What is the recommended dosage and frequency of colchicine (Colchicine) for treating acute gout and familial Mediterranean fever, especially in patients with Impaired renal function?

Colchicine Dosage and Frequency

Acute Gout 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 one hour), then continue 0.6 mg once or twice daily starting 12 hours later until the attack resolves. 1, 2, 3

Critical Timing Requirement

• Colchicine is only effective if started within 36 hours of symptom onset 1, 2, 3
• Treatment initiated beyond this window has significantly reduced effectiveness 2

Continuation Dosing After Initial Treatment

• After the initial 1.8 mg loading dose, wait at least 12 hours before continuing with prophylactic dosing of 0.6 mg once or twice daily until the acute attack resolves 1, 2
• This regimen is based on pharmacokinetics showing drug exposure becomes markedly reduced approximately 12 hours after administration 1

Evidence Supporting Low-Dose Regimen

• The low-dose regimen (1.8 mg total in first hour) is as effective as the older high-dose regimen (4.8 mg over 6 hours) but with significantly fewer gastrointestinal side effects 2, 4
• Number needed to treat is 5 for achieving ≥50% pain reduction at 24 hours 2

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Gout Prophylaxis (Prevention of Recurrent Attacks)

For prophylaxis of gout flares, use colchicine 0.6 mg once or twice daily. 1, 3

Duration of Prophylaxis

• Continue prophylaxis for the greater of: 1, 3
  • 6 months minimum duration (Evidence A) 1
  • 3 months after achieving target serum urate in patients without tophi 1, 3
  • 6 months after achieving target serum urate in patients with resolution of previously detected tophi 1, 3

When to Initiate Prophylaxis

• Start prophylaxis when initiating urate-lowering therapy, as acute gout attack rates are high in the first 6 months of treatment 1

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Dosing in Renal Impairment

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

For acute gout treatment:

• No dose adjustment required for the initial treatment regimen 5
• Monitor closely for adverse effects 5
• Treatment courses should not be repeated more frequently than every 2 weeks in moderate impairment (CrCl 30-50 mL/min) 5

For prophylaxis:

• No dose adjustment required, but monitor closely 5

Severe Renal Impairment (CrCl <30 mL/min)

For acute gout treatment:

• Use single dose of 0.6 mg only 3, 5
• Do not repeat treatment course more than once every 2 weeks 5

For prophylaxis:

• Start with 0.3 mg once daily 3, 5
• Any dose increase requires close monitoring 5

Dialysis Patients

For acute gout treatment:

• Single dose of 0.6 mg only 3, 5
• Do not repeat more than once every 2 weeks 3, 5

For prophylaxis:

• Start with 0.3 mg twice weekly 5
• Monitor closely for toxicity 5

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Familial Mediterranean Fever (FMF)

For FMF, the usual adult dose is 1.2-2.4 mg/day in divided doses. 6

Dosing in Renal Impairment for FMF

• Mild to moderate impairment (CrCl 30-80 mL/min): Monitor closely; dose reduction may be necessary 5
• Severe impairment (CrCl <30 mL/min): Start with 0.3 mg/day; increase cautiously with monitoring 5
• Dialysis patients: Start with 0.3 mg/day; increase cautiously with monitoring 5

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Critical Drug Interactions Requiring Dose Adjustment

Absolute Contraindications (Do Not Use Colchicine)

• Strong CYP3A4 inhibitors (clarithromycin, erythromycin, ketoconazole, ritonavir, atazanavir) in patients with renal OR hepatic impairment 1, 5
• P-glycoprotein inhibitors (cyclosporine) in patients with renal OR hepatic impairment 1, 5
• Fatal colchicine toxicity has been reported with clarithromycin and cyclosporine 5, 6

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

With strong CYP3A4 or P-gp inhibitors:

• Acute gout: 0.6 mg × 1 dose, followed by 0.3 mg 1 hour later; do not repeat for 3 days 5
• Prophylaxis: Maximum 0.3 mg once daily 5
• FMF: Maximum 0.6 mg once daily (or 0.3 mg twice daily) 5

With moderate CYP3A4 inhibitors (diltiazem, verapamil, fluconazole, grapefruit juice):

• Acute gout: 1.2 mg × 1 dose only; do not repeat for 3 days 5
• Prophylaxis: Maximum 0.6 mg once daily (or 0.3 mg twice daily) 5
• FMF: Maximum 1.2 mg daily 5

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Hepatic Impairment

Mild to moderate hepatic impairment:

• No dose adjustment required for acute treatment or prophylaxis 5
• Monitor closely for adverse effects 5

Severe hepatic impairment:

• Acute gout: No dose adjustment needed, but do not repeat treatment course more than once every 2 weeks 5
• Prophylaxis: Consider dose reduction with careful monitoring 5
• FMF: Dose reduction should be considered 5

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Critical Safety Warnings

Toxicity Risk Factors

• Colchicine has a narrow therapeutic index with no clear distinction between toxic and lethal doses 6
• High fatality rates reported after acute ingestions exceeding 0.5 mg/kg 6
• Lowest reported lethal oral doses are 7-26 mg 6
• Risk factors for toxicity include renal impairment, hepatic impairment, drug interactions (especially with statins, CYP3A4 inhibitors, P-gp inhibitors), and advanced age 1, 6, 7

Combination with Statins

• Co-administration with statins increases risk of severe myopathy and rhabdomyolysis 6, 7
• Extra vigilance required in patients on both medications, particularly those with renal impairment 7

Signs of Toxicity

• Severe diarrhea, progressive muscle weakness, elevated CPK, axonal sensorimotor neuropathy 7
• Multi-organ dysfunction can occur, particularly in patients with renal impairment 6, 7

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Alternative Therapies When Colchicine is Contraindicated

For acute gout:

• NSAIDs at full FDA-approved doses (naproxen, indomethacin, sulindac) until complete resolution 1, 2, 3
• Oral corticosteroids: prednisone 30-35 mg/day for 3-5 days 2, 3
• Intra-articular corticosteroid injection for 1-2 joint involvement 1, 3

For prophylaxis:

• Low-dose NSAIDs (e.g., naproxen 250 mg twice daily) with proton pump inhibitor if indicated 1
• Low-dose prednisone or prednisolone (≤10 mg/day) only if colchicine and NSAIDs are contraindicated 1