Buprenorphine and Haloperidol: 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
Haloperidol
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.
Taking buprenorphine and haloperidol together needs some extra care. Buprenorphine is a strong pain and addiction-treatment medicine, and haloperidol treats certain mental health conditions. Both can slow your breathing, make you very drowsy, and both can affect your heart's rhythm (something called QT prolongation). When you take them together, those effects can add up.
Signs to watch for include feeling unusually sleepy, confused, slow or shallow breathing, fainting, or a fluttering heartbeat. Please don't stop or change either medicine on your own. Your care team can manage this safely by picking the right doses and watching you a bit more closely, so keep taking them as prescribed and talk with your pharmacist or doctor.
Effect: Additive QT prolongation and additive CNS/respiratory depression. Neither drug is a prodrug; this is a pharmacodynamic interaction, not a metabolic one.
- Direction/mechanism: Buprenorphine (opioid, dose-dependent QT effect and respiratory depressant) plus haloperidol (known QT prolongation, sedation) produce additive risk of torsades, profound sedation, respiratory depression, coma, and death.
- Evidence: Probable. Severity major. Onset unspecified.
- Management: Avoid combination where possible. If necessary, use lowest effective doses, obtain baseline/follow-up ECG, correct electrolytes (K+, Mg2+), monitor sedation and respiratory status, and strongly consider prescribing naloxone. Do not withhold MAT.
What happens
An increased risk of QT interval prolongation and an increased risk of CNS and respiratory depression
Interaction Deep Dive
Do not use buprenorphine together with agents capable of prolonging the QT interval. Combining these medications also raises the likelihood of respiratory depression, profound sedation, coma, and death. Discontinuing a benzodiazepine or another CNS depressant is favored rather than using it alongside buprenorphine. For certain patients, a taper or observation within a higher level of care may be suitable. For others, it may be suitable to slowly wean the patient off a prescribed benzodiazepine or other CNS depressant, or to reduce the dose to the smallest amount that remains effective. When combined use cannot be avoided, exercise caution in monitoring and management; weigh alternative therapies for treating anxiety or insomnia, and give strong consideration to prescribing naloxone as an emergency treatment for opioid overdose2. 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 instance, medications used for insomnia) face a heightened risk of death. Analysis of pooled nationwide death certificate records covering 2010 through 2014 showed that most overdose deaths involving buprenorphine and methadone also involved concurrent CNS depressant use. Whether the risk of overdose death from concurrent CNS depressant drugs varied between buprenorphine and methadone remains unknown 3.
Why it happens (mechanism)
Additive QT interval prolongation; additive CNS depression
How to manage this interaction
Your care team can manage this. Because both medicines can add to each other's effects on breathing, alertness, and heart rhythm, your prescribers will weigh whether both are truly needed.
- Keep taking both exactly as prescribed unless your doctor tells you otherwise.
- Your team may use the lowest effective doses and monitor you more closely, sometimes including heart tracing (ECG) checks.
- They may consider alternative options for anxiety, sleep, or other symptoms.
- Ask whether a naloxone rescue kit is right for you, just in case.
- Get urgent help for very slow or shallow breathing, extreme drowsiness, fainting, or an irregular heartbeat.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
3 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 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 by comparing periods when CNS depressants were prescribed to 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 combined with benzodiazepine treatment, but 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 when MAT and non-benzodiazepines were coadministered, 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 of use for the drugs 3.
b) According to an analysis of pooled nationwide death certificate data spanning 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone and other CNS depressants were commonly identified as contributors to those deaths. Concurrent ALPRAZolam use appeared 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 absolute 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 concomitant CNS depressant drugs differed between buprenorphine and methadone remains unknown 3.
c) Comprehensive QT studies of buprenorphine products have shown modest QT prolongation of 15 msec or less 1.
Common questions
Can I take Buprenorphine and Haloperidol together?
Buprenorphine and haloperidol together add up to a higher risk of dangerous sedation, slowed breathing, and heart-rhythm problems, so use the lowest effective doses with close monitoring and never stop either drug on your own. Talk with your pharmacist or doctor, and ask about a naloxone kit. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Haloperidol 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 Haloperidol interaction managed?
Your care team can manage this. Because both medicines can add to each other's effects on breathing, alertness, and heart rhythm, your prescribers will weigh whether both are truly needed. Keep taking both exactly as prescribed unless your doctor tells you otherwise. Your team may use the lowest effective doses and monitor you more closely, sometimes including heart tracing (ECG) checks. They may… 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 Haloperidol 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 Haloperidol
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