Chlorzoxazone

Usage

• Chlorzoxazone is prescribed as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions. It is used for short-term relief of muscle spasms, pain, and stiffness.
• Pharmacological Classification: Centrally-acting skeletal muscle relaxant.
• Mechanism of Action: While the exact mechanism is not fully understood, chlorzoxazone is believed to inhibit multisynaptic reflex arcs in the spinal cord and subcortical areas of the brain, reducing muscle spasm and pain. It does not directly relax skeletal muscles. It may also alter pain perception.

Alternate Names

• No widely used alternate names.
• Brand Names: Lorzone, Paraflex, Parafon Forte DSC, Relax-DS, Remular, Remular-S

How It Works

• Pharmacodynamics: Chlorzoxazone primarily acts on the central nervous system (CNS) to reduce muscle spasm and pain. It depresses polysynaptic reflexes involved in muscle tone regulation without directly affecting skeletal muscle fibers or neuromuscular junctions.
• Pharmacokinetics:
  • Absorption: Chlorzoxazone is rapidly absorbed after oral administration, reaching detectable blood levels within 30 minutes and peak levels in 1-2 hours. Taking the medication with food can reduce gastrointestinal upset but may slightly delay absorption.
  • Metabolism: Extensively metabolized in the liver, primarily by conjugation to glucuronide.
  • Elimination: Excreted primarily in urine, mainly as metabolites; less than 1% is excreted unchanged. No dose adjustment is recommended for renal impairment though caution should be exercised.
• Mode of Action: Acts centrally on the spinal cord and subcortical areas of the brain to inhibit multisynaptic reflex arcs that contribute to muscle spasm.
• Receptor binding, enzyme inhibition, or neurotransmitter modulation: Not definitively established. However, the inhibitory action of chlorzoxazone is thought to be related to its sedative properties.
• Elimination pathways: Primarily renal excretion of metabolites, mainly glucuronide conjugates.

Dosage

Standard Dosage

Adults:

• 250-500 mg orally 3-4 times a day.
• For severe muscle spasms: Dose can be increased to 750 mg orally 3-4 times per day.
• Maximum daily dose: 3000 mg.

Children:

• 20 mg/kg/day orally divided into 3-4 doses or 600 mg/m²/day divided into 3-4 doses.
• Pediatric use must be determined by a doctor.

Special Cases:

• Elderly Patients: Start with 250 mg orally every 6-12 hours; increase to 750 mg orally 3-4 times per day if necessary and tolerated. Use with extreme caution due to risk of hepatotoxicity. Close monitoring is necessary.
• Patients with Renal Impairment: Use with caution. No dose adjustment is required, but monitor closely.
• Patients with Hepatic Dysfunction: Contraindicated or avoid use if possible due to the risk of hepatotoxicity.
• Patients with Comorbid Conditions: Evaluate carefully based on individual circumstances. Conditions like diabetes, cardiovascular disease, or concurrent CNS depression warrant closer monitoring and potential dose adjustments.

Clinical Use Cases Clinical use cases for this medication are limited to acute musculoskeletal conditions associated with muscle spasm and pain. Its use in settings like intubation, surgical procedures, mechanical ventilation, ICU, and emergency situations isn’t indicated.

Dosage Adjustments

• Dosage should be individualized based on patient response and tolerance.
• Adjust dosages for elderly patients and those with renal or hepatic impairment as detailed above.
• Consider comorbid conditions when adjusting doses.

Side Effects

Common Side Effects

• Drowsiness
• Dizziness
• Lightheadedness
• Malaise
• Gastrointestinal upset (e.g., nausea, vomiting)

Rare but Serious Side Effects

• Hepatotoxicity (liver damage)
• Allergic reactions (e.g., skin rash, itching, hives, angioedema, anaphylaxis)
• Gastrointestinal bleeding

Long-Term Effects

• Chronic complications from long-term use are not well-documented but liver function monitoring should continue if prolonged use is deemed absolutely necessary.

