Buprenorphine and Diacetylmorphine: 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
Diacetylmorphine
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 of these are strong opioids. Buprenorphine is used for pain or opioid treatment, and diacetylmorphine is heroin, a powerful opioid. Taking them together stacks their effects on your brain and breathing. That can lead to very heavy drowsiness, dangerously slow or shallow breathing, and in the worst cases coma or death.
This is a serious combination, so please don't stop or change anything on your own. Talk with your doctor or pharmacist right away so they can guide you safely. If you ever feel extremely sleepy, confused, or find it hard to breathe, get emergency help immediately.
Mechanism: additive CNS and respiratory depression. Both agents are mu-opioid receptor agonists (buprenorphine a high-affinity partial agonist; diacetylmorphine a full agonist), producing pharmacodynamic, not pharmacokinetic, potentiation. Neither is a prodrug relevant to this interaction direction.
- Effect: increased respiratory depression, profound sedation, coma, death.
- Evidence: probable; epidemiologic data link concomitant opioid/CNS depressant use to higher overdose mortality.
- Management: avoid combination where possible. If MAT is involved, do not withhold buprenorphine; monitor closely, use lowest effective doses, consider higher level of care. Watch respiratory rate, sedation, and oxygenation.
What happens
An increased risk of respiratory depression and CNS depression
Interaction Deep Dive
Taking buprenorphine together with a CNS depressant can produce additive CNS depression, raising the likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing the CNS depressant is favored rather than using the two together. Certain situations may call for observation at a higher level of care or a tapering strategy. In other situations, it may be suitable to gradually withdraw a patient from a prescribed CNS depressant or to reduce it to the lowest dose that remains effective. When combined use cannot be avoided, exercise careful monitoring and management, and weigh alternative treatments for 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) faced a heightened risk of death. Based on an analysis of pooled nationwide death certificate data spanning 2010 to 2014, most overdose deaths that involved buprenorphine and methadone also involved concurrent CNS depressant use. Whether the risk of fatal overdose from 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
Take this seriously, but don't stop your medication on your own. Your care team is the right place to sort this out.
- Keep taking your prescribed medication exactly as directed until your prescriber tells you otherwise.
- Combining these opioids is generally avoided; your team may reduce doses to the lowest effective amount, taper one agent, or watch you more closely, sometimes in a higher level of care.
- If you are in medication-assisted treatment, you should not be denied that care, but it must be managed carefully.
- Get emergency help for extreme drowsiness, confusion, 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 reported that patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, medications used to treat insomnia) have an increased risk of death. Between July 1, 2005 and 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 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 combined MAT and benzodiazepine treatment; however, these data were not deemed statistically significant. Although the results indicated an increased risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods of concurrent 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. A comparison between the benzodiazepine cohort and the non-benzodiazepine cohort was not performed because the authors did not adjust for the indication for which the drugs were used 3.
b) According to 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 named as contributors 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. 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. It remains unknown whether the risk of overdose death with concomitant CNS depressant drugs differed between buprenorphine and methadone 3.
Common questions
Can I take Buprenorphine and Diacetylmorphine together?
Buprenorphine plus diacetylmorphine (heroin) stacks opioid effects and can dangerously slow your breathing; do not combine them without close medical oversight, and contact your doctor or pharmacist promptly. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Diacetylmorphine 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 Diacetylmorphine interaction managed?
Take this seriously, but don't stop your medication on your own. Your care team is the right place to sort this out. Keep taking your prescribed medication exactly as directed until your prescriber tells you otherwise. Combining these opioids is generally avoided; your team may reduce doses to the lowest effective amount, taper one agent, or watch you more closely, sometimes in a higher level of c… 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 Diacetylmorphine 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 Diacetylmorphine
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