Isoflurane 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
Isoflurane
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 is a strong opioid used for pain or for treating opioid use disorder, and isoflurane is a gas used to put people to sleep for surgery. Both of these calm down your brain and slow your breathing. Used together, those effects can add up, which can lead to very deep sedation, dangerously slow breathing, and, in rare cases, heart rhythm changes.
The good news is that this is a well-known combination in the operating room, and your anesthesia and surgical teams plan for it. They watch your breathing and heart closely and adjust the anesthesia dose as needed. Please don't stop your buprenorphine on your own. Just make sure every provider knows you take it so they can keep you safe.
Additive CNS and respiratory depression from combining buprenorphine (opioid) with isoflurane (volatile anesthetic). Neither is a prodrug; this is a pharmacodynamic, not metabolic, interaction.
- Direction/effect: increased sedation, respiratory depression, and additive QT prolongation with torsade risk. Opioids also lower isoflurane MAC requirements.
- Evidence: probable; severity: major; onset unspecified.
- Management: titrate isoflurane to lowest effective dose (reduced MAC), monitor respiratory status and QT/telemetry, consider higher level of care perioperatively.
- Do not withhold MAT buprenorphine solely due to this interaction; balance against opioid use disorder mortality risk.
What happens
An increased risk of respiratory depression, an increased risk of CNS depression, reduced isoflurane (MAC) exposure and an increased risk of QT interval prolongation
Interaction Deep Dive
When buprenorphine (an opioid) is given alongside isoflurane (a CNS depressant), the combination can produce additive CNS depression along with a heightened likelihood of respiratory depression, profound sedation, coma, and death. Discontinuing isoflurane is favored rather than using the two together. Certain patients may require observation in a higher level of care or a taper, while others may need to be gradually withdrawn from isoflurane or brought down to the lowest dose that remains effective. Should the drugs be given together, watch for respiratory depression, proceed with caution, and weigh alternative therapies for anxiety or insomnia1. Their combined use can additionally raise the risk of QT interval prolongation together with torsade de pointes, so the QT interval should be monitored. Opioids may also lower the minimum alveolar concentration (MAC) of isoflurane 3. Patients receiving isoflurane should not be refused medication-assisted treatment (MAT) drugs such as buprenorphine. Even though concurrent use raises the risk of serious adverse effects, overdose, and death, denying access to MAT can produce a greater risk of morbidity and mortality tied to opioid use disorder 2.
Why it happens (mechanism)
Additive CNS depression; unknown; additive QT interval prolongation
How to manage this interaction
This combination almost always happens in a monitored setting like surgery, where your care team manages it directly.
- Keep taking buprenorphine as prescribed unless your prescriber tells you otherwise. Access to this medication should not be denied.
- Tell your surgical and anesthesia teams that you take buprenorphine before any procedure.
- Your team may lower the anesthesia (isoflurane) dose, since opioids reduce how much is needed, and monitor your breathing and heart rhythm (QT) more closely.
- Watch for very slow or shallow breathing, extreme drowsiness, or trouble waking; report these right away.
Ask your pharmacist or doctor about anything you're unsure of.
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 receiving methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, medications used to treat insomnia) have an increased risk of death. Among MAT-prescribed patients (aged 18 to 50), the risk of fatal overdose, non-overdose related mortality, and all-cause mortality during periods when CNS depressants were prescribed was compared with periods without CNS depressant therapy, over the interval from July 1, 2005 to December 31, 2012. The findings showed a higher 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 an increased risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods when MAT and non-benzodiazepines were given together, only the fatal overdose and all-cause mortality data 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 and the non-benzodiazepine cohort were not compared with each other because the authors did not adjust for the indication for which the drugs were used 2.
b) A study of pooled nationwide death certificate data spanning 2010 to 2014 reported 3495 drug overdose deaths in 2014. Methadone and other CNS depressants were commonly named 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 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 count 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 concomitant CNS depressant drugs differed between buprenorphine and methadone is not known 2.
Common questions
Can I take Isoflurane and Buprenorphine together?
Buprenorphine and isoflurane both depress breathing and the nervous system, so combining them raises the risk of deep sedation, slowed breathing, and heart rhythm changes; this is managed with dose adjustment and close monitoring in a supervised setting, and buprenorphine should not simply be withheld. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Isoflurane 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 Isoflurane and Buprenorphine interaction managed?
This combination almost always happens in a monitored setting like surgery, where your care team manages it directly. Keep taking buprenorphine as prescribed unless your prescriber tells you otherwise. Access to this medication should not be denied. Tell your surgical and anesthesia teams that you take buprenorphine before any procedure. Your team may lower the anesthesia (isoflurane) dose, since… 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 Isoflurane 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
- 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: FORANE inhalation liquid, isoflurane inhalation liquid. Baxter Healthcare Corporation (per FDA), Deerfield, IL, 2024. DailyMed
Keep reading about Buprenorphine
Keep reading about Isoflurane
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