VA Class:MS200
Metaxalone is a centrally acting skeletal muscle relaxant.
Metaxalone is used as an adjunct to rest, physical therapy, analgesics, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions.1, 15, 112
Evidence supporting the efficacy of skeletal muscle relaxants is generally low to moderate in quality; while these agents appear to be more effective than placebo in providing symptomatic relief of acute low back pain, they are associated with a high incidence of adverse effects (e.g., sedation).103, 104, 106, 109, 110, 111, 112 Although comparative studies are limited, available data suggest that various skeletal muscle relaxants generally have similar efficacy for such use.103, 104, 106, 108 Acute low back pain usually is a benign and self-limiting condition that improves spontaneously over time;105, 106, 108, 109 therefore, nonpharmacologic treatment strategies (e.g., heat, massage) are recommended.109 If pharmacologic therapy is required, experts state that a nonsteroidal anti-inflammatory agent (NSAIA) or a skeletal muscle relaxant may be used; however, these drugs have been shown to result in only small improvements in pain relief and can increase the risk of adverse effects.104, 106, 107, 108, 109 In general, skeletal muscle relaxants should be used with caution after weighing the potential risks against the benefits in individual patients.104, 106, 107, 108 Although skeletal muscle relaxants are often used in combination with NSAIAs for the treatment of acute low back pain, randomized controlled studies generally have not demonstrated any additional improvement in pain or functional outcomes with such combination therapy compared with use of an NSAIA alone.110, 112, 113
It is unclear whether relief of musculoskeletal pain by metaxalone results from skeletal muscle relaxant effects, sedative effects, or a placebo effect of the drug. Most authorities attribute the beneficial effects of skeletal muscle relaxants to their sedative properties.
Metaxalone is ineffective in the treatment of skeletal muscle hyperactivity secondary to chronic neurologic disorders such as cerebral palsy and other dyskinesias.
Metaxalone is administered orally.1 Although administration with food increases the extent of exposure to the drug, which can increase its sedative effects, the manufacturer makes no specific recommendation regarding administration of metaxalone with food.1 (See Pharmacokinetics: Absorption.)
The usual dosage of metaxalone for adults and children older than 12 years of age is 800 mg given orally 3 or 4 times daily.1
The most frequent adverse effects of metaxalone are drowsiness, dizziness, headache, nervousness or irritability, nausea, vomiting, and GI upset. Other adverse effects include confusion, anorexia, dry mouth, and urinary retention. Exacerbation of tonic-clonic (grand mal) seizures has also been reported.
Hypersensitivity reactions and rash (with or without pruritus) have occurred in patients receiving metaxalone. Anaphylactoid reactions, leukopenia, hemolytic anemia, and jaundice have occurred rarely. Abnormalities in liver function tests, such as increased serum concentrations of AST, ALT, alkaline phosphatase, and bilirubin, have occurred in patients receiving metaxalone. Although a causal relationship to metaxalone has not been established, nephrotoxicity and proteinuria have occurred rarely during treatment with the drug; pyuria and nephrolithiasis have also been reported.
