Amobarbital 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
Amobarbital
Buprenorphine
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.
Amobarbital (Amytal) and buprenorphine both slow down your brain and body. Amobarbital is a barbiturate that calms the nervous system, and buprenorphine is an opioid medicine. When you take them together, those calming effects can stack up. That can lead to heavy drowsiness, very slow or shallow breathing, and in serious cases dangerous sedation.
This does not mean you have to stop either one on your own. Never stop a medicine suddenly without guidance. Your care team can manage this safely by adjusting doses, watching you more closely, or looking at other options. Please talk with your pharmacist or doctor so they can tailor the plan to you.
Mechanism: Additive CNS depression. Amobarbital (barbiturate) and buprenorphine (partial mu-opioid agonist) both depress the CNS; neither is a prodrug here, so the effect is pharmacodynamic, not a metabolic activation issue.
- Effect / direction: Increased respiratory depression, profound sedation, risk of coma and death.
- Severity / evidence: Major; probable, supported by epidemiologic overdose data.
- Onset: Unspecified.
- Management: Avoid concomitant use when possible; if unavoidable, use lowest effective doses, taper where appropriate, monitor for respiratory depression, and consider higher level of care. Do not withhold MAT (buprenorphine) solely due to CNS depressant use.
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 depressant effects can heighten the likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing the CNS depressant is favored rather than using both agents at once. Depending on the situation, it may be suitable to monitor the patient in a higher level of care or to taper. In other circumstances, it may be appropriate to slowly wean a patient off a prescribed CNS depressant or to reduce it to the lowest dose that remains effective. Should combined use be required, exercise caution in monitoring and management, and weigh alternative treatments for insomnia or anxiety2. 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 instance, medications used to treat insomnia) face a greater risk of death. A study drawing on 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 with concurrent 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 exactly as prescribed unless your care team tells you otherwise. This combination is managed, not forbidden. Buprenorphine used for opioid use disorder should not be withheld just because you take a CNS depressant.
- Your team may reduce the amobarbital to the lowest effective dose or gradually taper it.
- They may monitor you more closely, sometimes in a higher level of care.
- They may consider alternatives for anxiety or sleep problems.
Watch for very slow or shallow breathing, extreme drowsiness, confusion, or trouble waking up, and get help right away. Ask your pharmacist or prescriber before making any changes.
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 on methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for instance, agents used to treat insomnia) have an increased risk of death. From July 1, 2005 through December 31, 2012, investigators 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 in patients receiving MAT (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 of coadministration of MAT and non-benzodiazepines, only the fatal overdose and all-cause mortality data were regarded as statistically significant; HR 2.34 (95% CI, 1.37 to 3.99) and HR 1.33 (95% CI, 1.12 to 2.45), respectively. A comparison between the benzodiazepine cohort and the non-benzodiazepine cohort was not performed 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, 3495 drug overdose deaths were reported in 2014. Methadone and other CNS depressants were often cited as contributing factors 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 count of methadone-involved deaths was 10 times the count of buprenorphine-involved deaths, although confounding factors and differences in drug utilization were not taken into account. It is not known whether the risk of overdose death with concurrent CNS depressant drugs differed between buprenorphine and methadone 3.
Common questions
Can I take Amobarbital and Buprenorphine together?
Combining amobarbital with buprenorphine adds up their sedating effects and can dangerously slow breathing, so use only under close medical supervision and never stop either drug on your own without talking to your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amobarbital 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 Amobarbital and Buprenorphine interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. This combination is managed, not forbidden. Buprenorphine used for opioid use disorder should not be withheld just because you take a CNS depressant. Your team may reduce the amobarbital to the lowest effective dose or gradually taper it. They may monitor you more closely, sometimes in a higher level of care. They ma… 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 Amobarbital 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 Amobarbital
Keep reading about Buprenorphine
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