Buprenorphine and Perphenazine: 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
Perphenazine
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 (a strong pain and addiction medicine) together with perphenazine (a medicine for certain mental health conditions) can add their effects together in a few ways. Both can slow your breathing and make you very sleepy, and both can affect your heart's rhythm (something called QT prolongation). They can also both slow down your gut, which can lead to bad constipation or even a blocked bowel.
This is a serious combination, but it is one your care team knows how to handle. Please keep taking both exactly as prescribed and don't stop either on your own. Talk with your pharmacist or doctor so they can watch you closely and keep you safe.
Additive toxicity, major severity, probable evidence. Both agents are CNS depressants and QT-prolonging drugs, and both reduce GI motility.
- Mechanism: additive respiratory/CNS depression, additive QT prolongation, additive slowing of gastric motility (risk of paralytic ileus). Not a metabolic/prodrug interaction.
- Direction: increased combined effect and toxicity risk.
- Management: avoid combination where possible; prefer tapering or lowest effective CNS-depressant dose. If coadministered, monitor sedation, respiratory rate, urinary retention, severe constipation, and consider ECG for QT. Consider naloxone prescription and non-sedating alternatives for anxiety/insomnia.
Do not withhold MAT solely due to concurrent CNS depressant use; individualize.
What happens
An increased risk of QT interval prolongation, an increased risk of CNS and respiratory depression and an increased risk of paralytic ileus
Interaction Deep Dive
Do not use buprenorphine together with agents that can lengthen the QT interval. When these drugs are combined, there is also a heightened likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing CNS depressants is favored over using them concurrently. For certain patients, monitoring within a higher level of care or performing a taper may be suitable. For others, it may be appropriate to slowly wean the patient off a prescribed CNS depressant or reduce it to the lowest effective dose. Should concurrent use be required, watch for urinary retention, severe constipation, sedation, and respiratory depression; think about alternative therapies for treating anxiety or insomnia and give strong consideration to prescribing naloxone for emergency management of opioid overdose1. A Swedish epidemiological study found that patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) who were also taking benzodiazepines or other CNS depressants (for instance, medications used for insomnia) face an elevated risk of death. Based on an analysis of aggregate 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 remains unknown 2.
Why it happens (mechanism)
Additive QT interval prolongation; additive CNS depression; additive effects on gastric motility
How to manage this interaction
Your care team can manage this safely. Keep taking both medicines as prescribed unless told otherwise.
- Your team may avoid the combination where possible, or adjust and individualize doses to the lowest effective amount.
- They may monitor you more closely for heavy sedation, slowed breathing, severe constipation, or trouble urinating, and may check your heart rhythm (ECG).
- They might consider alternatives for anxiety or sleep, and may prescribe naloxone for emergencies.
Call your pharmacist or doctor right away if you feel very drowsy, breathe slowly, feel faint, or become badly constipated.
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 on 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 to December 31, 2012, investigators examined the risk of fatal overdose, non-overdose related mortality, and all-cause mortality by comparing periods of prescribed CNS depressants with periods without CNS depressant therapy among MAT-prescribed 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 plus benzodiazepine treatment; however, these data were not deemed 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 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. A comparison between the benzodiazepine cohort and the non-benzodiazepine cohort was not performed because the authors did not adjust for the indication of use for the drugs 2.
b) According to a study of aggregate nationwide death certificate data from 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone and other CNS depressants were often cited 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 involving buprenorphine. Of 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. 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 Perphenazine together?
Combining buprenorphine and perphenazine adds up their effects on breathing, alertness, heart rhythm, and the gut, so avoid the combination if you can and let your care team monitor you closely; never stop either drug on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Perphenazine 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 Perphenazine interaction managed?
Your care team can manage this safely. Keep taking both medicines as prescribed unless told otherwise. Your team may avoid the combination where possible, or adjust and individualize doses to the lowest effective amount. They may monitor you more closely for heavy sedation, slowed breathing, severe constipation, or trouble urinating, and may check your heart rhythm (ECG). They might consider alter… 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 Perphenazine 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 Perphenazine
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