Buprenorphine and Trifluperidol: 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
Trifluperidol
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 pain and opioid-treatment medicine, and trifluperidol is an older antipsychotic. Both can slow down your brain and your breathing. When you take them together, those calming effects can add up, which can make you very sleepy, slow your breathing too much, and in serious cases lead to unresponsiveness.
Please don't stop either medicine on your own, that can cause its own problems. The good news is that your care team can manage this. They may adjust doses, watch you more closely, or space out timing. Tell your pharmacist or doctor that you take both, and reach out right away if you feel unusually drowsy, confused, or short of breath.
Mechanism: additive CNS depression from a partial opioid agonist (buprenorphine) combined with a butyrophenone antipsychotic (trifluperidol). This is a pharmacodynamic, not pharmacokinetic, interaction; neither is a prodrug and direction is straightforward additive potentiation.
- Effect: increased risk of respiratory depression, profound sedation, coma, death.
- Severity/evidence: major; probable.
- Onset: unspecified.
- Management: avoid concomitant use where possible; use lowest effective doses and shortest duration; monitor sedation and respiratory status. Consider higher level of care if both are required. Do not withhold medication-assisted treatment; individualize dosing.
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 add together, raising the likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing CNS depressants is favored over 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 suitable to slowly withdraw a patient from a prescribed CNS depressant or to reduce the dose to the lowest that remains effective. When simultaneous use cannot be avoided, exercise caution in monitoring and management; alternative treatments for insomnia or anxiety 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 example, medications for insomnia) face a higher 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 fatal overdose associated with concomitant CNS depressant drugs varied between buprenorphine and methadone remains unknown3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Your care team can manage this combination safely by tailoring your treatment. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Expect closer monitoring for excessive sleepiness or slowed breathing.
- Doses may be adjusted and individualized, often to the lowest effective dose.
- Your team may explore alternatives if the trifluperidol is treating something like anxiety or agitation.
- Make sure every prescriber and your pharmacist know you take both.
Seek help right away if you notice heavy 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 receiving methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, medications used for 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 periods when CNS depressants were prescribed compared with 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 regarded as statistically significant. Although the results indicated an increased risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods when MAT and non-benzodiazepines were given together, 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. No comparison between the benzodiazepine cohort and the non-benzodiazepine cohort was performed because the authors did not adjust for the indication of use for the drugs 3.
b) According to an analysis 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 these 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. 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 concurrent CNS depressant drugs differed between buprenorphine and methadone is unknown 3.
Common questions
Can I take Buprenorphine and Trifluperidol together?
Taking buprenorphine with trifluperidol adds up their sedating effects and raises the risk of dangerously slowed breathing, so use both only under close medical supervision and never stop either on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Trifluperidol 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 Trifluperidol interaction managed?
Your care team can manage this combination safely by tailoring your treatment. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Expect closer monitoring for excessive sleepiness or slowed breathing. Doses may be adjusted and individualized, often to the lowest effective dose. Your team may explore alternatives if the trifluperidol is treating something l… 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 Trifluperidol 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 Trifluperidol
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