Clobazam 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
Clobazam
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, Suboxone, or Sublocade) and clobazam (Onfi) are both medicines that slow down your brain and body. Buprenorphine is an opioid, and clobazam is a benzodiazepine used for seizures. When you take them together, their calming effects add up.
This matters because both can slow your breathing. Together, they can cause heavy drowsiness, very slow breathing, and in serious cases even coma or death. Watch for signs like being hard to wake up, confusion, or slow, shallow breathing. Please don't stop either medicine on your own. Your care team can manage this safely by adjusting doses and keeping a closer eye on you. Talk with your pharmacist or doctor about your specific situation.
Additive CNS and respiratory depression from combining buprenorphine (partial opioid agonist) with clobazam (benzodiazepine). This is a pharmacodynamic, not pharmacokinetic, interaction. Neither is a prodrug relevant here; the risk is additive sedation. Severity major, evidence probable, onset unspecified.
- Risk: profound sedation, respiratory depression, coma, death; epidemiologic data link concomitant CNS depressants to overdose deaths in MAT patients.
- Prefer tapering/discontinuing the benzodiazepine or using the lowest effective dose; consider alternatives for anxiety/insomnia.
- If coadministration is necessary, monitor mental status and respiratory status; consider higher level of care.
- Do not withhold MAT solely due to concurrent CNS depressant use.
What happens
An increased risk of CNS depression and respiratory depression
Interaction Deep Dive
Using buprenorphine together with a benzodiazepine can produce additive CNS depression, raising the likelihood of respiratory depression, profound sedation, coma, and death. Rather than concurrent use, discontinuing benzodiazepines or other CNS depressants is the preferred approach. Depending on the situation, it may be suitable to monitor the patient in a higher level of care or to implement a taper. In other circumstances, appropriate management may involve slowly tapering a patient off a prescribed benzodiazepine or other CNS depressant, or lowering the dose to the minimum effective amount. When concurrent 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 example, medications used for insomnia) face an elevated risk of death. Based on analysis of aggregate nationwide death certificate data spanning 2010 to 2014, most overdose deaths involving buprenorphine and methadone also involved concurrent CNS depressant use. Whether the risk of fatal overdose from concomitant CNS depressant drugs varied between buprenorphine and methadone remains unknown 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Both drugs are prescribed for real reasons, so keep taking both exactly as prescribed unless your care team tells you otherwise. Here is what teams typically do:
- Use the lowest effective dose of the benzodiazepine, or gradually taper it off when appropriate. Doses may need to be individualized by your team.
- Consider alternative treatments for anxiety or insomnia.
- Monitor more closely for excess sedation or slowed breathing, sometimes in a higher level of care.
Tell your pharmacist or prescriber about all sedating medicines, alcohol, or supplements you use. Get urgent help for extreme drowsiness, confusion, or slow/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 found that patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, medications used to treat insomnia) have a heightened risk of death. From July 1, 2005 to December 31, 2012, investigators examined the risk of fatal overdose, non-overdose related mortality, and all-cause mortality by comparing periods when CNS depressants were prescribed to periods without CNS depressant therapy in MAT-treated 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) when MAT was combined with benzodiazepine treatment; however, these data were not deemed statistically significant. Although the results indicated an increased risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods when MAT and non-benzodiazepines were coadministered, 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 of use for the drugs 3.
b) Based on a study of pooled nationwide death certificate data spanning 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone and other CNS depressants were commonly identified as contributors to those deaths. Concomitant 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 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 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. 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 Clobazam and Buprenorphine together?
Combining buprenorphine and clobazam adds up their sedating effects and can dangerously slow breathing, so use the lowest needed benzodiazepine dose with close monitoring and never stop either drug on your own without your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Clobazam 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 Clobazam and Buprenorphine interaction managed?
Both drugs are prescribed for real reasons, so keep taking both exactly as prescribed unless your care team tells you otherwise. Here is what teams typically do: Use the lowest effective dose of the benzodiazepine, or gradually taper it off when appropriate. Doses may need to be individualized by your team. Consider alternative treatments for anxiety or insomnia. Monitor more closely for excess se… 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 Clobazam 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 Clobazam
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.
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