Clorazepate 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
Clorazepate
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 (like Belbuca or Suboxone) and clorazepate (Tranxene) both slow down your brain and body. Buprenorphine is an opioid, and clorazepate is a benzodiazepine used for anxiety. When you take them together, their calming effects add up. That can make you very sleepy, slow your breathing, and in serious cases lead to trouble waking up or even death.
This is a real and important concern, but it does not mean you have to give up either medicine on your own. If buprenorphine is treating opioid use disorder, it is very important to stay on it. The safest step is to talk with your doctor or pharmacist so they can review both medicines and manage them safely for you.
Additive CNS and respiratory depression from combining buprenorphine (partial opioid agonist) with clorazepate (benzodiazepine). Neither is a prodrug issue here; this is a pharmacodynamic, not pharmacokinetic, interaction. Risk includes profound sedation, respiratory depression, coma, and death.
- Severity: Major; evidence: probable (epidemiologic overdose-death data).
- Preferred: avoid concomitant use; taper the benzodiazepine or reduce to lowest effective dose.
- Do not withhold MAT (buprenorphine) solely because of CNS depressant use.
- If combined, monitor mental status and respiratory function; consider alternatives for anxiety/insomnia.
What happens
An increased risk of CNS depression and respiratory depression
Interaction Deep Dive
When buprenorphine is given together with a benzodiazepine, the combined depressant effects on the CNS may occur, raising the likelihood of respiratory depression, deep sedation, coma, and death. Rather than using these agents concurrently, discontinuing the benzodiazepine or other CNS depressant is the preferred approach. Depending on the situation, it may be suitable to monitor the patient at a higher level of care or to institute a taper. Alternatively, slowly weaning a patient from a prescribed benzodiazepine or other CNS depressant, or reducing to the smallest effective dose, may be appropriate. Should concurrent use be required, cautious management with monitoring for respiratory depression is warranted1. 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, agents used to treat insomnia) had an elevated 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 CNS depressant use. Whether the overdose death risk associated 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 safely. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise, and never stop buprenorphine on your own if it treats opioid use disorder.
- Your team may prefer to gradually taper the clorazepate or lower it to the smallest effective dose.
- They may explore non-benzodiazepine options for anxiety.
- They may monitor you more closely, sometimes in a higher level of care.
Tell your pharmacist or doctor right away if you notice unusual drowsiness, confusion, or slow or 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, the risk of fatal overdose, non-overdose related mortality, and all-cause mortality was compared between periods of prescribed CNS depressants and periods without CNS depressant therapy among MAT prescribed patients (aged 18 to 50). 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, these data were not considered statistically significant. Although results demonstrated a raised 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 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. A comparison between the benzodiazepine cohort and the non-benzodiazepine cohort was not carried out because the authors did not adjust for the indication of use for the drugs 3.
b) According to a study of pooled 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 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 that involved 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, although confounding factors and differences in drug utilization were not taken into account. It is not known whether the risk of overdose death with concomitant CNS depressant drugs differed between buprenorphine and methadone 3.
Common questions
Can I take Clorazepate and Buprenorphine together?
Buprenorphine and clorazepate together can dangerously add up their sedating effects and slow breathing, so let your doctor or pharmacist coordinate both, but do not stop either one on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Clorazepate 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 Clorazepate and Buprenorphine interaction managed?
Your care team can manage this safely. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise, and never stop buprenorphine on your own if it treats opioid use disorder. Your team may prefer to gradually taper the clorazepate or lower it to the smallest effective dose. They may explore non-benzodiazepine options for anxiety. They may monitor you more closely, s… 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 Clorazepate 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 Clorazepate
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