Adverse Drug Reactions (ADR)

• Severe allergic reactions (e.g., anaphylaxis)
• Liver dysfunction
• Severe gastrointestinal bleeding

Contraindications

• Hypersensitivity to chlorzoxazone
• Active liver disease
• Severe hepatic impairment

Drug Interactions

• CNS depressants: Alcohol, opioids, benzodiazepines, sedating antihistamines - may cause additive CNS depression, increasing the risk of drowsiness and respiratory depression.
• CYP450 interactions: Minimal known interactions.
• Other: Monitor for potential interactions with other medications, including OTC drugs and supplements.
• Food and lifestyle factors: Alcohol should be avoided as it can exacerbate CNS depression.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Not assigned.
• Fetal risks: Insufficient data available to establish safety. Use only if potential benefit outweighs the risk.
• Breastfeeding: Insufficient data available. Use with caution. Consider the risk of infant exposure and possible adverse effects.

Drug Profile Summary

• Mechanism of Action: Centrally acting muscle relaxant, inhibits multisynaptic reflex arcs in the spinal cord and brain.
• Side Effects: Drowsiness, dizziness, lightheadedness, malaise, gastrointestinal upset, rarely hepatotoxicity and allergic reactions.
• Contraindications: Hypersensitivity, active liver disease, severe hepatic impairment.
• Drug Interactions: CNS depressants (alcohol, opioids, benzodiazepines, antihistamines).
• Pregnancy & Breastfeeding: Use with caution. Insufficient data to ensure safety.
• Dosage: Adults: 250-750 mg 3-4 times/day. Children: 20 mg/kg/day or 600 mg/m²/day divided 3-4 times/day. Elderly: Start low, monitor closely.
• Monitoring Parameters: Liver function tests (LFTs) especially during prolonged therapy.

Popular Combinations

• Chlorzoxazone is sometimes combined with nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen for enhanced pain relief.
• However, the combination may increase the risk of gastrointestinal side effects or liver toxicity.

Precautions

• General Precautions: Monitor liver function, especially during long-term treatment.
• Specific Populations: Use with caution in patients with a history of allergies, renal/hepatic dysfunction, and older adults. In pregnancy and breastfeeding, use only if the benefits outweigh the risks.
• Lifestyle Considerations: Avoid alcohol; use caution when driving or operating machinery due to the potential for drowsiness.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Chlorzoxazone?

A: Adults: 250-500 mg orally 3-4 times daily. For severe spasm, up to 750 mg 3-4 times daily. Max dose: 3000 mg/day. Children: 20 mg/kg/day or 600 mg/m²/day, divided 3-4 times/day. Adjust dose for geriatric patients and those with liver or kidney problems.

Q2: What are the common side effects?

A: Drowsiness, dizziness, lightheadedness, malaise, gastrointestinal upset.

Q3: What are the serious side effects?

A: Hepatotoxicity (liver damage), allergic reactions (anaphylaxis), gastrointestinal bleeding.

Q4: What are the contraindications to using Chlorzoxazone?

A: Hypersensitivity to the drug, active liver disease, severe hepatic impairment.

Q5: Can Chlorzoxazone be used during pregnancy or breastfeeding?

A: Use with caution. Limited data are available. Consider the potential risks and benefits.

Q6: How does Chlorzoxazone work?

A: It inhibits multisynaptic reflex arcs in the spinal cord and brain, leading to reduced muscle spasm and pain. It does not directly relax muscles.

Q7: What should patients be advised regarding lifestyle while on this medicine?

A: Avoid alcohol and activities requiring alertness, like driving, as the drug may cause drowsiness.

Q8: Are there any drug interactions I should be aware of?

A: Yes, chlorzoxazone can interact with CNS depressants (like alcohol, opioids, benzodiazepines, and certain antihistamines). This can lead to increased drowsiness and other adverse effects.

Q9: How should I monitor patients on chlorzoxazone?

A: Monitor liver function tests regularly, especially in long-term use and elderly patients. Observe for signs of allergic reactions or gastrointestinal bleeding. Assess for efficacy in managing muscle spasm and pain.