What is the recommended acute and chronic management for an adult with gout, including first‑line medications, dosing, and indications for urate‑lowering therapy?

Gout Treatment: Acute and Chronic Management

Acute Gout Flare: First-Line Pharmacologic Options

For an acute gout attack, initiate treatment within 24 hours using NSAIDs, colchicine, or corticosteroids as equally effective first-line monotherapy; select based on renal function, cardiovascular risk, and gastrointestinal comorbidities. 1, 2

NSAID Regimen

• Prescribe full FDA-approved anti-inflammatory doses: naproxen 500 mg twice daily, indomethacin 50 mg three times daily, or sulindac 200 mg twice daily 1, 2
• Continue the full dose throughout the entire attack until complete symptom resolution—do not taper early, as this markedly reduces efficacy 1, 2
• No single NSAID demonstrates superior efficacy; selection depends on availability and patient tolerance 2
• Contraindications: severe renal impairment (eGFR <30 mL/min), active GI bleeding, heart failure, cirrhosis, or anticoagulation therapy 1, 2, 3

Colchicine Regimen

• Administer 1.2 mg orally at symptom onset, followed by 0.6 mg one hour later (total 1.8 mg over one hour) 1, 2
• After a 12-hour pause, resume 0.6 mg once or twice daily until the attack resolves 1, 2
• Critical timing: colchicine must be started within 36 hours of symptom onset—efficacy drops sharply beyond this window 1, 2
• This low-dose regimen achieves ~42% treatment success versus ~17% with placebo, with significantly fewer gastrointestinal adverse effects than high-dose protocols 2
• Absolute contraindications: concurrent use of strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, cyclosporine, ketoconazole, ritonavir, verapamil), especially with any degree of renal or hepatic impairment 2; severe renal impairment (CrCl <30 mL/min) 1, 2

Corticosteroid Regimen

• Prescribe prednisone 0.5 mg/kg per day (approximately 30–35 mg daily) for 5–10 days at full dose then stop, or give 2–5 days at full dose followed by a 7–10 day taper 1, 4
• Corticosteroids provide efficacy equal to NSAIDs but with fewer adverse events (27% vs 63% with indomethacin) 4
• Preferred in: severe renal impairment, cardiovascular disease, heart failure, cirrhosis, peptic ulcer disease, or anticoagulation therapy 2, 4
• Intra-articular injection: for monoarticular or oligoarticular involvement of accessible large joints, inject triamcinolone acetonide 40 mg (knee) or 20–30 mg (ankle) 2, 4
• Intramuscular option: triamcinolone acetonide 60 mg IM for patients unable to take oral medications 2, 4

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Combination Therapy for Severe Attacks

For severe acute gout involving ≥4 joints or multiple large joints, initiate combination therapy with colchicine + NSAID, oral corticosteroid + colchicine, or intra-articular steroid + any oral agent. 2, 4

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

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Chronic Gout Management: Urate-Lowering Therapy (ULT)

Indications to Initiate ULT

Do not initiate ULT after a first gout attack or in patients with infrequent attacks (<2 per year). 1

Strongly recommend starting ULT after the first flare when any of these high-risk features are present:

• Subcutaneous tophi 2
• Radiographic joint damage attributable to gout 2
• Chronic kidney disease stage ≥3 2

Conditionally recommend initiating ULT after the first flare when:

• Patient preference for early intervention 2
• Young age at disease onset 2
• Serum urate >9 mg/dL 2
• Recurrent gout attacks (≥2 episodes per year) 1, 5

Allopurinol Initiation and Titration

• Start allopurinol at ≤100 mg daily (lower in CKD: 50–100 mg daily in renal impairment) 2
• Titrate upward by 100 mg every 2–4 weeks until serum urate falls below 6 mg/dL 2, 6
• This "go low, go slow" approach reduces the likelihood of gout flares and allopurinol-related hypersensitivity syndrome 2
• In CKD stage ≥3 (especially Korean populations), screen for HLA-B*58:01 allele before starting allopurinol, as this genotype markedly increases the risk of fatal hypersensitivity reactions 2

