Buprenorphine and Pipotiazine: 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
Pipotiazine
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 treating opioid use disorder, and pipotiazine is an antipsychotic that can make you very drowsy. Taking both together can add up, making you more sleepy and, more seriously, slowing your breathing. In rare cases this can become dangerous.
The good news is your care team can manage this. Please don't stop either medicine on your own. Let your doctor or pharmacist know you take both so they can watch you more closely and use the lowest doses that still work for you. If you notice heavy drowsiness, confusion, or slow or shallow breathing, get help right away.
Mechanism: additive CNS depression. Buprenorphine (partial mu-opioid agonist) combined with pipotiazine (phenothiazine antipsychotic with sedative properties) produces pharmacodynamic potentiation of sedation and respiratory depression. Neither drug is a prodrug; this is a PD, not PK, interaction.
- Direction: increased CNS and respiratory depression.
- Severity/evidence: major; probable.
- Risks: profound sedation, respiratory depression, coma, death.
Management: Do not withhold MAT if indicated. Use lowest effective doses, minimize duration, and monitor sedation and respiratory status. Consider alternative agents for anxiety/psychosis where feasible, or taper the CNS depressant. Escalate level of care if warranted.
What happens
An increased risk of respiratory depression and CNS depression
Interaction Deep Dive
When buprenorphine is given together with a CNS depressant, the effects on the CNS may be additive, raising the likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing CNS depressants is favored rather than using them at the same time. For certain patients, tapering or observation within a higher level of care may be suitable. For others, it may be appropriate to slowly wean the patient off a prescribed CNS depressant or to reduce the dose to the smallest effective amount. When concurrent use cannot be avoided, exercise careful monitoring and management; alternatives for treating insomnia or anxiety should be considered2. A Swedish epidemiological study found that patients undergoing medication-assisted treatment (MAT) based on methadone or buprenorphine while also taking benzodiazepines or other CNS depressants (for example, medications for 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 buprenorphine and methadone differ in the risk of overdose death when combined with CNS depressant drugs is not known 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Both medicines can slow your breathing and increase sedation when combined, so your care team will manage this carefully rather than simply stopping treatment.
- Keep taking both as prescribed unless your doctor tells you otherwise. Do not stop buprenorphine on your own.
- Your team may use the lowest effective doses, and doses may be adjusted and individualized for you.
- They may monitor you more closely for drowsiness and breathing changes, or consider tapering or an alternative medicine over time.
- Get emergency help for slow or shallow breathing, extreme sleepiness, or confusion.
Tell your pharmacist or prescriber that you take both so they can watch for problems.
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 receiving methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, drugs used to treat insomnia) have an increased risk of death. Between July 1, 2005 and December 31, 2012, investigators 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 in 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 MAT plus benzodiazepine treatment; however, these data were not deemed statistically significant. Although results showed a raised risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods of coadministration of MAT and non-benzodiazepines, only the data for fatal overdose and all-cause mortality were considered statistically significant; HR 2.34 (95% CI, 1.37 to 3.99) and HR 1.33 (95% CI, 1.12 to 2.45), respectively. A comparison between the benzodiazepine cohort and the non-benzodiazepine cohort was not performed because the authors did not adjust for the indication for use of the drugs 3.
b) Based on 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 identified as contributors to those deaths. Concomitant 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. Of 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, although 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 Pipotiazine together?
Combining buprenorphine and pipotiazine adds up their sedating effects and can dangerously slow breathing, so keep taking both as prescribed but tell your care team so they can use the lowest doses and monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Pipotiazine 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 Pipotiazine interaction managed?
Both medicines can slow your breathing and increase sedation when combined, so your care team will manage this carefully rather than simply stopping treatment. Keep taking both as prescribed unless your doctor tells you otherwise. Do not stop buprenorphine on your own. Your team may use the lowest effective doses, and doses may be adjusted and individualized for you. 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 Buprenorphine or Pipotiazine 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 Pipotiazine
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