Buprenorphine and Nordazepam: 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
Nordazepam
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 nordazepam (a benzodiazepine, in the same family as Valium) both slow down your brain and body. When you take them together, those calming effects add up. That can mean heavy drowsiness, confusion, and, most seriously, slowed or shallow breathing. In rare cases this can become dangerous.
The good news is that your care team can manage this safely. They may adjust doses, keep them as low as they work, or watch you more closely. Please don't stop either medicine on your own. Instead, talk with your pharmacist or doctor, and get help right away if you feel very sleepy, foggy, or short of breath.
Mechanism: additive CNS and respiratory depression from a partial opioid agonist (buprenorphine) combined with a long-acting benzodiazepine (nordazepam). This is a pharmacodynamic interaction, not enzyme-mediated; neither is a prodrug concern here.
Effect / evidence: increased risk of profound sedation, respiratory depression, coma, and death. Severity major, evidence probable, supported by nationwide overdose and MAT epidemiological data.
Management:
- Avoid concomitant use where possible; prefer alternatives for anxiety/insomnia.
- If needed, use lowest effective doses and consider taper of the benzodiazepine.
- Monitor mental status and respiratory function; escalate level of care if warranted.
- Do not withhold MAT (buprenorphine) solely due to 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 fatal outcomes. Rather than using them concurrently, discontinuing the benzodiazepine or other CNS depressant is the preferred approach. For certain patients, it may be suitable to provide monitoring within a higher level of care or to implement a taper. For others, it may be appropriate to slowly wean the patient from a prescribed benzodiazepine or other CNS depressant, or to reduce the dose to the lowest amount that remains effective. 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 instance, medications used for insomnia) face a heightened risk of death. Based on analysis of pooled nationwide death certificate data spanning 2010 to 2014, most overdose deaths involving buprenorphine and methadone also involved the concurrent use of a CNS depressant. Whether the risk of overdose death associated with concomitant CNS depressant drugs was different for buprenorphine versus methadone remains unknown 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Keep taking both medications exactly as prescribed unless your care team tells you otherwise. This combination can be used when necessary, but it is managed carefully.
- Your team may lower the dose of the benzodiazepine to the lowest amount that works, or slowly taper it over time.
- They may monitor you more closely, sometimes in a higher level of care.
- They may consider alternative treatments for anxiety or insomnia.
Ask your pharmacist or prescriber before making any changes. Seek help urgently for extreme drowsiness, confusion, or slow or shallow breathing. Avoid alcohol and 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 receiving methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, medications used to treat insomnia) have an increased risk of death. From July 1, 2005 to December 31, 2012, investigators compared the risk of fatal overdose, non-overdose related mortality, and all-cause mortality during periods when CNS depressants were prescribed versus periods without CNS depressant therapy in 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 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 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. 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) 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 commonly identified 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, although 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 Nordazepam together?
Taking buprenorphine with nordazepam adds up their sedating effects and can dangerously slow breathing, so use both only under close medical supervision and never adjust or stop either drug on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Nordazepam 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 Nordazepam interaction managed?
Keep taking both medications exactly as prescribed unless your care team tells you otherwise. This combination can be used when necessary, but it is managed carefully. Your team may lower the dose of the benzodiazepine to the lowest amount that works, or slowly taper it over time. They may monitor you more closely, sometimes in a higher level of care. They may consider alternative treatments for a… 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 Nordazepam 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 Nordazepam
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