Enflurane 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
Enflurane
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.
Let me explain this one. Buprenorphine is a strong opioid pain and addiction medicine, and enflurane is a general anesthetic gas used during surgery. Both of these can slow down your breathing and make you very drowsy. When they are used together, those effects can stack up. This raises the risk of dangerously slow breathing, very deep sedation, and in serious cases coma.
The good news is that if you ever need surgery, your anesthesia and surgical team already know about buprenorphine and will plan for it. Please make sure every doctor knows you take it, and never adjust it on your own. Your care team can manage this safely.
Additive CNS and respiratory depression from combining buprenorphine (partial mu-opioid agonist) with enflurane (volatile general anesthetic). This is a pharmacodynamic interaction, not metabolic; neither depends on the other for activation.
- Direction: potentiated sedation and respiratory depression.
- Severity: major. Evidence: probable. Onset: unspecified (expect intraoperative/perioperative).
- Management: use only when necessary; titrate anesthetic cautiously to lowest effective dose; monitor respiratory rate, oxygenation, sedation, and hemodynamics; ensure airway/ventilatory support and reversal readiness.
Do not withhold medication-assisted treatment without a plan; coordinate perioperative opioid strategy across the care team.
What happens
An increased risk of respiratory depression and CNS depression
Interaction Deep Dive
When buprenorphine is given together with a CNS depressant, the CNS depressant effects can add together, raising the likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing CNS depressants is favored rather than using them at the same time. For certain patients, tapering or observation within a higher level of care may be suitable. For others, it may be appropriate to slowly withdraw the patient from a prescribed CNS depressant or to reduce the dose to the lowest amount that remains effective. When simultaneous use cannot be avoided, exercise caution in monitoring and management, and think about alternative therapies for treating anxiety or insomnia2. 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. An analysis of pooled nationwide death certificate records spanning 2010 to 2014 showed that concurrent CNS depressant use was present in most overdose deaths involving buprenorphine and methadone. Whether the risk of fatal overdose from concomitant CNS depressant drugs varied between buprenorphine and methadone is not known 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Keep taking your buprenorphine as prescribed, and make sure your surgical and anesthesia team knows about it well before any procedure. Enflurane is given by your anesthesia provider, so this combination happens under close monitoring.
- Tell every prescriber and your pharmacist that you take buprenorphine.
- Your anesthesia team may adjust and individualize your doses and watch your breathing, oxygen levels, and sedation closely.
- Do not stop or change buprenorphine on your own; your team will make any changes.
- Report unusual drowsiness or trouble breathing right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) A Swedish epidemiological study found that patients undergoing methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, agents used for insomnia) face a greater risk of death. In MAT-treated patients aged 18 to 50, investigators examined the risk of fatal overdose, non-overdose related mortality, and all-cause mortality by comparing periods when CNS depressants were prescribed to periods without CNS depressant therapy, over the interval from July 1, 2005 to December 31, 2012. 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) during MAT combined with benzodiazepine treatment; however, these data were not deemed statistically significant. Although the results indicated an increased risk of fatal overdose, non-overdose mortality, and all-cause mortality during co-use of MAT and non-benzodiazepines, only the fatal overdose and all-cause mortality figures 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 benzodiazepine cohort was not compared with the non-benzodiazepine cohort because the authors did not adjust for the indication for which the drugs were used 3.
b) Based on a study of pooled nationwide death certificate data covering 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 appeared in 18.1% of cases, followed by oxyCODONE (10.1%), cocaine (9.6%), heroin (9%), and diazePAM (6.6%). The FDA documented 322 drug overdose deaths in 2014 that involved buprenorphine. Among 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 that of buprenorphine-involved deaths, though confounding factors and differences in drug utilization were not taken into account. Whether the risk of overdose death with concurrent CNS depressant drugs differed between buprenorphine and methadone is not known 3.
Common questions
Can I take Enflurane and Buprenorphine together?
Buprenorphine and enflurane both depress breathing and the nervous system, so together they raise the risk of dangerous sedation and slow breathing. Make sure your anesthesia team knows you take buprenorphine so they can monitor and dose carefully. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Enflurane 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 Enflurane and Buprenorphine interaction managed?
Keep taking your buprenorphine as prescribed, and make sure your surgical and anesthesia team knows about it well before any procedure. Enflurane is given by your anesthesia provider, so this combination happens under close monitoring. Tell every prescriber and your pharmacist that you take buprenorphine. Your anesthesia team may adjust and individualize your doses and watch your breathing, oxygen… 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 Enflurane 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 Enflurane
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