Ethopropazine 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
Ethopropazine
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 ethopropazine is used for Parkinson-type symptoms. Both can make you sleepy and slow down your breathing. When you take them together, those effects can add up. In serious cases this can lead to heavy sedation, very slow breathing, or worse.
The good news is this can be managed. Please don't stop either medicine on your own. Your care team can adjust your doses, pick the lowest amount that works, or watch you more closely. Let your pharmacist or doctor know if you feel unusually drowsy, confused, or short of breath.
Interaction: Additive CNS and respiratory depression from combining buprenorphine (partial opioid agonist) with ethopropazine (a centrally acting anticholinergic with sedating properties). This is a pharmacodynamic (additive), not pharmacokinetic, interaction. Neither is a prodrug relevant here.
- Direction: Increased sedation, respiratory depression, risk of profound sedation, coma, death.
- Severity/Evidence: Major; probable.
- Onset: Unspecified.
- Management: Avoid concurrent use where possible; use lowest effective doses, monitor for respiratory depression and sedation, consider higher level of care. Do not withhold MAT when indicated.
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 be additive, raising the likelihood of respiratory depression, deep sedation, coma, and death. Stopping the CNS depressant is favored rather than using the two together. For certain patients, it may be suitable to monitor them in a higher level of care or to implement a taper. For others, the appropriate approach may involve slowly weaning the patient off a prescribed CNS depressant or reducing it to the lowest dose that remains effective. When the combination cannot be avoided, exercise caution in monitoring and management, and think about alternative treatments for insomnia or anxiety2. A Swedish epidemiological investigation 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) had an elevated risk of death. Analysis of pooled nationwide death certificate records covering 2010 through 2014 showed that most overdose deaths involving buprenorphine and methadone also involved concurrent CNS depressant use. Whether buprenorphine and methadone differ in the risk of overdose death when combined with CNS depressant drugs has not been established 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
These two medicines can both cause drowsiness and slowed breathing, so your care team will take steps to keep you safe.
- Keep taking both as prescribed unless your doctor tells you otherwise. Do not stop either on your own.
- Your team may adjust and individualize the doses, aiming for the lowest effective amount, or monitor you more closely.
- They may also consider alternatives if one drug is being used for symptoms that could be treated another way.
- Call your pharmacist or prescriber right away if you notice extreme sleepiness, confusion, slow or shallow breathing, or trouble waking.
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 undergoing methadone- or buprenorphine-based medication-assisted treatment (MAT) together with 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 examined the risk of fatal overdose, non-overdose related mortality, and all-cause mortality by comparing periods when CNS depressants were prescribed with periods lacking 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 MAT plus benzodiazepine treatment; however, these data were not deemed statistically significant. Although the results indicated an elevated 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 data were considered statistically significant; 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 of use for the drugs 3.
b) Based on 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 cited 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 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 concomitant CNS depressant drugs differed between buprenorphine and methadone is unknown 3.
Common questions
Can I take Ethopropazine and Buprenorphine together?
Taking buprenorphine and ethopropazine together adds up their sedating and breathing-slowing effects, so keep both as prescribed but let your care team monitor and adjust the doses. Seek help immediately for severe drowsiness or slow breathing. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ethopropazine 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 Ethopropazine and Buprenorphine interaction managed?
These two medicines can both cause drowsiness and slowed breathing, so your care team will take steps to keep you safe. Keep taking both as prescribed unless your doctor tells you otherwise. Do not stop either on your own. Your team may adjust and individualize the doses, aiming for the lowest effective amount, or monitor you more closely. They may also consider alternatives if one drug is being u… 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 Ethopropazine 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 (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 Ethopropazine
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