Buprenorphine and Butabarbital: 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
Butabarbital
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 an opioid used for pain or to treat opioid use disorder, and butabarbital is a barbiturate that calms the brain and helps with sleep or anxiety. Both slow down your central nervous system. When you take them together, those calming effects add up. That can make you very drowsy and, more seriously, can slow your breathing to a dangerous level, which can lead to coma or even death.
This is a real and serious combination, but it can be managed. Please don't stop or change either medicine on your own. Talk with your doctor or pharmacist. They can adjust doses, watch you more closely, or suggest safer options for sleep or anxiety.
Mechanism: Additive CNS depression. Buprenorphine (opioid partial agonist) plus butabarbital (barbiturate sedative-hypnotic) produce pharmacodynamic additive respiratory and CNS depression. Neither is a prodrug; this is a PD, not PK, interaction.
Effect/direction: Increased risk of profound sedation, respiratory depression, coma, and death.
Evidence: Probable; supported by epidemiologic overdose-death data. Onset unspecified.
- Prefer avoiding concomitant use; consider tapering the CNS depressant to lowest effective dose or discontinuing.
- If co-use is necessary, monitor for respiratory depression, consider a higher level of care, and use alternatives for anxiety/insomnia.
- Do not withhold MAT solely because of concurrent CNS depressant therapy.
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 the CNS depressant is preferred to using the two agents together. Depending on the situation, it may be suitable either to observe the patient at a higher level of care or to pursue a taper. In other situations, it may be suitable to slowly wean the patient off a prescribed CNS depressant or to lower it to the smallest effective dose. When combined use cannot be avoided, cautious monitoring and management are warranted; alternative approaches for treating anxiety or insomnia should be considered2. 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, agents used for insomnia) had a heightened risk of death. Based on an analysis of pooled nationwide death certificate records spanning 2010 to 2014, most overdose deaths involving buprenorphine and methadone also involved concurrent CNS depressant use. Whether the risk of overdose death associated with concurrent CNS depressant drugs was different for buprenorphine versus methadone remains unknown 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Both drugs slow breathing and brain activity, so combining them raises real risk. Here is what a care team typically does:
- Keep taking both as prescribed unless your prescriber tells you otherwise, especially if buprenorphine is treating opioid use disorder.
- Your team may lower the barbiturate dose, taper it, or switch you to a safer option for sleep or anxiety.
- They may monitor you more closely, sometimes in a higher level of care.
What to do: Ask your pharmacist or prescriber before making any change. Get emergency help right away for very slow or shallow breathing, extreme sleepiness, confusion, or trouble waking someone up.
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) have a heightened risk of death. From July 1, 2005 through December 31, 2012, investigators examined the risk of fatal overdose, mortality unrelated to overdose, and all-cause mortality during periods when CNS depressants were prescribed compared with periods without CNS depressant therapy in MAT 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 combined with 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 fatal overdose and all-cause mortality figures were deemed statistically significant; 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) Based on a study of pooled nationwide death certificate data spanning 2010 to 2014, 3495 drug overdose deaths were recorded in 2014. Methadone and other CNS depressants were commonly identified as contributing agents in those deaths. Simultaneous 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 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 Buprenorphine and Butabarbital together?
Buprenorphine and butabarbital both depress breathing and the brain, and taking them together can be life-threatening. Don't change either medicine on your own, but talk to your prescriber or pharmacist soon so they can adjust doses, monitor you, or find a safer option. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Butabarbital 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 Butabarbital interaction managed?
Both drugs slow breathing and brain activity, so combining them raises real risk. Here is what a care team typically does: Keep taking both as prescribed unless your prescriber tells you otherwise, especially if buprenorphine is treating opioid use disorder. Your team may lower the barbiturate dose, taper it, or switch you to a safer option for sleep or anxiety. They may monitor you more closely,… 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 Butabarbital 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 Butabarbital
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