What are the indications for colchicine (Colcrys)?

Colchicine Indications

Colchicine is FDA-approved for three specific indications: treatment of acute gout flares, prophylaxis of gout flares, and treatment of familial Mediterranean fever (FMF) in adults and children four years or older. 1

FDA-Approved Indications

1. Acute Gout Flares (Treatment)

• Colchicine is indicated for treatment of acute gout attacks when taken at the first sign of a flare. 1
• Must be initiated within 12-36 hours of symptom onset for effectiveness, as efficacy significantly decreases beyond this timeframe. 2, 3
• The recommended regimen is 1.2 mg (two tablets) at the first sign of flare, followed by 0.6 mg (one tablet) one hour later (total 1.8 mg over one hour). 2, 3, 1
• This low-dose regimen is as effective as higher doses but with significantly fewer gastrointestinal side effects. 2, 4
• Higher doses have not been found to be more effective and should not be used. 1

2. Gout Flare Prophylaxis

• Colchicine is indicated for prophylaxis of gout flares in adults and adolescents older than 16 years. 1
• The recommended dose is 0.6 mg once or twice daily (maximum 1.2 mg/day). 2, 3, 1
• Prophylaxis should be initiated with or just prior to starting urate-lowering therapy (allopurinol, febuxostat, pegloticase), as mobilization of urate from tissue deposits increases flare risk. 1, 2
• Continue prophylaxis for at least 6 months, OR 3 months after achieving target serum urate if no tophi are present, OR 6 months after achieving target serum urate if tophi were previously detected. 2, 3

3. Familial Mediterranean Fever (FMF)

• Colchicine is indicated for treatment of FMF in adults and children four years or older. 1
• Adult dosing: 1.2 to 2.4 mg daily, administered in one to two divided doses. 1
• Pediatric dosing based on age: 1
  • 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
• Dose should be increased as needed to control disease in increments of 0.3 mg/day to maximum recommended dose. 1

Emerging Cardiovascular Indications (Off-Label)

Pericarditis

• Clinical trials in >1,600 patients demonstrate that colchicine halves the risk of recurrence in acute and recurrent pericarditis (relative risk 0.50,95% CI 0.42-0.60). 5

Coronary Artery Disease

• Randomized controlled trials in >11,000 patients followed for up to 5 years show colchicine may reduce cardiovascular death, myocardial infarction, ischemic stroke, and ischemia-driven revascularization by >30% (relative risk 0.63,95% CI 0.49-0.81). 5

Critical Contraindications and Precautions

Absolute Contraindications

• Severe renal impairment (eGFR <30 mL/min): colchicine should be avoided due to decreased clearance and risk of toxicity. 2, 3
• Concomitant use with strong P-glycoprotein and/or CYP3A4 inhibitors (cyclosporine, clarithromycin, ketoconazole, ritonavir) is absolutely contraindicated. 2, 3

Important Safety Considerations

• Calculate eGFR before prescribing colchicine in all patients. 3
• Screen for drug interactions with CYP3A4/P-glycoprotein inhibitors before initiating therapy. 3
• In patients with moderate renal impairment or on statins, monitor for neurotoxicity and muscular toxicity. 2
• For dialysis patients, limit to a single 0.6 mg dose with no repeat treatment for at least two weeks. 3
• Gastrointestinal side effects (diarrhea, vomiting) occur in approximately 10% of patients but 90% tolerate long-term therapy well. 5

Drug Interactions Requiring Dose Adjustment

• Moderate CYP3A4 inhibitors (erythromycin, verapamil, diltiazem) require dose reduction. 3, 1
• Concomitant statin use increases risk of myopathy. 2, 6
• Grapefruit juice can increase colchicine concentrations. 6

Clinical Pearls

• Colchicine is not an analgesic and should not be used to treat pain from other causes. 1
• The narrow therapeutic index means there is no clear distinction between nontoxic, toxic, and lethal doses—lowest reported lethal oral doses are 7-26 mg. 6
• All participants in the pivotal trial experienced gastrointestinal side effects with older high-dose regimens, but the current low-dose regimen has a safety profile comparable to placebo. 2, 4
• Colchicine can be administered without regard to meals. 1