METAXALONE

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Metaxalone is a centrally acting muscle relaxant whose exact mechanism is unknown. It is thought to produce skeletal muscle relaxation by depressing the central nervous system (CNS), possibly through general CNS depression or by blocking polysynaptic reflexes in the spinal cord.

What the body does with it

Metabolism	Extensively metabolized in the liver via cytochrome P450 enzymes (CYP1A2, CYP2D6, CYP3A4, CYP2C19, and CYP2E1) to unidentified metabolites. Less than 1% excreted unchanged in urine.
Excretion	Primarily renal; approximately 90% of a dose is excreted in urine as glucuronide conjugates and unchanged drug, with less than 1% eliminated in feces via biliary excretion.
Half-life	Terminal elimination half-life is approximately 0.5 to 1.5 hours, reflecting rapid clearance and supporting short-lived clinical effects.
Protein binding	Approximately 98% bound to plasma proteins, primarily albumin.
Volume of Distribution	Approximately 0.3–0.5 L/kg, indicating moderate distribution into total body water and peripheral tissues.
Bioavailability	Oral bioavailability is high, estimated at >80% based on urinary recovery studies.
Onset of Action	Oral: 30–60 minutes following administration.
Duration of Action	Approximately 3–6 hours; clinical muscle relaxation typically persists for this period, though individual variability exists.

Classification & Brands

Dosing & administration

800 mg orally 3 to 4 times daily

Dosage form	TABLET
Renal impairment	No specific dose adjustment guidelines available; use with caution in severe renal impairment (CrCl <30 mL/min) due to potential for accumulation.
Liver impairment	No specific dose adjustment guidelines available; use with caution in severe hepatic impairment (Child-Pugh class C) as metabolism may be reduced.
Pediatric use	Safety and efficacy not established; not recommended for use in children under 12 years of age.
Geriatric use	Start at lower end of dosing range (e.g., 800 mg 3 times daily) due to increased sensitivity and risk of adverse effects; monitor closely.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

CNS depressants may enhance sedative effects Can cause hemolytic anemia in patients with G6PD deficiency.

Breastfeeding

Unknown if excreted in human milk. M/P ratio not established. Caution advised due to potential for sedation in the infant. Monitor for drowsiness, poor feeding, or weight loss. Consider alternative agents with more safety data.

Teratogenic Risk

FDA pregnancy category C. No adequate studies in pregnant women. Animal studies have shown adverse effects (fetal resorptions, decreased fetal weight) at doses 5-10 times the human dose. Risk cannot be ruled out. Use only if potential benefit justifies potential risk to fetus. First trimester: Avoid; data insufficient. Second/third trimester: Limited data; may cause maternal sedation and neonatal respiratory depression if used near term.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Common Effects	Drowsiness
Serious Effects

Absolute Contraindications

["Hypersensitivity to metaxalone or any component of the formulation.","Significant hepatic impairment (e.g., severe liver disease, cirrhosis).","History of drug-induced hemolytic anemia.","Concurrent use of MAOIs or within 14 days of MAOI therapy (potential for serotonin syndrome)."]

Clinical Precautions

Precautions

["Serotonin syndrome risk when co-administered with serotonergic drugs (e.g., SSRIs, SNRIs, MAOIs).","Hepatic toxicity: rare reports of liver injury; use caution in patients with hepatic impairment.","CNS depressant effects: may impair mental and physical abilities; avoid concurrent alcohol or other CNS depressants.","Elderly may be more sensitive to sedative effects."]

Clinical Tips & Counseling

Drug interactions

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