Buprenorphine and Ethylmorphine: 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
Ethylmorphine
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 opioids, and taking them together can be risky. Buprenorphine and ethylmorphine both slow down your breathing and your brain. Stacked on top of each other, that effect adds up, so you could become very sleepy, breathe too slowly, or in serious cases stop breathing.
There is also a chance of something called serotonin syndrome, which can cause agitation, a fast heartbeat, sweating, shivering, or muscle twitching. This is considered a serious combination, but your care team can manage it. Please don't stop or change either medicine on your own. Talk with your pharmacist or doctor so they can decide the safest plan for you.
Interaction: Additive CNS and respiratory depression plus additive serotonergic effects when buprenorphine (partial opioid agonist) is combined with ethylmorphine (opioid analgesic/antitussive). Both are active drugs, not relevant prodrugs here for this PD interaction.
- Direction: Increased opioid effect; risk of profound sedation, respiratory depression, coma, and serotonin syndrome.
- Mechanism: Pharmacodynamic (additive), not primarily PK-driven.
- Evidence/onset: Probable; onset unspecified.
- Management: Avoid where possible; cessation of the other CNS depressant is preferred. If combined, use lowest effective dose, monitor sedation, respiratory status, and serotonin syndrome signs, especially at initiation and dose changes. Discontinue buprenorphine if serotonin syndrome is suspected.
What happens
An increased risk of serotonin syndrome and an increased risk of respiratory and CNS depression
Interaction Deep Dive
Giving buprenorphine together with a serotonergic CNS depressant can produce additive CNS depression, along with a heightened likelihood of serotonin syndrome and respiratory depression, deep sedation, coma, and death. Rather than using these agents together, stopping the other CNS depressants is the preferred approach. Depending on the situation, it may be suitable to monitor the patient at a higher level of care or to implement a taper. In other circumstances, slowly weaning a patient from a prescribed benzodiazepine or another CNS depressant, or reducing to the lowest effective dose, may be appropriate. When combined use cannot be avoided, watch for sedation, respiratory depression, and the signs and symptoms of serotonin syndrome. Observe the patient closely, especially when therapy is being started and while the dose of the serotonergic drug is being adjusted. If serotonin syndrome is suspected, stop buprenorphine and consider alternative treatments for anxiety or insomnia21.
Why it happens (mechanism)
Additive serotonergic effects; additive CNS and respiratory depression
How to manage this interaction
Keep taking both exactly as prescribed unless your care team tells you otherwise. This is a serious combination, but it can be managed.
- Your team generally prefers avoiding the other CNS depressant if it can be safely stopped, sometimes with a gradual taper.
- If both are truly needed, they may use the lowest effective dose and monitor you more closely, especially when starting or adjusting a dose.
- Watch for very heavy drowsiness, slow or shallow breathing, confusion, agitation, fast heartbeat, sweating, or muscle twitching, and get help right away if these occur.
Ask your pharmacist or prescriber whether a safer alternative is available for your situation.
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 receiving methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, agents used to treat insomnia) have an increased risk of death. From July 1, 2005 through 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-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 deemed statistically significant. Although the results demonstrated a raised risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods of coadministration of MAT and non-benzodiazepines, only the data for fatal overdose and all-cause mortality 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. A comparison between the benzodiazepine cohort and the non-benzodiazepine cohort was not performed because the authors 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 commonly cited as contributors in 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.
Common questions
Can I take Buprenorphine and Ethylmorphine together?
Buprenorphine and ethylmorphine together can dangerously add up breathing and brain slowing and may trigger serotonin syndrome, so don't combine them without your care team's guidance. Keep taking what you're prescribed, but ask your pharmacist or doctor to review this pairing. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Ethylmorphine 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 Ethylmorphine interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. This is a serious combination, but it can be managed. Your team generally prefers avoiding the other CNS depressant if it can be safely stopped, sometimes with a gradual taper. If both are truly needed, they may use the lowest effective dose and monitor you more closely, especially when starting or adjusting a dose.… 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 Ethylmorphine 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 Ethylmorphine
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist