Buprenorphine and Perazine: 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
Perazine
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 opioid use disorder, and perazine is an antipsychotic. Both can slow down your brain and your breathing. When you take them together, those calming effects can add up. This can make you very drowsy, slow your breathing too much, or in serious cases lead to a dangerous level of sedation.
Please don't stop either medicine on your own, since both may be important for your health. The good news is your care team can manage this. Let your pharmacist or doctor know you take both so they can check your doses, watch you more closely, and tell you what warning signs (like heavy sleepiness or slow breathing) to look out for.
Mechanism: additive CNS depression from a partial opioid agonist (buprenorphine) combined with a phenothiazine antipsychotic (perazine). This is a pharmacodynamic interaction, not enzyme-based; neither is a prodrug relevant to the effect direction.
Effect/direction: increased CNS and respiratory depression, risk of profound sedation, coma, and death. Severity major, evidence probable, onset unspecified.
- Prefer avoiding or minimizing concomitant use; taper to lowest effective dose where feasible.
- If combined use is necessary, monitor respiratory status, sedation, and mental status; consider a higher level of care.
- Do not withhold buprenorphine-based MAT 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 CNS depressant effects can be additive, raising the likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing the CNS depressant is favored over using the two agents at the same time. Depending on the situation, it may be suitable to monitor the patient in a higher level of care or to taper; in other situations, it may be appropriate to slowly wean a patient off a prescribed CNS depressant or reduce it to the lowest effective dose. When concurrent use cannot be avoided, exercise caution in monitoring and management, and think about 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 example, medications for insomnia) faced a greater risk of death. An analysis 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 risk of overdose death with concomitant CNS depressant drugs varied between buprenorphine and methadone remains unknown 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Both drugs can be important, so keep taking them exactly as prescribed unless your prescriber tells you otherwise.
- Tell your pharmacist and doctor you take both buprenorphine and perazine so they can review the plan.
- Your care team may adjust and individualize the doses, aim for the lowest effective dose, or monitor you more closely.
- They may consider alternatives if perazine is being used for anxiety or a similar purpose.
- Seek urgent help for severe drowsiness, confusion, very slow or shallow breathing, or trouble waking.
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) had an increased risk of death. Among MAT-treated patients aged 18 to 50, the analysis 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, over the interval from July 1, 2005 to December 31, 2012. 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 also indicated a raised risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods of concurrent MAT and non-benzodiazepine use, 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 of aggregate nationwide death certificate data spanning 2010 to 2014 reported 3495 drug overdose deaths in 2014. Methadone and other CNS depressants were commonly 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 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 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 concomitant CNS depressant drugs differed between buprenorphine and methadone is not known 3.
Common questions
Can I take Buprenorphine and Perazine together?
Taking buprenorphine and perazine together can add up to dangerous sedation and slowed breathing, so tell your care team; they can adjust doses and monitor you rather than having you stop on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Perazine 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 Perazine interaction managed?
Both drugs can be important, so keep taking them exactly as prescribed unless your prescriber tells you otherwise. Tell your pharmacist and doctor you take both buprenorphine and perazine so they can review the plan. Your care team may adjust and individualize the doses, aim for the lowest effective dose, or monitor you more closely. They may consider alternatives if perazine is being used for anx… 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 Perazine 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 Perazine
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