Section 09 · Monograph

Metaxalone

Reviewed Nov 2026FDA label

SkelaxinMuscle relaxant

Indications

Adjunct to rest, physical therapy, and other measures for the relief of discomforts associated with acute, painful musculoskeletal conditions (FDA-approved indication; patients ≥13 years old).FDA-labeled
Note: Metaxalone is NOT FDA-approved for spasticity of central (upper motor neuron) origin (e.g., cerebral palsy, MS, spinal cord injury) — its labeled use is for acute, localized musculoskeletal spasm/pain, not chronic spasticity. Included here because sometimes used empirically in mixed pain-spasm presentations; baclofen, tizanidine, dantrolene, or diazepam are the evidence-based choices for true spasticity.FDA-labeled

Chronic low back pain / myofascial pain syndrome (short-course adjunct) — limited evidence.Off-label
Fibromyalgia-associated muscle discomfort — anecdotal/limited clinical use, not evidence-based first line.Off-label

Exact mechanism of action is unknown.
Believed to act primarily through general central nervous system (CNS) depression rather than a direct effect on skeletal muscle, the motor end plate, or the nerve fiber.
Does not directly relax tense skeletal muscles; clinical effect is thought to reflect sedative/CNS-depressant properties rather than a specific antispasmodic or antispastic mechanism (in contrast to baclofen [GABA-B agonism] or dantrolene [direct muscle action]).

Maximum: up to 3200 mg/day (Skelaxin 800 mg tablets) has been described in product literature; the 640 mg generic label caps recommended use at 4 tablets (2560 mg)/day — follow the specific product's labeling, as formulations are pharmacokinetically distinct.
IMPORTANT: The 640 mg generic tablet and the 800 mg Skelaxin brand tablet are NOT interchangeable on a strict milligram-for-milligram basis due to differences in bioavailability/pharmacokinetics.
Elderly patients: use lowest effective dose given increased sensitivity to CNS depressant effects.
Typical duration: short-term (days to a few weeks) for acute musculoskeletal conditions; long-term use has not been well studied.

No renal/hepatic dose-adjustment guidance is provided because metaxalone is contraindicated in significant renal or hepatic impairment.

Adults and pediatric patients ≥13 years: 800 mg (Skelaxin brand) or 640 mg (generic metaxalone tablet) orally 3-4 times daily; may be taken with or without food.

CNS depressants (alcohol, benzodiazepines, opioids, barbiturates, other sedative-hypnotics): additive sedation, dizziness, and risk of respiratory depression/psychomotor impairment.
Serotonergic drugs (SSRIs, SNRIs, TCAs, triptans, opioids [especially tramadol/fentanyl], MAO inhibitors, linezolid, methylene blue): increased risk of serotonin syndrome.
False-positive reactions have been reported with Benedict's reagent (urine glucose test) — not a true drug-drug interaction but relevant to clinical interpretation.
No formal CYP450-based drug-interaction studies are highlighted in labeling; caution advised generally with other hepatically metabolized/CNS-active agents.

Very common/common: drowsiness, dizziness, headache, nausea, vomiting, GI upset, nervousness/irritability.
Serious but rare: hemolytic anemia, leukopenia, jaundice/hepatic dysfunction, anaphylactoid reactions/hypersensitivity (rash, pruritus, angioedema).
Serotonin syndrome (rare, with concomitant serotonergic drugs): agitation, hallucinations, tachycardia, hyperthermia, tremor, incoordination, diaphoresis, diarrhea.
CNS depression may impair mental and/or physical abilities required for hazardous tasks (driving, operating machinery).

Baseline and periodic liver function tests, particularly with prolonged use or in patients with any history of hepatic dysfunction.
CBC if signs/symptoms of anemia or hemolysis develop (pallor, fatigue, jaundice, dark urine).
Monitor for excessive sedation/CNS depression, particularly in the elderly and with concomitant CNS depressants.
Watch for signs/symptoms of serotonin syndrome if co-administered with serotonergic agents.

Pregnancy: No adequate, well-controlled human studies despite decades of marketed use; animal reproduction studies have not shown fetal harm, but human risk cannot be ruled out. Use during pregnancy only if potential benefit justifies potential risk to the fetus.
Lactation: No data on presence in human milk, effects on the breastfed infant, or effects on milk production.