What are the side effects of chlorzoxazone?

Side Effects of Chlorzoxazone

The most critical side effect of chlorzoxazone is potentially fatal hepatocellular toxicity, which occurs unpredictably and requires immediate discontinuation if any signs of liver injury develop. 1

Serious and Life-Threatening Side Effects

Hepatotoxicity (Most Critical)

• Fatal hepatocellular toxicity has been reported, though rare, with an idiosyncratic and unpredictable mechanism. 1
• Two deaths from hepatic failure have been documented in FDA records and medical literature since 1970. 2
• Discontinue chlorzoxazone immediately if patients develop fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, jaundice, or abnormal liver enzymes (AST, ALT, alkaline phosphatase, bilirubin). 1
• Swedish adverse reaction data shows chlorzoxazone has a comparatively greater incidence of hepatotoxic reactions among commonly used muscle relaxants. 2

Central Nervous System Depression

• Chlorzoxazone causes CNS depression with sedation, drowsiness, dizziness, and light-headedness. 1
• Concomitant use with alcohol or other CNS depressants produces additive effects and significantly increases respiratory depression risk. 1
• Overdose can cause coma requiring intubation and mechanical ventilation. 3
• The drug may interact with benzodiazepine receptors, making flumazenil potentially useful in overdose reversal. 3

Common Side Effects

Gastrointestinal Effects

• Gastrointestinal bleeding has been rarely associated with chlorzoxazone. 1
• Nausea and vomiting may occur, particularly as early signs of hepatotoxicity. 1

Neurological Effects

• Drowsiness, dizziness, and light-headedness are commonly reported. 1
• Malaise or overstimulation may occur in occasional patients. 1

Dermatologic and Allergic Reactions

• Allergic-type skin rashes, petechiae, or ecchymoses may develop during treatment. 1
• Angioneurotic edema or anaphylactic reactions are extremely rare. 1

Other Effects

• Urine discoloration may occur from a phenolic metabolite of chlorzoxazone, which has no known clinical significance. 1
• Tachycardia and postural hypotension have been reported. 4
• Ataxia can occur, particularly concerning for fall risk. 4

Special Population Concerns

Older Adults

• The American Geriatrics Society identifies chlorzoxazone as potentially inappropriate for older adults due to high risk of anticholinergic effects, sedation, and CNS depression. 5, 6
• Older adults face significantly increased fall risk from CNS effects, which is particularly dangerous in diabetic patients already at 1.79 times higher hip fracture risk. 6

Pregnancy

• Safe use has not been established regarding possible adverse effects on fetal development. 1
• Use only when potential benefits outweigh possible risks in women of childbearing potential. 1

Chronic Use

• Chronic chlorzoxazone use is associated with hepatotoxicity, CNS depression, and abuse risk, and should be avoided for long-term therapy. 5
• Most clinical trials evaluating chlorzoxazone are short-term, with insufficient evidence supporting long-term efficacy. 5

Clinical Monitoring Recommendations

• Instruct patients to report early hepatotoxicity signs immediately: fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, or jaundice. 1
• Monitor liver enzymes if hepatotoxicity is suspected. 1
• Assess fall risk at baseline and during treatment, especially in older adults and diabetic patients. 6
• Avoid combining with alcohol or other CNS depressants. 1
• There is no evidence that chlorzoxazone causes renal damage. 1