Diazepam Rectal and Buprenorphine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Buprenorphine
Diazepam Rectal
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.
What happens
An increased risk of CNS depression and respiratory depression
Interaction Deep Dive
Coadministration of buprenorphine with a benzodiazepine may result in additive CNS depression and an increased risk of respiratory depression, profound sedation, coma, and death. Cessation of benzodiazepines or other CNS depressants is preferred over concomitant use. In some cases, monitoring in a higher level of care or taper may be appropriate. In others, gradually tapering a patient off a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate. If concomitant use is necessary, monitor for respiratory depression and manage cautiously3. An epidemiological study from Sweden reported that patients receiving methadone- or buprenorphine-based medication-assisted treatment (MAT) along with benzodiazepines or other CNS depressants (e.g., drugs that treat insomnia), increase the risk of death. According to a study of aggregate nationwide death certificate data from 2010 to 2014, the majority of buprenorphine- and methadone-involved overdose deaths involved concomitant CNS depressant use. It is unknown whether the risk of overdose death with concomitant CNS depressant drugs differed between buprenorphine and methadone 1.
Why it happens (mechanism)
Additive CNS depression
Literature reports
2 reports — tap to read
a) An epidemiological study from Sweden reported that patients receiving methadone- or buprenorphine-based medication-assisted treatment (MAT) along with benzodiazepines or other CNS depressants (e.g., drugs that treat insomnia), increase the risk of death. Between July 1, 2005 and December 31, 2012, the risk of fatal overdose, non-overdose related mortality, and all-cause mortality during periods of prescribed CNS depressants to periods of time without CNS depressant therapy were analyzed in MAT prescribed patients (aged 18 to 50). The results found 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, the data was not considered statistically significant. While results demonstrated an elevated risk of fatal overdose, non-overdose morality, and all-cause mortality during periods of coadministration of MAT and non-benzodiazepines, only the data for fatal overdose and all-cause mortality was 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. A comparison between the benzodiazepine cohort and non-benzodiazepine cohort was not conducted due to the authors not adjusting for the indication of use for the drugs 1.
b) According to a study of aggregate nationwide death certificate data from 2010 to 2014, there were 3495 drug overdose deaths reported in 2014. Methadone and other CNS depressants were frequently reported as culprits 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 is unknown whether the risk of overdose death with concomitant CNS depressant drugs differed between buprenorphine and methadone 1.
Common questions
Can I take Diazepam Rectal and Buprenorphine together?
An increased risk of CNS depression and respiratory depression Always confirm with your pharmacist or prescriber before making any change.
How serious is the Diazepam Rectal 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 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 Diazepam Rectal 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)
- 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.
- Product Information: SUBUTEX(R) sublingual tablets, buprenorphine sublingual tablets. Indivior Inc (per FDA), North Chesterfield, VA, 2021. DailyMed
- Product Information: BRIXADI(TM) subcutaneous extended-release injection, buprenorphine subcutaneous extended-release injection. Braeburn Inc (per FDA), Plymouth Meeting, PA, 2023. DailyMed
Keep reading about Buprenorphine
Keep reading about Diazepam Rectal
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