Buprenorphine and Trifluoperazine: 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
Trifluoperazine
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 addiction medicine that slows your breathing and calms your nervous system. Trifluoperazine is used for mental health conditions, and it also causes drowsiness and can slow down your gut and bladder. Taken together, these effects add up.
That means more chance of heavy sedation, slowed or shallow breathing, and trouble with your bladder or bowels (severe constipation that can become a serious blockage). This is worth taking seriously, but please don't stop either medicine on your own. Your care team can manage this safely by adjusting doses and watching you more closely. Talk with your pharmacist or doctor about the best plan for you.
Effect: Additive CNS and respiratory depression plus additive anticholinergic effects on GI/GU motility, raising the risk of profound sedation, respiratory depression, urinary retention, severe constipation, and paralytic ileus. Neither agent is enzymatically activated; this is a pharmacodynamic (additive) interaction, not PK.
- Direction: Increased combined depressant and anticholinergic burden.
- Onset: Unspecified; evidence: probable; severity: major.
- Management: Use lowest effective doses; do not withhold MAT. Monitor sedation, respiratory rate, urinary retention, and bowel function. Consider alternatives for the psychiatric/sedating indication where feasible; escalate level of care if warranted.
What happens
An increased risk of respiratory and CNS depression and an increased risk of paralytic ileus
Interaction Deep Dive
When buprenorphine is given together with an anticholinergic CNS depressant, the CNS depressant effects can be additive, raising the likelihood of respiratory depression, deep sedation, coma, and death, and it can also produce urinary retention and/or severe constipation, potentially progressing to paralytic ileus. Discontinuing benzodiazepines or other CNS depressants is favored rather than using them at the same time. For certain patients, oversight in a higher level of care or a taper may be suitable. For others, slowly tapering the patient off a prescribed benzodiazepine or other CNS depressant, or lowering it to the smallest effective dose, may be suitable. When concurrent use cannot be avoided, watch for urinary retention, severe constipation, sedation, and respiratory depression; think about alternative approaches for managing anxiety or insomnia1. A Swedish epidemiological study found that patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants face a greater risk of death. Based on an analysis of pooled nationwide death certificate data spanning 2010 to 2014, 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 is not known 2.
Why it happens (mechanism)
Additive CNS depression; additive effects on gastric motility
How to manage this interaction
The main concern is that both drugs can add up to make you very drowsy, slow your breathing, and slow your gut and bladder. Your care team can manage this.
- Keep taking both as prescribed unless your prescriber tells you otherwise, do not stop on your own.
- Your team may use the lowest effective doses, and doses may be adjusted and individualized for you.
- They may monitor you more closely for heavy sedation and slow breathing.
- Watch for and report trouble urinating, severe constipation, or belly pain and bloating.
- Ask your pharmacist or doctor whether an alternative for anxiety or your mental health symptoms might be an option.
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 receiving 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. Between July 1, 2005 and December 31, 2012, researchers 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 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 results indicated a raised risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods of coadministration of MAT and non-benzodiazepines, 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 compare the benzodiazepine cohort with the non-benzodiazepine cohort because they did not adjust for the indication of use for the drugs 2.
b) In a study using aggregate nationwide death certificate data from 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone and other CNS depressants were commonly cited as contributors in 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 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 that of buprenorphine-involved deaths, though confounding factors and differences in drug utilization were not taken into account. It remains unknown whether the risk of overdose death with concomitant CNS depressant drugs differed between buprenorphine and methadone 2.
Common questions
Can I take Buprenorphine and Trifluoperazine together?
Combining buprenorphine and trifluoperazine adds up their sedating effects and can dangerously slow breathing plus cause severe constipation or bladder problems, so use the lowest effective doses and let your care team monitor you closely. Do not stop either medicine on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Trifluoperazine 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 Trifluoperazine interaction managed?
The main concern is that both drugs can add up to make you very drowsy, slow your breathing, and slow your gut and bladder. Your care team can manage this. Keep taking both as prescribed unless your prescriber tells you otherwise, do not stop on your own. Your team may use the lowest effective doses, and doses may be adjusted and individualized for you. They may monitor you more closely for heavy… 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 Trifluoperazine 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 (2)
- 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 Trifluoperazine
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