What is the dosage and administration of colchicine for acute gout and familial Mediterranean fever?

Colchicine Dosage and Administration for Acute Gout and Familial Mediterranean Fever

For acute gout flares, colchicine should be administered as 1.2 mg (two tablets) at the first sign of a flare followed by 0.6 mg (one tablet) one hour later, with a maximum dose of 1.8 mg over a one-hour period. For familial Mediterranean fever (FMF), the recommended dosage is 1.2-2.4 mg daily for adults. 1, 2

Acute Gout Management

Recommended Dosing Regimen

• Initial dose: 1.2 mg (two tablets) at the first sign of gout flare
• Follow-up dose: 0.6 mg (one tablet) one hour later
• Maximum dose: 1.8 mg over a one-hour period 1

This low-dose regimen represents a significant shift from historical high-dose protocols that caused severe gastrointestinal side effects 2. The American College of Rheumatology (ACR) guidelines strongly support this dosing approach, which provides effective pain relief while minimizing adverse effects 3, 2.

Prophylaxis of Gout Flares

• Recommended dose: 0.6 mg once or twice daily
• Maximum daily dose: 1.2 mg/day 1
• Duration: At least 6 months, or 3 months after achieving target serum urate in patients without tophi 2

Prophylaxis is particularly important when initiating urate-lowering therapy to prevent flares due to mobilization of urate from tissue deposits 2, 1.

Familial Mediterranean Fever (FMF) Management

Adult Dosing

• Recommended dose: 1.2-2.4 mg daily 1
• Administration: May be given as a single dose or divided into two doses 1
• Dose adjustment: Increase as needed in increments of 0.3 mg/day to control disease; decrease in same increments if side effects develop 1

Pediatric Dosing for FMF

• Children 4-6 years: 0.3-1.8 mg daily
• Children 6-12 years: 0.9-1.8 mg daily
• Adolescents >12 years: 1.2-2.4 mg daily 1

Dose Modifications for Special Populations

Renal Impairment

• Mild to moderate impairment: No dose adjustment needed for acute flares
• Severe impairment: Limit to once every two weeks for acute flares; start with 0.3 mg/day for prophylaxis
• Dialysis patients: Single dose of 0.6 mg for acute flares (no more than once every two weeks); 0.3 mg twice weekly for prophylaxis 2

Drug Interactions

Colchicine requires dose adjustment when co-administered with CYP3A4 and/or P-glycoprotein inhibitors 1:

• Strong inhibitors (e.g., clarithromycin, ketoconazole):

  • Acute gout: 0.6 mg (1 tablet) followed by 0.3 mg (1/2 tablet) one hour later
  • Prophylaxis: 0.3 mg once daily or every other day
  • FMF: Maximum daily dose of 0.6 mg 1

• Moderate inhibitors (e.g., diltiazem, verapamil):

  • Prophylaxis: 0.3 mg twice daily or 0.6 mg once daily
  • Acute gout: 1.2 mg (2 tablets) as a single dose 1

Common Pitfalls and Safety Considerations

Potential Adverse Effects

• Gastrointestinal effects (diarrhea, nausea, vomiting) are common, especially with higher doses 2, 4
• Risk of myopathy and rhabdomyolysis, particularly in patients with renal impairment or those taking CYP3A4 inhibitors 2

Important Precautions

• Colchicine has a narrow therapeutic index with no clear distinction between therapeutic, toxic, and lethal doses 4
• The lowest reported lethal doses of oral colchicine are 7-26 mg 4
• Never use intravenous colchicine due to potential for severe and fatal toxicity 3
• Avoid high-dose regimens which significantly increase risk of adverse effects 2
• Do not use colchicine as an analgesic for pain from other causes 1

Alternative Treatments When Colchicine is Contraindicated

• NSAIDs (e.g., naproxen 500 mg twice daily)
• Oral glucocorticoids (prednisone 30-35 mg/day for 3-5 days)
• Intra-articular corticosteroid injection for monoarticular gout 2

By following these evidence-based dosing recommendations, clinicians can effectively manage acute gout flares and FMF while minimizing the risk of adverse effects associated with colchicine therapy.