Chlorzoxazone + Paracetamol

Usage

• Medical Conditions: Chlorzoxazone + Paracetamol is prescribed for the relief of muscle spasm and pain associated with acute, painful musculoskeletal conditions such as low back pain, sprains, strains, myalgia, tension headaches, traumatic muscle injuries, cervical root and disc syndrome, torticollis, and fibrositis. It’s also used for pain relief and muscle spasm associated with inflammatory and degenerative processes, including fibrositis, myositis, bursitis, tenosynovitis, torticollis, osteoarthritis, trauma, intervertebral disc syndrome, lumbago, sacroiliac pain, and post-surgical or post-tooth extraction myalgia.
• Pharmacological Classification: Analgesic (Paracetamol) and Skeletal Muscle Relaxant (Chlorzoxazone).
• Mechanism of Action: Paracetamol inhibits prostaglandin synthesis, reducing pain and fever. Chlorzoxazone acts on the central nervous system, depressing reflexes in the spinal cord and subcortical areas of the brain, leading to muscle relaxation and reduced spasm.

Alternate Names

• International/Regional Variations: Chlorzoxazone and Paracetamol combination.
• Brand Names: Myospaz, Parafon Forte, Lorzone, Relaxopyx, Cetachlor, and others.

How It Works

• Pharmacodynamics: Paracetamol exerts its analgesic and antipyretic effects by inhibiting prostaglandin synthesis, primarily in the central nervous system. It has minimal anti-inflammatory action. Chlorzoxazone’s muscle relaxant effect is due to its central action on the spinal cord and subcortical areas of the brain, inhibiting multisynaptic reflexes involved in muscle spasm.

• Pharmacokinetics:

  • Absorption: Chlorzoxazone is well absorbed orally, reaching peak plasma concentrations in 1-2 hours. Paracetamol is rapidly absorbed from the gastrointestinal tract.
  • Metabolism: Both drugs are primarily metabolized in the liver. Chlorzoxazone is metabolized mainly by CYP2E1 to 6-hydroxychlorzoxazone. Paracetamol is metabolized via glucuronidation and sulfation pathways.
  • Elimination: Metabolites of both drugs are primarily excreted in the urine. Less than 5% of Paracetamol is excreted unchanged.

• Mode of Action: Chlorzoxazone acts centrally to inhibit multisynaptic reflexes involved in muscle spasm. Paracetamol reduces pain by inhibiting prostaglandin synthesis.

Dosage

Standard Dosage

Adults:

• One or two tablets three or four times a day. Some sources suggest 250-750 mg of Chlorzoxazone every 6-8 hours, or 500 mg three or four times daily, possibly increasing to 750 mg three or four times daily if needed.
• The maximum recommended dose for Chlorzoxazone is 3000 mg per day. The maximum daily dose for Paracetamol is 4 g.

Children:

• 7 to 12 years: One-half to one tablet three or four times a day. Another source suggests 20 mg/kg/day of Chlorzoxazone divided every 6-8 hours, or 600 mg/m²/day divided every 6-8 hours. Not recommended for children under 6 years of age or, in some sources, under 10. Pediatric use requires careful consideration of safety and efficacy.

Special Cases:

• Elderly Patients: Lower initial doses are advised due to potential age-related decline in hepatic and renal function. Close monitoring for adverse effects is important.
• Patients with Renal Impairment: Use with caution; dose adjustment may be necessary. Monitor renal function.
• Patients with Hepatic Dysfunction: Use with extreme caution due to risk of hepatotoxicity. Dose reduction or avoidance is advisable. Monitor liver function tests.
• Patients with Comorbid Conditions: Adjust dose based on the specific condition. Use cautiously in patients with a history of peptic ulcer or gastrointestinal bleeding.

Clinical Use Cases

Dosage for clinical use cases like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations should be individualized based on the specific patient’s needs and condition. No specific dosage guidelines for these cases were found in the provided sources.

Dosage Adjustments

• Dose modifications might be needed based on renal or hepatic function, other medical conditions, and concomitant medications.

Side Effects

Common Side Effects:

Dizziness, drowsiness, lightheadedness, malaise, nausea, vomiting, gastrointestinal disturbances (e.g., indigestion, diarrhea, stomach pain, heartburn), overstimulation, allergic-type skin rashes (e.g., urticaria, swelling, itching), headache, weakness.

Rare but Serious Side Effects:

Hepatotoxicity (liver damage, jaundice), Steven-Johnson syndrome, anaphylactic reaction, anemia, edema, acute renal tubular necrosis, blood dyscrasias, angioedema, bronchospasm, petechiae, urine discoloration (orange or purple-red).

Long-Term Effects:

Chronic complications from prolonged use can include hepatotoxicity and renal impairment.

