What is the proper dosing of colchicine (Colcrys) for acute and prophylactic treatment of gout, especially in patients with impaired renal function?

Colchicine Dosing for Gout Management

For acute gout flares, colchicine should be administered as a low-dose regimen of 1.2 mg initially followed by 0.6 mg one hour later, and should be started within 36 hours of symptom onset for optimal efficacy. 1

Acute Gout Flare Treatment

Standard Dosing

• Initial dose: 1.2 mg (2 tablets)
• Follow-up dose: 0.6 mg (1 tablet) one hour later
• Total dose: 1.8 mg within first 2 hours
• Do not repeat treatment course within 3 days 1, 2

Renal Impairment Adjustments

• Mild to moderate impairment (CrCl 30-80 mL/min):
  • No dose adjustment required, but monitor closely for adverse effects
• Severe impairment (CrCl <30 mL/min):
  • Same initial dose (1.2 mg followed by 0.6 mg)
  • Do not repeat treatment more than once every 2 weeks
• Dialysis patients:
  • Reduced to single dose of 0.6 mg
  • Do not repeat more than once every 2 weeks 2

Hepatic Impairment

• Mild to moderate impairment: No dose adjustment required, but monitor closely
• Severe impairment: Consider dose reduction 2

Prophylactic Treatment

Standard Prophylactic Dosing

• 0.6 mg once or twice daily 1, 3

Renal Impairment Adjustments for Prophylaxis

• Mild to moderate impairment (CrCl 30-80 mL/min):
  • No dose adjustment required, but monitor closely
• Severe impairment (CrCl <30 mL/min):
  • Start with 0.3 mg/day
  • Increase dose only with close monitoring
• Dialysis patients:
  • Start with 0.3 mg twice weekly
  • Increase dose only with close monitoring 2

Drug Interactions

Colchicine has significant interactions with CYP3A4 inhibitors and P-glycoprotein inhibitors. Dose adjustments are mandatory:

With Strong CYP3A4 Inhibitors (e.g., ritonavir, ketoconazole)

• Acute gout treatment: 0.6 mg (1 tablet) initially, no follow-up dose
• Prophylaxis: Reduce to 0.3 mg once daily or 0.3 mg every other day 2, 4

Patients with Both Renal/Hepatic Impairment AND Taking CYP3A4 Inhibitors

• Colchicine should be avoided completely 2

Important Clinical Considerations

1. Narrow therapeutic window: Colchicine has a narrow therapeutic-toxicity window with significant variability in tolerance between patients 5, 4

2. Early administration: Efficacy is maximized when colchicine is administered within 36 hours of symptom onset 1

3. Common adverse effects: Diarrhea is the most common side effect, typically occurring after a median time of 24 hours 6

4. Toxicity warning signs: Monitor for gastrointestinal symptoms (nausea, vomiting, diarrhea), which may precede more serious toxicity 4

5. Lethal dose awareness: Fatality has been reported with acute ingestions exceeding 0.5 mg/kg; lowest reported lethal doses are 7-26 mg 4

6. Duration of prophylaxis: When initiating urate-lowering therapy, prophylaxis should continue for at least 8 weeks, ideally 3-6 months after achieving target uric acid levels 1

7. Avoid high-dose regimens: The older regimen of continuing colchicine until GI side effects develop is no longer recommended due to toxicity concerns 1

8. Do not use treatment doses in patients already on prophylaxis: Treatment of gout flares with colchicine is not recommended in patients already receiving prophylactic colchicine 2

The low-dose colchicine regimen (1.8 mg total over 1 hour) has been shown to be as effective as higher doses while significantly reducing gastrointestinal adverse effects 3, 5.