Buprenorphine and Pentobarbital: 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
Pentobarbital
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. Buprenorphine is a strong opioid, and pentobarbital is a barbiturate that calms the nervous system. When you take them together, those calming effects stack on top of each other. That can make you very drowsy, slow your breathing too much, and in serious cases lead to unresponsiveness or even become life-threatening.
Please don't stop either medicine on your own. This is something your care team handles all the time. Talk with your doctor or pharmacist so they can review your doses, watch you more closely if needed, and make a plan that keeps you safe while still treating your pain or opioid therapy.
Mechanism: Additive CNS and respiratory depression. Buprenorphine (partial mu-opioid agonist) plus pentobarbital (barbiturate, GABA-A potentiation) produce overlapping pharmacodynamic depression. Neither is a prodrug; this is a PD interaction, not PK.
Effect/direction: Increased sedation, respiratory depression, profound sedation, coma, and death. Severity: major. Evidence: probable, supported by epidemiologic overdose-death data (MAT plus CNS depressants).
- Avoid concurrent use where possible; taper the CNS depressant or use lowest effective dose.
- If combined, monitor respiratory rate and sedation; consider higher level of care.
- Do not withhold MAT solely due to CNS depressant use; balance overdose risk against untreated OUD.
- Consider alternatives for anxiety/insomnia.
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 may combine, raising the likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing the CNS depressant is favored rather than using both agents together. Depending on the situation, it may be suitable to observe the patient in a higher level of care or to implement a taper. In other situations, slowly weaning a patient off a prescribed CNS depressant, or reducing it to the smallest effective dose, may be appropriate. Should concurrent use be required, use caution in monitoring and management, and consider alternative treatments for 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 example, medications used for insomnia) had an elevated risk of death. Based on an analysis of pooled nationwide death certificate records spanning 2010 to 2014, most overdose deaths that involved 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
Keep taking both medicines as prescribed unless your care team tells you otherwise. This combination is manageable when your team is aware of it.
- Your prescriber may lower a dose to the lowest effective amount, gradually taper the pentobarbital, or watch you more closely, sometimes in a higher level of care.
- They may suggest alternative options for anxiety or insomnia if that is why the depressant was prescribed.
- Get emergency help for very slow or shallow breathing, extreme drowsiness, confusion, or trouble waking.
Talk with your pharmacist or doctor before making any change, and make sure both are on your record together.
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 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. Between July 1, 2005 and December 31, 2012, investigators evaluated the risk of fatal overdose, non-overdose related mortality, and all-cause mortality by comparing periods during which CNS depressants were prescribed with periods without CNS depressant therapy in MAT prescribed 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 MAT plus benzodiazepine treatment; however, these data were not regarded as statistically significant. Although the results indicated an increased risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods of coadministration of MAT and non-benzodiazepines, only the data for fatal overdose and all-cause mortality 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. No comparison between the benzodiazepine cohort and the non-benzodiazepine cohort was performed because the authors did not adjust for the indication for which the drugs were used 3.
b) According to a study of aggregate nationwide death certificate data from 2010 to 2014, 3495 drug overdose deaths were 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 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 taken into account. Whether the risk of overdose death with concomitant CNS depressant drugs differed between buprenorphine and methadone is unknown 3.
Common questions
Can I take Buprenorphine and Pentobarbital together?
Taking buprenorphine with pentobarbital adds up their sedating effects and can dangerously slow breathing, so keep both providers informed and let your care team adjust doses or monitor you rather than changing anything yourself. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Pentobarbital 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 Pentobarbital interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This combination is manageable when your team is aware of it. Your prescriber may lower a dose to the lowest effective amount, gradually taper the pentobarbital, or watch you more closely, sometimes in a higher level of care. They may suggest alternative options for anxiety or insomnia if that is why the depressant… 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 Pentobarbital 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 Pentobarbital
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