Buprenorphine and Tilidine: 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
Tilidine
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 that work on your brain and breathing. Buprenorphine and tilidine can each slow your breathing and make you very sleepy. Taken together, those effects can add up, which can lead to dangerous drowsiness, very slow breathing, or worse. There is also a smaller chance of something called serotonin syndrome, which can cause shakiness, a fast heartbeat, sweating, and confusion.
The good news is that your care team can manage this. Please don't stop or change either medicine on your own. Instead, talk with your pharmacist or doctor so they can decide the safest plan and watch you more closely if you need both.
Interaction: Additive CNS and respiratory depression plus additive serotonergic effects when buprenorphine (partial mu-opioid agonist) is combined with tilidine (opioid analgesic, active via nortilidine).
- Direction/effect: Increased risk of profound sedation, respiratory depression, and serotonin syndrome (coma/death possible).
- Mechanism: Pharmacodynamic (additive), not a single enzyme/transporter effect.
- Evidence: Probable. Severity: major. Onset: unspecified.
- Management: Avoid where possible; cessation preferred. If necessary, use lowest effective doses, taper the CNS depressant, and monitor sedation, respiratory rate, and serotonergic signs, especially at initiation/titration. 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 combination can produce additive CNS depression, raising the likelihood of serotonin syndrome as well as respiratory depression, deep sedation, coma, and death. Discontinuing the other CNS depressants is favored rather than using them concurrently. For certain patients, either observation within a higher level of care or a taper may be suitable. For others, it may be appropriate to slowly wean the patient off a prescribed benzodiazepine or other CNS depressant, or to reduce the dose to the lowest effective level. Should concurrent use be required, watch for sedation, respiratory depression, and the signs and symptoms of serotonin syndrome. Observe the patient closely, especially when therapy is being initiated 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
Keep taking both exactly as prescribed until your care team advises otherwise. This combination is generally avoided when possible, so your prescriber may prefer stopping or tapering one drug rather than using them together.
- Your team may lower one medicine to the lowest effective dose or gradually taper it.
- They may monitor you more closely, especially when starting or changing a dose.
- Watch for heavy drowsiness, slow or shallow breathing, confusion, or signs of serotonin syndrome (agitation, fast heartbeat, sweating, tremor, fever).
- Get urgent help for severe drowsiness or trouble breathing, and tell your pharmacist or doctor about any of these symptoms.
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 undergoing 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, the risk of fatal overdose, non-overdose related mortality, and all-cause mortality was evaluated in MAT prescribed patients (aged 18 to 50), comparing periods when CNS depressants were prescribed to periods without CNS depressant therapy. 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 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 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 often reported as contributing agents 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, 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 Tilidine together?
Combining buprenorphine and tilidine adds up their sedating and breathing-slowing effects and carries a serotonin syndrome risk, so this pairing is best avoided; do not change either drug on your own and check with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Tilidine 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 Tilidine interaction managed?
Keep taking both exactly as prescribed until your care team advises otherwise. This combination is generally avoided when possible, so your prescriber may prefer stopping or tapering one drug rather than using them together. Your team may lower one medicine to the lowest effective dose or gradually taper it. They may monitor you more closely, especially when starting or changing a dose. Watch for… 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 Tilidine 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 Tilidine
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