What are the recommended colchicine dosing regimens for acute gout flares, gout prophylaxis when initiating urate‑lowering therapy, and familial Mediterranean fever, and how should the dose be adjusted in patients with moderate to severe renal impairment, hepatic dysfunction, elderly patients, or those taking strong CYP3A4 or P‑glycoprotein inhibitors?

Colchicine Dosing Recommendations

Acute Gout Flare

Administer colchicine 1.2 mg orally at the first sign of flare, followed by 0.6 mg one hour later (total 1.8 mg), then after a 12-hour pause resume 0.6 mg once or twice daily until the attack resolves. 1, 2, 3

Critical Timing Requirements

• Treatment must be initiated within 36 hours of symptom onset; efficacy declines sharply beyond this window, with optimal benefit achieved when started within 12 hours. 1, 2
• Do not initiate colchicine after 36 hours from symptom onset—select an alternative agent (NSAID or corticosteroid) instead. 1

Evidence Supporting Low-Dose Regimen

• This low-dose protocol (1.8 mg total) achieves equal efficacy to the obsolete high-dose regimen (4.8 mg over 6 hours) for ≥50% pain reduction at 24 hours, with a number needed to treat of 5, but produces significantly fewer gastrointestinal adverse effects. 1, 2, 4
• The older regimen of 0.5 mg every 2 hours until relief or toxicity is obsolete and causes severe diarrhea in most patients. 1

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Gout Prophylaxis When Initiating Urate-Lowering Therapy

Prescribe colchicine 0.6 mg once or twice daily for at least 6 months when starting or adjusting allopurinol or febuxostat. 1

Duration of Prophylaxis

• Continue prophylaxis for at least 6 months, or for 3 months after achieving target serum urate (<6 mg/dL) if no tophi are present, or for 6 months after achieving target serum urate if tophi are present. 1
• Maintain prophylaxis until the serum urate target is reached and there is no clinical evidence of ongoing gout activity. 1

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Familial Mediterranean Fever (FMF)

The usual adult dose for FMF is 1.2–2.4 mg/day. 5

• Dosing should be individualized based on disease severity and patient response. 3

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Dose Adjustments in Renal Impairment

Mild to Moderate Renal Impairment (CrCl 30–80 mL/min)

For acute gout flares: Use the standard regimen (1.2 mg followed by 0.6 mg one hour later) with close monitoring for adverse effects; no dose adjustment is required, but patients must be monitored closely. 1, 3

For prophylaxis: Adjustment of the recommended dose (0.6 mg once or twice daily) is not required, but patients should be monitored closely for adverse effects. 3

For FMF: Patients with mild and moderate renal impairment should be monitored closely; dose reduction may be necessary. 3

Severe Renal Impairment (CrCl <30 mL/min)

For acute gout flares: The dose does not need to be adjusted, but a treatment course should be repeated no more than once every two weeks. 3

For prophylaxis: Start with 0.3 mg/day; any increase in dose should be done with close monitoring. 3

For FMF: Start with 0.3 mg/day; any increase in dose should be done with adequate monitoring. 3

• Absolute contraindication: Colchicine should be avoided entirely in severe renal impairment (GFR <30 mL/min) according to European guidelines, where only a single 0.6 mg dose is the maximum allowed and cannot be repeated for at least two weeks. 1, 2

Dialysis Patients

For acute gout flares: Reduce the total dose to a single 0.6 mg dose; the treatment course should not be repeated more than once every two weeks. 3

For prophylaxis: Start with 0.3 mg given twice a week with close monitoring. 3

For FMF: Start with 0.3 mg per day; dosing can be increased with close monitoring. 3

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Dose Adjustments in Hepatic Impairment

Mild to Moderate Hepatic Impairment

For prophylaxis of gout flares: Adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects. 3

Severe Hepatic Impairment

For prophylaxis of gout flares: Dose reduction should be considered. 3

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Dose Adjustments with Strong CYP3A4 or P-Glycoprotein Inhibitors