Febuxostat as Alternative

• Initiate febuxostat at ≤40 mg per day and titrate upward until serum urate <6 mg/dL 2
• Febuxostat is associated with increased all-cause and cardiovascular mortality compared to allopurinol, so it is not routinely recommended as first-line therapy 5

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Flare Prophylaxis During ULT Initiation

Provide colchicine prophylaxis (0.6 mg once or twice daily) for at least 6 months when starting or adjusting ULT to prevent acute flares. 1, 2

• Continue prophylaxis for at least 6 months, 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
• Alternative prophylaxis options if colchicine is contraindicated: low-dose NSAID with proton pump inhibitor, or low-dose prednisone (<10 mg/day) as second-line 2, 4
• Do not use high-dose prednisone (>10 mg/day) for prophylaxis, as this increases long-term corticosteroid complications without proportional benefit 2, 4

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Management During an Acute Flare in Patients Already on ULT

Do not discontinue ongoing urate-lowering therapy (allopurinol or febuxostat) when a patient experiences an acute gout flare. 2

• Continuation helps maintain serum urate control and does not worsen the attack 2
• Treat the acute flare with NSAIDs, colchicine, or corticosteroids as outlined above while continuing ULT 2

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Special Populations and Drug Interactions

Renal Impairment (CrCl 30–80 mL/min)

• Colchicine: use standard acute regimen (1.2 mg followed by 0.6 mg one hour later) with close monitoring; reduce prophylactic dose to 0.5–0.6 mg once daily 2
• NSAIDs: use with extreme caution and close renal monitoring 2
• Corticosteroids: no dose adjustment required—safest first-line option 2, 4

Severe Renal Impairment (CrCl <30 mL/min)

• Avoid colchicine entirely—risk of fatal toxicity 2
• Avoid NSAIDs—can precipitate or worsen acute kidney injury 2, 4
• Corticosteroids are the safest first-line option: prednisone 30–35 mg daily for 5 days 2, 4

Patients on Anticoagulation (e.g., Apixaban)

• Colchicine and allopurinol do not interact with apixaban and can be safely co-prescribed 2
• Apixaban is not a CYP3A4 or P-glycoprotein inhibitor, so it does not raise colchicine plasma concentrations 2
• Avoid NSAIDs in anticoagulated patients due to additive bleeding risk; colchicine is preferred for flare prophylaxis 2

Patients on Strong CYP3A4/P-gp Inhibitors (e.g., Verapamil, Clarithromycin)

• Colchicine is absolutely contraindicated when co-administered with verapamil, clarithromycin, cyclosporine, ketoconazole, or ritonavir, especially with any degree of renal or hepatic impairment—this combination can cause life-threatening toxicity, multiorgan failure, and death 2
• Use oral corticosteroids instead: prednisone 30–35 mg daily for 5 days 2

Diabetes Mellitus

• Corticosteroids cause transient hyperglycemia, but short-term courses (5–10 days) are safe and manageable 4
• Increase prandial insulin doses during the day; monitor blood glucose closely with proactive medication adjustments 4

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Common Pitfalls to Avoid

• Do not delay treatment beyond 24 hours—efficacy of all agents drops markedly 2
• Do not start colchicine after 36 hours from symptom onset—it becomes ineffective 1, 2
• Do not taper NSAIDs early—maintain full dose throughout the entire attack 1, 2
• Do not initiate ULT during an acute flare unless the patient is already on ULT 2
• Do not use high-dose colchicine regimens (>1.8 mg in first hour)—they provide no additional benefit but substantially increase gastrointestinal toxicity 2
• Do not combine NSAIDs with systemic corticosteroids—synergistic GI toxicity 2
• Do not omit colchicine prophylaxis when starting ULT—this markedly raises the risk of acute flares during the first 6 months 2