Buprenorphine and Loprazolam: 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
Loprazolam
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 a strong opioid used for pain or for treating opioid use disorder, and loprazolam is a benzodiazepine used for sleep or anxiety. When taken together, their calming effects add up. This can make you very drowsy and, more seriously, can slow your breathing down to a dangerous level. In the worst cases this can lead to deep sedation, coma, or death.
Please do not stop either medicine on your own. Your care team can manage this safely by adjusting doses, watching you more closely, or choosing another option. Talk with your doctor or pharmacist before making any changes.
Additive CNS and respiratory depression from combining buprenorphine (partial mu-opioid agonist) with loprazolam (benzodiazepine, GABA-A potentiation). This is a pharmacodynamic interaction, not a metabolic one; neither is a prodrug and no CYP mechanism is implicated.
- Direction: synergistic increase in sedation and respiratory depression.
- Evidence: probable; epidemiologic data (Swedish MAT cohort, US overdose death certificates) link concomitant CNS depressants with increased mortality.
- Severity: major.
- Management: prefer cessation or taper of the benzodiazepine to lowest effective dose; consider alternatives for anxiety/insomnia. If co-prescribed, monitor mental status and respiratory function, possibly at a higher level of care. Do not withhold MAT 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 resulting additive CNS depression can heighten the likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing benzodiazepines or other CNS depressants is favored rather than using them concurrently. Depending on the situation, it may be suitable to observe the patient in a higher level of care or to pursue a taper. In other situations, slowly weaning a patient from a prescribed benzodiazepine or other CNS depressant, or reducing to the smallest effective dose, may be appropriate. Should combined use be required, watch for respiratory depression and proceed with caution in management1. 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) have an elevated risk of death. Based on an analysis of nationwide aggregate death certificate data spanning 2010 to 2014, most overdose deaths that involved 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
The key concern is combined slowing of breathing and heavy sedation, so your care team will aim to keep the total sedative burden as low as safely possible.
- Keep taking both exactly as prescribed unless your prescriber tells you otherwise; do not stop suddenly on your own.
- Your team may gradually taper the benzodiazepine, lower it to the smallest effective dose, or explore other options for sleep or anxiety.
- They may monitor you more closely for excessive drowsiness or breathing changes.
Get emergency help for very slow or shallow breathing, extreme sleepiness, or trouble waking. Raise any concerns with your pharmacist or prescriber.
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 on 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 examined 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 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 plus benzodiazepine treatment; however, these data were not deemed statistically significant. Although the results indicated a heightened 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) Based on 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 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 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. 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 Loprazolam together?
Buprenorphine plus loprazolam adds up to dangerous sedation and slowed breathing; keep taking both as prescribed but ask your doctor or pharmacist about lowering or tapering the sedative and watch closely for excessive drowsiness or breathing problems. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Loprazolam 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 Loprazolam interaction managed?
The key concern is combined slowing of breathing and heavy sedation, so your care team will aim to keep the total sedative burden as low as safely possible. Keep taking both exactly as prescribed unless your prescriber tells you otherwise; do not stop suddenly on your own. Your team may gradually taper the benzodiazepine, lower it to the smallest effective dose, or explore other options for sleep… 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 Loprazolam 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 Loprazolam
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