Buprenorphine and Prochlorperazine: 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
Prochlorperazine
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.
You've been prescribed buprenorphine (an opioid used for pain or for opioid use disorder) along with prochlorperazine (often used for nausea). Taken together, these two can add up in a few ways. Both can slow your breathing and make you very sleepy, and both can affect your heart's electrical rhythm (called QT prolongation). They can also slow your gut, which may cause bad constipation or trouble urinating.
This is worth taking seriously, but please don't stop either medicine on your own. Your care team can manage this by adjusting doses, watching you more closely, and choosing the safest options for you. Reach out to your pharmacist or doctor to talk it through.
Additive toxicity between buprenorphine and prochlorperazine across three axes:
- QT prolongation (additive effects on cardiac repolarization)
- CNS and respiratory depression (additive sedation, risk of profound sedation, coma, death)
- Paralytic ileus / GI hypomotility (additive anticholinergic and opioid effects on gastric motility)
Direction: both agents contribute; neither reverses the other. Severity major, evidence probable, onset unspecified.
Management: avoid concomitant use where possible; prefer tapering/lowest effective dose of the CNS depressant. If coadministered, monitor for sedation, respiratory depression, urinary retention, and severe constipation; consider baseline/follow-up ECG in patients with QT risk factors; consider naloxone co-prescribing. Do not withhold MAT.
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
Steer clear of using 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 CNS depressants is favored rather than using them concurrently. For certain patients, it may be suitable to provide monitoring at a higher level of care or to taper. For others, it may be appropriate to slowly wean the patient off a prescribed CNS depressant or to reduce to the lowest effective dose. When concurrent use cannot be avoided, watch for urinary retention, severe constipation, sedation, and respiratory depression; think about alternative treatments for anxiety or insomnia and strongly consider prescribing naloxone for emergency management of opioid overdose1. A Swedish epidemiological study found that patients undergoing methadone- or buprenorphine-based medication-assisted treatment (MAT) alongside benzodiazepines or other CNS depressants (for instance, medications used for insomnia) face a heightened risk of death. Based on a review 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 with concurrent 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
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. This combination is manageable with the right precautions.
- Your team may adjust doses, use the lowest effective dose, or consider an alternative anti-nausea option.
- They may monitor you more closely, including watching your heart rhythm and your breathing.
- Watch for heavy drowsiness, slowed or shallow breathing, severe constipation, or trouble urinating, and report these promptly.
- Your prescriber may discuss having naloxone on hand for emergencies.
If you feel faint, unusually sleepy, or hard to wake, get medical help right away. Bring up any concerns with your pharmacist or doctor.
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 to treat insomnia) have a heightened 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 with periods without CNS depressant therapy in MAT-prescribed patients (aged 18 to 50). The findings showed an increased 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; however, these data were not deemed statistically significant. Although the results also 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. 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 of the drugs 2.
b) A study drawing on aggregate nationwide death certificate data from 2010 to 2014 identified 3495 drug overdose deaths reported in 2014. Methadone and other CNS depressants were commonly cited as contributors to those deaths. Concurrent use of alprazolam was noted 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 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 deaths involving methadone was 10 times the number involving buprenorphine, though 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 not known 2.
Common questions
Can I take Buprenorphine and Prochlorperazine together?
Combining buprenorphine and prochlorperazine adds up the risks of heart rhythm changes, dangerous sedation and slowed breathing, and severe constipation, so use them together only under close medical supervision. Don't stop either drug on your own, but talk with your pharmacist or doctor about dose adjustments and monitoring. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Prochlorperazine 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 Prochlorperazine interaction managed?
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. This combination is manageable with the right precautions. Your team may adjust doses, use the lowest effective dose, or consider an alternative anti-nausea option. They may monitor you more closely, including watching your heart rhythm and your breathing. Watch for heavy drowsiness, slowed or shallow breat… 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 Prochlorperazine 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 Prochlorperazine
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