Flibanserin 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
Flibanserin
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 can slow down your brain and breathing, and taking them together adds those effects up. Buprenorphine is a strong opioid pain and addiction medicine, and flibanserin (Addyi) can also cause drowsiness and low blood pressure. Together they can make you very sleepy, dizzy, or fainty, and in serious cases slow your breathing too much.
The good news is that your care team can manage this. Please don't stop either medicine on your own. Instead, tell your doctor or pharmacist you take both so they can watch you more closely, adjust doses if needed, and let you know what warning signs to look for.
Mechanism: additive CNS depression (pharmacodynamic). Neither agent's effect here depends on prodrug activation; the concern is simply overlapping sedative/respiratory-depressant activity.
Direction/effect: increased risk of respiratory depression, profound sedation, coma, and death. Flibanserin also carries independent hypotension and syncope risk, compounding sedation.
- Severity: major; evidence: probable; onset: unspecified.
- Management: avoid or minimize concurrent use; use lowest effective dose or taper the CNS depressant where clinically appropriate. If combined, monitor for respiratory depression and excessive sedation; consider alternatives for the flibanserin indication.
- Do not withhold buprenorphine-based MAT solely due to this interaction; balance overdose risk against untreated opioid use disorder.
What happens
An increased risk of respiratory depression and CNS depression
Interaction Deep Dive
When buprenorphine is given together with a CNS depressant, the combined effects on the central nervous system can be additive, raising the likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing CNS depressants is favored rather than using them alongside buprenorphine. Monitoring within a higher level of care, or a taper, may be suitable in certain situations. In other situations, it may be appropriate to slowly wean a patient off a prescribed CNS depressant or to reduce the dose to the lowest amount that remains effective. When concurrent use cannot be avoided, exercise caution in monitoring and management; alternative treatments for anxiety or insomnia may be worth considering2. A Swedish epidemiological study found that patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) who also took benzodiazepines or other CNS depressants (for instance, medications used for insomnia) had a heightened risk of death. Analysis of pooled nationwide death certificate records spanning 2010 to 2014 showed that most overdose deaths involving buprenorphine and methadone also involved concurrent CNS depressant use. Whether the risk of fatal overdose from concurrent CNS depressant drugs was different for buprenorphine versus methadone remains unknown 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Keep taking both exactly as prescribed unless your prescriber tells you otherwise. This combination is managed by careful oversight, not by you stopping a drug on your own.
- Tell your pharmacist and prescriber you take both so they can decide if a dose should be adjusted and individualized, or if an alternative for your symptoms makes sense.
- Your team may monitor you more closely for heavy drowsiness, confusion, dizziness, fainting, or slow/shallow breathing.
- Avoid alcohol and other sedating substances, which add to the risk.
- Seek emergency help right away for very slow breathing, extreme sleepiness you can't wake from, or fainting.
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 on methadone- or buprenorphine-based medication-assisted treatment (MAT) who also took benzodiazepines or other CNS depressants (for example, agents used to treat insomnia) had an increased risk of death. From July 1, 2005 through December 31, 2012, investigators examined the risk of fatal overdose, non-overdose related mortality, and all-cause mortality by comparing periods when CNS depressants were prescribed to periods without such therapy in MAT patients (aged 18 to 50). 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 combined MAT and benzodiazepine treatment; however, these data were not deemed 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 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 for which the drugs were used 3.
b) In an analysis of pooled nationwide death certificate data from 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone together with other CNS depressants were commonly cited as contributing to those deaths. Concurrent ALPRAZolam use was noted 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. 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 deaths involving methadone was 10 times that of deaths involving buprenorphine, though confounding factors and differences in drug utilization were not taken into account. Whether the risk of overdose death with concurrent CNS depressant drugs differed between buprenorphine and methadone is unknown 3.
Common questions
Can I take Flibanserin and Buprenorphine together?
Buprenorphine and flibanserin both depress the brain and can add up to dangerous sedation and slowed breathing. Don't stop either on your own, but tell your doctor or pharmacist you take both so they can adjust doses and monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Flibanserin 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 Flibanserin and Buprenorphine interaction managed?
Keep taking both exactly as prescribed unless your prescriber tells you otherwise. This combination is managed by careful oversight, not by you stopping a drug on your own. Tell your pharmacist and prescriber you take both so they can decide if a dose should be adjusted and individualized, or if an alternative for your symptoms makes sense. Your team may monitor you more closely for heavy drowsine… 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 Flibanserin 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 Flibanserin
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