Buprenorphine and Cloxazolam: 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
Cloxazolam
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.
Both of these medicines slow down your brain and body. Buprenorphine is an opioid used for pain or opioid use disorder, and cloxazolam is a benzodiazepine used for anxiety. When taken together, their calming effects add up. This can make you very sleepy, slow your breathing, and in serious cases lead to trouble that can be life threatening.
The good news is that your care team can manage this. Please don't stop either medicine on your own. Instead, talk with your doctor or pharmacist so they can decide the safest plan for you, whether that means adjusting doses, watching you more closely, or looking at other options for anxiety.
Effect: Additive CNS depression with increased risk of respiratory depression, profound sedation, coma, and death.
Mechanism: Pharmacodynamic (additive) CNS depression from a mu-opioid partial agonist (buprenorphine) plus a benzodiazepine (cloxazolam). Neither is a relevant prodrug here; this is a PD, not PK, interaction.
Evidence: Probable; epidemiologic data link concomitant MAT and benzodiazepine/CNS depressant use to increased overdose death.
- Prefer avoiding combined use; taper or reduce the benzodiazepine to lowest effective dose.
- If co-use is necessary, monitor mental status and respiratory function; consider higher level of care.
- 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 CNS depression, 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. Under certain circumstances, either observation within a higher level of care or a taper may be warranted. In other situations, it may be suitable to slowly wean a patient off a prescribed benzodiazepine or other CNS depressant, or to reduce it to the smallest effective dose. When simultaneous use cannot be avoided, 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 took benzodiazepines or other CNS depressants (for instance, medications used for insomnia) had a greater risk of death. A study drawing on aggregate national death certificate data spanning 2010 to 2014 showed that most overdose deaths involving buprenorphine and methadone also involved concurrent CNS depressant use. Whether the risk of fatal overdose with concomitant CNS depressant drugs varied between buprenorphine and methadone remains unknown3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
This is a serious combination, but your care team has clear ways to handle it. The most important thing is keep taking both medicines exactly as prescribed and do not stop either one suddenly on your own, since stopping a benzodiazepine abruptly can be dangerous.
- Your team may lower the cloxazolam dose to the lowest effective amount or gradually taper it.
- They may consider other options for anxiety that don't add sedation.
- They may monitor you more closely for heavy sedation or slowed breathing.
Tell your prescriber or pharmacist about extreme drowsiness, confusion, or trouble breathing, and avoid alcohol or 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 reported that patients undergoing methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, medications used for 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 during periods when CNS depressants were prescribed was compared to periods without CNS depressant therapy among MAT-prescribed patients (aged 18 to 50). The findings showed a higher 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. 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 Cloxazolam together?
Combining buprenorphine with cloxazolam adds up their sedating effects and raises the risk of dangerously slowed breathing, so keep taking both as prescribed and talk with your care team, who can adjust doses and monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Cloxazolam 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 Cloxazolam interaction managed?
This is a serious combination, but your care team has clear ways to handle it. The most important thing is keep taking both medicines exactly as prescribed and do not stop either one suddenly on your own, since stopping a benzodiazepine abruptly can be dangerous. Your team may lower the cloxazolam dose to the lowest effective amount or gradually taper it. They may consider other options for anxiet… 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 Cloxazolam 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 Cloxazolam
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