What is the recommended dosage of colchicine (Colcrys) for treating acute gout attacks and chronic gout prevention?

Colchicine Dosing for Gout

Acute Gout Flare Treatment

For acute gout attacks, administer colchicine 1.2 mg at the first sign of flare, followed by 0.6 mg one hour later (total 1.8 mg over one hour), then continue 0.6 mg once or twice daily until the attack resolves. 1, 2

Critical Timing Requirements

• Treatment must be initiated within 36 hours of symptom onset for colchicine to be effective; efficacy significantly decreases beyond this timeframe. 1, 3
• Ideally, start within 12 hours of symptom onset for maximum benefit. 4, 3
• Consider a "pill in the pocket" approach for fully informed patients to self-medicate at the first warning symptoms. 4

Evidence for Low-Dose Regimen

• The low-dose regimen (1.8 mg total) is as effective as high-dose colchicine (4.8 mg over 6 hours) for achieving 50% or greater pain reduction at 24 hours, with a number needed to treat (NNT) of 5. 1, 5
• High-dose regimens provide no additional benefit but substantially increase gastrointestinal toxicity (diarrhea, nausea, vomiting), with a number needed to harm (NNTH) of 2. 1, 5
• The older regimen of 0.5 mg every 2 hours until relief or toxicity is obsolete and causes severe diarrhea in most patients. 1

Continuation Dosing

• After the initial loading doses, continue with 0.6 mg once or twice daily (beginning 12 hours after the initial doses) until the gout attack resolves, typically within a few days. 1, 4

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Prophylaxis of Gout Flares

For prevention of gout flares, the recommended dose is 0.6 mg once or twice daily, with a maximum dose of 1.2 mg/day. 1, 2

When to Initiate Prophylaxis

• Start prophylaxis with or just prior to initiating urate-lowering therapy (allopurinol, febuxostat, pegloticase). 1, 3
• An increase in gout flares commonly occurs after starting urate-lowering therapy due to mobilization of urate from tissue deposits. 2

Duration of Prophylaxis

• Continue prophylaxis for at least 6 months during urate-lowering therapy. 1, 3
• Alternative approach: continue for 3 months after achieving target serum urate if no tophi are detected on physical exam, or 6 months after achieving target if tophi are present. 1

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Special Populations and Dose Adjustments

Severe Renal Impairment (eGFR <30 mL/min)

• Avoid colchicine in patients with severe renal impairment. 1, 4
• If absolutely necessary, reduce to a single dose of 0.6 mg with no repeat treatment for at least two weeks. 1
• For patients on dialysis, administer a single dose of 0.6 mg and do not repeat before two weeks. 1
• Glucocorticoids are the preferred first-line treatment over colchicine in this population. 1

Moderate Renal Impairment (eGFR 30-60 mL/min)

• Low-dose colchicine (1.2 mg followed by 0.6 mg one hour later) can be used if eGFR ≥30 mL/min. 1
• Reduce prophylactic dosing frequency and monitor closely for toxicity. 1

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Critical Drug Interactions

Absolute Contraindications

Colchicine is absolutely contraindicated with concurrent use of strong CYP3A4 and/or P-glycoprotein inhibitors, especially in patients with renal or hepatic impairment. 1, 4, 2

Strong CYP3A4/P-gp Inhibitors Requiring Dose Adjustment

If no alternative is available and patient has normal renal/hepatic function: 2

• For acute gout treatment: Reduce to 0.6 mg × 1 dose, followed by 0.3 mg one hour later. Do not repeat for at least 3 days. 2
• For prophylaxis: Reduce to 0.3 mg once daily (maximum 0.6 mg/day given as 0.3 mg twice daily). 2

Specific Interacting Drugs

Major interactions requiring dose adjustment or avoidance include: 1, 2

• Clarithromycin, erythromycin, telithromycin
• Cyclosporine
• Ketoconazole, itraconazole
• Ritonavir, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, saquinavir, tipranavir
• Verapamil, diltiazem
• Nirmatrelvir/ritonavir (Paxlovid)

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Alternative Treatment Options

When Colchicine is Contraindicated

NSAIDs at full FDA-approved doses (naproxen, indomethacin, sulindac) until complete resolution of the attack. 1, 4

Oral corticosteroids: Prednisone 30-35 mg/day (or 0.5 mg/kg/day) for 3-10 days, then stopped or tapered over 7-10 days. 1, 4

Intra-articular corticosteroid injection for monoarticular or oligoarticular involvement (1-2 large joints). 1, 4

Combination Therapy for Severe Attacks

• For severe attacks involving multiple large joints or polyarticular arthritis, combination therapy with colchicine and NSAIDs provides synergistic anti-inflammatory effects. 4
• If administering colchicine during ongoing prophylaxis, give up to 1.2 mg followed by 0.6 mg one hour later, then wait 12 hours before resuming prophylactic dosing. 2

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Common Pitfalls to Avoid

• Delaying treatment beyond 36 hours significantly reduces colchicine effectiveness. 1, 3
• Using high-dose regimens (>1.8 mg in first hour) provides no additional benefit but substantially increases gastrointestinal toxicity. 1, 5
• Failing to adjust dose in renal impairment or with interacting medications can lead to life-threatening toxicity; fatal colchicine toxicity has been reported with clarithromycin. 1, 2
• Not screening for drug interactions with CYP3A4/P-glycoprotein inhibitors before prescribing. 1
• Discontinuing prophylaxis too early when starting urate-lowering therapy leads to recurrent flares. 3
• Using colchicine as an analgesic for pain from other causes; it is not an analgesic medication. 2