Chlorpromazine and Buprenorphine: 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
Chlorpromazine
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.
Both buprenorphine (a pain and addiction medicine) and chlorpromazine (used for mood, nausea, or psychosis) can slow your breathing and make you very sleepy. Taken together, those effects add up, so there is a higher chance of deep sedation, dangerously slow breathing, and slowed gut movement (bad constipation or trouble emptying your bladder).
They can also each affect your heart's rhythm, and together that risk grows too. This sounds scary, but your care team can manage it. Please don't start or stop either drug on your own. Talk with your doctor or pharmacist so they can watch you closely and keep your doses as safe as possible.
Additive pharmacodynamic interaction between buprenorphine (partial mu-opioid agonist) and chlorpromazine (phenothiazine). Neither is a relevant prodrug here; the concern is PD, not PK.
- QT prolongation: additive effect; both agents prolong QTc.
- CNS/respiratory depression: additive, risking profound sedation, coma, death.
- GI: additive reduction in motility, risk of paralytic ileus and urinary retention.
Evidence: probable. Onset: unspecified. Management: avoid combination where possible; prefer tapering the CNS depressant or using lowest effective dose. If coadministered, monitor sedation, respiratory rate, ECG/QTc, bowel and bladder function; consider naloxone co-prescription. 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 at the same time as agents that can prolong the QT interval. Giving them together also raises the likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing CNS depressants is favored rather than using them concurrently. Depending on the situation, it may be suitable to monitor the patient in a setting offering a higher level of care or to implement a taper. In other situations, it may be appropriate to slowly wean a patient from a prescribed CNS depressant or reduce the dose to the smallest amount that remains effective. Should concurrent use be required, watch for urinary retention, severe constipation, sedation, and respiratory depression; think about alternative treatments for anxiety or insomnia and give strong consideration to prescribing naloxone for the emergency management of opioid overdose1. A Swedish epidemiological study found that patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) combined with benzodiazepines or other CNS depressants (for instance, medications used to treat insomnia) have an elevated risk of death. Based on an analysis of pooled nationwide death certificate data spanning 2010 to 2014, the majority of overdose deaths involving buprenorphine and methadone also involved concurrent CNS depressant use. Whether the risk of fatal overdose with concurrent CNS depressant drugs varied between buprenorphine and methadone is not known 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 prescriber tells you otherwise. Your care team may take steps such as:
- Using the lowest effective dose or gradually tapering one medicine if appropriate (doses may be adjusted and individualized by your team).
- Monitoring you more closely for sedation, slowed breathing, severe constipation, or trouble urinating, and possibly checking your heart rhythm (ECG).
- Considering alternatives for anxiety, sleep, or nausea, and possibly prescribing naloxone for emergencies.
Call your pharmacist or prescriber right away, or seek emergency help, if you notice extreme drowsiness, very slow or shallow breathing, fainting, or a racing/irregular heartbeat. Do not stop your addiction or pain treatment 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 undergoing methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, medications used for insomnia) have a heightened risk of death. From July 1, 2005 to 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 among 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 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. 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) Based on a study of aggregate nationwide death certificate data spanning 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone and other CNS depressants were commonly identified as contributors to these 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 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 differences in drug utilization were not taken into account. It remains unknown whether the risk of overdose death with concurrent CNS depressant drugs differed between buprenorphine and methadone 2.
Common questions
Can I take Chlorpromazine and Buprenorphine together?
Combining buprenorphine and chlorpromazine adds up their sedating, breathing-slowing, gut-slowing, and heart-rhythm effects, so it should generally be avoided; if you need both, your care team will use the lowest doses and monitor you closely, and you should never stop either drug on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Chlorpromazine and Buprenorphine 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 Chlorpromazine and Buprenorphine interaction managed?
Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Your care team may take steps such as: Using the lowest effective dose or gradually tapering one medicine if appropriate (doses may be adjusted and individualized by your team). Monitoring you more closely for sedation, slowed breathing, severe constipation, or trouble urinating, and possibly checking your… 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 Chlorpromazine or Buprenorphine 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 Chlorpromazine
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