Buprenorphine and Metaxalone: 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
Metaxalone
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 is an opioid used for pain or opioid dependence, and metaxalone (Skelaxin) is a muscle relaxant. Taken together, they can both slow down your brain and breathing more than either one alone. That can cause heavy drowsiness, very slow breathing, and in rare cases something serious.
There is also a small, mostly theoretical chance of serotonin syndrome, which can cause agitation, a fast heartbeat, sweating, shaking, or confusion. This does not mean you can't take both. It means your care team will keep the doses low and watch you closely. Let them know right away if you feel unusually sleepy, hard to wake, or short of breath.
Effect: Additive CNS and respiratory depression, plus a theoretical risk of serotonin syndrome (metaxalone has serotonergic activity; buprenorphine is an opioid agonist/partial agonist). Neither agent is a prodrug; this is a pharmacodynamic, not pharmacokinetic, interaction.
- Direction: Increased sedation, respiratory depression, profound sedation, coma, and death risk.
- Severity/evidence: Major; substantiation theoretical. Onset unspecified.
- Management: Reserve concomitant use for when alternatives are inadequate. Use lowest effective dose and shortest duration. Monitor for sedation, respiratory depression, urinary retention, and severe constipation. Watch for serotonergic signs (clonus, hyperthermia, autonomic instability). Strongly consider prescribing naloxone.
What happens
Increased risk of serotonin syndrome, an increased risk of respiratory depression and an increased risk of CNS depression
Interaction Deep Dive
Cases of serotonin syndrome have occurred when metaxalone (given at doses within the standard therapeutic range) is taken alongside serotonergic drugs1. Furthermore, using muscle relaxants together with opioids can produce additive CNS depression, raising the likelihood of respiratory depression, profound sedation, coma, and death. Limit concurrent prescribing to patients whose alternative treatment options are insufficient. When such combined use cannot be avoided, apply the lowest effective dose for the shortest possible time. Watch for sedation and respiratory depression, urinary retention, and severe constipation, and give strong consideration to prescribing naloxone for the emergency management of opioid overdose23.
Why it happens (mechanism)
Additive serotonergic effects; additive CNS depression
How to manage this interaction
If both are prescribed, keep taking them exactly as directed. Your care team can manage this safely by tailoring your plan.
- Your team will typically use the lowest effective dose for the shortest time needed and may reserve this combination for when other options aren't enough.
- They may monitor you more closely for excessive drowsiness, slow or shallow breathing, urinary retention, and severe constipation.
- Your prescriber may also offer a naloxone rescue kit and show you and a family member how to use it.
Call your pharmacist or prescriber before making any change, and seek urgent help for very slow breathing, extreme sleepiness, agitation, high fever, or shaking.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Buprenorphine and Metaxalone together?
Combining buprenorphine and metaxalone can add up to dangerous sedation and slowed breathing, with a small theoretical risk of serotonin syndrome. Use only when needed, at the lowest dose, watch for heavy drowsiness or breathing trouble, and ask about a naloxone kit. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Metaxalone 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 Buprenorphine and Metaxalone interaction managed?
If both are prescribed, keep taking them exactly as directed. Your care team can manage this safely by tailoring your plan. Your team will typically use the lowest effective dose for the shortest time needed and may reserve this combination for when other options aren't enough. They may monitor you more closely for excessive drowsiness, slow or shallow breathing, urinary retention, and severe cons… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Buprenorphine or Metaxalone 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: SKELAXIN(R) oral tablets, metaxalone oral tablets. King Pharmaceuticals, Inc. (per FDA), Bristol, TN, 2018. DailyMed
- Product Information: Oxycodone HCl acetaminophen oral tablets, oxycodone HCl acetaminophen oral tablets. Mayne Pharma (per DailyMed), Greenville, NC, 2021.
- Product Information: CARISOPRODOL, ASPIRIN, CODEINE PHOSPHATE oral tablets, carisoprodol, aspirin, codeine phosphate oral tablets. Ingenus Pharmaceuticals LLC (per DailyMed), Orlando, FL, 2021. DailyMed
Keep reading about Buprenorphine
Keep reading about Metaxalone
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.
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