Chlordiazepoxide 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
Chlordiazepoxide
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 is an opioid used for pain or to treat opioid use disorder, and chlordiazepoxide is a benzodiazepine used for anxiety. Both slow down your brain and body. Taken together, those calming effects add up. That can make you very sleepy, slow your breathing, and in serious cases lead to unconsciousness or worse.
This is a real and serious combination, but it is not a reason to panic or to stop anything on your own. Many people do need both at times. The important thing is that your care team knows you take both so they can watch you closely and keep your doses as low and safe as possible. Please talk with your doctor or pharmacist before making any change.
Effect: Additive CNS and respiratory depression from combining buprenorphine (partial opioid agonist) with chlordiazepoxide (benzodiazepine). Risk includes profound sedation, respiratory depression, coma, and death.
- Mechanism: Pharmacodynamic (additive CNS depression); not a CYP-mediated PK interaction. Neither agent's activation is the issue here.
- Evidence/onset: Probable; epidemiologic data link concomitant CNS depressant use to increased overdose mortality in MAT patients. Onset unspecified.
- Management: Prefer avoidance; taper the benzodiazepine or use lowest effective dose. Consider alternatives for anxiety. If combined, monitor mental status and respiratory status. Do not withhold MAT solely because of benzodiazepine use.
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 concurrently, discontinuing the benzodiazepine or other CNS depressant is the preferred approach. Depending on the situation, it may be suitable to observe the patient in a higher level of care or to carry out a taper. In other circumstances, slowly withdrawing a patient from a prescribed benzodiazepine or other CNS depressant, or reducing to the lowest dose that remains effective, may be the right course. Should concurrent use be unavoidable, watch for respiratory depression and manage the patient 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, agents used for insomnia) had a heightened risk of death. Analysis of pooled nationwide death certificate records covering 2010 through 2014 showed that 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
Keep taking both exactly as prescribed unless your care team tells you otherwise. Do not stop either drug suddenly on your own, especially the benzodiazepine, which can be dangerous to stop abruptly.
- Tell your prescriber and pharmacist that you take both so they can manage this together.
- Your team may lower a dose, slowly taper the benzodiazepine, or consider a non-sedating option for anxiety or sleep.
- They may also monitor you more closely for excess drowsiness or slowed breathing.
- Get help right away for severe sleepiness, confusion, or trouble breathing.
Importantly, needing a sedative is not a reason to be denied buprenorphine treatment.
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. Between July 1, 2005 and December 31, 2012, investigators analyzed 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 in MAT prescribed patients (aged 18 to 50). The findings showed an elevated 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 the results showed an elevated 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 frequently identified 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 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, although confounding factors and differences in drug utilization were not accounted for. It remains unknown whether the risk of overdose death with concomitant CNS depressant drugs differed between buprenorphine and methadone 3.
Common questions
Can I take Chlordiazepoxide and Buprenorphine together?
Combining buprenorphine with chlordiazepoxide adds up their sedating effects and can dangerously slow breathing, so use both only under close medical supervision and never change doses on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Chlordiazepoxide 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 Chlordiazepoxide and Buprenorphine interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. Do not stop either drug suddenly on your own, especially the benzodiazepine, which can be dangerous to stop abruptly. Tell your prescriber and pharmacist that you take both so they can manage this together. Your team may lower a dose, slowly taper the benzodiazepine, or consider a non-sedating option for anxiety or 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 Chlordiazepoxide 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 Chlordiazepoxide
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist