What is the recommended dose, frequency, and duration of colchicine for various conditions, including acute gout and familial Mediterranean fever, in patients with normal and impaired renal function?

Colchicine Dosing: Dose, Frequency, and Duration

Acute Gout Flare Treatment

For acute gout flares, administer colchicine 1.2 mg at the first sign of symptoms, followed by 0.6 mg one hour later (total 1.8 mg over 1 hour), but only if treatment can be initiated within 36 hours of symptom onset. 1, 2, 3

Standard Dosing (Normal Renal Function)

• Initial loading: 1.2 mg followed by 0.6 mg one hour later 1, 4, 5
• Continuation: After 12 hours from initial doses, continue with 0.6 mg once or twice daily until the attack completely resolves 1, 3
• Critical timing window: Colchicine is only effective if started within 36 hours of symptom onset; effectiveness significantly decreases beyond this timeframe 1, 2, 6

Renal Impairment Adjustments

• Mild to moderate impairment (CrCl 30-80 mL/min): No dose adjustment required for acute treatment, but monitor closely for adverse effects 4
• Severe impairment (CrCl <30 mL/min): Use the standard acute dose (1.2 mg + 0.6 mg), but do not repeat treatment course more than once every two weeks 4
• Dialysis patients: Single dose of 0.6 mg only; do not repeat for at least two weeks 2, 4

Important caveat: Treatment of acute gout flares is not recommended in patients with renal impairment who are already receiving colchicine for prophylaxis 4

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Gout Flare Prophylaxis

For prophylaxis of gout flares, use colchicine 0.6 mg once or twice daily, initiated with or just prior to starting urate-lowering therapy. 1, 3, 6

Standard Prophylactic Dosing

• Dose: 0.6 mg once or twice daily 1, 3
• Initiation timing: Start with or just before beginning urate-lowering therapy 3, 6

Duration of Prophylaxis

Continue prophylaxis for the longest of these three options: 1, 3, 6

• Minimum: 6 months duration
• Without tophi: 3 months after achieving target serum urate
• With tophi: 6 months after achieving target serum urate and resolution of tophi on physical exam

Renal Impairment Adjustments for Prophylaxis

• Mild to moderate impairment (CrCl 30-80 mL/min): No adjustment required, but monitor closely 4
• Severe impairment (CrCl <30 mL/min): Start with 0.3 mg once daily; increase cautiously with close monitoring 4
• Dialysis patients: 0.3 mg twice weekly with close monitoring 4

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Familial Mediterranean Fever (FMF)

Standard Dosing

• Adults: Minimum dose 1.0 mg/day, though specific optimal dosing varies 7
• Renal impairment (CrCl <30 mL/min): Start with 0.3 mg/day; increase cautiously with adequate monitoring 4
• Dialysis patients: Start with 0.3 mg/day; increase cautiously with adequate monitoring 4

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Critical Drug Interactions Requiring Dose Reduction

Colchicine is absolutely contraindicated with strong P-glycoprotein and/or CYP3A4 inhibitors in patients with renal or hepatic impairment. 6, 4

Major Interactions Requiring Dose Adjustment

When used with the following medications, significant dose reductions are mandatory 1, 3, 4:

• Clarithromycin, erythromycin
• Cyclosporine
• Protease inhibitors (ritonavir, indinavir, lopinavir, saquinavir, etc.)
• Azole antifungals (ketoconazole, itraconazole)
• Calcium channel blockers (verapamil, diltiazem)
• Nirmatrelvir/ritonavir (Paxlovid)

For acute gout with these interactions: Maximum 0.6 mg × 1 dose, followed by 0.3 mg one hour later; do not repeat for at least 3 days 4

For prophylaxis with these interactions: Reduce to 0.3 mg once daily or 0.3 mg every other day, depending on specific drug 4

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Hepatic Impairment Adjustments

• Mild to moderate hepatic impairment: No dose adjustment required, but monitor closely 4
• Severe hepatic impairment (prophylaxis): Consider dose reduction with careful monitoring 4
• Severe hepatic impairment (acute treatment): Use standard dose but do not repeat more than once every two weeks; consider alternative therapy for repeated courses 4

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Common Pitfalls to Avoid

• Do not use the outdated high-dose regimen for acute gout (multiple doses until diarrhea occurs); the low-dose regimen (1.8 mg total over 1 hour) is equally effective with significantly fewer side effects 1, 8
• Do not treat acute flares in patients already on prophylactic colchicine who are also taking CYP3A4 inhibitors 4
• Do not ignore the 36-hour window; colchicine loses effectiveness rapidly after this timeframe 1, 2, 6
• Do not combine colchicine with statins in patients with renal impairment; this significantly increases risk of severe neuromyopathy 9
• Always calculate creatinine clearance before prescribing, especially in elderly patients 6, 4