Buprenorphine and Benperidol: 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
Benperidol
No brand names on recordBuprenorphine
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.
Benperidol is an antipsychotic and buprenorphine is a strong pain and addiction medicine. Both can slow down your brain and calm your body. When you take them together, those calming effects can add up. That may make you very sleepy, foggy, or short of breath, and in serious cases your breathing can slow too much.
The good news is that your care team can manage this. Please don't stop either medicine on your own. Instead, let your doctor or pharmacist know you take both. They can adjust doses, watch you more closely, or choose a safer option if needed. Call for help right away if you feel extremely drowsy or have trouble breathing.
Mechanism: Additive CNS depression. Benperidol (butyrophenone antipsychotic) contributes sedation and CNS depression that compounds buprenorphine's opioid-mediated respiratory and CNS depression. Neither is a prodrug; this is a pharmacodynamic, not pharmacokinetic, interaction.
Direction/effect: Increased risk of profound sedation, respiratory depression, coma, and death.
- Severity: Major; evidence: probable (supported by epidemiologic overdose data).
- Onset: unspecified.
- Management: Do not withhold MAT. Use lowest effective doses, monitor for respiratory depression and sedation, consider higher level of care or taper of the CNS depressant, and consider alternative agents for anxiety/insomnia.
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 central nervous system may combine, raising the likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing the CNS depressant is favored rather than using both 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 institute a taper. In other circumstances, slowly weaning a patient from a prescribed CNS depressant, or reducing the dose to the smallest effective amount, may be the right approach. When both drugs must be used together, 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 used for insomnia) have a heightened 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 from concomitant CNS depressant drugs varies between buprenorphine and methadone is not known 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
This combination can be used when necessary, but it calls for care and close attention.
- Keep taking both as prescribed unless your prescriber tells you otherwise. Do not stop suddenly on your own.
- Your care team may adjust and individualize your doses, aiming for the lowest effective dose, and may monitor you more closely for slowed breathing or heavy sedation.
- They may consider tapering the CNS depressant or choosing an alternative for anxiety or sleep if that applies.
- Tell your pharmacist or doctor about all sedating medicines, alcohol, or new drowsiness.
- Get emergency help for severe drowsiness, confusion, or trouble breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) A Swedish epidemiological study reported that patients receiving methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, agents used to treat insomnia) have an increased risk of death. From July 1, 2005 through December 31, 2012, the risk of fatal overdose, non-overdose related mortality, and all-cause mortality was compared between periods of prescribed CNS depressants and periods without CNS depressant therapy in patients prescribed MAT (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 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 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 which the drugs were used 3.
b) According to a study of aggregate 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 reported 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, although 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 Benperidol together?
Taking benperidol with buprenorphine adds up their sedating effects and can dangerously slow breathing, so keep both only under your prescriber's guidance with close monitoring and the lowest effective doses. Never stop either drug on your own, and get emergency help for extreme drowsiness or breathing trouble. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Benperidol 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 Benperidol interaction managed?
This combination can be used when necessary, but it calls for care and close attention. Keep taking both as prescribed unless your prescriber tells you otherwise. Do not stop suddenly on your own. Your care team may adjust and individualize your doses, aiming for the lowest effective dose, and may monitor you more closely for slowed breathing or heavy sedation. They may consider tapering the CNS d… 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 Benperidol 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 Benperidol
Keep reading about Buprenorphine
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