Buprenorphine and Ketobemidone: 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
Ketobemidone
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 buprenorphine and ketobemidone are strong opioid pain medicines. When they are taken together, their effects add up. That can make you very sleepy, slow your breathing, and in serious cases lead to dangerously deep sedation. There is also a small added risk of serotonin syndrome, which can cause agitation, a fast heartbeat, sweating, shivering, or muscle twitching.
This is a serious combination, but it is one your care team knows how to handle. Please don't stop or change either medicine on your own. Talk with your doctor or pharmacist, watch for unusual drowsiness or breathing trouble, and get help right away if breathing becomes very slow.
Effect: Combining buprenorphine (partial mu-opioid agonist) with ketobemidone (full opioid agonist) produces additive CNS and respiratory depression, plus an increased risk of serotonin syndrome from additive serotonergic activity.
- Direction: Additive PD interaction, enhanced sedation and respiratory depression; risk of profound sedation, coma, death.
- Evidence: Probable. Onset: unspecified. Severity: major.
- Management: Avoid concomitant use where possible. If unavoidable, use lowest effective doses, consider taper of the co-depressant, and monitor closely for sedation, respiratory depression, and serotonin syndrome, especially at initiation and dose adjustment. 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
When buprenorphine is given together with a serotonergic CNS depressant, the combined effect can produce additive CNS depression, raising the likelihood of serotonin syndrome, respiratory depression, deep sedation, coma, and death. Stopping the other CNS depressants is favored rather than using them at the same time. Certain situations may call for observation within a higher level of care or a taper. In other situations, it may be suitable to slowly wean a patient off a prescribed benzodiazepine or another CNS depressant, or to reduce the dose to the smallest amount that remains effective. Should concurrent use be required, watch for sedation, respiratory depression, and the signs and symptoms of serotonin syndrome. The patient should be observed closely, especially when treatment begins and when the dose of the serotonergic agent is being adjusted. If serotonin syndrome is suspected, stop buprenorphine and consider alternative approaches for managing anxiety or insomnia21.
Why it happens (mechanism)
Additive serotonergic effects; additive CNS and respiratory depression
How to manage this interaction
This combination can be managed, but it calls for caution and close teamwork with your prescribers.
- Keep taking both exactly as prescribed unless your care team tells you otherwise. Do not stop or change doses on your own.
- Your team may prefer to avoid using both together, taper one down, or use the lowest effective dose that controls your symptoms.
- They may monitor you more closely, especially when either drug is started or the dose is changed.
- Get urgent help for very slow or shallow breathing, extreme drowsiness, or signs of serotonin syndrome (agitation, fast heartbeat, sweating, shivering, muscle twitching).
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, drugs used to treat insomnia) have an increased risk of death. Between July 1, 2005 and December 31, 2012, the risk of fatal overdose, non-overdose related mortality, and all-cause mortality was compared between periods when CNS depressants were prescribed and periods without CNS depressant therapy in MAT-prescribed patients (aged 18 to 50). The findings showed an increased 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 the results showed an increased 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 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. 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 often cited 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, although 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 Ketobemidone together?
Taking buprenorphine and ketobemidone together adds up their sedating effects and raises the risk of dangerously slow breathing and serotonin syndrome; use them together only under close medical supervision and get emergency help for severe drowsiness or breathing trouble. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Ketobemidone 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 Ketobemidone interaction managed?
This combination can be managed, but it calls for caution and close teamwork with your prescribers. Keep taking both exactly as prescribed unless your care team tells you otherwise. Do not stop or change doses on your own. Your team may prefer to avoid using both together, taper one down, or use the lowest effective dose that controls your symptoms. They may monitor you more closely, especially wh… 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 Ketobemidone 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 Ketobemidone
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