Buprenorphine and Hexobarbital: 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
Hexobarbital
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.
Buprenorphine is a strong opioid used for pain or for treating opioid use disorder, and hexobarbital is a barbiturate, an older sedative. Both of these slow down your brain and your breathing. When you take them together, those calming effects can stack up. That means you could become very drowsy, breathe too slowly or too shallowly, or in the worst cases stop breathing.
This is a serious combination, but it is one your care team can manage. Please keep taking both exactly as prescribed and do not stop either one on your own. Talk with your pharmacist or doctor so they can decide on the safest plan and watch you more closely.
Interaction: Additive CNS and respiratory depression from combining buprenorphine (partial opioid agonist) with hexobarbital (a barbiturate CNS depressant). Neither is a prodrug here; the effect is pharmacodynamic, not metabolic.
- Direction: Enhanced sedation, respiratory depression, profound sedation, coma, potential death.
- Evidence: Probable; severity major. Onset unspecified.
- Management: Cessation of the CNS depressant is preferred over concomitant use. If unavoidable, use the lowest effective dose, consider taper, monitor for respiratory depression, and consider alternatives for anxiety/insomnia. Higher level of care may be warranted.
Do not withhold MAT (buprenorphine); balance overdose risk against untreated opioid use disorder.
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 effect on the central nervous system can be additive, heightening the likelihood of respiratory depression, deep sedation, coma, and death. Stopping the CNS depressant is favored over using the two together. Depending on the situation, it may be suitable to monitor the patient in a higher level of care or to implement a taper. In other situations, slowly weaning the patient off a prescribed CNS depressant, or lowering it to the smallest dose that remains effective, may be the appropriate course. When the drugs must be used concurrently, exercise caution in monitoring and management, and think about 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) faced an elevated risk of death. Analysis of pooled nationwide death certificate records 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 from concomitant CNS depressant drugs was different for buprenorphine versus methadone remains unknown 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Your care team can manage this combination safely. Keep taking both medications exactly as prescribed and do not start or stop either one on your own.
- Your team may prefer to reduce or gradually taper the barbiturate, or lower it to the smallest effective dose.
- They may monitor you more closely, sometimes in a higher level of care, especially for breathing problems and heavy sedation.
- They may consider other options for anxiety or sleep that do not add to the sedation.
Tell your pharmacist or doctor right away if you feel unusually drowsy, confused, or short of breath. If you are on buprenorphine for opioid use disorder, do not let this interaction cause you to stop that treatment.
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 for insomnia) had 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 in MAT-prescribed patients (aged 18 to 50), comparing periods when CNS depressants were prescribed with periods when no CNS depressant therapy was in place. The analysis 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) when MAT was combined with benzodiazepine treatment, but these findings were not deemed statistically significant. Although the results also showed a raised risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods of coadministration 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 authors did not compare the benzodiazepine cohort with the non-benzodiazepine cohort because they did not adjust for the indication for which the drugs were used 3.
b) In a study using 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 contributing agents in 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 documented 322 drug overdose deaths in 2014 involving 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 the number 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 Buprenorphine and Hexobarbital together?
Buprenorphine and hexobarbital both depress the brain and breathing, so together they raise the risk of dangerous sedation and slowed breathing. Keep taking both as prescribed and talk to your pharmacist or doctor about the safest plan and closer monitoring. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Hexobarbital 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 Hexobarbital interaction managed?
Your care team can manage this combination safely. Keep taking both medications exactly as prescribed and do not start or stop either one on your own. Your team may prefer to reduce or gradually taper the barbiturate, or lower it to the smallest effective dose. They may monitor you more closely, sometimes in a higher level of care, especially for breathing problems and heavy sedation. They may con… 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 Hexobarbital 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 Hexobarbital
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