Tolonium Chloride 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
Tolonium Chloride
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 an opioid used for pain or for treating opioid use disorder. Tolonium chloride (toluidine blue) can, in some people, add to the sedating and breathing-slowing effects of buprenorphine. When two things that calm the brain and slow breathing are used together, the effect can stack up. That can mean feeling very drowsy, breathing too slowly, or in serious cases, not waking up.
Please don't stop or change either medicine on your own. This is something your care team can manage safely by choosing the right doses and watching you more closely. Talk with your pharmacist or doctor so they can look at your full picture.
Effect: Additive CNS and respiratory depression when buprenorphine is combined with a CNS depressant. Neither agent's activation depends on a shared enzyme; this is a pharmacodynamic (additive), not pharmacokinetic, interaction.
- Direction: Increased sedative/respiratory-depressant effect.
- Severity/evidence: Major; probable. Epidemiologic data link concomitant CNS depressants with buprenorphine to increased overdose mortality.
- Onset: Unspecified.
- Management: Avoid or minimize concurrent use where possible; use lowest effective dose and shortest duration. Monitor for respiratory depression and profound sedation, escalate level of care if needed. Do not withhold medication-assisted treatment solely due to this interaction.
What happens
An increased risk of respiratory depression and CNS depression
Interaction Deep Dive
When buprenorphine is given together with a CNS depressant, the combined effect on the central nervous system can be additive, raising the likelihood of respiratory depression, deep sedation, coma, and death. Rather than using these agents together, discontinuing the CNS depressant is the preferred approach. Depending on the situation, it may be suitable to observe the patient in a higher level of care or to implement a taper. In other circumstances, slowly weaning a patient off a prescribed CNS depressant, or reducing the dose to the lowest effective amount, may be appropriate. Should concurrent use be required, exercise careful monitoring and management, and consider alternative therapies for treating anxiety or insomnia2. A Swedish epidemiological study 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) face an elevated risk of death. Analysis of pooled 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 fatal overdose from concurrent CNS depressant drugs differs between buprenorphine and methadone is not known 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
The most important thing: keep taking both exactly as prescribed unless your care team tells you otherwise. Do not stop your buprenorphine on your own.
Here is how a care team typically handles this:
- Uses the lowest effective dose and shortest necessary duration of the CNS depressant.
- Monitors you more closely for slowed breathing or heavy sedation, sometimes in a higher level of care.
- Considers alternatives if the second drug is for anxiety or sleep.
Tell your pharmacist or prescriber about every medicine you take, and get help right away if you feel unusually sleepy, confused, or short of breath.
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 took benzodiazepines or other CNS depressants (for example, agents used to manage insomnia) had 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 such therapy among MAT patients (aged 18 to 50). The findings showed a heightened 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, but this data was not deemed statistically significant. Although results indicated an increased risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods of combined MAT and non-benzodiazepine use, 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 for which the drugs were used 3.
b) Based on a study of pooled nationwide death certificate data spanning 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 documented 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. Whether the risk of overdose death with concurrent CNS depressant drugs differed between buprenorphine and methadone is not known 3.
Common questions
Can I take Tolonium Chloride and Buprenorphine together?
Combining buprenorphine with another CNS depressant can add up to dangerous sedation and slowed breathing, so keep both providers informed and let your care team manage the doses and monitoring. Never stop either drug on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Tolonium Chloride 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 Tolonium Chloride and Buprenorphine interaction managed?
The most important thing: keep taking both exactly as prescribed unless your care team tells you otherwise. Do not stop your buprenorphine on your own. Here is how a care team typically handles this: Uses the lowest effective dose and shortest necessary duration of the CNS depressant. Monitors you more closely for slowed breathing or heavy sedation, sometimes in a higher level of care. Considers a… 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 Tolonium Chloride 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 Tolonium Chloride
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