Flunitrazepam 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
Flunitrazepam
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 for treating opioid use disorder, and flunitrazepam is a benzodiazepine (a strong sedative). When you take them together, their calming effects add up. That can make you very sleepy, slow your breathing, and in serious cases lead to coma or even death.
This is a real and serious combination, but it can be managed. Please don't stop either medicine on your own. Talk with your doctor or pharmacist so they can decide the safest plan for you, which may mean adjusting doses or watching you more closely.
Additive CNS and respiratory depression. Buprenorphine (opioid partial agonist) plus flunitrazepam (a potent benzodiazepine) produce pharmacodynamic synergy at the CNS level, raising the risk of profound sedation, respiratory depression, coma, and death. Neither drug is a prodrug; this is a PD interaction, not enzyme-mediated.
- Severity: major; evidence: probable (supported by nationwide overdose data).
- Onset: unspecified.
- Management: avoid coadministration where possible; taper the benzodiazepine or use lowest effective dose; consider alternatives for anxiety/insomnia. If combined, monitor mental status and respiratory status, possibly in higher-level care. 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 effects on CNS depression can be additive, 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. For certain patients, observation in a higher level of care or a taper may be suitable. For others, it may be appropriate to slowly wean the patient off a prescribed benzodiazepine or other CNS depressant, or to reduce the dose to the lowest effective amount. 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 take benzodiazepines or other CNS depressants (for instance, medications used for insomnia) face a greater risk of death. Based on an 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 fatal overdose with concurrent CNS depressant medications was different for buprenorphine versus methadone remains unknown 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
This combination is serious, but your care team can manage it safely. Do not stop or change either medicine on your own, since stopping opioid treatment abruptly carries its own risks.
- Your team may prefer to taper the benzodiazepine or use the lowest effective dose.
- They may look at alternative treatments for anxiety or sleep.
- If both are truly needed, they may monitor you more closely for excessive sleepiness or slowed breathing.
Tell your pharmacist or prescriber about every sedating medicine, and get help right away if you feel very drowsy, confused, or short of breath.
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 that treat insomnia) have an increased risk of death. From July 1, 2005 through December 31, 2012, investigators analyzed the risk of fatal overdose, non-overdose related mortality, and all-cause mortality in MAT prescribed patients (aged 18 to 50) by comparing periods when CNS depressants were prescribed to periods without CNS depressant therapy. The findings showed a raised 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 indicated a raised 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. 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 spanning 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone and other CNS depressants were commonly 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 accounted for. Whether the risk of overdose death with concomitant CNS depressant drugs differed between buprenorphine and methadone is unknown 3.
Common questions
Can I take Flunitrazepam and Buprenorphine together?
Taking buprenorphine with flunitrazepam adds up their sedating effects and raises the risk of dangerously slowed breathing, so use both only under close medical supervision and never adjust either dose on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Flunitrazepam 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 Flunitrazepam and Buprenorphine interaction managed?
This combination is serious, but your care team can manage it safely. Do not stop or change either medicine on your own, since stopping opioid treatment abruptly carries its own risks. Your team may prefer to taper the benzodiazepine or use the lowest effective dose. They may look at alternative treatments for anxiety or sleep. If both are truly needed, they may monitor you more closely for excess… 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 Flunitrazepam 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 Flunitrazepam
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