VA Class:MS200
Chlorzoxazone is a centrally acting skeletal muscle relaxant.
Chlorzoxazone 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, 18
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 therefore, nonpharmacologic treatment modalities (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 chlorzoxazone 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.
Chlorzoxazone is ineffective in the treatment of skeletal muscle hyperactivity secondary to chronic neurologic disorders such as cerebral palsy and other dyskinesias.
Chlorzoxazone is administered orally.1, 100, 102
The usual adult dosage of chlorzoxazone is 250-500 mg 3 or 4 times daily.1, 100, 102 For painful musculoskeletal conditions, some manufacturers state that dosage should be initiated with 500 mg 3 or 4 times daily and, if necessary, dosage may be increased to 750 mg 3 or 4 times daily.1, 102 When the desired response is obtained, dosage should be reduced to the lowest effective level.1, 100, 102
Chlorzoxazone generally is well tolerated and seldom produces severe adverse effects.
The most frequent adverse effects of chlorzoxazone are drowsiness and dizziness. Lightheadedness, malaise, headache, and overstimulation have occurred occasionally. Disorientation, paresthesia, and amnesia have occurred in at least one patient.
Sensitivity reactions including rash, petechiae, redness, ecchymoses, urticaria, and pruritus have occurred rarely in patients receiving chlorzoxazone; angioedema and anaphylactic reactions are extremely rare.
Adverse GI effects of chlorzoxazone include anorexia, nausea, vomiting, heartburn, abdominal distress, constipation, diarrhea, and, rarely, GI bleeding.
Serious, sometimes fatal, hepatocellular toxicity has been reported rarely in patients receiving chlorzoxazone.1, 101 Hepatotoxicity has been associated with abnormal liver function test results including increases in serum AST, ALT, alkaline phosphatase, and bilirubin concentrations.101
Onset of hepatotoxicity has been variable, occurring within 1 month after initiation of therapy in some patients but after 5 or more months of therapy in others.101 In patients with evidence of hepatitis, hepatic manifestations usually resolved following discontinuance of chlorzoxazone.101 Biopsy or autopsy findings in patients with hepatotoxicity associated with use of chlorzoxazone include severe bridging or centrizonal hepatic necrosis,101 centrilobular cholestasis with moderate hepatocellular injury,101 and hepatitis with early periportal fibrosis;101 cholelithiasis was present in a few patients.101 The mechanism of chlorzoxazone-induced hepatotoxicity is not known, but the reaction is unpredictable and idiosyncratic;1, 101 although there is some evidence suggesting metabolic idiosyncrasy (i.e., secondary to a toxic metabolite), other evidence suggests hypersensitivity.101
Adverse CNS effects including drowsiness, dizziness, lightheadedness, malaise, and overstimulation occur rarely with chlorzoxazone.1
Dermatologic and Hypersensitivity Reactions
Allergic-type skin rashes, petechiae, and ecchymosis have been reported in patients receiving chlorzoxazone.1 Angioedema or anaphylactic reactions occur very rarely.1
Anemia and granulocytopenia have been reported rarely in patients receiving chlorzoxazone. There is no evidence of chlorzoxazone-induced renal damage.1 Although not expected to be clinically important, a phenolic metabolite of chlorzoxazone may produce discoloration of the urine.1
Precautions and Contraindications
Patients should be warned that chlorzoxazone may impair their ability to perform hazardous activities requiring mental alertness or physical coordination such as operating machinery or driving a motor vehicle.
Since serious, sometimes fatal, hepatocellular toxicity has been reported rarely in patients receiving chlorzoxazone, patients receiving the drug should be instructed to report to their clinician any early signs or symptoms of possible hepatic dysfunction (e.g., fatigue, anorexia, nausea and/or vomiting, fever, rash, jaundice, dark urine, right upper quadrant pain).1 Chlorzoxazone should be discontinued immediately if any of these conditions occur.1 It may be advisable to perform liver function tests (e.g., serum aminotransferase concentrations) periodically in patients receiving long-term therapy with the drug.101 If abnormal liver function test results, including elevations in serum AST, ALT, alkaline phosphatase, or bilirubin concentrations, occur, chlorzoxazone should be discontinued.1
Chlorzoxazone should be used with caution in patients with allergies or with a history of allergic reactions to drugs.1 If a sensitivity reaction occurs during chlorzoxazone therapy, the drug should be discontinued.1 Chlorzoxazone is contraindicated in patients with known intolerance to the drug.1
Because of the risk of injury, skeletal muscle relaxants should generally be avoided in geriatric patients.111
Safe use of chlorzoxazone during pregnancy has not been established.1 The drug should not be used in women who are or may become pregnant unless the potential benefits outweigh the possible risks.1
Additive CNS depression may occur when chlorzoxazone is administered concomitantly with other CNS depressants, including alcohol. If chlorzoxazone is used concomitantly with other CNS depressant drugs, caution should be used to avoid overdosage.
