What is the first‑line medication for an acute gout flare in a typical adult without contraindications?

First-Line Medication for Active Gout

For a typical adult without contraindications experiencing an acute gout flare, NSAIDs at full FDA-approved doses, colchicine (1.2 mg followed by 0.6 mg one hour later), or oral corticosteroids (prednisone 30–35 mg daily for 5 days) are equally effective first-line options, with the critical determinant of success being initiation within 24 hours of symptom onset rather than which specific agent is chosen. 1, 2, 3

Treatment Selection Algorithm

The choice among the three first-line options should be guided by:

• Timing of presentation: If the patient presents within 36 hours of symptom onset, colchicine remains highly effective; beyond this window, colchicine efficacy drops sharply and NSAIDs or corticosteroids should be selected instead 1, 2

• Renal function: In patients with severe renal impairment (eGFR <30 mL/min), oral corticosteroids are the safest option, as both colchicine and NSAIDs should be avoided 1, 3

• Cardiovascular disease: Corticosteroids are preferred over NSAIDs in patients with heart failure, uncontrolled hypertension, or significant cardiovascular disease, as NSAIDs carry cardiovascular risks 1, 3

• Gastrointestinal risk: Corticosteroids are the preferred choice in patients with peptic ulcer disease, active GI bleeding, or those on anticoagulation, as NSAIDs increase bleeding risk 1, 2, 3

• Drug interactions: Colchicine is absolutely contraindicated in patients receiving strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, cyclosporine, ketoconazole, ritonavir, verapamil), especially when any degree of renal or hepatic impairment is present 1, 2

Specific Dosing Regimens

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 1, 2
• Continue at full dose throughout the entire attack until complete resolution—do not taper early, as this markedly reduces efficacy 1, 2
• No single NSAID has demonstrated superior efficacy; selection should be based on availability and individual tolerance 2

Colchicine

• 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, 2, 4
• After a 12-hour pause, resume maintenance dosing of 0.6 mg once or twice daily until the attack resolves 1, 2
• 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, 2
• Must be started within 36 hours of symptom onset for optimal efficacy 1, 2

Oral Corticosteroids

• Prednisone 30–35 mg daily for 5 days (fixed-dose regimen, no taper needed for short courses) 1, 3
• Alternative regimen: prednisone 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 1
• Level A evidence supports corticosteroids as equally effective as NSAIDs and colchicine, with potentially fewer adverse effects 1

Alternative Routes for Specific Scenarios

• Intra-articular corticosteroid injection is highly effective for monoarticular or oligoarticular involvement of one or two large, accessible joints (e.g., triamcinolone acetonide 40 mg for the knee, 20–30 mg for the ankle), providing targeted anti-inflammatory control with minimal systemic exposure 1, 3

• Parenteral glucocorticoids (intramuscular triamcinolone acetonide 60 mg or IV methylprednisolone) are strongly recommended over IL-1 inhibitors when oral medications cannot be taken 1

Combination Therapy for Severe Attacks

For severe acute gout involving ≥4 joints or multiple large joints, initial combination therapy provides synergistic anti-inflammatory effects and is more effective than monotherapy 1, 2:

• Acceptable combinations include: oral corticosteroids + colchicine, intra-articular steroids + any oral modality, or colchicine + NSAIDs 1, 2
• Avoid combining systemic NSAIDs with systemic corticosteroids due to synergistic gastrointestinal toxicity 2

Critical Timing Considerations

The single most important factor determining treatment success is early initiation—within 12–24 hours of symptom onset. 1, 2, 3 Delays beyond 24 hours markedly reduce the effectiveness of all agents, regardless of which medication is chosen. For colchicine specifically, initiation after 36 hours is ineffective and should be avoided. 1, 2

Common Pitfalls to Avoid

• Delaying treatment is the most critical error; early intervention is the primary determinant of success, not agent selection 1, 3

• Early dose reduction of NSAIDs compromises treatment success—maintain full dose throughout the entire attack 1, 2

• Using colchicine in severe renal impairment (CrCl <30 mL/min) or with strong CYP3A4/P-gp inhibitors can cause fatal toxicity 1, 2

• Attempting the obsolete high-dose colchicine regimen (0.5 mg every 2 hours) provides no additional benefit and causes severe diarrhea in most patients 1, 2

• Stopping urate-lowering therapy (allopurinol, febuxostat) during an acute flare if the patient is already taking it—these should be continued without interruption 1, 3