Buprenorphine and Dichloralphenazone: 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
Dichloralphenazone
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 dichloralphenazone is a sedative often used to help with sleep. Both of these slow down your brain and breathing. When you take them together, those calming effects can stack on top of each other. That can leave you very drowsy, very sleepy, or breathing too slowly, and in serious cases this can be dangerous.
The good news is that your care team can manage this. Please do not stop either medicine on your own. Instead, tell your doctor or pharmacist that you take both so they can decide the safest plan, watch you a little more closely, or suggest a different sleep option if needed.
Mechanism: additive CNS depression. Neither agent activates the other; the effect is pharmacodynamic, not a prodrug or enzyme issue.
Direction/effect: combined opioid (buprenorphine) plus sedative (dichloralphenazone, a chloral hydrate/antipyrine complex) increases risk of respiratory depression, profound sedation, coma, and death.
- Severity: major; evidence: probable; onset: unspecified.
- Management: avoid concomitant use where possible; prefer cessation or taper of the CNS depressant, or lowest effective dose. If combined, monitor respiratory status and sedation, consider higher level of care. Do NOT withhold MAT; consider alternative agents for insomnia/anxiety.
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 CNS depression can heighten the likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing the CNS depressant is favored rather than using both drugs at the same time. Depending on the situation, it may be suitable to monitor the patient in a higher level of care or to taper. In other situations, it may be appropriate to slowly wean a patient off a prescribed CNS depressant or to reduce it to the lowest dose that remains effective. Should concurrent use be required, exercise caution in monitoring and management; alternative therapies for treating anxiety or insomnia should be considered2. 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) faced a greater risk of death. A study analyzing 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 overdose death with concurrent CNS depressant drugs varied between buprenorphine and methadone is not known 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Both medicines calm the brain and can slow breathing, so combining them takes extra care. Here is how a care team usually handles this:
- They may lower the dose of the sedative to the smallest amount that works, or gradually taper it off.
- They may watch you more closely, sometimes in a higher level of care, especially early on.
- They may suggest a non-sedating option for sleep or anxiety instead.
Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Never stop suddenly on your own. Ask your pharmacist or doctor about the safest plan, and get urgent help for extreme drowsiness or slow, shallow breathing.
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, medications used for insomnia) face a greater risk of death. From July 1, 2005 to December 31, 2012, researchers examined the risk of fatal overdose, non-overdose related mortality, and all-cause mortality in MAT patients (aged 18 to 50), comparing intervals when CNS depressants were prescribed against intervals without CNS depressant therapy. 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 combined with benzodiazepine treatment; however, these data were not deemed statistically significant. Although the results showed a raised 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 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 identified as contributing to those deaths. Concurrent ALPRAZolam use 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 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 remains unknown 3.
Common questions
Can I take Buprenorphine and Dichloralphenazone together?
Buprenorphine and dichloralphenazone both depress the brain and breathing, so together they raise the risk of dangerous oversedation. Keep taking both as prescribed, but talk to your prescriber or pharmacist about the safest plan and closer monitoring. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Dichloralphenazone 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 Dichloralphenazone interaction managed?
Both medicines calm the brain and can slow breathing, so combining them takes extra care. Here is how a care team usually handles this: They may lower the dose of the sedative to the smallest amount that works, or gradually taper it off. They may watch you more closely, sometimes in a higher level of care, especially early on. They may suggest a non-sedating option for sleep or anxiety instead. Ke… 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 Dichloralphenazone 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 Dichloralphenazone
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