Methohexital 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
Methohexital
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 methohexital (Brevital) is a fast-acting barbiturate used to help you sleep during procedures like anesthesia. Both of these drugs slow down your brain and your breathing. When they are used together, those effects can add up, which can lead to very heavy sedation, dangerously slow breathing, or worse.
The good news is this is a well-known combination that your care team can manage safely. If you ever need both, it is usually given in a closely watched setting like a hospital or clinic. Please don't stop either medicine on your own. Just talk with your doctor or pharmacist so they can plan the safest approach for you.
Interaction: Additive CNS and respiratory depression when buprenorphine (opioid partial agonist) is combined with methohexital (a short-acting barbiturate/general anesthetic). This is a pharmacodynamic interaction, not a CYP-mediated one; neither drug requires activation, so the effect is straightforwardly additive.
- Direction: increased CNS/respiratory depression, risk of profound sedation, coma, death.
- Severity/evidence: major; probable.
- Management: avoid or minimize concurrent use; if unavoidable (e.g., procedural anesthesia), administer in a monitored setting with respiratory support available, titrate to lowest effective dose, and monitor sedation, respiratory rate, and oxygen saturation.
Do not withhold MAT solely because of CNS depressant therapy; balance risks individually.
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 be additive, 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, it may be suitable to observe them in a higher level of care or to institute a taper. For others, it may be appropriate to slowly wean the patient off a prescribed CNS depressant or to reduce it to the smallest dose that remains effective. When simultaneous use cannot be avoided, monitor and handle the situation with caution, and consider alternative agents for managing anxiety or insomnia2. A Swedish epidemiological study found that patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) who also received benzodiazepines or other CNS depressants (for instance, medications used for insomnia) have a heightened risk of death. An 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 fatal overdose with 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
This is a serious but manageable combination. Because both drugs slow breathing and sedation, your care team will take steps to keep you safe.
- Keep taking both only as prescribed and do not stop either drug on your own.
- Methohexital is typically given in a monitored medical setting (such as during a procedure), where your breathing and oxygen can be watched closely.
- Your team may use the lowest effective dose and adjust and individualize your plan.
- Tell your doctor or pharmacist about all sedating medicines you take, including sleep aids, anxiety medicines, and alcohol.
- Seek help right away for very slow breathing, extreme drowsiness, or trouble waking.
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 on methadone- or buprenorphine-based medication-assisted treatment (MAT) who also took benzodiazepines or other CNS depressants (for example, medications used to treat insomnia) had an increased risk of death. Among MAT-prescribed patients (aged 18 to 50), researchers compared the risk of fatal overdose, non-overdose related mortality, and all-cause mortality during periods when CNS depressants were prescribed versus 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 combined MAT and benzodiazepine treatment; however, these data were not regarded as statistically significant. Although the results also indicated a raised 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 authors did not compare the benzodiazepine cohort with the non-benzodiazepine cohort because they did not adjust for the indication of use for the drugs 3.
b) A study using aggregate nationwide death certificate data spanning 2010 to 2014 reported 3495 drug overdose deaths in 2014. Methadone together with other CNS depressants were commonly cited as contributing agents in those deaths. Concurrent use of ALPRAZolam was noted 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 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 concurrent CNS depressant drugs differed between buprenorphine and methadone is not known 3.
Common questions
Can I take Methohexital and Buprenorphine together?
Combining buprenorphine with methohexital adds up their sedating effects and can dangerously slow breathing, so it should only be done under close medical monitoring. Never stop either medicine on your own; talk with your doctor or pharmacist about the safest plan. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Methohexital 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 Methohexital and Buprenorphine interaction managed?
This is a serious but manageable combination. Because both drugs slow breathing and sedation, your care team will take steps to keep you safe. Keep taking both only as prescribed and do not stop either drug on your own. Methohexital is typically given in a monitored medical setting (such as during a procedure), where your breathing and oxygen can be watched closely. Your team may use the lowest ef… 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 Methohexital 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 Methohexital
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