Methocarbamol 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
Methocarbamol
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 (found in medicines like Belbuca, Suboxone, or BuTrans) is a strong opioid, and methocarbamol (Robaxin) is a muscle relaxant. Both can slow down your brain and your breathing. When you take them together, that slowing effect can add up, so you may feel very drowsy, and in more serious cases your breathing can become too slow or shallow.
Watch for heavy sleepiness, confusion, or trouble breathing, especially when you first combine them. The good news is your care team can manage this safely by adjusting your doses and keeping a closer eye on you. Please talk with your pharmacist or doctor before changing anything.
Effect: Additive CNS and respiratory depression; muscle relaxant may enhance neuromuscular effects. Both agents are active drugs (not prodrugs); this is a pharmacodynamic, not metabolic, interaction.
- Direction/magnitude: Increased sedation and greater-than-expected respiratory depression risk.
- Onset: Unspecified; consider with initiation or dose increases.
- Evidence: Probable; epidemiologic overdose-death data support concomitant CNS depressant risk.
- Management: Monitor for respiratory depression and oversedation; reduce methocarbamol dose as needed; consider co-prescribing naloxone. Do not withhold MAT solely due to this interaction.
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 can be intensified, along with a greater level of respiratory depression. For patients taking both a muscle relaxant and buprenorphine, watch for respiratory depression that could exceed what would ordinarily be anticipated, reduce the muscle relaxant dose when needed, and consider prescribing naloxone so that opioid overdose can be treated as an emergency1. A Swedish epidemiological study found that mortality risk rises in patients undergoing methadone- or buprenorphine-based medication-assisted treatment (MAT) who also use benzodiazepines or other CNS depressants (for instance, medications for insomnia). An analysis of pooled nationwide death certificate data spanning 2010 to 2014 showed that concurrent CNS depressant use was present in most overdose deaths involving buprenorphine and methadone. Whether the risk of fatal overdose associated with concomitant CNS depressant drugs varies between buprenorphine and methadone has not been established2.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
This combination is sometimes used when clinically necessary, so keep taking both exactly as prescribed unless your care team tells you otherwise. Do not stop your buprenorphine on your own.
- Your team may lower the methocarbamol dose and monitor you more closely for excessive drowsiness or slowed breathing.
- They may prescribe naloxone as an emergency rescue medicine, and can show you and your family how to use it.
- Tell your pharmacist or prescriber about any other sedating medicines, alcohol, or sleep aids.
- Seek help right away for severe sleepiness, confusion, or slow or shallow breathing.
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, drugs used to treat insomnia) have an increased risk of death. From July 1, 2005 to December 31, 2012, the risk of fatal overdose, non-overdose related mortality, and all-cause mortality was compared between periods when CNS depressants were prescribed and periods without CNS depressant therapy in MAT prescribed patients (aged 18 to 50). The findings showed a higher 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, this data was 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 data for fatal overdose and all-cause mortality was considered statistically significant; 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 2.
b) According to a study of aggregate 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 culprits in 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 Methocarbamol and Buprenorphine together?
Combining buprenorphine and methocarbamol adds up their sedating effects and can dangerously slow breathing, so use both only under your care team's guidance, which may include a lower muscle relaxant dose, closer monitoring, and a naloxone prescription. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Methocarbamol 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 Methocarbamol and Buprenorphine interaction managed?
This combination is sometimes used when clinically necessary, so keep taking both exactly as prescribed unless your care team tells you otherwise. Do not stop your buprenorphine on your own. Your team may lower the methocarbamol dose and monitor you more closely for excessive drowsiness or slowed breathing. They may prescribe naloxone as an emergency rescue medicine, and can show you and your fami… 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 Methocarbamol 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 Methocarbamol
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