What is the maximum dose of colchicine for an adult patient with acute gout or familial Mediterranean fever, considering impaired renal function?

Maximum Dose of Colchicine

For acute gout flares, the maximum dose is 1.8 mg total over one hour (1.2 mg initially, followed by 0.6 mg one hour later), and this regimen should not be repeated for at least 3 days in patients with normal renal and hepatic function. 1, 2

Acute Gout Treatment Dosing

Standard Dosing (Normal Renal/Hepatic Function)

• Initial dose: 1.2 mg at first sign of flare, followed by 0.6 mg one hour later (total 1.8 mg over one hour) 3, 1, 2
• After the initial loading dose, wait 12 hours, then resume prophylactic dosing of 0.6 mg once or twice daily until the attack resolves 1, 4
• Critical timing: Colchicine is only effective if started within 36 hours of symptom onset; effectiveness drops significantly beyond this window 1, 4
• The treatment course should not be repeated more frequently than once every 3 days 2

Renal Impairment Adjustments

• Mild to moderate impairment (CrCl 30-80 mL/min): No dose adjustment needed for acute treatment, but monitor closely for adverse effects 2
• Severe impairment (CrCl <30 mL/min): Use the standard 1.8 mg dose, but do not repeat the treatment course more than once every 2 weeks 2
• Dialysis patients: Maximum single dose of 0.6 mg only, not to be repeated more than once every 2 weeks 4, 2

Prophylaxis Dosing (Maximum Daily Dose)

Standard Prophylaxis

• Maximum daily dose: 1.2 mg/day (0.6 mg once or twice daily) 1, 2
• Duration: At least 6 months, or 3 months after achieving target serum urate without tophi, or 6 months after resolution of tophi 1, 4

Renal Impairment Adjustments for Prophylaxis

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

Familial Mediterranean Fever (FMF) Dosing

Adult Dosing

• Range: 1.2 to 2.4 mg daily, administered in one or two divided doses 2
• Increase in 0.3 mg/day increments as needed to control disease, up to maximum of 2.4 mg/day 2
• If intolerable side effects develop, decrease in 0.3 mg/day increments 2

Pediatric FMF Dosing

• Ages 4-6 years: 0.3 to 1.8 mg daily 2
• Ages 6-12 years: 0.9 to 1.8 mg daily 2
• Adolescents >12 years: 1.2 to 2.4 mg daily 2

Renal Impairment in FMF

• Severe impairment (CrCl <30 mL/min): Start with 0.3 mg/day; increase cautiously with adequate monitoring 2
• Dialysis patients: Start with 0.3 mg/day; increase cautiously with adequate monitoring 2

Absolute Contraindications to Any Colchicine Dosing

Critical Drug Interactions

• Colchicine is absolutely contraindicated with strong P-glycoprotein and/or CYP3A4 inhibitors in patients with renal or hepatic impairment 1, 5
• Contraindicated drugs include: clarithromycin, erythromycin, cyclosporine, ketoconazole, ritonavir, and other protease inhibitors 1, 5, 2, 6
• Combined renal and hepatic disease is an absolute contraindication 7

Dose Adjustments with Drug Interactions (Normal Renal/Hepatic Function)

• When taking strong CYP3A4/P-gp inhibitors, maximum acute gout dose is reduced to 0.6 mg × 1 dose, followed by 0.3 mg one hour later, not to be repeated for at least 3 days 2
• Prophylactic dose reduced to maximum 0.3 mg once daily or 0.3 mg every other day depending on the specific inhibitor 2

Common Pitfalls to Avoid

• Never use the outdated high-dose regimen (>1.8 mg in first hour): The low-dose regimen is equally effective with significantly fewer gastrointestinal side effects 1, 5
• Do not ignore the 36-hour treatment window: Colchicine effectiveness drops dramatically if not started within 36 hours of symptom onset 1, 4
• Always calculate creatinine clearance before prescribing, especially in elderly patients who may have normal serum creatinine but reduced clearance 1
• Do not treat acute gout flares with colchicine in patients already on prophylactic colchicine who are also taking CYP3A4/P-gp inhibitors 2
• Fatal toxicity has been reported with acute ingestions exceeding 0.5 mg/kg, with lowest reported lethal doses of 7-26 mg 8