What is the initial dose and treatment protocol for colchicine (Colchicine) in patients with gout or familial Mediterranean fever?

Colchicine Dosing Protocol for Gout and Familial Mediterranean Fever

For patients with gout or Familial Mediterranean Fever (FMF), colchicine should be initiated at 1.0-1.5 mg/day for adults and adjusted based on response and tolerability, with maximum doses of 3 mg daily for adults and 2 mg daily for children with FMF. 1

Initial Dosing by Condition and Age

For Familial Mediterranean Fever (FMF):

Adults:

• Starting dose: 1.0-1.5 mg/day
• Maximum dose: 3 mg/day
• Dose adjustments: Increase in increments of 0.3 mg/day as needed to control disease 1, 2

Children:

• Age <5 years: 0.5 mg/day (0.6 mg/day if tablets contain 0.6 mg)
• Age 5-10 years: 0.5-1.0 mg/day
• Age >10 years: 1.0-1.5 mg/day
• Maximum doses: 1.2 mg/day (<5 years), 1.8 mg/day (5-10 years), 2 mg/day (>10 years) 1

For Gout:

Prophylaxis:

• Adults and adolescents >16 years: 0.6 mg once or twice daily
• Maximum dose: 1.2 mg/day 2

Acute Flare Treatment:

• Initial dose: 1.2 mg (two tablets) at first sign of flare
• Follow with: 0.6 mg (one tablet) one hour later
• Maximum dose: 1.8 mg over a one-hour period 2

Administration Protocol

1. Initiation:

   • Start at the recommended dose based on age and condition
   • Can be administered without regard to meals
   • May be given as single or divided doses (once or twice daily)

2. Monitoring:

   • Follow patients closely for 3-6 months after starting treatment
   • Monitor CRP, SAA protein, or both at least every 3 months during dose escalation
   • Regular monitoring every 6 months once stable 1

3. Dose Adjustment:

   • If attacks persist or inflammation continues (elevated APR), increase dose by 0.5 mg/day
   • If side effects occur, reduce dose gradually
   • For gastrointestinal side effects, consider divided doses or temporary dose reduction

Special Considerations

Hepatic Impairment

• Colchicine's elimination half-life may be up to sevenfold longer in patients with liver cirrhosis
• Reduce dose by 50-75% in patients with liver cirrhosis
• Contraindicated in severe hepatic impairment (Child-Pugh C) 3

Renal Impairment

• Requires significant dose reduction
• Start at 0.3 mg/day in severe renal impairment
• Monitor closely for signs of toxicity 3

Drug Interactions

• Strong CYP3A4 inhibitors (clarithromycin, ketoconazole, ritonavir) can increase colchicine levels by 200-300%
• P-glycoprotein inhibitors (cyclosporine, verapamil) increase risk of toxicity
• Adjust dose accordingly when these medications cannot be avoided 1, 3

Managing Side Effects

Gastrointestinal Side Effects

• Common side effects include cramping, abdominal pain, diarrhea, and vomiting
• Management strategies:
  • Split doses to reduce side effects
  • Temporary dose reduction
  • Dietary modification (reduce dairy products if lactose intolerance suspected)
  • Antidiarrheal and spasmolytic agents as needed 1

Toxicity Warning Signs

• Early signs: GI symptoms, neuromuscular symptoms, laboratory abnormalities
• Severe toxicity: bone marrow suppression, renal failure, respiratory distress
• No effective means to remove colchicine once toxicity occurs - prevention is critical 3, 4

Treatment Resistance Protocol

If a patient continues to have ≥1 attack per month despite maximum tolerated dose for 6 months:

1. Verify medication adherence
2. Consider biological treatments, preferably IL-1 inhibitors:
   • Anakinra: 100 mg/day or 2 mg/kg subcutaneously daily
   • Canakinumab: 150-300 mg or 2-4 mg/kg subcutaneously every 4-8 weeks
   • Rilonacept: 2.2 mg/kg (maximum 160 mg) weekly subcutaneously 1

Important Caveats

• Pregnancy and Lactation: Colchicine should not be discontinued during conception, pregnancy, or lactation 1
• Monitoring Requirements: Regular liver enzyme monitoring; reduce dose if elevated >2x upper limit of normal 1
• Narrow Therapeutic Index: No clear distinction between therapeutic, toxic, and lethal doses; lowest reported lethal doses are 7-26 mg 4
• Long-term Use: If a patient is stable with no attacks for >5 years and no elevated inflammatory markers, dose reduction could be considered after expert consultation 1

Colchicine has a narrow therapeutic window, so careful dosing and monitoring are essential to balance efficacy against the risk of serious toxicity.