Zopiclone 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
Zopiclone
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 slow down your body. Buprenorphine is an opioid used for pain or to treat opioid use disorder, and zopiclone is a sleep medicine. When taken together, they can add up and make your breathing too slow and your brain too sleepy. In serious cases this can lead to very deep sedation, trouble breathing, or worse.
This does not mean you have to stop either drug on your own. Please don't do that. The good news is your care team can manage this safely by adjusting doses, watching you more closely, or choosing a different sleep option. Talk with your pharmacist or doctor before making any changes.
Additive CNS depression. Buprenorphine (opioid partial agonist) plus zopiclone (nonbenzodiazepine sedative-hypnotic) produce pharmacodynamic additive respiratory and CNS depression. Neither is a prodrug here; the mechanism is PD, not PK.
- Direction: increased combined effect (sedation, respiratory depression, profound sedation, coma, death).
- Evidence: probable; supported by epidemiologic mortality data in MAT populations.
- Severity: major. Onset: unspecified.
Management: Prefer avoiding concomitant use; taper or use lowest effective zopiclone dose, or an alternative insomnia agent. If combined, monitor for respiratory depression and consider higher level of care. 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 at the same time. In certain situations, it may be suitable to observe the patient in a higher level of care or to implement a taper. 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. Should simultaneous use be required, 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, medications used for insomnia) had an elevated risk of death. Based on an analysis of pooled nationwide death certificate data spanning 2010 to 2014, most overdose deaths involving buprenorphine or methadone also involved concurrent CNS depressant use. Whether the risk of fatal overdose from concurrent CNS depressant drugs varied between buprenorphine and methadone remains unknown 3.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. Do not stop suddenly on your own.
Here is what your team may do:
- Consider a different treatment for sleep instead of zopiclone.
- Lower the zopiclone to the lowest effective dose, or gradually taper it off.
- Watch you more closely, sometimes in a higher level of care, especially for slowed breathing.
Tell your pharmacist or prescriber right away if you feel unusually drowsy, confused, or short of breath. Ask them whether a safer sleep option is right for you.
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, medications used for insomnia) have an increased risk of death. From July 1, 2005 to 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 with periods when no CNS depressant therapy was given, 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 MAT combined with benzodiazepine treatment, but these data were not deemed statistically significant. Although the results also indicated a raised risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods when MAT was coadministered 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 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 using aggregated nationwide death certificate data from 2010 to 2014 identified 3495 drug overdose deaths reported in 2014. Methadone and other CNS depressants were often cited as contributors 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 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 differed between buprenorphine and methadone is unknown 3.
Common questions
Can I take Zopiclone and Buprenorphine together?
Combining buprenorphine and zopiclone adds up to dangerous sedation and slowed breathing, so your care team may switch, lower, or taper the sleep medicine and monitor you closely. Do not stop either drug on your own; talk with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Zopiclone 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 Zopiclone and Buprenorphine interaction managed?
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. Do not stop suddenly on your own. Here is what your team may do: Consider a different treatment for sleep instead of zopiclone. Lower the zopiclone to the lowest effective dose, or gradually taper it off. Watch you more closely, sometimes in a higher level of care, especially for slowed breathing. Tell your… 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 Zopiclone 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 Zopiclone
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