Chlorzoxazone 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
Chlorzoxazone
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 opioid use disorder) and chlorzoxazone (a muscle relaxer) both calm down your central nervous system. When you take them together, that calming effect can stack up. This can make you very sleepy or slow, and most importantly, it can slow your breathing more than expected.
The good news is that this is very manageable. Your care team can adjust your muscle relaxer dose and keep a closer eye on you. Some doctors will also prescribe naloxone just in case. Please don't stop either medicine on your own. Just tell your pharmacist or doctor you take both, and watch for unusual drowsiness or trouble breathing.
Mechanism: Additive CNS depression. Neither agent's effect here depends on prodrug activation; the concern is pharmacodynamic overlap, not a metabolic (PK) interaction.
Direction/effect: Enhanced neuromuscular blockade from chlorzoxazone plus buprenorphine-mediated respiratory and CNS depression, increasing risk of clinically significant respiratory depression, sedation, and (per nationwide overdose data) death.
- Evidence: Probable; severity: major; onset unspecified.
- Management: Monitor for greater-than-expected respiratory depression and sedation; reduce the muscle relaxant dose as needed; consider prescribing naloxone.
- Do not withhold MAT (buprenorphine) solely due to concomitant CNS depressant use.
What happens
Enhanced neuromuscular blocking action and an increased risk of respiratory depression and CNS depression
Interaction Deep Dive
When buprenorphine is given together with skeletal muscle relaxants, the neuromuscular blocking effect of the muscle relaxants may be intensified, and a greater degree of respiratory depression may result. Patients taking both muscle relaxants and buprenorphine should be observed for signs of respiratory depression that could exceed what would normally be anticipated; reduce the muscle relaxant dose when needed and consider prescribing naloxone as an emergency remedy for opioid overdose1. A Swedish epidemiological study found that patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) who also used benzodiazepines or other CNS depressants (for instance, medications for insomnia) face a heightened risk of death. Analysis of aggregate nationwide death certificate data spanning 2010 to 2014 showed that the majority of overdose deaths involving buprenorphine and methadone also involved concurrent use of CNS depressants. Whether this risk of overdose death with concomitant CNS depressant drugs differs between buprenorphine and methadone is not known2.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
The main goal is to use both medicines safely, not to stop them.
- Keep taking both as prescribed unless your prescriber tells you otherwise.
- Your team may lower the chlorzoxazone dose and monitor you more closely for slowed or shallow breathing and heavy drowsiness.
- Your doctor may prescribe naloxone to have on hand for an opioid emergency, and can show you and family how to use it.
- Call for help right away if you notice severe sleepiness, confusion, or trouble breathing.
Tell your pharmacist and prescriber you take both 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) An epidemiological study conducted in Sweden reported that patients receiving methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, drugs used to treat insomnia) have an increased risk of death. Between July 1, 2005 and December 31, 2012, investigators analyzed the risk of fatal overdose, non-overdose related mortality, and all-cause mortality by comparing periods when CNS depressants were prescribed to periods without CNS depressant therapy in MAT-treated 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 and benzodiazepine therapy; however, these data were not deemed statistically significant. Although results showed a raised 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 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. 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 2.
b) According to a study of pooled nationwide death certificate data from 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone and other CNS depressants were commonly identified as contributors to 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 accounted for. Whether the risk of overdose death with concomitant CNS depressant drugs differed between buprenorphine and methadone is unknown 2.
Common questions
Can I take Chlorzoxazone and Buprenorphine together?
Buprenorphine and chlorzoxazone both depress the nervous system, so combining them can dangerously slow breathing. Keep taking both as prescribed, but tell your care team so they can adjust the dose, monitor you, and possibly provide naloxone. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Chlorzoxazone 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 Chlorzoxazone and Buprenorphine interaction managed?
The main goal is to use both medicines safely, not to stop them. Keep taking both as prescribed unless your prescriber tells you otherwise. Your team may lower the chlorzoxazone dose and monitor you more closely for slowed or shallow breathing and heavy drowsiness. Your doctor may prescribe naloxone to have on hand for an opioid emergency, and can show you and family how to use it. Call for help r… 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 Chlorzoxazone 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 (2)
- Product Information: BRIXADI(TM) subcutaneous extended-release injection, buprenorphine subcutaneous extended-release injection. Braeburn Inc (per FDA), Plymouth Meeting, PA, 2023. 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 Chlorzoxazone
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