Buprenorphine and Methotrimeprazine: 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
Methotrimeprazine
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 opioid use disorder) and methotrimeprazine (a medicine that calms the nervous system and can also affect heart rhythm). When taken together, their effects can add up.
The main concerns are two-fold. First, both can slow your breathing and make you very drowsy, which in serious cases can be dangerous. Second, both can affect your heart's electrical timing (called the QT interval), which can lead to an irregular heartbeat. The good news is that your care team can manage this. Watch for unusual sleepiness, slow or shallow breathing, dizziness, or fainting, and talk with your doctor or pharmacist before changing anything.
Additive risk, two mechanisms. Buprenorphine and methotrimeprazine (a phenothiazine) together produce:
- Additive QT prolongation, raising torsades de pointes risk.
- Additive CNS and respiratory depression, risking profound sedation, coma, and death.
This is a pharmacodynamic (not metabolic) interaction; neither is a prodrug relevant here. Severity major, evidence probable, onset unspecified.
Management: avoid concurrent use where possible. If unavoidable, use the lowest effective doses, monitor sedation and respiratory status closely, and consider baseline/follow-up ECG and electrolytes (K+, Mg2+). Consider alternative agents for anxiety/insomnia and strongly consider prescribing naloxone. Do not withhold MAT solely due to this interaction.
What happens
An increased risk of QT interval prolongation and an increased risk of CNS and respiratory depression
Interaction Deep Dive
Do not use buprenorphine together with medications capable of prolonging the QT interval. Combining these agents also heightens the likelihood of respiratory depression, profound sedation, coma, and death. Discontinuing a benzodiazepine or other CNS depressant is favored over using it alongside buprenorphine. For certain patients, it may be suitable to monitor them in a higher level of care or to implement a taper. For others, slowly tapering the patient off a prescribed benzodiazepine or other CNS depressant, or reducing to the lowest effective dose, may be appropriate. When concurrent use cannot be avoided, monitor and manage the patient with caution; weigh alternative therapies for anxiety or insomnia, and give strong consideration to prescribing naloxone for emergency management of opioid overdose2. 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 example, medications used for insomnia) have a heightened risk of death. Analysis of aggregate nationwide death certificate data spanning 2010 to 2014 showed that most overdose deaths involving buprenorphine and methadone also involved concurrent CNS depressant use. Whether the risk of overdose death with concomitant CNS depressant drugs varied between buprenorphine and methadone is not known 3.
Why it happens (mechanism)
Additive QT interval prolongation; additive CNS depression
How to manage this interaction
This combination is generally best avoided, but your care team can manage it if both are truly needed.
- Keep taking both as prescribed unless your prescriber tells you otherwise. Do not stop suddenly on your own.
- Your team may use the lowest effective doses and monitor you more closely, including your breathing, alertness, and possibly your heart rhythm (ECG).
- They may consider a different option for anxiety or sleep if that is why methotrimeprazine is used.
- Ask whether a naloxone rescue kit is right for you, and make sure loved ones know how to use it.
Get emergency help for very slow breathing, extreme drowsiness, fainting, or a pounding/irregular heartbeat.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
3 reports — tap to read
a) A Swedish epidemiological study reported that patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) who also received benzodiazepines or other CNS depressants (for example, drugs that treat insomnia) have an increased risk of death. Between July 1, 2005 and December 31, 2012, investigators analyzed the risk of fatal overdose, non-overdose related mortality, and all-cause mortality during periods when CNS depressants were prescribed compared with periods without CNS depressant therapy in 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 and benzodiazepine treatment; however, these data were not regarded as statistically significant. Although results also demonstrated a raised risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods when MAT and non-benzodiazepines were coadministered, only the data for fatal overdose and all-cause mortality were regarded as 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 compare the benzodiazepine cohort with the non-benzodiazepine cohort because they did not adjust for the indication of use for the drugs 3.
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 frequently identified 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, 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.
c) Thorough QT studies of buprenorphine products have shown modest QT prolongation equal to 15 msec or less 1.
Common questions
Can I take Buprenorphine and Methotrimeprazine together?
Combining buprenorphine and methotrimeprazine adds up their heart-rhythm and breathing/sedation risks, so this pairing is best avoided; if both are needed, expect lower doses, close monitoring, and possibly a naloxone kit. Do not change either medicine without talking to your prescriber or pharmacist. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Methotrimeprazine 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 Methotrimeprazine interaction managed?
This combination is generally best avoided, but your care team can manage it if both are truly needed. Keep taking both as prescribed unless your prescriber tells you otherwise. Do not stop suddenly on your own. Your team may use the lowest effective doses and monitor you more closely, including your breathing, alertness, and possibly your heart rhythm (ECG). They may consider a different option f… 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 Methotrimeprazine 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 Methotrimeprazine
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