What is the appropriate dosing regimen of colchicine 0.5 mg tablets for gout prophylaxis, acute gout flare, and familial Mediterranean fever based on my creatinine clearance?

Colchicine 0.5 mg Tablet Dosing Guide

Acute Gout Flare Treatment

For an acute gout attack, give 1.2 mg (2.5 tablets) initially, followed by 0.6 mg (1 tablet) one hour later, but only if treatment starts within 36 hours of symptom onset. 1, 2

• After the loading doses, continue with 0.5 mg (1 tablet) once or twice daily until the attack resolves 1
• Do not repeat this treatment course more frequently than every 3 days in patients with normal renal function 2
• This low-dose regimen is equally effective but far less toxic than older high-dose protocols 1

Renal Impairment Adjustments for Acute Gout:

• Mild-moderate impairment (CrCl 30-80 mL/min): Use standard dosing but monitor closely for toxicity 2
• Severe impairment (CrCl <30 mL/min): Give only 0.6 mg (1 tablet) as a single dose, repeat no more than once every 2 weeks 2
• Dialysis patients: Maximum 0.6 mg (1 tablet) single dose, repeat no more than once every 2 weeks 2

Gout Prophylaxis (Prevention of Flares)

Start with 0.5 mg (1 tablet) once or twice daily when initiating urate-lowering therapy. 1

• Continue prophylaxis for at least 6 months, or 3 months after achieving target serum urate (whichever is longer) 1
• If tophi were present, continue for 6 months after achieving target serum urate and tophus resolution 1

Renal Impairment Adjustments for Prophylaxis:

• Mild-moderate impairment (CrCl 30-80 mL/min): Standard dosing with close monitoring 2
• Severe impairment (CrCl <30 mL/min): Start with 0.3 mg (half tablet) daily, increase cautiously only if tolerated 2
• Dialysis patients: Start with 0.3 mg (half tablet) twice weekly 2

Familial Mediterranean Fever (FMF)

The standard adult dose is 1.0-1.5 mg daily (2-3 tablets), which can be given as a single dose or divided. 3, 4

• Start at 1.0 mg daily and titrate up to 1.5 mg if attacks persist 3
• Maximum dose is 2.0 mg daily for mucocutaneous disease 5
• In children, dosing is weight-based but typically ranges from 0.5-1.5 mg daily 6

Renal Impairment Adjustments for FMF:

• Mild impairment (CrCl 50-80 mL/min): Standard dosing with close monitoring 2
• Moderate impairment (CrCl 30-50 mL/min): Reduce dose and monitor closely; dose reduction may be necessary 2
• Severe impairment (CrCl <30 mL/min): Start with 0.3 mg (half tablet) daily, increase cautiously with intensive monitoring 2
• Dialysis patients: Start with 0.3 mg (half tablet) daily, increase only with careful monitoring 2
• FMF with amyloidosis and renal failure: Colchicine remains essential despite renal impairment to suppress serum amyloid A production; start at 0.3 mg daily and titrate cautiously 3

Critical Drug Interactions Requiring Dose Reduction

If the patient is taking strong CYP3A4 or P-glycoprotein inhibitors, colchicine doses must be drastically reduced or the combination avoided entirely in renal/hepatic impairment. 2, 3

Contraindicated combinations (especially with renal impairment):

• Clarithromycin, erythromycin (macrolides) 1, 3
• Cyclosporine, tacrolimus (calcineurin inhibitors) 3
• Ketoconazole, itraconazole (azole antifungals) 3
• HIV protease inhibitors (ritonavir, atazanavir, etc.) 2
• Verapamil, diltiazem (calcium channel blockers) 3

Dose adjustments with moderate inhibitors (in normal renal function):

• For acute gout: Maximum 0.6 mg loading dose, then 0.3 mg one hour later; do not repeat for 3 days 2
• For prophylaxis: Reduce from 0.6 mg twice daily to 0.3 mg once daily, or from 0.6 mg once daily to 0.3 mg every other day 2

Mandatory Monitoring Requirements

Before starting colchicine, check baseline complete blood count, creatinine/creatinine clearance, liver enzymes (AST/ALT), and creatine phosphokinase (CPK). 3, 7

• Repeat monitoring every 3-6 months during chronic therapy 3
• In renal impairment, monitor more frequently (every 1-3 months) 3
• For FMF patients, measure CRP or serum amyloid A every 3 months during dose titration 3

Signs of toxicity requiring immediate discontinuation:

• Diarrhea, nausea, vomiting (most common) 1, 3
• Progressive muscle weakness, myalgia, elevated CPK 3
• Cytopenias (low blood counts) 3
• Acute worsening of renal function 3
• Peripheral neuropathy 3

Special Warnings for Statin Users

Patients taking statins with colchicine face increased risk of myopathy and rhabdomyolysis, especially with atorvastatin or simvastatin. 3, 7

• Monitor for muscle symptoms (weakness, pain, tenderness) at every visit 3
• Check CPK if any muscle symptoms develop 3
• Preferred statins with colchicine: rosuvastatin, pravastatin, fluvastatin (lower interaction risk) 3
• Avoid simvastatin if possible; it has the highest risk of severe myopathy when combined with colchicine 3

Common Pitfalls to Avoid

• Do not use old high-dose regimens (e.g., 0.5-0.6 mg every 1-2 hours) for acute gout—they cause severe toxicity without added benefit 1
• Do not treat acute gout flares in patients already on prophylactic colchicine who are also taking CYP3A4 inhibitors—toxicity risk is extremely high 2
• Do not assume standard dosing is safe in elderly patients—calculate creatinine clearance using Cockcroft-Gault formula, as serum creatinine alone underestimates renal impairment 3
• Do not discontinue colchicine during pregnancy in FMF patients—the drug is safe and necessary to prevent attacks and amyloidosis 5
• Do not attribute all GI symptoms to colchicine intolerance—consider lactose-free diet and treatment of H. pylori or bacterial overgrowth, which may improve tolerance 4