How should I manage an acute gout flare, including first‑line NSAIDs, colchicine, and corticosteroids, and what adjustments are needed for elderly patients, chronic kidney disease, or anticoagulation therapy?

Management of Acute Gout Flare

First-Line Treatment Selection

For most patients presenting with an acute gout flare, initiate therapy within 24 hours using NSAIDs, colchicine, or oral corticosteroids—selecting the agent based on renal function, cardiovascular risk, gastrointestinal comorbidities, and drug interactions. 1

Treatment Algorithm by Patient Characteristics

Renal Function:

• eGFR ≥60 mL/min: All three first-line options (NSAIDs, colchicine, corticosteroids) are appropriate; select based on other comorbidities 1
• eGFR 30–59 mL/min: Avoid NSAIDs due to acute kidney injury risk; use colchicine with dose reduction (0.6 mg once daily for prophylaxis) or corticosteroids 1, 2
• eGFR <30 mL/min: Oral prednisone 30–35 mg daily for 5 days is the only safe first-line option—both NSAIDs and colchicine are absolutely contraindicated due to fatal toxicity risk 1, 2, 3

Drug Interactions:

• If receiving strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, erythromycin, cyclosporine, ketoconazole, ritonavir, verapamil), colchicine is absolutely contraindicated—choose NSAIDs or corticosteroids instead 1

Cardiovascular Disease:

• Heart failure, established cardiovascular disease, or significant cardiac comorbidity: Prednisone 30–35 mg daily for 5 days is preferred over NSAIDs due to cardiovascular and fluid retention risks 1, 2, 3

Gastrointestinal Risk:

• Active peptic ulcer disease or recent GI bleeding: NSAIDs are absolutely contraindicated; use prednisone 30–35 mg daily for 5 days or colchicine (if no contraindications) 1, 2
• History of peptic ulcer disease: If NSAIDs are selected, add a proton-pump inhibitor 1

Anticoagulation Therapy:

• Patients on warfarin, apixaban, or other anticoagulants: Prednisone 30–35 mg daily for 5 days is preferred because NSAIDs increase bleeding risk 1

Hepatic Impairment:

• Cirrhosis or significant hepatic disease: NSAIDs are contraindicated; prednisone 30–35 mg daily for 5 days is the safest option 2, 3

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Specific Drug Regimens

NSAIDs (When Appropriate)

Use full FDA-approved anti-inflammatory doses for the entire attack without early tapering:

• Naproxen 500 mg twice daily 1
• Indomethacin 50 mg three times daily 1
• Sulindac 200 mg twice daily 1

Continue at full dose until complete resolution of the gout attack—reducing the dose early markedly compromises treatment success 1. No single NSAID has demonstrated superior efficacy; selection should be based on availability and individual tolerance 1.

Colchicine (When Appropriate)

Timing is critical: Colchicine must be started within 36 hours of symptom onset; efficacy declines sharply after this window and it should not be initiated beyond 36 hours 1.

Dosing regimen:

• Loading dose: 1.2 mg orally at the first sign of flare, followed 1 hour later by 0.6 mg (total 1.8 mg) 1, 3
• After a 12-hour pause: Resume 0.6 mg once or twice daily until the attack resolves 1

This low-dose regimen achieves ≥50% pain reduction (NNT = 3–5) and causes significantly fewer gastrointestinal adverse effects (23% diarrhea) compared with obsolete high-dose protocols (77% diarrhea) 1.

Absolute contraindications:

• Severe renal impairment (CrCl <30 mL/min) 1, 4
• Concurrent use of strong CYP3A4 or P-glycoprotein inhibitors, especially with any renal or hepatic impairment 1

Corticosteroids (When Appropriate)

Oral prednisone regimens (choose one):

• Fixed-dose (simplest): Prednisone 30–35 mg once daily for 5 days without taper 1, 2, 3
• Weight-based: Prednisone 0.5 mg/kg/day for 5–10 days at full dose then stop abruptly 1, 2
• Tapered (for severe attacks): Prednisone 0.5 mg/kg/day for 2–5 days at full dose, then taper over 7–10 days 1, 2

Prednisone is equally effective as NSAIDs and colchicine (Level A evidence) but results in fewer adverse events (27% vs 63% with indomethacin) 1, 2.

