What are the consequences of taking chlorzoxazone (a muscle relaxant) chronically?

Consequences of Chronic Chlorzoxazone Use

Chronic use of chlorzoxazone is associated with potentially serious adverse effects including hepatotoxicity, central nervous system depression, and risk of abuse, and should be avoided for long-term use, especially in older adults. 1, 2

Hepatotoxicity Risk

• Chlorzoxazone is associated with hepatotoxicity that is generally reversible but can be serious in rare cases 1, 3
• Case reports have documented severe hepatocellular damage with jaundice and coagulopathy even at therapeutic doses 4
• There have been documented cases of chlorzoxazone-associated hepatotoxic reactions, including two deaths involving hepatic failure 3
• Patients with risk factors such as alcoholism or heart failure may be at increased risk for liver damage when taking chlorzoxazone 4

Central Nervous System Effects

• As a centrally-acting skeletal muscle relaxant, chlorzoxazone commonly causes sedation and other CNS effects 2
• Chronic use can lead to drowsiness, dizziness, light-headedness, and malaise, which can significantly impact quality of life and daily functioning 2
• These CNS effects may increase the risk of falls and accidents, particularly in older adults 1

Potential for Abuse and Dependence

• Centrally acting skeletal muscle relaxants, including chlorzoxazone, have potential for abuse 5
• They are often used in combination with other CNS depressants like narcotics or alcohol, increasing risk of respiratory depression and coma 5
• The abuse potential is often iatrogenically initiated and sustained, meaning it may begin with legitimate medical use 5

Concerns for Older Adults

• The American Geriatrics Society Beers Criteria identifies muscle relaxants, including chlorzoxazone, as potentially inappropriate medications for older adults 1
• Older adults are particularly vulnerable to the anticholinergic effects and sedation associated with muscle relaxants 1
• The 2019 AGS Beers Criteria strongly recommends avoiding muscle relaxants in older adults due to their high risk of adverse effects 1

Limited Evidence for Long-term Efficacy

• There is insufficient evidence supporting the long-term efficacy of skeletal muscle relaxants like chlorzoxazone 1
• Most clinical trials evaluating chlorzoxazone are short-term, with limited data on long-term benefits 1
• A recent randomized controlled trial found no analgesic effect of chlorzoxazone even for acute pain after spine surgery 6

Other Adverse Effects

• Gastrointestinal effects: Rare instances of gastrointestinal bleeding have been reported 2
• Allergic reactions: Skin rashes, petechiae, or ecchymoses may develop during treatment 2
• Extremely rare but serious reactions include angioneurotic edema or anaphylactic reactions 2
• Discoloration of urine due to phenolic metabolites of chlorzoxazone may occur, though this is of no known clinical significance 2

Monitoring Recommendations

• Regular liver function tests should be considered for patients on long-term chlorzoxazone therapy due to the risk of hepatotoxicity 3, 4
• Patients should be monitored for signs of abuse or dependence, especially if they have a history of substance use disorders 5
• Vigilance for CNS side effects is necessary, particularly in older adults or those taking other CNS depressants 1

Alternative Approaches

• For chronic pain management, consider NSAIDs, acetaminophen, or antidepressants as alternatives with better safety profiles for long-term use 1
• For older adults specifically, avoid muscle relaxants altogether and consider safer alternatives as recommended by the Beers Criteria 1
• If muscle relaxation is needed for spasticity rather than pain, consider agents with established efficacy for spasticity such as baclofen 1

The evidence strongly suggests that chlorzoxazone should be used only for short-term relief of acute musculoskeletal conditions rather than chronically, with particular caution in older adults and those with liver disease 1, 3.