Buprenorphine and Thiethylperazine: 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
Thiethylperazine
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 thiethylperazine is a medicine used to calm nausea and vomiting. Both can slow down your brain and your breathing. When you take them together, those calming effects can stack up, which can make you very sleepy, slow your breathing, and in serious cases become dangerous.
Watch for unusual drowsiness, confusion, or slow or shallow breathing. The good news is your care team can manage this safely by choosing the right doses and keeping an eye on you. Please don't stop or change either medicine on your own; talk with your pharmacist or doctor about how to use them together safely.
Mechanism: additive CNS depression. Neither agent is a prodrug requiring activation, so this is a pharmacodynamic, not pharmacokinetic, interaction. Buprenorphine (opioid, respiratory depressant) plus thiethylperazine (phenothiazine antiemetic with sedative properties) increases risk of profound sedation, respiratory depression, coma, and death.
- Direction: increased combined CNS/respiratory depressant effect
- Onset: unspecified; evidence rated probable, severity major
- Management: avoid concurrent use where possible; use lowest effective dose and shortest duration; monitor respiratory rate and sedation. Do not withhold MAT solely due to CNS depressant use. Consider alternative antiemetics if clinically appropriate.
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 combine, raising the likelihood of respiratory depression, deep sedation, coma, and death. Rather than using them together, discontinuing the CNS depressant is the preferred approach. In certain situations, it may be suitable to monitor the patient in a higher level of care or to implement a taper. In other situations, it may be suitable to slowly wean the patient off a prescribed CNS depressant or to lower it to the smallest effective dose. When concurrent use cannot be avoided, 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 for insomnia) had an elevated risk of death. 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 buprenorphine and methadone differ in their 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
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. This combination is manageable when handled carefully.
- Your team may use the lowest effective dose of each and the shortest necessary duration, adjusting and individualizing your plan.
- They may monitor you more closely for sedation and slowed breathing, sometimes in a higher level of care.
- An alternative anti-nausea option may be considered if appropriate.
Call your pharmacist or prescriber right away if you notice heavy drowsiness, confusion, or slow or shallow breathing. If you take buprenorphine for opioid use disorder, do not stop it on your own.
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) taken together with benzodiazepines or other CNS depressants (for example, medications used for insomnia) have an increased risk of death. From July 1, 2005 through December 31, 2012, researchers examined the risk of fatal overdose, mortality not related to overdose, 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 of non-overdose related mortality (HR 1.74; 95% CI 1.00 to 3.01) with combined MAT and benzodiazepine treatment; however, these data were not deemed statistically significant. Although the results indicated a raised 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 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. The benzodiazepine cohort and the non-benzodiazepine cohort were not compared because the authors did not adjust for the drugs' indication of use 3.
b) A study using pooled nationwide death certificate data from 2010 to 2014 reported 3495 drug overdose deaths in 2014. Methadone and other CNS depressants were often cited as contributors to these deaths. Simultaneous 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 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 count of methadone-involved deaths was 10 times that of buprenorphine-involved deaths, though confounding factors and variations 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 Thiethylperazine together?
Combining buprenorphine and thiethylperazine can add up to dangerous sedation and slowed breathing, so use both only under close medical supervision and report heavy drowsiness or breathing changes right away. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Thiethylperazine 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 Thiethylperazine interaction managed?
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. This combination is manageable when handled carefully. Your team may use the lowest effective dose of each and the shortest necessary duration, adjusting and individualizing your plan. They may monitor you more closely for sedation and slowed breathing, sometimes in a higher level of care. An alternative an… 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 Thiethylperazine 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 Thiethylperazine
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