Dantrolene 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
Dantrolene
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 body in overlapping ways. Buprenorphine is an opioid that eases pain or treats opioid use disorder, and dantrolene is a muscle relaxant. Taken together, they can add up and cause too much sleepiness and, more seriously, slowed or shallow breathing.
This does not mean you cannot take both. It just means your care team keeps a closer eye on you. Watch for unusual drowsiness, confusion, or trouble breathing, and get help right away if those happen. Please keep taking both exactly as prescribed and talk with your pharmacist or doctor about any concerns, including whether keeping naloxone on hand makes sense for you.
Effect: Additive CNS and respiratory depression; possible enhanced neuromuscular effect when buprenorphine is combined with the skeletal muscle relaxant dantrolene.
Mechanism: Additive pharmacodynamic CNS depression (not a metabolic/prodrug interaction). Direction: increased combined depressant effect. Evidence: probable; onset: unspecified; severity: major.
- Monitor for greater-than-expected sedation and respiratory depression.
- Reduce the muscle relaxant dose as necessary and individualize to the patient.
- Consider prescribing naloxone.
- Do not withhold medication-assisted treatment solely because of concurrent CNS depressant use; balance against opioid use disorder risk.
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 a muscle relaxant and buprenorphine should be watched for respiratory depression that could exceed what would ordinarily be anticipated; reduce the muscle relaxant dose when needed and consider prescribing naloxone for emergency management of opioid overdose1. A Swedish epidemiological study found that when patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) also received benzodiazepines or other CNS depressants (for instance, agents used to treat insomnia), the risk of death was raised. An analysis of pooled nationwide death certificate data spanning 2010 to 2014 indicated that most overdose deaths involving buprenorphine and methadone also involved concurrent use of a CNS depressant. Whether the risk of overdose death with concurrent CNS depressant drugs varied between buprenorphine and methadone has not been established 2.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Your care team can manage this combination safely with a few steps:
- Closer monitoring for extra drowsiness, confusion, or slowed breathing, especially when either dose changes.
- The muscle relaxant dose may be adjusted and individualized by your prescriber as needed.
- Your team may prescribe naloxone to keep on hand for emergencies.
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. If you are on buprenorphine for opioid use disorder, do not stop it on your own. Ask your pharmacist or doctor what warning signs to watch for and when to seek help.
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 receiving methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, medications used to treat insomnia) have an increased risk of death. From July 1, 2005 to December 31, 2012, investigators analyzed the risk of fatal overdose, non-overdose related mortality, and all-cause mortality during periods when CNS depressants were prescribed compared with periods without CNS depressant therapy in MAT prescribed 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 treatment; however, these data were not deemed statistically significant. Although the results indicated an elevated 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. 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 2.
b) According to a study of pooled nationwide death certificate data spanning 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone and other CNS depressants were commonly reported as contributors to these 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. 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 2.
Common questions
Can I take Dantrolene and Buprenorphine together?
Combining buprenorphine and dantrolene can add up to dangerous sleepiness and slowed breathing, so your care team will monitor you closely and may adjust the muscle relaxant dose and offer naloxone. Keep taking both as prescribed and report any unusual drowsiness or breathing trouble. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Dantrolene 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 Dantrolene and Buprenorphine interaction managed?
Your care team can manage this combination safely with a few steps: Closer monitoring for extra drowsiness, confusion, or slowed breathing, especially when either dose changes. The muscle relaxant dose may be adjusted and individualized by your prescriber as needed. Your team may prescribe naloxone to keep on hand for emergencies. Keep taking both medicines as prescribed unless your prescriber tel… 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 Dantrolene 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 Dantrolene
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