What is the recommended dose of colchicine (Colcrys) for treating acute gout and familial Mediterranean fever, especially in patients with impaired renal function?

From the Guidelines

For acute gout, the recommended colchicine (Colcrys) dosing is 1.2 mg at first onset of symptoms, followed by 0.6 mg one hour later (total 1.8 mg). This dosing regimen is based on moderate-quality evidence that suggests lower doses of colchicine are as effective as higher doses at reducing pain and are associated with fewer gastrointestinal adverse effects 1.

Key Considerations for Colchicine Use

• For familial Mediterranean fever (FMF), adults typically take 1.2-2.4 mg daily, which can be given as a single dose or divided into two doses.
• Dose adjustments are crucial for patients with renal impairment.
• For those with moderate renal impairment (creatinine clearance 30-50 mL/min), the acute gout dose should be reduced to 0.6 mg initially, with no additional dose within 24 hours.
• For severe renal impairment (creatinine clearance less than 30 mL/min), colchicine is generally not recommended.
• Patients on dialysis should avoid colchicine if possible.

Important Drug Interactions and Side Effects

• Drug interactions are important to consider, particularly with CYP3A4 inhibitors and P-glycoprotein inhibitors like clarithromycin, which can significantly increase colchicine levels and toxicity risk.
• Colchicine works by preventing neutrophil migration and activation, thereby reducing inflammation in affected joints or tissues.
• Common side effects include diarrhea, nausea, and vomiting, which can signal early toxicity.
• Monitoring for muscle pain is important as myopathy and rhabdomyolysis are serious potential complications, especially in patients with renal dysfunction.

Clinical Guidelines and Recommendations

• The American College of Physicians recommends using low-dose colchicine when treating acute gout, based on moderate-quality evidence 1.
• Clinicians should discuss benefits, harms, costs, and individual preferences with patients before initiating urate-lowering therapy, including concomitant prophylaxis, in patients with recurrent gout attacks 1.

From the FDA Drug Label

For prophylaxis of gout flares in patients with mild (estimated creatinine clearance [Cl cr] 50 to 80 mL/min) to moderate (Cl cr 30 to 50 mL/min) renal function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. However, in patients with severe impairment, the starting dose should be 0.3 mg/day and any increase in dose should be done with close monitoring. For the prophylaxis of gout flares in patients undergoing dialysis, the starting doses should be 0.3 mg given twice a week with close monitoring. For treatment of gout flares in patients with mild (Cl cr 50 to 80 mL/min) to moderate (Cl cr 30 to 50 mL/min) renal function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine However, in patients with severe impairment, while the dose does not need to be adjusted for the treatment of gout flares, a treatment course should be repeated no more than once every two weeks. For patients undergoing dialysis, the total recommended dose for the treatment of gout flares should be reduced to a single dose of 0.6 mg (one tablet). Caution should be taken in dosing patients with moderate and severe renal impairment and in patients undergoing dialysis. For these patients, the dosage should be reduced. Patients with mild (Cl cr 50 to 80 mL/min) and moderate (Cl cr 30 to 50 mL/min) renal impairment should be monitored closely for adverse effects of colchicine. Dose reduction may be necessary. For patients with severe renal failure (Cl cr less than 30 mL/min), start with 0.3 mg/day; any increase in dose should be done with adequate monitoring of the patient for adverse effects of colchicine. For patients undergoing dialysis, the total recommended starting dose should be 0.3 mg (half tablet) per day. Dosing can be increased with close monitoring.

The recommended dose of colchicine for:

• Gout flares in patients with normal renal function is 1.2 mg at the first sign of a gout flare, followed by 0.6 mg one hour later.
• Gout flares in patients with mild to moderate renal impairment is the same as for patients with normal renal function.
• Gout flares in patients with severe renal impairment is 0.6 mg as a single dose.
• Prophylaxis of gout flares in patients with mild to moderate renal impairment is 0.6 mg once a day.
• Prophylaxis of gout flares in patients with severe renal impairment is 0.3 mg once a day.
• FMF in patients with mild to moderate renal impairment is 1.2 to 2.4 mg per day.
• FMF in patients with severe renal impairment is 0.3 to 1.2 mg per day.
• FMF in patients undergoing dialysis is 0.3 mg per day. 2

From the Research

Colchicine Dose for Acute Gout and Familial Mediterranean Fever

The recommended dose of colchicine for treating acute gout and familial Mediterranean fever varies, especially in patients with impaired renal function.

• For acute gout, the lowest dose currently used decreases digestive toxicity, and doses should be adapted to renal function and age, considering possible drug interactions 3.
• For familial Mediterranean fever, the minimal daily dose in adults is 1.0 mg/day, but there is no definite dose for children 4.

Dose Adjustment for Impaired Renal Function

• Doses of colchicine should be adapted to renal function, as the really plasma half-life is prolonged in patients with liver or renal failure 4.
• In patients with impaired renal function, the dose of colchicine may need to be reduced to avoid toxicity 3, 5.

Potential Interactions and Toxicity

• Colchicine treatment can be complicated by frequent gastrointestinal side effects, and patients may benefit from a lactose-free diet and treatment of intestinal bacterial overgrowth and/or Hp-infection 4.
• Drug-drug interactions, such as with clarithromycin, can result in colchicine intoxication, even in patients with normal kidney function 6.
• Combination of colchicine with non-steroidal anti-inflammatory drugs (NSAIDs) can cause acute kidney injury 5.

Special Considerations

• Colchicine is mainly indicated for the treatment and prophylaxis of gout and familial Mediterranean fever, and its mode of action includes modulation of chemokine and prostanoid production and inhibition of neutrophil and endothelial cell adhesion molecules 7.
• High dosages of colchicine may interfere with male and female fertility and children's growth, but current guidelines recommend its use in familial Mediterranean fever patients due to its rare side effects 4.