Buprenorphine and Triflupromazine: 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
Triflupromazine
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 triflupromazine is an older antipsychotic. Both can slow down your brain and your breathing. When you take them together, those calming effects can stack on top of each other. This can make you very sleepy, slow your breathing too much, and in serious cases lead to a dangerous emergency.
Please don't stop either medicine on your own. Both may be important for you. The good news is your care team can manage this safely by choosing the right doses, keeping the amounts as low as they work well, and watching you more closely. Talk with your pharmacist or doctor, and get help right away if you feel very drowsy, confused, or short of breath.
Mechanism: additive CNS depression. Buprenorphine (partial mu-opioid agonist) plus triflupromazine (sedating phenothiazine antipsychotic) produce pharmacodynamic summation of sedation and respiratory depression. Neither is a prodrug here; this is a PD interaction, not enzyme-mediated.
- Direction: increased combined CNS/respiratory depressant effect.
- Severity/evidence: major; probable. Epidemiologic data link concomitant CNS depressants with higher overdose mortality in MAT patients.
- Onset: unspecified.
- Management: use lowest effective doses, minimize duration, monitor for respiratory depression and sedation; consider higher level of care or taper. Do not withhold MAT solely due to this interaction.
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. Discontinuing the CNS depressant is favored rather than using the two together. Depending on the situation, it may be suitable to monitor the patient in a higher level of care or to carry out a taper. In other situations, it may be appropriate to slowly wean a patient off a prescribed CNS depressant or to reduce it to the lowest dose that remains effective. When the two must be used at the same time, exercise careful monitoring and management, and consider alternative agents for managing anxiety or insomnia2. 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) faced a heightened 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 the risk of fatal overdose from concomitant CNS depressant drugs varied between buprenorphine and methadone 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 used sometimes, but it needs care.
- Your team may keep each drug at the lowest effective dose and for the shortest time needed.
- They may monitor you more closely for excessive sedation or slowed breathing, or gradually taper a medicine if appropriate.
- They may consider alternative options for anxiety or sleep if triflupromazine is being used that way.
- Ask your pharmacist or prescriber before adding alcohol, sleep aids, or other sedating medicines.
Seek urgent 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 found that patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) who also received 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, 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-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 combined MAT and benzodiazepine treatment; however, 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 of concurrent MAT and non-benzodiazepine use, only the fatal overdose and all-cause mortality figures 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 perform a comparison between the benzodiazepine cohort and the non-benzodiazepine cohort because they did not adjust for the indication for which the drugs were used 3.
b) In a study 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 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. Of those 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, although 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 Triflupromazine together?
Taking buprenorphine with triflupromazine can add up to dangerous sedation and slowed breathing, so use the lowest effective doses and stay in close contact with your care team. 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 Triflupromazine 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 Triflupromazine interaction managed?
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. This combination is used sometimes, but it needs care. Your team may keep each drug at the lowest effective dose and for the shortest time needed. They may monitor you more closely for excessive sedation or slowed breathing, or gradually taper a medicine if appropriate. They may consider alternative options… 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 Triflupromazine 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 Triflupromazine
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