Buprenorphine and Nicomorphine: 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
Nicomorphine
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 treats pain or opioid dependence, and nicomorphine is a powerful morphine-based pain medicine. When taken together, their effects add up. That can make you very drowsy and, more importantly, can slow down your breathing to a dangerous level. There is also a smaller chance of a reaction called serotonin syndrome (things like agitation, shaking, sweating, or a fast heartbeat).
Please do not stop or change either medicine on your own. Your care team can manage this safely by adjusting doses, watching you more closely, or choosing another option. If you ever feel unusually sleepy, confused, or find it hard to breathe, get medical help right away.
Effect: Additive CNS and respiratory depression, plus an increased risk of serotonin syndrome, when buprenorphine (partial mu-opioid agonist) is combined with nicomorphine (a full mu-opioid agonist and serotonergic CNS depressant).
- Mechanism: Pharmacodynamic (additive), not primarily metabolic. Additive sedation, respiratory depression, and serotonergic activity.
- Direction: Increased opioid and serotonergic effect. Neither drug is a prodrug relevant to reversing this.
- Severity/Evidence: Major; probable. Onset unspecified.
- Management: Avoid combination where possible; cessation or taper of the other CNS depressant is preferred. If concurrent use is necessary, use the lowest effective doses and monitor for sedation, hypoventilation, 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 effects on the CNS can be additive, raising the likelihood of serotonin syndrome and respiratory depression, deep sedation, coma, and death. Discontinuing the other CNS depressants is favored rather than using them alongside buprenorphine. For certain patients, it may be suitable to observe them in a higher level of care or to implement a taper. For others, an appropriate approach may involve slowly tapering the patient off a prescribed benzodiazepine or another CNS depressant, or reducing to the lowest dose that remains effective. Should combined use be required, watch for sedation, respiratory depression, and the signs and symptoms of serotonin syndrome. Observe the patient closely, especially when treatment is being started and when the dose of the serotonergic drug is being adjusted. If serotonin syndrome is suspected, stop buprenorphine and consider alternative options for 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 unless your prescriber tells you otherwise. This combination is managed carefully, not ignored.
- Your care team generally prefers avoiding two overlapping CNS depressants, so they may taper one off or reduce it to the lowest effective dose.
- Doses may need to be adjusted and individualized by your care team, and they may monitor you more closely, especially when starting or changing a dose.
- Watch for heavy drowsiness, slowed or shallow breathing, confusion, or signs of serotonin syndrome (agitation, shakiness, sweating, fast heartbeat).
- Ask your pharmacist or prescriber whether a safer alternative for pain, anxiety, or sleep is possible.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) A Swedish epidemiological study found that patients receiving methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, medications used for insomnia) have an increased risk of death. From July 1, 2005 to December 31, 2012, investigators evaluated the risk of fatal overdose, non-overdose related mortality, and all-cause mortality during periods when CNS depressants were prescribed compared with periods without CNS depressant therapy in MAT-prescribed patients aged 18 to 50. The findings showed a higher 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, this data was not deemed statistically significant. Although the results indicated an elevated 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 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. 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) A study of pooled nationwide death certificate data from 2010 to 2014 reported 3495 drug overdose deaths in 2014. Methadone and other CNS depressants were commonly identified as contributors in those deaths. Concurrent alprazolam use appeared 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. Among 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 differs between buprenorphine and methadone is unknown 3.
Common questions
Can I take Buprenorphine and Nicomorphine together?
Combining buprenorphine and nicomorphine adds up their opioid effects and can cause dangerous sedation and slowed breathing, with a smaller risk of serotonin syndrome. Do not change anything on your own; your care team can manage this with dose adjustments and closer monitoring, and get emergency help for extreme drowsiness or breathing trouble. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Nicomorphine 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 Nicomorphine interaction managed?
Keep taking both exactly as prescribed unless your prescriber tells you otherwise. This combination is managed carefully, not ignored. Your care team generally prefers avoiding two overlapping CNS depressants, so they may taper one off or reduce it to the lowest effective dose. Doses may need to be adjusted and individualized by your care team, and they may monitor you more closely, especially whe… 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 Nicomorphine 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 Nicomorphine
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