Precautions and Contraindications
Patients should be warned that metaxalone may impair their ability to perform hazardous activities requiring mental alertness or physical coordination, such as operating machinery or driving a motor vehicle.1 In addition, patients should be warned that additive CNS depression may occur when the drug is administered concomitantly with other CNS depressants, including alcohol.1
Serotonin syndrome has occurred in patients receiving higher than recommended doses of metaxalone or concomitant therapy with serotonergic drugs.1 (See Drug Interactions: Serotonergic Drugs.) Serotonin syndrome is characterized by mental status and behavioral changes (e.g., agitation, hallucinations, coma), altered muscle tone or neuromuscular activity (e.g., hyperreflexia, incoordination, rigidity), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), and GI symptoms (e.g., nausea, vomiting, diarrhea).1 Metaxalone should be discontinued if serotonin syndrome is suspected.1 Patients should be advised of the symptoms of serotonin syndrome and instructed to seek immediate medical care if they develop any such symptoms.1 Patients should also be advised to inform their clinicians if they are using or plan to use any serotonergic agents.1
Metaxalone should be used with caution in patients with hepatic or renal impairment.1 Liver function studies should be performed periodically during metaxalone therapy in patients with preexisting liver damage.1 The drug is contraindicated in patients with substantially impaired hepatic or renal function, known hypersensitivity to the drug or any ingredient in the formulation, or a history of drug-induced, hemolytic, or other anemias.1
Safety and efficacy of metaxalone in children 12 years of age or younger have not been established.1
Because of the risk of injury, skeletal muscle relaxants should generally be avoided in geriatric patients.111
The carcinogenic potential of metaxalone has not been determined.1
Pregnancy, Fertility, and Lactation
Safe use of metaxalone during pregnancy has not been established.1 Reproduction studies in rats have not revealed evidence of harm to the fetus.1 Although postmarketing surveillance has not revealed evidence of fetal injury in humans, the reported experience to date cannot exclude the possibility of adverse fetal effects of the drug.1 Therefore, metaxalone should not be used in women who are or may become pregnant unless the possible benefits outweigh the potential risks.1
Reproduction studies in rats have not revealed evidence of impaired fertility.1
It is not known whether metaxalone is distributed into milk.1 In general, the drug should not be used in nursing women.1
Additive CNS depression may occur when metaxalone is administered concomitantly with other CNS depressants, including alcohol.1 If metaxalone is used concomitantly with other depressant drugs (e.g., benzodiazepines, opiate agonists, tricyclic antidepressants), caution is advised and patients should be monitored closely for respiratory depression and sedation.1 (See Acute Toxicity.)
Concomitant use of metaxalone with serotonergic agents has been reported to cause serotonin syndrome.1 (See Cautions: Precautions and Contraindications.) Examples of serotonergic agents include selective serotonin-reuptake inhibitors (SSRIs), serotonin- and norepinephrine-reuptake inhibitors (SNRIs), tricyclic antidepressants, meperidine, monoamine oxidase (MAO) inhibitors, and tramadol.1
If concomitant use of metaxalone with a serotonergic agent is necessary, the patient should be carefully monitored, particularly during treatment initiation and dosage adjustments.1 Metaxalone should be discontinued if serotonin syndrome is suspected.1
A reducing substance in the urine of patients receiving metaxalone may produce false-positive results for glucose determinations utilizing cupric sulfate (Benedict's Solution, Clinitest®, Fehling's Solution), but the drug does not interfere with glucose tests using glucose oxidase (Clinistix®, Diastix®, Tes-Tape®).
Fatalities have been reported following inadvertent or intentional overdosage of metaxalone, particularly in conjunction with other CNS depressants (i.e., alcohol and/or antidepressants).1 Serotonin syndrome has been reported when metaxalone was used at higher than recommended doses.1 (See Cautions: Precautions and Contraindications.)
In acute toxicity studies in rats and mice, progressive sedation, hypnosis, and respiratory failure were observed with increasing doses of metaxalone.1 The LD50 of metaxalone in dogs could not be determined because higher doses of the drug produced emesis within 15-30 minutes following administration.1
Treatment of metaxalone overdosage includes gastric lavage and general supportive therapy.1 Clinicians should consider consulting a poison control center for additional information on the management of metaxalone overdosage.1
Metaxalone is a CNS depressant that has sedative and skeletal muscle relaxant effects. The precise mechanism of action of the drug is not known. The skeletal muscle relaxant effects of metaxalone are minimal and are probably related to its sedative effect. The drug does not directly relax skeletal muscle and, unlike neuromuscular blocking agents, does not depress neuronal conduction, neuromuscular transmission, or muscle excitability.
The absolute bioavailability of orally administered metaxalone has not been determined.1 Following oral administration of a single 400- or 800-mg dose of the drug in the fasted state, mean peak plasma concentrations of approximately 983 or 1816 ng/mL, respectively, were attained in 3-3.3 hours.1 Plasma concentrations of metaxalone required for sedative, skeletal muscle relaxant, or toxic effects are not known. The onset of action is usually within 1 hour, and the duration of action is about 4-6 hours.
