What is the recommended dosage and treatment regimen for colchicine (Colchicine) in patients with gout?

Colchicine Dosing for Gout

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), and this regimen must be initiated within 36 hours of symptom onset to be effective. 1

Acute Gout Treatment

Standard Dosing Regimen

• The FDA-approved dose is 1.2 mg (two tablets) followed by 0.6 mg (one tablet) one hour later, for a total of 1.8 mg over one hour. 1
• Higher doses have not been found to be more effective and cause significantly more gastrointestinal adverse events. 1
• This low-dose regimen (1.8 mg total) is as effective as the older high-dose regimens (4.8 mg) but with substantially fewer side effects—specifically, low-dose colchicine causes adverse events in only 26% of patients compared to 77% with high-dose regimens. 2, 3

Critical Timing Window

• Colchicine must be started within 12-36 hours of symptom onset for maximum effectiveness; efficacy decreases significantly beyond this timeframe. 2, 4
• Patients should be counseled to keep colchicine available and initiate treatment at the first sign of a flare ("pills in the pocket" approach). 5

Continuation After Acute Treatment

• After the initial 1.8 mg dose, wait 12 hours, then resume prophylactic dosing of 0.6 mg once or twice daily until the gout attack resolves. 2, 1
• The safety and efficacy of repeat treatment for gout flares within short intervals has not been established; do not repeat the acute treatment dose for at least 3 days. 1

Prophylaxis of Gout Flares

Standard Prophylactic Dosing

• The recommended dose for prophylaxis is 0.6 mg once or twice daily (maximum 1.2 mg/day). 1
• Prophylaxis should be initiated with or just prior to starting urate-lowering therapy (allopurinol, febuxostat, or pegloticase). 2, 1

Duration of Prophylaxis

• Continue prophylaxis for at least 6 months during urate-lowering therapy, or 3 months after achieving target serum urate if no tophi are present, or 6 months after achieving target serum urate if tophi are present. 2
• Prophylactic therapy may be beneficial for at least the first six months of uric acid-lowering therapy to prevent mobilization flares. 1

Dose Adjustments for Renal Impairment

Severe Renal Impairment (eGFR <30 mL/min)

• For patients with severe renal impairment, reduce the acute treatment dose to a single 0.6 mg dose with no repeat treatment for at least two weeks. 2, 4
• Colchicine should generally be avoided in severe renal impairment; glucocorticoids are the preferred first-line treatment in this population. 2
• For prophylaxis in severe renal impairment, reduce the dose to 0.3 mg once daily. 1

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

• The low-dose acute regimen (1.2 mg followed by 0.6 mg) can be used if eGFR ≥30 mL/min. 2
• Calculate eGFR immediately when considering colchicine for acute gout to guide dosing decisions. 2

Dialysis Patients

• Administer a single dose of 0.6 mg and do not repeat before two weeks. 2

Critical Drug Interactions

Absolute Contraindications

• Colchicine is absolutely contraindicated with strong P-glycoprotein and/or CYP3A4 inhibitors in patients with renal or hepatic impairment. 2, 1
• Strong CYP3A4 inhibitors include: clarithromycin, ketoconazole, itraconazole, ritonavir, atazanavir, indinavir, nelfinavir, saquinavir, and telithromycin. 1

Required Dose Adjustments with Moderate Inhibitors

• If patients are taking moderate CYP3A4 or P-glycoprotein inhibitors (cyclosporine, diltiazem, verapamil, erythromycin), dose reduction is required. 2, 1
• For acute treatment with strong inhibitors (if no alternative available): reduce to 0.6 mg × 1 dose, followed by 0.3 mg one hour later; do not repeat for at least 3 days. 1
• For prophylaxis with strong inhibitors: reduce to maximum 0.3 mg once daily (or 0.3 mg twice daily if original dose was higher). 1

Alternative Treatments When Colchicine is Contraindicated

NSAIDs

• Full FDA-approved doses of NSAIDs until complete resolution of symptoms are recommended as an alternative. 2
• However, NSAIDs carry risks of gastrointestinal bleeding and potential cardiovascular toxicity, particularly problematic since gout often co-exists with cardiovascular disease. 6

Corticosteroids

• Oral corticosteroids: prednisone 0.5 mg/kg/day (or 30-35 mg/day) for 5-10 days, then stopped or tapered over 7-10 days. 2
• Intra-articular corticosteroid injection is effective for involvement of 1-2 large joints (triamcinolone acetonide 10 mg resulted in pain relief within 48 hours in all patients in one study). 6, 2
• Systemic corticosteroids are preferred for severe polyarticular flares. 2

Common Pitfalls to Avoid

• Failing to start colchicine within 36 hours of symptom onset significantly reduces effectiveness. 2, 4
• Using high-dose colchicine regimens (the older 0.5 mg every 2 hours until diarrhea approach) causes severe gastrointestinal toxicity in the majority of patients without additional benefit. 6, 7, 3
• Not screening for drug interactions with CYP3A4/P-glycoprotein inhibitors can lead to life-threatening colchicine toxicity; fatal toxicity has been reported with clarithromycin. 2, 1
• Not adjusting doses in renal impairment increases risk of toxicity, as colchicine has a narrow therapeutic window. 2, 5
• Failing to provide prophylaxis when initiating urate-lowering therapy leads to increased flare frequency during the first 6 months. 2, 1