Initially, acute chlorzoxazone overdosage may cause nausea, vomiting, diarrhea, drowsiness, dizziness, lightheadedness, and headache. Malaise or sluggishness may occur early in the course of intoxication, followed by loss of muscle tone which may be marked enough to make voluntary movement impossible. Deep tendon reflexes may be decreased or absent. The sensorium remains intact, and there is no peripheral loss of sensation. Respiratory depression may occur with rapid, irregular respiration and intercostal and substernal retraction. Hypotension may occur, but shock has not been observed.
In acute chlorzoxazone overdosage, the stomach should be emptied immediately by inducing emesis or by gastric lavage, followed by administration of activated charcoal. Management of overdosage includes general supportive therapy, maintenance of adequate airway, assisted respiration, and cautious administration of pressor agents, such as norepinephrine, if necessary.
Chlorzoxazone is a CNS depressant with sedative and skeletal muscle relaxant effects. There is some evidence indicating that the drug inhibits multisynaptic reflex arcs at the level of the spinal cord and subcortical areas of the brain, resulting in a reduction of skeletal muscle spasm with relief of pain and increased mobility of involved muscles.1 The skeletal muscle relaxant effects of orally administered chlorzoxazone 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.
Chlorzoxazone is rapidly and completely absorbed from the GI tract.24 Plasma concentrations of chlorzoxazone required for sedative, skeletal muscle relaxant, or toxic effects are not known. Following oral administration, peak plasma concentrations are generally attained in about 1-2 hours.1 The onset of action is usually within 1 hour and the duration of action is 3-4 hours.
It is not known if chlorzoxazone crosses the placenta or is distributed into milk.
Chlorzoxazone has an elimination half-life of approximately 66 minutes.
Chlorzoxazone is rapidly metabolized in the liver to 6-hydroxychlorzoxazone, which apparently is inactive and excreted in urine primarily as the glucuronide.1, 24 Less than 1% of a dose is excreted unchanged in urine within 24 hours.1
Chlorzoxazone is a benzoxazole-derivative, centrally acting skeletal muscle relaxant. Chlorzoxazone occurs as a white or practically white, practically odorless, crystalline powder and is slightly soluble in water and sparingly soluble in alcohol.1 The drug has a pKa of 8.2.
Chlorzoxazone tablets should be stored in tight containers at 20-25°C.1, 100, 102
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 | 250 mg* | Chlorzoxazone Tablets | |
375 mg* | Chlorzoxazone Tablets | |||
500 mg* | Chlorzoxazone Tablets | |||
750 mg* | Chlorzoxazone Tablets | |||
Lorzone® | Vertical Pharmaceuticals |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions March 2, 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. Vertical Pharmaceuticals. Lorzone® (chlorzoxazone) prescribing information. Bridgewater, NJ; 2017 Jan.
18. SCHWAB RS. MUSCLE RELAXANTS. Practitioner . 1964; 192:104-8. [PubMed 14106636]
24. CONNEY AH, BURNS JJ. Physiological disposition and metabolic fate of chlorzoxazone (paraflex) in man. J Pharmacol Exp Ther . 1960; 128:340-3. [PubMed 13811547]
100. Actavis. Chlorzoxazone tablets 500 mg prescribing information. Parsippany, NJ; 2015 Mar.
101. Powers BJ, Cattau EL Jr, Zimmerman HJ. Chlorzoxazone hepatotoxic reactions. Arch Intern Med . 1986; 146:1183-6. [PubMed 3521519]
102. Mikart. Chlorzoxazone tablets 250 mg prescribing information. Atlanta, GA; 2018 Aug.
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]