Intra-articular corticosteroid injection (for mono- or oligoarticular involvement of 1–2 large, accessible joints):

• Knee: Triamcinolone acetonide 40 mg 1, 2
• Ankle: Triamcinolone acetonide 20–30 mg 1, 2

Parenteral options (when oral route is not feasible):

• Intramuscular: Triamcinolone acetonide 60 mg single injection 1, 2
• Intravenous: Methylprednisolone 0.5–2.0 mg/kg (approximately 40–140 mg for most adults), repeat as clinically indicated 1, 2

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Combination Therapy for Severe or Polyarticular Attacks

For severe acute gout involving ≥4 joints or multiple large joints, initiate combination therapy:

• Colchicine + NSAID 1
• Oral corticosteroid + colchicine 1, 3
• Intra-articular steroid + any oral agent 1

Never combine systemic NSAIDs with systemic corticosteroids due to synergistic gastrointestinal toxicity 1.

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Special Populations

Elderly Patients

For elderly patients with multiple comorbidities (renal impairment, cardiovascular disease, GI risk):

• Prednisone 30–35 mg daily for 5 days is the safest first-line option 1, 2, 3
• Avoid NSAIDs due to increased risk of acute kidney injury, cardiovascular events, and GI bleeding 1, 4
• If colchicine is used, reduce prophylactic dose to 0.6 mg once daily in moderate renal impairment 1

Chronic Kidney Disease

CKD Stage 3 (eGFR 30–59 mL/min):

• Prednisone 30–35 mg daily for 5 days is preferred 1, 3
• If colchicine is selected, reduce dose to 0.6 mg once daily for prophylaxis with close monitoring 1
• Avoid NSAIDs due to acute kidney injury risk 1, 4

CKD Stage 4–5 (eGFR <30 mL/min):

• Prednisone 30–35 mg daily for 5 days is the only safe option—no dose adjustment required 1, 3
• Colchicine and NSAIDs are absolutely contraindicated 1, 4

Anticoagulation Therapy

For patients on warfarin, apixaban, rivaroxaban, or other anticoagulants:

• Prednisone 30–35 mg daily for 5 days is preferred because NSAIDs increase bleeding risk 1
• Colchicine is safe (no interaction with anticoagulants) if no other contraindications exist 1

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Management of Ongoing Urate-Lowering Therapy

If the patient is already receiving allopurinol or febuxostat, continue the urate-lowering therapy without interruption during the acute flare—discontinuation can worsen the attack and complicate long-term control 1, 5.

Do not initiate new urate-lowering therapy during an acute flare; wait until the flare has completely resolved, then start allopurinol 100 mg daily with colchicine prophylaxis (0.6 mg once or twice daily) for at least 6 months 1.

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Prophylaxis When Initiating Urate-Lowering Therapy

When starting allopurinol or febuxostat after the acute flare resolves:

• First-line prophylaxis: Colchicine 0.6 mg once or twice daily for at least 6 months 1, 6
• Second-line prophylaxis (if colchicine is contraindicated): Low-dose NSAID with a proton-pump inhibitor, or low-dose prednisone (<10 mg/day) 1, 3

Duration of prophylaxis:

• Continue for ≥6 months, or
• Continue for 3 months after achieving target serum urate <6 mg/dL if no tophi are present 1
• Continue for 6 months after achieving target serum urate <6 mg/dL if tophi are present 1

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Critical Timing Considerations

The optimal therapeutic window for any anti-inflammatory agent is within the first 12–24 hours of symptom onset—delays beyond 24 hours markedly reduce effectiveness 1.

Colchicine-specific timing:

• Most effective when started within 12 hours of symptom onset 1
• Should not be initiated after 36 hours from symptom onset; choose NSAIDs or corticosteroids instead 1

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Common Pitfalls to Avoid

• Do not delay treatment beyond 24 hours—effectiveness declines sharply 1
• Do not start colchicine after 36 hours from symptom onset 1
• Do not taper NSAIDs early—maintain full dose throughout the attack 1
• Do not combine colchicine with strong CYP3A4/P-gp inhibitors in patients with any renal or hepatic impairment due to fatal toxicity risk 1
• Do not use obsolete high-dose colchicine regimens (e.g., 0.5 mg every 2 hours); they cause severe diarrhea without added benefit 1
• Do not stop urate-lowering therapy during an acute flare if the patient is already on it 1, 5
• Do not use NSAIDs in severe renal impairment (eGFR <30 mL/min), heart failure, active peptic ulcer disease, or on anticoagulation therapy 1, 4
• Do not use high-dose prednisone (>10 mg/day) for prophylaxis—it increases adverse effects without additional benefit 1, 3