Buprenorphine and Propofol: 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
Propofol
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 breathing, so taking them together makes that effect stronger. Buprenorphine is an opioid used for pain or for treating opioid use disorder, and propofol is a strong sedative used to put people to sleep for procedures or surgery. When they are combined, you can become very drowsy, breathe too slowly or too shallowly, or in serious cases fall into a very deep sleep that can be dangerous.
The good news is that propofol is almost always given in a controlled setting like an operating room or ICU, where trained staff watch your breathing closely and can adjust the dose. Just make sure your care team knows you take buprenorphine.
Additive CNS and respiratory depression. This is a pharmacodynamic interaction, not a metabolic one. Buprenorphine (a partial mu-opioid agonist) combined with propofol (a GABA-A potentiating sedative-hypnotic) produces additive depression of respiratory drive and consciousness, risking profound sedation, respiratory depression, coma, and death.
- Direction: increased combined depressant effect
- Onset: unspecified; expect acute effect with propofol administration
- Evidence: probable
- Management: administer propofol only in monitored settings with airway/ventilatory support; titrate to lowest effective dose; continuous monitoring of respiratory rate, SpO2, and sedation depth. Do not withhold buprenorphine-based MAT without weighing OUD risk.
What happens
An increased risk of respiratory depression and CNS depression
Interaction Deep Dive
When buprenorphine is given together with a CNS depressant, the combined CNS depression can heighten the likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing the CNS depressant is favored over using the two agents together. For certain patients, it may be suitable to observe them in a higher level of care or to implement a taper. For others, slowly weaning the patient off a prescribed CNS depressant or reducing it to the smallest effective dose may be suitable. When concurrent use cannot be avoided, exercise careful monitoring and management, and weigh alternative therapies for treating anxiety or insomnia2. A Swedish epidemiological study found that patients undergoing methadone- or buprenorphine-based medication-assisted treatment (MAT) who also took benzodiazepines or other CNS depressants (for instance, medications used for insomnia) had an elevated risk of death. Analysis of pooled nationwide death certificate data spanning 2010 to 2014 showed that most overdose deaths involving buprenorphine and methadone also involved concurrent CNS depressant use. Whether the risk of overdose death 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
Propofol is nearly always given by an anesthesia or critical care team, so this combination is managed in a monitored setting.
- Tell your care team you take buprenorphine (including brand and dose) before any procedure or sedation.
- Keep taking your buprenorphine as prescribed unless your prescriber tells you otherwise. Do not stop your medication-assisted treatment on your own.
- Your team may use the lowest effective propofol dose, watch your breathing and oxygen closely, and adjust dosing to fit you.
- Raise any questions with your pharmacist or prescriber ahead of time.
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 undergoing methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, agents used to treat insomnia) have an increased risk of death. From July 1, 2005 to December 31, 2012, investigators examined the risk of fatal overdose, non-overdose related mortality, and all-cause mortality by comparing intervals when CNS depressants were prescribed against intervals without CNS depressant therapy in MAT-treated 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 combined MAT and 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 taken 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 because the authors did not adjust for the indication of use for the drugs 3.
b) According to a study of pooled nationwide death certificate data spanning 2010 to 2014, there were 3495 drug overdose deaths reported in 2014. Methadone and other CNS depressants were often cited as contributors 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 that involved 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 count of methadone-involved deaths was 10 times the count 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 3.
Common questions
Can I take Buprenorphine and Propofol together?
Buprenorphine and propofol both depress breathing and alertness, so combined they raise the risk of dangerous sedation and slowed breathing. Propofol is given in monitored settings, so make sure the team knows you take buprenorphine and keep taking it as prescribed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Propofol 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 Propofol interaction managed?
Propofol is nearly always given by an anesthesia or critical care team, so this combination is managed in a monitored setting. Tell your care team you take buprenorphine (including brand and dose) before any procedure or sedation. Keep taking your buprenorphine as prescribed unless your prescriber tells you otherwise. Do not stop your medication-assisted treatment on your own. Your team may use th… 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 Propofol 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 Propofol
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