In an adult with an acute gout flare and no major NSAID contraindications, should indomethacin or colchicine be used as first‑line therapy, and what are the appropriate dosing regimens?

Indomethacin vs Colchicine for Acute Gout Flare

For an adult with an acute gout flare and no major NSAID contraindications, either indomethacin or colchicine is equally appropriate as first-line therapy; the choice should be driven by timing of presentation and patient-specific factors rather than superiority of one agent over the other. 1, 2

Evidence-Based Treatment Selection Algorithm

Timing-Based Decision Point

• If presenting within 36 hours of symptom onset: Colchicine is a viable option with the FDA-approved regimen of 1.2 mg immediately followed by 0.6 mg one hour later, then 0.6 mg once or twice daily starting 12 hours after the second dose until attack resolves. 1, 2

• If presenting beyond 36 hours of symptom onset: Colchicine effectiveness drops significantly; indomethacin at full anti-inflammatory doses becomes the preferred choice. 2, 3

• Optimal efficacy window: Both agents work best when initiated within 24 hours of symptom onset. 2, 3

Patient-Specific Contraindications That Favor One Over the Other

Choose corticosteroids (NOT indomethacin) if:

• Severe renal impairment (CrCl <30 mL/min) – NSAIDs can precipitate acute kidney injury 2, 4
• Cardiovascular disease or heart failure – NSAIDs carry cardiovascular risks 2, 4
• Active peptic ulcer disease or recent GI bleeding – NSAIDs increase bleeding risk 2, 4
• Cirrhosis or hepatic impairment – NSAIDs are contraindicated 4
• Current anticoagulation therapy – NSAIDs increase bleeding risk 2, 4

Choose indomethacin (NOT colchicine) if:

• Severe renal impairment (CrCl <30 mL/min) – colchicine carries fatal toxicity risk 2, 3
• Concurrent use of strong CYP3A4 inhibitors (clarithromycin, erythromycin, ketoconazole) or P-glycoprotein inhibitors (cyclosporine) – absolute contraindication to colchicine 1, 3
• Combined hepatic-renal insufficiency – colchicine should not be prescribed 5

Comparative Efficacy and Safety Profile

Colchicine advantages:

• Low-dose regimen (1.8 mg total over 1 hour) achieves equal efficacy to high-dose colchicine (4.8 mg) with significantly fewer gastrointestinal adverse effects (27% vs 63% compared to indomethacin). 2, 3
• Number needed to treat (NNT) of 5 for achieving 50% or greater pain reduction at 24 hours. 3
• Can be safely combined with NSAIDs for severe polyarticular attacks. 3

Indomethacin advantages:

• No strict timing window – effective beyond 36 hours of symptom onset. 2, 3
• FDA-approved at full anti-inflammatory doses for acute gout. 2
• No dose adjustment needed for mild-to-moderate renal impairment (though caution required). 5

Specific Dosing Regimens

Colchicine (FDA-approved):

• Loading: 1.2 mg immediately, then 0.6 mg one hour later (total 1.8 mg over 1 hour) 1, 2, 3
• Maintenance: Wait 12 hours after second loading dose, then 0.6 mg once or twice daily until attack resolves 2, 3
• Critical caveat: Only use if symptom onset was ≤36 hours prior to treatment initiation 2, 3

Indomethacin:

• Full FDA-approved anti-inflammatory doses until complete attack resolution 2, 3
• Continue at full dose throughout the attack rather than early dose reduction 2
• Typical dosing: 50 mg three times daily for 3 days, then 25 mg three times daily for up to 9 days 6

When Neither Agent is Appropriate

Use oral corticosteroids (prednisone 30-35 mg daily for 5 days) when:

• Both NSAIDs and colchicine are contraindicated due to renal impairment, cardiovascular disease, or drug interactions 1, 2, 4
• Patient has multiple contraindications to both agents 4
• Level A evidence supports corticosteroids as equally effective as NSAIDs with fewer adverse effects 4

Common Pitfalls to Avoid

• Do NOT use high-dose colchicine regimens (the obsolete 0.5 mg every 2 hours until relief or toxicity) – this causes severe diarrhea in most patients with no additional benefit. 3

• Do NOT delay treatment beyond 24 hours – efficacy of all agents drops markedly. 2, 3

• Do NOT combine indomethacin with systemic corticosteroids – synergistic gastrointestinal toxicity. 3

• Do NOT interrupt ongoing urate-lowering therapy during an acute attack if patient is already on it. 4, 3

• Do NOT use colchicine in patients on strong CYP3A4/P-glycoprotein inhibitors – this combination dramatically increases colchicine plasma concentrations and risk of fatal toxicity. 1, 3

Combination Therapy for Severe Attacks

• For severe acute gout with polyarticular involvement (≥4 joints) or multiple large joints, initial combination therapy with colchicine + indomethacin is appropriate and provides synergistic anti-inflammatory effects. 3

• Acceptable combinations include: colchicine + NSAIDs, oral corticosteroids + colchicine, or intra-articular steroids + any oral modality. 4, 3