Acepromazine 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
Acepromazine
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.
Acepromazine is a sedative (often used in animals, sometimes as a tranquilizer), and buprenorphine is an opioid used for pain or to treat opioid use disorder. Both of these can slow down your brain and your breathing. When you take them together, those effects add up.
That can mean feeling very drowsy or foggy, and in serious cases breathing can slow down too much. This is why it matters. The good news is that your care team can manage this safely by choosing the right doses and keeping an eye on you. Please don't stop or change either medicine on your own, just talk with your doctor or pharmacist about the best plan for you.
Interaction: Additive CNS and respiratory depression from combining acepromazine (a phenothiazine sedative) with buprenorphine (a partial mu-opioid agonist).
- Mechanism: Pharmacodynamic additive CNS depression (not a metabolic/prodrug interaction).
- Direction: Increased sedation, respiratory depression, profound sedation, coma, potentially death.
- Evidence: Probable; severity major. Onset unspecified.
- Management: Avoid or minimize concomitant use where feasible. If necessary, use lowest effective doses, monitor respiratory status and sedation, and consider higher-level monitoring. Do not withhold MAT (buprenorphine) solely due to CNS depressant use, given the countervailing risk of opioid use disorder morbidity/mortality.
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 favored rather than using the two together. Depending on the situation, it may be suitable to monitor the patient at a higher level of care or to implement a taper. In other circumstances, it may be appropriate to slowly wean a patient from a prescribed CNS depressant or to reduce it to the smallest effective dose. Should combined use be required, exercise caution in monitoring and management, and consider alternative approaches for managing anxiety or insomnia2. A Swedish epidemiological study found that patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) who also received benzodiazepines or other CNS depressants (for example, agents used to treat insomnia) had an elevated risk of death. A review of 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 overdose death risk associated 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
Both drugs are sedating, so your care team's main goal is to limit that overlap safely.
- Keep taking both as prescribed unless your prescriber tells you otherwise.
- Your team may use the lowest effective dose of the CNS depressant, or gradually taper it, and may monitor you more closely for slowed breathing or heavy sedation.
- They may consider alternatives if one drug is being used for anxiety or sleep.
- Get help right away for severe drowsiness, confusion, or slow/shallow breathing.
Ask your pharmacist or prescriber to review this combination and confirm your plan.
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, agents that treat insomnia) have 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 during intervals of prescribed CNS depressants compared with intervals without CNS depressant therapy among MAT-treated 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 combined MAT and benzodiazepine therapy; however, these data were not deemed statistically significant. Although results indicated an increased risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods of concurrent MAT and non-benzodiazepines, only the figures 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. The authors did not compare the benzodiazepine cohort with the non-benzodiazepine cohort because they did not adjust for the indication of use for the drugs 3.
b) According to a study of pooled nationwide death certificate data from 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone and other CNS depressants were commonly reported as contributors to 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 reported 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 the count 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 unknown 3.
Common questions
Can I take Acepromazine and Buprenorphine together?
Acepromazine and buprenorphine both depress the brain and breathing, so combining them raises the risk of dangerous sedation and slowed breathing. Keep taking both as prescribed but have your care team review doses and monitoring. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acepromazine 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 Acepromazine and Buprenorphine interaction managed?
Both drugs are sedating, so your care team's main goal is to limit that overlap safely. Keep taking both as prescribed unless your prescriber tells you otherwise. Your team may use the lowest effective dose of the CNS depressant, or gradually taper it, and may monitor you more closely for slowed breathing or heavy sedation. They may consider alternatives if one drug is being used for anxiety or sl… 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 Acepromazine 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 Acepromazine
Keep reading about Buprenorphine
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