Absolute Contraindication

Patients with renal or hepatic impairment who are concurrently receiving potent CYP3A4 or P-glycoprotein inhibitors (e.g., clarithromycin, erythromycin, cyclosporine, ketoconazole, ritonavir, verapamil) must not be given colchicine because the combination markedly raises plasma colchicine concentrations and can cause fatal toxicity. 1, 3, 5, 6, 7

Patients with Normal Renal and Hepatic Function

For acute gout flares: When taking strong CYP3A4/P-glycoprotein inhibitors (e.g., clarithromycin, cyclosporine, ketoconazole, ritonavir), reduce the dose to 0.6 mg × 1 dose, followed by 0.3 mg one hour later; the dose should be repeated no earlier than 3 days. 3

For prophylaxis: When taking strong CYP3A4/P-glycoprotein inhibitors, reduce the maximum daily dose to 0.3 mg once a day or 0.3 mg once every other day (depending on the specific inhibitor). 3

For FMF: When taking strong CYP3A4/P-glycoprotein inhibitors, reduce the maximum daily dose to 0.6 mg once a day or 0.3 mg once a day (depending on the specific inhibitor). 3

Specific Inhibitors and Dose Adjustments

The FDA label provides detailed dose-reduction tables for specific inhibitors including clarithromycin, cyclosporine, ketoconazole, ritonavir, and HIV protease inhibitors (fosamprenavir, indinavir, lopinavir/ritonavir, nelfinavir, saquinavir, tipranavir). 3

• Verapamil: Colchicine should not be prescribed to any patient receiving verapamil because the combination can produce life-threatening toxicity, multiorgan failure, and death; verapamil raises colchicine plasma concentrations by approximately 93–103%. 1

Moderate CYP3A4/P-Glycoprotein Inhibitors

For diltiazem ER and verapamil ER: Recommended colchicine dose reductions of 33–66% for the treatment of acute gout and 50–75% for prophylaxis. 7

For azithromycin: No dose adjustment is required when colchicine is used in combination with azithromycin. 7

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Dose Adjustments in Elderly Patients

• Elderly patients are at increased risk of adverse effects with colchicine use. 1
• Close monitoring is required, particularly in the presence of renal impairment, which is common in this population. 1, 3
• Consider starting with lower prophylactic doses (0.3 mg once daily) and titrating cautiously. 3

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Alternative Treatment Options When Colchicine is Contraindicated

For acute gout flares:

• Oral corticosteroids: Prednisone 0.5 mg/kg per day (approximately 30–35 mg) for 5–10 days, either as a single course or 2–5 days at full dose followed by a 7–10-day taper. 1, 2
• Intra-articular corticosteroid injection: For monoarticular or oligoarticular involvement of accessible large joints (e.g., triamcinolone acetonide 40 mg for the knee, 20–30 mg for the ankle). 1
• NSAIDs: Full FDA-approved doses (e.g., naproxen 500 mg twice daily, indomethacin 50 mg three times daily, or sulindac 200 mg twice daily) until complete resolution, but use with extreme caution in renal impairment. 1, 2

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Common Pitfalls to Avoid

• Do not attempt dose reduction of colchicine as a "compromise" in patients with renal or hepatic impairment taking strong CYP3A4/P-glycoprotein inhibitors—even a single 0.6 mg dose carries an unacceptable risk of fatal toxicity. 1
• Do not use high-dose regimens (>1.8 mg in the first hour)—they provide no additional benefit but substantially increase gastrointestinal toxicity. 1
• Do not delay treatment beyond 24 hours—efficacy drops significantly, and colchicine should not be started after 36 hours from symptom onset. 1, 2
• Do not discontinue urate-lowering therapy during an acute gout flare if the patient is already on allopurinol or febuxostat. 1
• Treatment of gout flares with colchicine is not recommended in patients receiving prophylactic colchicine and CYP3A4 inhibitors. 3
• Treatment of gout flares with colchicine is not recommended in patients with renal impairment who are receiving colchicine for prophylaxis. 3