Buprenorphine and Nitrazepam: 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
Nitrazepam
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 nitrazepam (a benzodiazepine used for sleep or anxiety) both slow down your brain and breathing. Taken together, that slowing adds up. This can cause heavy sedation, very slow or shallow breathing, and in serious cases coma or death.
Please don't stop either medicine on your own, since both are often needed. The good news is your care team can manage this safely by adjusting doses, watching you more closely, or finding another option for sleep or anxiety. Talk with your pharmacist or doctor, and get help right away if you feel very drowsy, confused, or short of breath.
Effect: Additive CNS and respiratory depression from combining buprenorphine (partial opioid agonist) with nitrazepam (benzodiazepine). Risk includes profound sedation, respiratory depression, coma, and death.
Mechanism: Pharmacodynamic additive CNS depression (no prodrug considerations). Evidence: probable; epidemiologic data link concomitant MAT plus benzodiazepine use to increased overdose mortality.
- Prefer discontinuation/taper of the benzodiazepine or use of the lowest effective dose.
- Consider alternatives for anxiety/insomnia.
- If used together, monitor mental status and respiratory function closely; higher level of care may be warranted.
- Do not withhold MAT solely due to CNS depressant use.
What happens
An increased risk of CNS depression and respiratory depression
Interaction Deep Dive
When buprenorphine is given together with a benzodiazepine, the combined CNS depressant effects can heighten 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 more intensive care setting or to implement a taper. Alternatively, slowly weaning the patient off a prescribed benzodiazepine or other CNS depressant, or reducing to the smallest dose that remains effective, may be appropriate. Should concurrent use be unavoidable, 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 (such as medications used for insomnia) faced a greater risk of death. An analysis of pooled nationwide death certificate records spanning 2010 to 2014 showed that most overdose deaths involving buprenorphine and methadone also involved concurrent CNS depressant use. Whether the overdose death risk associated with concurrent CNS depressant drugs varied between buprenorphine and methadone remains unknown3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Both drugs are often prescribed for good reasons, so keep taking them as directed unless your prescriber tells you otherwise. Here is how care teams typically handle this:
- They may lower the benzodiazepine to the lowest effective dose or gradually taper it off, since stopping the combination is preferred when possible.
- They may explore alternative treatments for anxiety or sleep.
- They may monitor you more closely for excess sedation and slowed breathing, sometimes in a higher level of care.
Ask your pharmacist or doctor before changing anything, and get emergency help for severe drowsiness, confusion, or trouble 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. Between July 1, 2005 and December 31, 2012, the risk of fatal overdose, non-overdose related mortality, and all-cause mortality was compared between periods when CNS depressants were prescribed and 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, the 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 when MAT and non-benzodiazepines were coadministered, 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 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 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 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 Nitrazepam together?
Combining buprenorphine and nitrazepam adds up their sedating effects and raises the risk of dangerously slow breathing, so use both only under close medical supervision and never stop either on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Nitrazepam 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 Nitrazepam interaction managed?
Both drugs are often prescribed for good reasons, so keep taking them as directed unless your prescriber tells you otherwise. Here is how care teams typically handle this: They may lower the benzodiazepine to the lowest effective dose or gradually taper it off, since stopping the combination is preferred when possible. They may explore alternative treatments for anxiety or sleep. They may monitor… 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 Nitrazepam 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 Nitrazepam
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