What is the recommended first‑line treatment for an acute gout flare, including dosing of NSAIDs, colchicine, and glucocorticoids, and alternative options when NSAIDs are contraindicated (e.g., chronic kidney disease, heart failure, gastric ulcer disease, or aspirin use)?

Acute Gout Flare Management

First-Line Treatment Selection

For acute gout flares, initiate treatment within 24 hours of symptom onset using NSAIDs, colchicine, or corticosteroids as monotherapy, with selection based on renal function, cardiovascular disease, gastrointestinal risk, and drug interactions. 1, 2

Treatment Algorithm by Patient Characteristics

For patients WITHOUT contraindications:

• NSAIDs at full FDA-approved anti-inflammatory doses (naproxen, indomethacin, or sulindac) until complete attack resolution 1, 2, 3
• Continue at full dose throughout the attack rather than early dose reduction 2, 3
• No single NSAID is superior to others for efficacy 2

For patients with renal impairment (CrCl <30 mL/min), heart failure, cirrhosis, peptic ulcer disease, or on anticoagulation:

• Prednisone 30-35 mg daily for 5 days (no taper needed for straightforward monoarticular cases) 2, 3, 4
• Alternative: 0.5 mg/kg/day for 5-10 days at full dose then stop, OR 2-5 days at full dose followed by 7-10 day taper 2, 3
• Level A evidence demonstrates corticosteroids are equally effective as NSAIDs with fewer adverse effects in high-risk patients 3, 4

For patients presenting within 36 hours of symptom onset (if NSAIDs/steroids contraindicated):

• Colchicine 1.2 mg immediately, followed by 0.6 mg one hour later (total 1.8 mg over one hour) 1, 2, 3
• Wait 12 hours, then resume 0.6 mg once or twice daily until attack resolves 2, 3
• This low-dose regimen achieves 42% treatment success vs 17% placebo, with significantly fewer gastrointestinal side effects than high-dose regimens 2, 4

Critical Contraindications and Safety Warnings

ABSOLUTE contraindications to colchicine:

• Concurrent use of strong CYP3A4 inhibitors (clarithromycin, erythromycin, ketoconazole) or P-glycoprotein inhibitors (cyclosporine) - this combination can cause fatal toxicity 2, 3
• Severe renal impairment (GFR <30 mL/min) 2, 4
• Combined hepatic-renal insufficiency 2

AVOID NSAIDs in:

• Active or recent gastrointestinal bleeding 2
• Chronic kidney disease (CrCl <30 mL/min) 2, 3
• Heart failure or significant cardiovascular disease 2, 5
• Patients on anticoagulation 2

AVOID systemic corticosteroids in:

• Uncontrolled diabetes 3
• Active systemic infection 3
• Systemic fungal infections 4

Combination Therapy for Severe Attacks

For polyarticular gout (≥4 joints) or multiple large joints:

• Colchicine + NSAID provides synergistic anti-inflammatory effects targeting different pathways 2
• Oral corticosteroid + colchicine is an acceptable alternative 2
• NEVER combine NSAIDs with systemic corticosteroids due to synergistic gastrointestinal toxicity 2, 3

For monoarticular or oligoarticular involvement of accessible large joints:

• Intra-articular corticosteroid injection is an excellent option, with dose varying by joint size 2, 4
• Can be combined with any oral modality 2

Colchicine Dosing Adjustments in Renal Impairment

Mild to moderate renal impairment (CrCl 30-80 mL/min):

• Use standard loading dose (1.2 mg followed by 0.6 mg one hour later) with close monitoring 2
• Continue prophylactic dosing 0.6 mg once or twice daily after 12 hours 2

Severe renal impairment (CrCl <30 mL/min):

• Avoid colchicine entirely - use corticosteroids instead 2, 4
• If patient is already on prophylactic colchicine when attack occurs, take loading dose then wait 12 hours before resuming prophylactic dose 2

Critical Timing Considerations

Treatment effectiveness drops significantly after 36 hours:

• Colchicine should NOT be initiated beyond 36 hours of symptom onset 1, 2, 3
• Optimal efficacy occurs when treatment begins within 12-24 hours 1, 2, 4
• Delaying treatment beyond 24 hours markedly reduces efficacy 2

Management During Urate-Lowering Therapy

Do NOT interrupt ongoing urate-lowering therapy during an acute flare 1, 2

When initiating or adjusting urate-lowering therapy:

• Provide prophylaxis with colchicine 0.6 mg once or twice daily for at least 6 months 2, 3, 6
• Continue for 3 months after achieving target serum urate if no tophi present 2, 3
• Continue for 6 months after achieving target serum urate if tophi are present 2, 6
• Alternative prophylaxis: low-dose NSAID with proton pump inhibitor or low-dose prednisone (<10 mg/day) if colchicine contraindicated 2, 3

Common Pitfalls to Avoid

• Never use high-dose colchicine regimens (hourly dosing until diarrhea) - these are obsolete and cause severe toxicity without additional benefit 2, 4
• Never prescribe colchicine with strong CYP3A4/P-glycoprotein inhibitors - this can be fatal 2, 3
• Never reduce NSAID dose early - maintain full anti-inflammatory dose until complete resolution 2, 3
• Never delay treatment waiting for definitive diagnosis - early empiric treatment is critical 2, 4
• Never combine NSAIDs with systemic corticosteroids due to additive GI toxicity 2, 3