Buprenorphine and Mephobarbital: 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
Mephobarbital
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.
Both of these medicines slow down your body. Buprenorphine is an opioid used for pain or to treat opioid use disorder, and mephobarbital is a barbiturate that calms the nervous system. Taken together, they can add up and make you very sleepy, slow your breathing, and in serious cases cause dangerous or life-threatening problems.
The good news is your care team can manage this. Please don't stop or change either drug on your own. Take them exactly as prescribed, and tell your pharmacist or doctor you're on both. They may adjust doses, watch you more closely, or look at other options for anxiety or sleep. If you ever feel unusually drowsy, confused, or short of breath, get medical help right away.
Additive CNS and respiratory depression from combining buprenorphine (opioid partial agonist) with mephobarbital (barbiturate CNS depressant). This is a pharmacodynamic interaction, not a prodrug or enzyme-based one, so both agents contribute directly to sedation, hypoventilation, and risk of coma or death.
- Severity: major; evidence: probable.
- Onset: unspecified.
- Management: avoid coadministration where possible; consider tapering or lowest effective dose of the depressant, and alternatives for anxiety/insomnia.
- Monitor: respiratory rate, sedation level, mental status; escalate level of care if needed.
Do not withhold buprenorphine-based MAT solely due to this interaction; weigh against opioid use disorder mortality risk.
What happens
An increased risk of respiratory depression and CNS depression
Interaction Deep Dive
When buprenorphine is given together with a CNS depressant, the depressant effects on the central nervous system may combine, raising the likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing CNS depressants is favored rather than using them at the same time. Depending on the situation, it may be suitable to observe the patient at a higher level of care or to taper. In other situations, slowly weaning a patient from a prescribed CNS depressant, or reducing to the smallest effective dose, may be suitable. Should concurrent use be required, exercise caution in monitoring and management; alternative therapies 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, medications used for insomnia) face a heightened risk of death. Based on an analysis of pooled nationwide death certificate data spanning 2010 to 2014, most overdose deaths involving buprenorphine and methadone also involved concurrent CNS depressant use. Whether the risk of fatal overdose from 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 automatically forbidden.
- Tell your pharmacist and prescriber you take both drugs.
- Your team may lower the dose of one, gradually taper a medicine, or monitor you more closely, sometimes in a higher level of care.
- They may suggest other options for anxiety or sleep if that's why the barbiturate is used.
- Watch for heavy drowsiness, confusion, or slow or shallow breathing, and get help immediately if these occur.
If you take buprenorphine for opioid use disorder, do not stop it on your own; talk with your team first.
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, agents used for insomnia) had 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 intervals when CNS depressants were prescribed versus intervals without CNS depressant therapy among MAT patients aged 18 to 50. 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) with combined MAT and benzodiazepine treatment; however, these findings were not deemed statistically significant. Although the results also indicated a raised risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods when MAT was given with 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) A study using pooled nationwide death certificate data from 2010 to 2014 identified 3495 drug overdose deaths reported in 2014. Methadone and other CNS depressants were often cited as contributors to those deaths. Concurrent ALPRAZolam use appeared 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 remains unknown 3.
Common questions
Can I take Buprenorphine and Mephobarbital together?
Buprenorphine and mephobarbital both depress the brain and breathing, so together they raise the risk of dangerous sedation and slowed breathing. Take both only as prescribed and ask your care team to manage the doses and monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Mephobarbital 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 Mephobarbital interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. This combination is managed, not automatically forbidden. Tell your pharmacist and prescriber you take both drugs. Your team may lower the dose of one, gradually taper a medicine, or monitor you more closely, sometimes in a higher level of care. They may suggest other options for anxiety or sleep if that's why the ba… 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 Mephobarbital 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 Mephobarbital
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