METAXALONE
Clinical safety rating
safeAnimal studies have demonstrated safety
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.
| 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. |
| Molecular Weight | 221.25 |
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. |
| 1st trimester | Insufficient human data; animal studies not conducted. Risk cannot be excluded. Use only if potential benefit justifies potential risk. |
| 2nd trimester | Insufficient human data; animal studies not conducted. Risk cannot be excluded. Use only if potential benefit justifies potential risk. |
| 3rd trimester | Avoid use near term due to risk of neonatal respiratory depression and floppy infant syndrome. |
Clinical note
CNS depressants may enhance sedative effects Can cause hemolytic anemia in patients with G6PD deficiency.
| Placental transfer | Likely crosses placenta based on molecular weight <500 Da; no specific data. |
| Breastfeeding | No data on presence in human milk. Caution due to potential for drug-induced sedation in neonate. |
| Lactation Rating | L3 |
| 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. |
| Fetal Monitoring | Monitor maternal liver function tests, complete blood count, and renal function periodically. In pregnancy, assess fetal growth and well-being via ultrasound if prolonged use. Watch for maternal sedation, hypotension, and hepatotoxicity. Neonatal monitoring after third-trimester exposure for respiratory depression and withdrawal symptoms. |
| Fertility Effects | No specific human studies. In animal studies, no impairment of fertility observed at therapeutic doses. Theoretical risk of hormonal disruption due to hepatic enzyme induction, but not substantiated. |
■ FDA Black Box Warning
None.
| Common Effects | Drowsiness |
| Serious Effects |
Hypersensitivity to metaxalone or any componentPre-existing or drug-induced hemolytic anemiaSignificant renal impairmentSignificant hepatic impairment
| 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. |
| Food/Dietary | Metaxalone may be taken with or without food. Grapefruit juice may increase metaxalone levels by inhibiting CYP1A2 and CYP3A4; avoid concurrent consumption. High-fat meals may slightly delay absorption but not clinically significant. |
| Clinical Pearls | Metaxalone is a centrally acting muscle relaxant with a unique chemical structure (oxazolidinone derivative). It is metabolized primarily by CYP1A2 and CYP2D6; caution with inhibitors or inducers of these enzymes. Onset of action is 1-2 hours; peak effect at 3-4 hours. Due to sedative properties, avoid concurrent use with alcohol or other CNS depressants. Use with caution in elderly due to anticholinergic effects and fall risk. Metaxalone is not recommended for patients with significant hepatic impairment (Child-Pugh Class C). It has no direct effect on skeletal muscle contraction but acts on CNS polysynaptic pathways. |
| Patient Advice | Take metaxalone exactly as prescribed; do not increase dose or frequency without consulting your doctor. · May cause drowsiness or dizziness; do not drive or operate heavy machinery until you know how this medication affects you. · Avoid alcohol or other sedatives while taking metaxalone as they may worsen drowsiness. · If you miss a dose, skip the missed dose and continue with your regular schedule; do not double the dose. · Contact your healthcare provider if you experience signs of an allergic reaction (rash, hives, difficulty breathing) or jaundice (yellowing of skin/eyes). · Store at room temperature, away from moisture and heat. · Do not stop abruptly; gradual dose reduction may be recommended to prevent withdrawal symptoms. |
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