Buprenorphine and Papaveretum: 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
Papaveretum
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 calm the brain and slow the body down. Buprenorphine is used for pain or opioid treatment, and papaveretum is a mix of opium-based painkillers. Taking them together adds up their effects, so your breathing and alertness can slow down more than either would alone. That can cause heavy drowsiness, very slow breathing, and in serious cases it can be dangerous.
There's also a smaller chance of something called serotonin syndrome, which can bring on agitation, a fast heartbeat, sweating, and shaking. The good news is your care team can manage this safely by adjusting doses and watching you closely. Please don't stop or change either medicine on your own, just talk with your doctor or pharmacist.
Effect: Additive CNS and respiratory depression, plus an increased risk of serotonin syndrome when buprenorphine is combined with papaveretum (an opium alkaloid mixture with serotonergic and opioid depressant activity). Neither is a prodrug in a way that alters direction; this is a pharmacodynamic, additive interaction.
- Direction/magnitude: Increased sedation, hypoventilation, risk of profound sedation, coma, death.
- Onset: Unspecified. Evidence: Probable. Severity: Major.
- Management: Avoid concurrent use where possible. If unavoidable, use lowest effective doses, monitor for sedation, respiratory depression, and serotonin toxicity, 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 CNS depressant effects may occur, raising the likelihood of serotonin syndrome as well as respiratory depression, profound 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 observe the patient at a higher level of care or to implement a taper. In other circumstances, slowly weaning a patient off a prescribed benzodiazepine or other CNS depressant, or lowering it to the smallest effective dose, may be the right course. Should concurrent use be required, watch for respiratory depression, sedation, and the manifestations of serotonin syndrome. The patient should be observed closely, especially when treatment is being started and while 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
Your care team takes this combination seriously because two opioids together can dangerously add up. Often, avoiding using both at the same time is preferred, but if you need both, your team can manage it carefully.
- Keep taking both exactly as prescribed unless your doctor tells you otherwise.
- Doses may be adjusted and individualized, often to the lowest effective dose, and your team may monitor you more closely, especially when starting or changing a dose.
- Get urgent help for very slow or shallow breathing, extreme sleepiness, or trouble waking up.
- Watch for agitation, sweating, fast heartbeat, shivering, or muscle twitching, and report these to your care team.
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, investigators analyzed the risk of fatal overdose, non-overdose related mortality, and all-cause mortality by comparing periods when CNS depressants were prescribed to 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 considered statistically significant. Although results showed an elevated 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) Based on 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 identified 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 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. 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 Papaveretum together?
Combining buprenorphine and papaveretum adds up their sedating and breathing-slowing effects and can raise the risk of serotonin syndrome, so this is usually avoided; if both are needed, your care team will use the lowest doses and monitor you closely. Never stop or change either drug on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Papaveretum 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 Papaveretum interaction managed?
Your care team takes this combination seriously because two opioids together can dangerously add up. Often, avoiding using both at the same time is preferred, but if you need both, your team can manage it carefully. Keep taking both exactly as prescribed unless your doctor tells you otherwise. Doses may be adjusted and individualized, often to the lowest effective dose, and your team may monitor y… 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 Papaveretum 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 Papaveretum
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