What is the recommended first‑line treatment for an acute gout flare in an otherwise healthy adult, and what alternatives and dosing should be used if NSAIDs are contraindicated?

Treatment of Acute Gout Flare

First-Line Therapy Selection

For an otherwise healthy adult with an acute gout flare, initiate treatment within 24 hours using NSAIDs, colchicine, or oral corticosteroids—all three are equally effective first-line options, with selection based on timing of presentation, renal function, cardiovascular risk, and gastrointestinal comorbidities. 1, 2

NSAID Regimen (When No Contraindications Exist)

• Use full FDA-approved doses: naproxen 500 mg twice daily, indomethacin 50 mg three times daily, or sulindac 200 mg twice daily, and maintain the full dose throughout the entire attack until complete resolution—do not taper early. 1, 2

• No single NSAID demonstrates superior efficacy; selection should be based on availability and individual tolerance. 1, 2

• NSAIDs are most effective when started within 24 hours of symptom onset; delays beyond this window markedly reduce effectiveness. 1, 2

Colchicine Regimen (When Started ≤36 Hours After Onset)

• Loading dose: 1.2 mg orally at the first sign of flare, followed 1 hour later by 0.6 mg (total 1.8 mg over one hour). 1

• After a 12-hour pause, resume maintenance dosing of 0.6 mg once or twice daily until the attack resolves. 1

• Critical timing constraint: Colchicine should not be started after 36 hours from symptom onset, as efficacy declines sharply beyond this window; maximum benefit occurs when initiated within 12 hours. 1

• This low-dose regimen achieves ≥50% pain reduction with a number needed to treat of 3–5 and causes significantly fewer gastrointestinal adverse effects (23% diarrhea) compared to obsolete high-dose protocols (77% diarrhea). 1

Oral Corticosteroid Regimen (Preferred When NSAIDs/Colchicine Contraindicated)

• Prednisone 0.5 mg/kg per day (approximately 30–35 mg daily) for 5–10 days at full dose then stop abruptly, or alternatively give for 2–5 days at full dose followed by a 7–10 day taper. 3

• Level A evidence supports oral corticosteroids as equally effective as NSAIDs with fewer adverse effects (27% vs 63% adverse event rate with indomethacin). 3

• Corticosteroids are the safest first-line option in patients with severe renal impairment (eGFR <30 mL/min), cardiovascular disease, heart failure, cirrhosis, or peptic ulcer disease. 3

When NSAIDs Are Contraindicated

Absolute Contraindications to NSAIDs

• Severe renal impairment (eGFR <30 mL/min)—NSAIDs can precipitate or worsen acute kidney injury. 3, 2

• Active or recent gastrointestinal bleeding. 1

• Heart failure or significant cardiovascular disease. 1, 2

• Cirrhosis or hepatic impairment. 3

• Patients on anticoagulant therapy (increased bleeding risk). 1

Alternative Treatment Algorithm When NSAIDs Contraindicated

Step 1: Assess timing and renal function

• If symptom onset ≤36 hours AND creatinine clearance ≥30 mL/min: Use colchicine regimen (1.2 mg followed by 0.6 mg one hour later, then 0.6 mg once or twice daily after 12-hour pause). 1

• If symptom onset >36 hours OR creatinine clearance <30 mL/min: Use oral corticosteroids (prednisone 30–35 mg daily for 5 days). 1, 3

Step 2: Check for colchicine contraindications

• Absolute contraindication: Concurrent use of strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, erythromycin, cyclosporine, ketoconazole, ritonavir, verapamil), especially with any degree of renal or hepatic impairment—this combination can cause fatal toxicity. 1

• Severe renal impairment (creatinine clearance <30 mL/min). 1

Step 3: If colchicine is contraindicated, use corticosteroids

• Oral prednisone 30–35 mg daily for 5 days (no taper needed for short course). 3

• For monoarticular or oligoarticular involvement of large, accessible joints: intra-articular corticosteroid injection (triamcinolone acetonide 40 mg for knee, 20–30 mg for ankle). 3

• For patients unable to take oral medications: intramuscular triamcinolone acetonide 60 mg. 3

Combination Therapy for Severe Attacks

• For polyarticular gout (≥4 joints) or severe attacks involving multiple large joints, initiate combination therapy: colchicine + NSAID, oral corticosteroid + colchicine, or intra-articular steroid + any oral agent. 1

• Avoid combining NSAIDs with systemic corticosteroids due to synergistic gastrointestinal toxicity. 1

Management of Ongoing Urate-Lowering Therapy

• Do not discontinue allopurinol or febuxostat during an acute flare if the patient is already receiving these agents; continue urate-lowering therapy and treat the flare separately. 1

• When initiating urate-lowering therapy after flare resolution, provide colchicine prophylaxis (0.6 mg once or twice daily) for at least 6 months to prevent recurrent flares. 1

Common Pitfalls to Avoid

• Delaying treatment beyond 24 hours of symptom onset—this markedly reduces effectiveness of all agents. 1, 2

• Starting colchicine after 36 hours from symptom onset—it will be ineffective. 1

• Using the obsolete high-dose colchicine regimen (0.5 mg every 2 hours)—this causes severe diarrhea in most patients with no additional benefit. 1

• Attempting dose reduction of colchicine in patients on CYP3A4/P-glycoprotein inhibitors—even a single 0.6 mg dose carries unacceptable toxicity risk. 1

• Tapering NSAIDs early—maintain full dose throughout the entire attack. 1, 2

• Prescribing NSAIDs to patients with renal impairment, heart failure, or on anticoagulation. 1, 2