What is the first‑line treatment for an adult with an acute gout attack, including dosing and alternatives for contraindications?

Treatment of Acute Gout

For an adult with an acute gout attack, initiate treatment within 24 hours using NSAIDs, colchicine, or corticosteroids as equally appropriate first-line monotherapy options, with selection based on renal function, cardiovascular risk, and gastrointestinal comorbidities. 1

First-Line Monotherapy Options

NSAIDs

• Use full FDA-approved anti-inflammatory doses (naproxen 500 mg twice daily, indomethacin 50 mg three times daily, or sulindac 200 mg twice daily) and maintain this dose throughout the entire attack until complete resolution. 1, 2
• No single NSAID has proven superior efficacy; selection depends on availability and patient tolerance. 1, 3
• Contraindications include: severe renal impairment (eGFR <30 mL/min), active or recent gastrointestinal bleeding, heart failure, cirrhosis, and concurrent anticoagulation. 2, 4

Colchicine

• Administer 1.2 mg orally at the first sign of flare, followed by 0.6 mg one hour later (total 1.8 mg over one hour), then wait 12 hours before resuming 0.6 mg once or twice daily until the attack resolves. 1, 2, 5
• Colchicine is only effective when started within 36 hours of symptom onset; efficacy drops sharply beyond this window. 1, 2
• Absolute contraindications: concurrent use of strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, cyclosporine, ketoconazole, ritonavir, verapamil), especially in patients with any degree of renal or hepatic impairment. 1, 2, 5
• Severe renal impairment (CrCl <30 mL/min) is an absolute contraindication due to fatal toxicity risk. 2
• In moderate renal impairment (CrCl 30-80 mL/min), use the standard acute regimen with close monitoring, then reduce prophylactic dosing to 0.6 mg once daily. 2

Corticosteroids

• Prednisone 0.5 mg/kg per day (approximately 30-35 mg daily) for 5-10 days at full dose then stop, OR 2-5 days at full dose followed by a 7-10 day taper. 1, 4
• Corticosteroids are the safest first-line option in patients with severe renal impairment, cardiovascular disease, heart failure, cirrhosis, peptic ulcer disease, or those on anticoagulation. 4
• Intramuscular triamcinolone acetonide 60 mg is an alternative for patients unable to take oral medications. 4
• Intra-articular corticosteroid injection (triamcinolone 40 mg for knee, 20-30 mg for ankle) is excellent for monoarticular or oligoarticular involvement of accessible large joints. 1, 4

Combination Therapy for Severe Attacks

For severe acute gout with polyarticular involvement (≥4 joints) or multiple large joints, initiate combination therapy with colchicine plus NSAIDs, oral corticosteroids plus colchicine, or intra-articular steroids plus any oral modality. 1, 2

• Avoid combining NSAIDs with systemic corticosteroids due to synergistic gastrointestinal toxicity. 2
• Combination therapy provides synergistic anti-inflammatory effects by targeting different inflammatory pathways. 2

Critical Timing Considerations

• Maximum therapeutic benefit occurs when treatment begins within 12-24 hours of symptom onset; delaying beyond 24 hours markedly reduces effectiveness of all agents. 2
• For colchicine specifically, do not initiate after 36 hours from symptom onset. 1, 2

Management of Ongoing Urate-Lowering Therapy

Do not discontinue ongoing allopurinol or febuxostat during an acute flare; continuation maintains serum urate control and does not worsen the attack. 2

Prophylaxis When Initiating Urate-Lowering Therapy

• Provide colchicine prophylaxis (0.6 mg once or twice daily) for at least 6 months when starting or adjusting urate-lowering therapy to prevent recurrent flares. 2, 5, 6
• Continue prophylaxis for 3 months after achieving target serum urate (<6 mg/dL) if no tophi present, or 6 months if tophi present. 2
• Alternative prophylaxis options include low-dose NSAIDs with proton pump inhibitor or low-dose prednisone (<10 mg/day) as second-line. 2, 4

Clinical Algorithm for Drug Selection

1. Assess renal function: If eGFR <30 mL/min, choose corticosteroids as first-line. 4
2. Evaluate cardiovascular risk: If heart failure or significant cardiovascular disease, avoid NSAIDs; choose colchicine or corticosteroids. 2, 4
3. Check gastrointestinal risk: If active ulcer, recent bleeding, or high bleeding risk, avoid NSAIDs; choose colchicine or corticosteroids. 2, 4
4. Review medication list: If patient takes strong CYP3A4/P-gp inhibitors, colchicine is absolutely contraindicated; choose NSAIDs or corticosteroids. 2, 5
5. Consider timing: If >36 hours since symptom onset, colchicine is ineffective; choose NSAIDs or corticosteroids. 1, 2
6. Assess severity: If polyarticular or severe attack, consider combination therapy. 1, 2

Common Pitfalls to Avoid

• Never use high-dose colchicine regimens (>1.8 mg in first hour); they provide no additional benefit but substantially increase gastrointestinal toxicity. 2
• Never attempt dose reduction of colchicine as a "compromise" in patients with renal impairment taking CYP3A4/P-gp inhibitors; even a single 0.6 mg dose carries unacceptable toxicity risk. 2
• Never taper NSAIDs early; maintain full dose throughout the entire attack. 1, 2
• Never use high-dose prednisone (>10 mg/day) for prophylaxis during urate-lowering therapy initiation. 2, 4
• Never stop urate-lowering therapy during an acute flare if the patient is already on it. 2

Monitoring Response

• Define inadequate response as <20% improvement in pain within 24 hours OR <50% improvement at ≥24 hours after initiating therapy. 2, 4
• If inadequate response occurs, consider alternative diagnoses or switch to another monotherapy or add a second agent. 4