Opium Alkaloids 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
Opium Alkaloids
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 medicines are opioids that slow down your body. Buprenorphine and opium alkaloids each calm the brain and slow your breathing. Taken together, those effects can stack up. This can make you very drowsy, slow your breathing too much, and in serious cases lead to dangerous sedation.
There is also a chance of something called serotonin syndrome, which can cause agitation, a fast heartbeat, sweating, shaking, or confusion. The good news is your care team can manage this. If you have been prescribed both, keep taking them as directed and talk with your pharmacist or doctor about the safest plan for you.
Additive CNS and respiratory depression, plus additive serotonergic risk. Both agents are opioid CNS depressants; buprenorphine also carries serotonergic potential. Concurrent use is a pharmacodynamic (not metabolic) interaction, raising the risk of profound sedation, respiratory depression, coma, serotonin syndrome, and death.
- Direction: increased combined depressant effect
- Evidence: probable; severity major
- Onset: unspecified
Management: avoidance or cessation of one agent is preferred. If concurrent use is unavoidable, use lowest effective doses, consider tapering, and monitor for sedation, respiratory depression, and serotonin syndrome, 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
When buprenorphine is given together with a serotonergic CNS depressant, the combined effect can produce additive CNS depression along with a heightened likelihood of serotonin syndrome, respiratory depression, deep sedation, coma, and death. Discontinuing the other CNS depressants is favored rather than using them concurrently. For certain patients, it may be suitable to monitor them in a higher level of care or to implement a taper. For others, slowly tapering the patient off a prescribed benzodiazepine or another CNS depressant, or reducing to the lowest effective dose, may be appropriate. Should concurrent use be required, watch for sedation, respiratory depression, and any signs and symptoms of serotonin syndrome. Observe the patient closely, especially when treatment is being initiated and when the dose of the serotonergic drug is being adjusted. If serotonin syndrome is suspected, stop buprenorphine, and consider alternative approaches to managing 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 and do not stop either on your own, but do bring this combination up with your prescriber or pharmacist soon.
- Your care team may prefer to avoid using both together, or to taper one down to the lowest effective dose.
- They may monitor you more closely, especially when starting or changing a dose.
- Watch for heavy drowsiness, slow or shallow breathing, confusion, or trouble waking, and get help right away if these happen.
- Report agitation, fast heartbeat, sweating, or shaking, which can signal serotonin syndrome.
Your team can tailor your doses and monitoring to keep you safe.
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) taken together with benzodiazepines or other CNS depressants (for example, medications used for insomnia) have an increased risk of death. Among MAT-prescribed patients (aged 18 to 50), the analysis compared the risk of fatal overdose, non-overdose related mortality, and all-cause mortality during periods with prescribed CNS depressants versus periods without CNS depressant therapy, between July 1, 2005 and December 31, 2012. 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 plus 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 coadministration of MAT and non-benzodiazepines, only the fatal overdose and all-cause mortality figures 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. The authors did not compare the benzodiazepine cohort with the non-benzodiazepine cohort because they did not adjust for the indication of use for the drugs 3.
b) In a study drawing on aggregate 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 in those deaths. Concurrent use of alprazolam 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 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 count of methadone-involved deaths was 10 times the count of buprenorphine-involved deaths, though confounding factors and differences in drug utilization were not accounted for. Whether the risk of overdose death with concomitant CNS depressant drugs differed between buprenorphine and methadone is unknown 3.
Common questions
Can I take Opium Alkaloids and Buprenorphine together?
Combining buprenorphine with opium alkaloids adds up their sedating effects and can dangerously slow breathing, so use both only under close medical supervision and contact your care team about the safest plan. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Opium Alkaloids 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 Opium Alkaloids and Buprenorphine interaction managed?
Keep taking both exactly as prescribed and do not stop either on your own, but do bring this combination up with your prescriber or pharmacist soon. Your care team may prefer to avoid using both together, or to taper one down to the lowest effective dose. They may monitor you more closely, especially when starting or changing a dose. Watch for heavy drowsiness, slow or shallow breathing, confusion… 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 Opium Alkaloids 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 Opium Alkaloids
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