Buprenorphine and Fluspirilene: 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
Fluspirilene
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 to treat opioid use disorder, and fluspirilene is an antipsychotic. Both can slow down your brain and your breathing. When you take them together, those calming effects add up, so you may feel very drowsy or your breathing could slow too much. In serious cases this can be dangerous.
The good news is your care team can manage this. Please don't stop or change either medicine on your own. Instead, tell your pharmacist or doctor you take both, and watch for signs like heavy sedation, confusion, or slow or shallow breathing, and get help right away if those happen.
Interaction: Additive CNS and respiratory depression from combining buprenorphine (opioid partial agonist) with fluspirilene (a diphenylbutylpiperidine antipsychotic and CNS depressant).
- Mechanism: Pharmacodynamic (additive CNS depression), not a metabolic or prodrug interaction.
- Direction/effect: Increased risk of profound sedation, respiratory depression, coma, death.
- Evidence: Probable; severity major; onset unspecified.
- Management: Avoid concurrent use where possible; use lowest effective doses; monitor respiratory status and sedation, consider higher level of care. Do not withhold MAT solely on this basis.
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 depression may be additive, raising the likelihood of respiratory depression, profound 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, gradually withdrawing a patient from a prescribed CNS depressant or reducing it to the lowest dose that remains effective may be appropriate. Should concurrent use be required, exercise caution in monitoring and management, and weigh alternative treatments for anxiety or insomnia2. A Swedish epidemiological study found that patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) who also take benzodiazepines or other CNS depressants (for instance, medications used for insomnia) face a heightened risk of death. Analysis of aggregate 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 from 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 depress the central nervous system, so the main goal is to use them together as safely as possible.
- Keep taking both as prescribed unless your care team tells you otherwise. Do not stop suddenly on your own.
- Your team may adjust and individualize the doses, aim for the lowest effective dose, or consider alternatives for anxiety or other symptoms.
- They may monitor you more closely for sedation and slowed breathing.
- Tell your pharmacist and prescriber about every sedating medicine, and seek help urgently for extreme drowsiness, confusion, or slow or shallow breathing.
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) together with benzodiazepines or other CNS depressants (for example, medications used to treat insomnia) have an increased risk of death. From July 1, 2005 through 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 patients (aged 18 to 50). The findings showed a higher 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 an increased 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 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) In a study of pooled nationwide death certificate data spanning 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone and other CNS depressants were often identified 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 involving 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 unknown 3.
Common questions
Can I take Buprenorphine and Fluspirilene together?
Buprenorphine and fluspirilene both slow breathing and the brain, and together they raise the risk of dangerous sedation. Keep taking both as prescribed but tell your care team so they can adjust doses and monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Fluspirilene 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 Fluspirilene interaction managed?
Both drugs depress the central nervous system, so the main goal is to use them together as safely as possible. Keep taking both as prescribed unless your care team tells you otherwise. Do not stop suddenly on your own. Your team may adjust and individualize the doses, aim for the lowest effective dose, or consider alternatives for anxiety or other symptoms. They may monitor you more closely for se… 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 Fluspirilene 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 Fluspirilene
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