Drug Interaction Report

Metaxalone and Nalbuphine Injection: Interaction Details

A pharmacist-reviewed analysis of the Metaxalone and Nalbuphine Injection interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Metaxalone

Skelaxin
+

Nalbuphine Injection

Nubain®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
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.

Of 30 documented Metaxalone interactions, 29 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
theoretical
Severity
Major

What happens

Increased risk of serotonin syndrome, an increased risk of respiratory depression and an increased risk of CNS depression

Interaction Deep Dive

Serotonin syndrome has been reported with concomitant use of metaxalone (dosed within the usual therapeutic range) and serotonergic agents1. Additionally, coadministration of muscle relaxants and opioids may result in additive CNS depression and an increased risk of respiratory depression, profound sedation, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate. If concomitant use is necessary, use the lowest effective dosage and minimum duration of use. Monitor for sedation and respiratory depression, urinary retention, severe constipation and strongly consider prescribing naloxone for the emergency treatment of opioid overdose 23.

Why it happens (mechanism)

Additive serotonergic effects; additive CNS depression

Common questions

Can I take Metaxalone and Nalbuphine Injection together?

Increased risk of serotonin syndrome, an increased risk of respiratory depression and an increased risk of CNS depression Always confirm with your pharmacist or prescriber before making any change.

How serious is the Metaxalone and Nalbuphine Injection 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 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 Metaxalone or Nalbuphine Injection 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)

  1. Product Information: SKELAXIN(R) oral tablets, metaxalone oral tablets. King Pharmaceuticals, Inc. (per FDA), Bristol, TN, 2018. DailyMed
  2. Product Information: Oxycodone HCl acetaminophen oral tablets, oxycodone HCl acetaminophen oral tablets. Mayne Pharma (per DailyMed), Greenville, NC, 2021.
  3. Product Information: CARISOPRODOL, ASPIRIN, CODEINE PHOSPHATE oral tablets, carisoprodol, aspirin, codeine phosphate oral tablets. Ingenus Pharmaceuticals LLC (per DailyMed), Orlando, FL, 2021. DailyMed
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Metaxalone

Keep reading about Metaxalone

All Metaxalone interactions (30)
Also serious with: Acetaminophen And Codeine Dolasetron Levodopa Oral Inhalation Diazepam Rectal
Nalbuphine Injection

Keep reading about Nalbuphine Injection

All Nalbuphine Injection interactions (257) Nalbuphine Injection drug information
Also serious with: Naltrexone Phenelzine Safinamide Samidorphan
Beyond drug–drug

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:

Metaxalone + Activated Charcoal Procaine Coffee Charcoal European Mandrake Glucomannan Guar Gum Gum Arabic Lithium + 12 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.