Piperacetazine 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
Buprenorphine
Piperacetazine
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 (like Belbuca or Suboxone) is an opioid, and piperacetazine is an antipsychotic. Both can slow down your brain and your breathing. When you take them together, those calming and sedating effects can add up, and that can make you very drowsy, slow your breathing, or in serious cases lead to dangerous or even life-threatening problems.
This does not mean you can't take both. It just means your care team wants to watch you a little more closely. Please don't stop or change either medicine on your own. Instead, let your doctor or pharmacist know you're on both so they can keep you safe. Tell them right away if you feel unusually sleepy, confused, or short of breath.
Mechanism: additive CNS and respiratory depression. Buprenorphine is a partial mu-opioid agonist; piperacetazine is a phenothiazine antipsychotic with sedating properties. Neither is a prodrug relevant here; this is a pharmacodynamic (additive), not pharmacokinetic, interaction.
- Effect: increased risk of profound sedation, respiratory depression, coma, death.
- Severity/evidence: major; probable. Onset unspecified.
- Management: avoid or minimize combination; use lowest effective dose and shortest duration. Monitor sedation and respiratory status. Consider alternatives for the underlying indication. Do not withhold MAT solely due to concurrent CNS depressant use.
What happens
An increased risk of respiratory depression and CNS depression
Interaction Deep Dive
Taking buprenorphine together with a CNS depressant can produce additive CNS depression, raising the likelihood of respiratory depression, profound sedation, coma, and death. Rather than using them concurrently, discontinuing the CNS depressant is the preferred approach. Depending on the situation, it may be suitable to observe the patient at a higher level of care or to carry out a taper. In other instances, gradually withdrawing a patient from a prescribed CNS depressant, or lowering it to the smallest effective dose, may be appropriate. When concurrent use cannot be avoided, exercise careful monitoring and management, and think about alternative treatments for anxiety or insomnia2. 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) face a greater risk of death. Based on an analysis of aggregate nationwide death certificate data spanning 2010 to 2014, 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 remains unknown 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Both drugs depress the central nervous system, so your care team's goal is to use them together as safely as possible if both are truly needed.
- Keep taking both as prescribed unless your prescriber tells you otherwise. Do not stop suddenly on your own.
- Your team may use the lowest effective dose, and doses may need to be adjusted and individualized by your care team.
- They may monitor you more closely for excessive drowsiness or slowed breathing, sometimes tapering one medicine or considering an alternative.
- Get help right away for severe sleepiness, confusion, or trouble breathing.
Ask your pharmacist or prescriber before adding any other sedating drug, alcohol, or sleep aid.
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 for insomnia) had a heightened risk of death. From July 1, 2005 to December 31, 2012, researchers examined the risk of fatal overdose, mortality unrelated to overdose, and all-cause mortality by comparing periods when CNS depressants were prescribed to periods without such therapy in MAT patients (aged 18 to 50). The findings showed an increased 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 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 pooled national death certificate data from 2010 to 2014 documented 3495 drug overdose deaths in 2014. Methadone and other CNS depressants were commonly cited 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 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 total number of methadone-involved deaths was 10 times greater than 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 concurrent CNS depressant drugs differed between buprenorphine and methadone is not known 3.
Common questions
Can I take Piperacetazine and Buprenorphine together?
Taking buprenorphine and piperacetazine together adds up their sedating effects and can dangerously slow breathing, so use both only under close medical supervision and never stop or change either on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Piperacetazine 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 Piperacetazine and Buprenorphine interaction managed?
Both drugs depress the central nervous system, so your care team's goal is to use them together as safely as possible if both are truly needed. Keep taking both as prescribed unless your prescriber tells you otherwise. Do not stop suddenly on your own. Your team may use the lowest effective dose, and doses may need to be adjusted and individualized by your care team. They may monitor you more clos… 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 Piperacetazine 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 Buprenorphine
Keep reading about Piperacetazine
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