Chlorzoxazone Dosing and Usage for Muscle Spasms
For acute muscle spasms, chlorzoxazone should be initiated at 250-500 mg three to four times daily, with the option to increase to 750 mg three to four times daily if needed, and should be discontinued as soon as symptoms resolve—typically within 2 weeks or less. 1
Standard Dosing Regimens
The FDA-approved dosing for chlorzoxazone varies by tablet strength 1:
- 375 mg tablets: Start with one tablet (375 mg) three or four times daily; may increase to two tablets (750 mg) three or four times daily if response is inadequate 1
- 500 mg tablets: Start with one tablet (500 mg) three or four times daily; may increase to 1.5 tablets (750 mg) three or four times daily if needed 1
- 750 mg tablets: Initial dosing for painful musculoskeletal conditions is 500 mg (2/3 tablet) three or four times daily, with potential escalation to 750 mg three or four times daily 1
As improvement occurs, dosage should be reduced to the lowest effective dose. 1
Duration of Treatment
Chlorzoxazone should only be used short-term, as all muscle relaxant trials were 2 weeks or less in duration. 2 Treatment should be time-limited and discontinued as soon as a pain-free state is achieved, with extended courses beyond the acute phase not supported by evidence. 3
Important Clinical Considerations
Efficacy and Mechanism
- Chlorzoxazone does not directly relax skeletal muscle and has no evidence of efficacy in chronic pain 2
- It is a centrally acting muscle relaxant that provides relief for localized muscle spasm in acute musculoskeletal conditions 1, 4
- The drug is absorbed with a time to maximum concentration (Tmax) of approximately 2 hours and has an elimination half-life of 1.5 hours 5
Safety Profile and Adverse Effects
Chlorzoxazone carries significant adverse effect risks, particularly CNS effects including sedation, dizziness, and drowsiness. 2, 6
- The primary adverse effects are CNS-related, with sedation being the most common 3
- In comparative studies, muscle relaxants showed a number needed to harm (NNTH) of 3 for adverse events, predominantly drowsiness and dizziness 6
- Hepatotoxicity is a serious concern: Chlorzoxazone undergoes metabolic activation via CYP3A enzymes, forming reactive oxirane intermediates that can cause idiosyncratic liver toxicity 7
Special Populations
Chlorzoxazone is particularly inappropriate for older adults due to increased risk of falls, sedation, and lack of efficacy evidence in this population. 2 Muscle relaxants may be associated with greater risk for falls in older persons. 8
Alternative Considerations
If chlorzoxazone is ineffective or poorly tolerated 2:
- Tizanidine has the strongest evidence base as an alternative, with efficacy demonstrated in 8 trials for acute low back pain 2
- Methocarbamol is generally well-tolerated with minimal adverse effects and may be considered for short-term relief 3
- Cyclobenzaprine 5 mg three times daily is preferred by some guidelines for muscle spasm, though it has significant anticholinergic effects 8
Critical Warnings
- Insufficient evidence exists for chronic use of chlorzoxazone for musculoskeletal pain 2
- Monitor for signs of hepatotoxicity, as the drug can cause idiosyncratic liver injury through formation of reactive metabolites 7
- Avoid use beyond 2 weeks unless absolutely necessary, as no evidence supports longer duration therapy 3, 2