Adverse Drug Reactions (ADR):

Severe allergic reactions, significant liver dysfunction, acute renal failure. Immediate medical attention is needed if such reactions occur.

Contraindications

• Hypersensitivity to Chlorzoxazone, Paracetamol, or any components of the formulation.
• Severe liver or kidney impairment.
• Porphyria.
• Active or history of recurrent peptic ulcer/hemorrhage.
• Patients with certain bleeding disorders.
• Patients with established heart disease or cerebrovascular disease.
• Peripheral arterial disease.
• Pregnancy (especially more than six months).

Drug Interactions

• Alcohol (increased drowsiness and dizziness, risk of stomach bleeding)
• CNS depressants (additive CNS depression)
• Anticoagulants (enhanced anticoagulant effects)
• Diuretics (inhibited diuretic activity)
• Lithium and Digoxin (increased plasma concentrations)
• Antacids (e.g., ranitidine)
• Hypnotics (e.g., zolpidem)
• Antidepressants (e.g., duloxetine, escitalopram)
• Antihistamines (e.g., diphenhydramine, cetirizine)
• Anticonvulsants (e.g., pregabalin, topiramate)
• Antihypertensives (e.g., metoprolol)
• Opioid pain or cough relievers (e.g., codeine, hydrocodone)
• Other muscle relaxants (e.g., carisoprodol, cyclobenzaprine)

Pregnancy and Breastfeeding

• Pregnancy: Use with caution, especially during the third trimester. Inform doctor if pregnant, planning pregnancy, or breastfeeding.
• Breastfeeding: Use with caution. Consult a doctor to assess risk/benefit.

Drug Profile Summary

• Mechanism of Action: Paracetamol inhibits prostaglandin synthesis. Chlorzoxazone inhibits multisynaptic reflexes.
• Side Effects: Dizziness, drowsiness, nausea, gastrointestinal disturbances, liver dysfunction (rare).
• Contraindications: Hypersensitivity, severe liver/kidney impairment, peptic ulcer, pregnancy.
• Drug Interactions: CNS depressants, anticoagulants, alcohol.
• Pregnancy & Breastfeeding: Use with caution. Consult a doctor.
• Dosage: Adults: 1-2 tablets 3-4 times/day. Children: Consult doctor.
• Monitoring Parameters: Liver function tests, renal function tests.

Popular Combinations

No specific information on popular combinations was found in the sources. Clinicians may combine this medication with other therapies such as physical therapy or other pain management strategies.

Precautions

• Pre-existing conditions like liver disease, kidney disease, heart disease, or history of peptic ulcers require careful evaluation before use.
• Alcohol should be avoided.
• Monitor for signs of hepatotoxicity.
• Use cautiously in elderly patients and those with renal impairment.
• Avoid driving or operating machinery until effects are known.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Chlorzoxazone + Paracetamol?

A: Adults: One or two tablets three or four times a day. Children (7-12 years): One-half to one tablet three or four times a day. Consult a doctor for specific dosing instructions, especially for children, elderly patients, and those with pre-existing conditions.

Q2: What are the common side effects?

A: Dizziness, drowsiness, nausea, and gastrointestinal upset.

Q3: Can I drink alcohol while taking this medication?

A: No, alcohol should be avoided as it can exacerbate side effects like drowsiness and dizziness and increase the risk of stomach bleeding.

Q4: Is it safe to use during pregnancy or breastfeeding?

A: It should be used cautiously during pregnancy, especially in the third trimester. Consult your doctor before use if pregnant, planning to become pregnant, or breastfeeding.

Q5: How does Chlorzoxazone + Paracetamol work?

A: Paracetamol reduces pain and fever, and Chlorzoxazone relaxes muscles.

Q6: Are there any serious side effects I should be aware of?

A: Although rare, serious side effects like liver damage can occur. Contact your doctor immediately if you experience symptoms like jaundice, dark urine, or abdominal pain.

Q7: Can I drive while taking this medication?

A: Use caution when driving or operating machinery as this medication can cause dizziness and drowsiness.

Q8: What should I do if I miss a dose?

A: Take the missed dose as soon as you remember, unless it is almost time for your next dose. Do not double the dose to catch up.

Q9: Are there any drug interactions I should be aware of?

A: Yes, this medication can interact with other drugs, including CNS depressants, anticoagulants, and certain other medications. Always inform your doctor about all medications you are taking, including over-the-counter drugs and supplements.

Q10: What are the contraindications for this medication?

A: Contraindications include hypersensitivity to Chlorzoxazone or Paracetamol, severe liver or kidney impairment, and active peptic ulcer disease. Consult your doctor if you have any pre-existing medical conditions.