Administration of metaxalone with a high-fat meal delays absorption of the drug, increases peak plasma concentrations, and increases the extent of exposure to the drug. Following oral administration of a single 400- or 800-mg dose of metaxalone with a high-fat meal, peak plasma concentrations and area under the plasma concentration-time curve (AUC) were increased by about 178-194 and 115-142%, respectively.1 In addition, the time to peak plasma concentration was delayed by about 1-2 hours.1
Bioavailability of the drug appears to increase with age under fasted, but not fed, conditions.1 Bioavailability also is higher and mean half-life is longer in females compared with males.1
It is not known whether metaxalone crosses the placenta or is distributed into milk.
The plasma half-life of metaxalone is about 2-4 hours, and the apparent oral clearance of the drug is about 59-68 L/hour. Metaxalone is metabolized by hepatic cytochrome P-450 (CYP) isoenzymes 1A2, 2D6, 2E1, and 3A4, and to a lesser extent, by CYP2C8, 2C9, and 2C19.1 The drug is excreted in urine as unidentified metabolites.1 The effect of renal or hepatic impairment on the elimination of metaxalone has not been established.1
Metaxalone, an oxazolidinone derivative, is a centrally acting skeletal muscle relaxant. The drug occurs as a white to almost white crystalline powder and is insoluble in water and soluble in alcohol.1
Metaxalone tablets should be stored at a controlled room temperature of 15-30°C.1
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets | 800 mg* | Metaxalone Tablets | |
Skelaxin® (scored) |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions February 24, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Pfizer. Skelaxin® (metaxalone) tablets prescribing information. NY, NY; 2018 Mar.
15. SCHWAB RS. MUSCLE RELAXANTS. Practitioner . 1964; 192:104-8. [PubMed 14106636]
103. See S, Ginzburg R. Skeletal muscle relaxants. Pharmacotherapy . 2008; 28:207-13. [PubMed 18225966]
104. van Tulder MW, Touray T, Furlan AD et al. Muscle relaxants for non-specific low back pain. Cochrane Database Syst Rev . 2003; :CD004252. [PubMed 12804507]
105. Roelofs PD, Deyo RA, Koes BW et al. Non-steroidal anti-inflammatory drugs for low back pain. Cochrane Database Syst Rev . 2008; :CD000396. [PubMed 18253976]
106. Chou R, Qaseem A, Snow V et al. Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society. Ann Intern Med . 2007; 147:478-91. [PubMed 17909209]
107. Institute for Clinical Systems Improvement. Health care guideline: adult acute and subacute low back pain. 15th ed. Bloomington, MN; 2012 Jan. From the ICSI website [Web]
108. Toth PP, Urtis J. Commonly used muscle relaxant therapies for acute low back pain: a review of carisoprodol, cyclobenzaprine hydrochloride, and metaxalone. Clin Ther . 2004; 26:1355-67. [PubMed 15530999]
109. Qaseem A, Wilt TJ, McLean RM et al. Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med . 2017; 166:514-530. [PubMed 28192789]
110. Friedman BW, Cisewski D, Irizarry E et al. A Randomized, Double-Blind, Placebo-Controlled Trial of Naproxen With or Without Orphenadrine or Methocarbamol for Acute Low Back Pain. Ann Emerg Med . 2018; 71:348-356.e5. [PubMed 29089169]
111. Spence MM, Shin PJ, Lee EA et al. Risk of injury associated with skeletal muscle relaxant use in older adults. Ann Pharmacother . 2013 Jul-Aug; 47:993-8. [PubMed 23821610]
112. Friedman BW, Irizarry E, Solorzano C et al. A Randomized, Placebo-Controlled Trial of Ibuprofen Plus Metaxalone, Tizanidine, or Baclofen for Acute Low Back Pain. Ann Emerg Med . 2019; [PubMed 30955985]
113. Friedman BW, Dym AA, Davitt M et al. Naproxen With Cyclobenzaprine, Oxycodone/Acetaminophen, or Placebo for Treating Acute Low Back Pain: A Randomized Clinical Trial. JAMA . 2015; 314:1572-80. [PubMed 26501533]