Delorazepam and Buprenorphine: 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
Delorazepam
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 (an opioid used for pain or opioid use disorder) and delorazepam (a benzodiazepine, related to Valium) both slow down your brain and body. When you take them together, those calming effects add up. This can make you very drowsy, slow your breathing, and in serious cases lead to dangerously low breathing or even coma.
This is a real and important concern, but it does not mean you have to stop your treatment. Never stop or change either medicine on your own. Your doctor or pharmacist can manage this safely, often by adjusting doses, watching you more closely, or exploring other options for anxiety or sleep. Please bring it up at your next visit.
Additive CNS and respiratory depression from combining buprenorphine (partial mu-opioid agonist) with delorazepam (long-acting benzodiazepine). This is a pharmacodynamic interaction, not a metabolic one; neither drug is a prodrug requiring activation. Risk includes profound sedation, respiratory depression, coma, and death.
- Severity: major; evidence: probable (epidemiologic overdose data).
- Management: avoid concomitant use where possible; taper the benzodiazepine or reduce to lowest effective dose; consider non-benzodiazepine options for anxiety/insomnia.
- If co-prescribed, monitor mental status and respiratory rate closely.
- Do not withhold MAT 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 CNS depressant effects can be additive, raising the likelihood of respiratory depression, deep sedation, coma, and death. Rather than using these agents together, discontinuing the benzodiazepine or other CNS depressant is the favored approach. For certain patients, it may be suitable to observe them at a higher level of care or to implement a taper. For others, it may be appropriate to slowly withdraw a prescribed benzodiazepine or other CNS depressant, or to reduce the dose to the smallest amount that remains effective. Should combined use be required, watch for respiratory depression and proceed with caution in management1. A Swedish epidemiological study found that patients undergoing methadone- or buprenorphine-based medication-assisted treatment (MAT) while also taking benzodiazepines or other CNS depressants (for instance, medications used for insomnia) face a heightened risk of death. Based on an analysis of pooled nationwide death certificate records spanning 2010 to 2014, most overdose deaths in which buprenorphine and methadone were involved also involved the concurrent use of a CNS depressant. Whether the risk of fatal overdose associated with concurrent CNS depressant medications varied between buprenorphine and methadone remains unknown 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. Do not stop the benzodiazepine suddenly on your own, as that can be dangerous.
Your care team can manage this by:
- Reviewing whether both drugs are truly needed, and using the lowest effective dose.
- Slowly tapering the benzodiazepine when appropriate.
- Considering other options for anxiety or sleep.
- Monitoring you more closely for heavy sedation or slowed breathing.
Call your prescriber or pharmacist right away if you notice extreme drowsiness, confusion, or slow or shallow breathing. Ask them how to store naloxone in case of emergency.
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, agents used to treat insomnia) have an increased risk of death. From July 1, 2005 through December 31, 2012, investigators examined 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 among MAT-treated patients (aged 18 to 50). The findings showed a heightened 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 indicated an elevated risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods of coadministration of MAT and non-benzodiazepines, only the fatal overdose and all-cause mortality data 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 for which the drugs were used 3.
b) According to a study of aggregate nationwide death certificate data spanning 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone and other CNS depressants were commonly reported as contributors to those deaths. Concurrent alprazolam use was noted 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. 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 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 concurrent CNS depressant drugs differed between buprenorphine and methadone is not known 3.
Common questions
Can I take Delorazepam and Buprenorphine together?
Combining buprenorphine and delorazepam adds up their sedating effects and can dangerously slow breathing, so use them together only under close medical supervision and never stop either one on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Delorazepam and Buprenorphine 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 Delorazepam and Buprenorphine interaction managed?
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. Do not stop the benzodiazepine suddenly on your own, as that can be dangerous. Your care team can manage this by: Reviewing whether both drugs are truly needed, and using the lowest effective dose. Slowly tapering the benzodiazepine when appropriate. Considering other options for anxiety or sleep. Monitorin… 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 Delorazepam or Buprenorphine 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 Delorazepam
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