tapered off over time.
- Consider other options for anxiety or sleep that don't add to sedation.
- Monitor you more closely for very heavy drowsiness or slowed breathing.
Call your prescriber or pharmacist right away if you notice unusual sleepiness, confusion, or slow or shallow breathing. Avoid alcohol and other sedating substances.
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 receiving methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for instance, drugs used to treat insomnia) have an increased risk of death. From July 1, 2005 to December 31, 2012, researchers examined the risk of fatal overdose, non-overdose related mortality, and all-cause mortality during periods when CNS depressants were prescribed versus 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 MAT plus benzodiazepine treatment; however, these data were 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. No comparison between the benzodiazepine cohort and the non-benzodiazepine cohort was performed because the authors did not adjust for the indication for which the drugs were used 3.
b) A study of pooled nationwide death certificate data spanning 2010 to 2014 reported 3495 drug overdose deaths in 2014. Methadone and other CNS depressants were commonly cited as contributors to these deaths. Concurrent alprazolam use appeared 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 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 absolute count 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. It remains unknown whether the risk of overdose death with concurrent CNS depressant drugs differed between buprenorphine and methadone 3.
Common questions
Can I take Buprenorphine and Diazepam together?
Buprenorphine and diazepam both depress the brain and breathing, and together they raise the risk of dangerous oversedation. Don't stop either on your own; ask your prescriber or pharmacist to review your doses and monitoring. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Diazepam 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 Diazepam interaction managed?
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise, and never stop your buprenorphine on your own. Here is what your team may do to keep you safe: Review whether the diazepam can be lowered to the smallest helpful dose or slowly tapered off over time. Consider other options for anxiety or sleep that don't add to sedation. Monitor you more closely for very he… 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Buprenorphine or Diazepam 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 Diazepam
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