Eszopiclone 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
Eszopiclone
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.
Buprenorphine (an opioid used for pain or to treat opioid use disorder) and eszopiclone (Lunesta, a sleep medicine) both calm down your brain and slow your breathing. When you take them together, those effects can add up. This can lead to very heavy drowsiness, dangerously slow or shallow breathing, and in serious cases, coma or even death.
Please don't stop either medicine on your own, both are important. The good news is your care team can manage this safely by adjusting doses, monitoring you more closely, or looking at other options for sleep. Talk with your pharmacist or doctor before your next dose so they can make a plan that fits you.
Effect: Additive CNS and respiratory depression. Both agents are CNS depressants (buprenorphine is a partial opioid agonist; eszopiclone is a nonbenzodiazepine hypnotic acting at GABA-A). Neither is a prodrug; the interaction is pharmacodynamic, not PK-driven.
Risk: Profound sedation, respiratory depression, coma, death. Epidemiologic data link concomitant CNS depressant use with most buprenorphine-involved overdose deaths.
- Severity: Major; evidence: probable; onset: unspecified.
- Management: Avoid coadministration where possible; taper or use lowest effective hypnotic dose. Consider alternative insomnia therapy. If combined, monitor respiratory status closely. Do NOT withhold MAT solely due to CNS depressant use.
What happens
An increased risk of respiratory depression and CNS depression
Interaction Deep Dive
When buprenorphine is given together with a CNS depressant, the CNS depressant effects can be additive, raising the likelihood of respiratory depression, deep sedation, coma, and death. Discontinuing CNS depressants is favored rather than using them concurrently. Depending on the situation, it may be suitable to observe the patient in a higher level of care or to implement a taper. In other cases, slowly weaning a patient from a prescribed CNS depressant, or reducing it to the lowest dose that remains effective, may be the right approach. When concurrent use cannot be avoided, exercise careful monitoring and management; alternative treatments for anxiety or insomnia should be considered2. A Swedish epidemiological study found that patients undergoing methadone- or buprenorphine-based medication-assisted treatment (MAT) who also took benzodiazepines or other CNS depressants (for example, agents used for insomnia) had an elevated risk of death. An analysis of pooled nationwide death certificate data spanning 2010 to 2014 showed that most overdose deaths involving buprenorphine and methadone also involved concurrent CNS depressant use. Whether the overdose death risk associated with concurrent CNS depressant drugs varied between buprenorphine and methadone remains unknown 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Your care team has clear ways to handle this combination safely:
- Keep taking both as prescribed unless your prescriber tells you otherwise. Buprenorphine, especially for opioid use disorder, should not be stopped just because you take a sleep aid.
- Your team may lower the eszopiclone to the lowest effective dose, gradually taper it, or suggest a different approach for your sleep.
- They may also monitor you more closely for heavy drowsiness or slowed breathing.
Call your pharmacist or doctor right away if you notice unusual sleepiness, confusion, or slow or shallow breathing. Bring up this combination at your next visit so they can tailor your plan.
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) taken 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, researchers examined the risk of fatal overdose, non-overdose related mortality, and all-cause mortality by comparing periods when CNS depressants were prescribed against periods without such therapy in MAT patients (aged 18 to 50). The findings showed a heightened 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, though these data were not regarded as statistically significant. Although the results indicated a raised risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods of MAT combined with non-benzodiazepines, only the fatal overdose and all-cause mortality data 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 benzodiazepine cohort and the non-benzodiazepine cohort were not compared because the authors did not adjust for the indication for which the drugs were used 3.
b) A study of pooled nationwide death certificate data spanning 2010 to 2014 reported 3495 drug overdose deaths in 2014. Methadone and other CNS depressants were often cited as contributors to those deaths. Simultaneous 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 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 count of methadone-involved deaths was 10 times that of buprenorphine-involved deaths, although confounding factors and differences in drug utilization were not taken into account. It remains unknown whether the risk of overdose death with concurrent CNS depressant drugs differed between buprenorphine and methadone 3.
Common questions
Can I take Eszopiclone and Buprenorphine together?
Buprenorphine and eszopiclone both slow the brain and breathing, so combining them raises the risk of dangerous sedation and respiratory depression. Don't stop either drug on your own, but talk with your prescriber or pharmacist so they can lower doses, monitor you, or find a safer sleep option. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Eszopiclone 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 Eszopiclone and Buprenorphine interaction managed?
Your care team has clear ways to handle this combination safely: Keep taking both as prescribed unless your prescriber tells you otherwise. Buprenorphine, especially for opioid use disorder, should not be stopped just because you take a sleep aid. Your team may lower the eszopiclone to the lowest effective dose, gradually taper it, or suggest a different approach for your sleep. They may also moni… 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 Eszopiclone 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 Eszopiclone
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