What are effective medications for managing gout?

Effective Medications for Managing Gout

For acute gout attacks, NSAIDs, colchicine, or corticosteroids are equally effective first-line options, while for long-term management, allopurinol is the primary urate-lowering therapy to prevent recurrent attacks. 1, 2

Acute Gout Attack Treatment

First-Line Medication Options

All three medication classes—NSAIDs, colchicine, and corticosteroids—have high-strength evidence supporting their effectiveness for acute gout, and the choice depends primarily on patient-specific contraindications rather than superiority of one agent over another. 1, 2

NSAIDs

• Use full FDA-approved anti-inflammatory doses until complete resolution of the attack. 1, 3
• FDA-approved options include naproxen, indomethacin, and sulindac, though other NSAIDs at analgesic doses are likely equally effective. 1, 3
• Indomethacin dosing: 50 mg three times daily for 2-3 days, then 25 mg three times daily for 3-5 days until resolution. 3
• Initiate treatment within 24 hours of symptom onset for optimal effectiveness. 1, 3
• Contraindications include severe renal impairment (GFR <30 mL/min), active GI bleeding, heart failure, and cirrhosis. 1, 3

Colchicine

• Low-dose regimen: 1.2 mg at first sign of flare, followed by 0.6 mg one hour later (total 1.8 mg), then 0.6 mg once or twice daily until attack resolves. 1, 4, 5
• This low-dose regimen is as effective as the older high-dose regimen (4.8 mg) but with significantly fewer gastrointestinal side effects. 1, 4
• Only effective if started within 36 hours of symptom onset; effectiveness drops significantly beyond this window. 1, 4, 5
• Absolute contraindications: concurrent use of strong CYP3A4 inhibitors (clarithromycin, ketoconazole) or P-glycoprotein inhibitors (cyclosporine), and severe renal impairment (GFR <30 mL/min). 4, 5

Corticosteroids

• Oral prednisone: 0.5 mg/kg per day (approximately 30-35 mg for average adults) for 5-10 days at full dose then stop, OR 2-5 days at full dose followed by 7-10 day taper. 1, 2
• Corticosteroids should be considered first-line therapy in patients with contraindications to NSAIDs (renal disease, heart failure, GI bleeding risk) because they are safer and lower cost. 1, 2
• Alternative routes: Intramuscular triamcinolone acetonide 60 mg for patients unable to take oral medications, or intra-articular injection for 1-2 large joint involvement. 1, 2
• Contraindications include systemic fungal infections, uncontrolled diabetes, and immunocompromised state. 2

Combination Therapy for Severe Attacks

• For severe pain with polyarticular involvement, initial combination therapy is appropriate, such as oral corticosteroids plus colchicine, or intra-articular steroids with any oral agent. 1, 2, 4
• Avoid combining NSAIDs with systemic corticosteroids due to synergistic gastrointestinal toxicity risk. 4

Long-Term Urate-Lowering Therapy

Indications for Starting Urate-Lowering Therapy

Urate-lowering therapy is indicated in patients with recurrent acute attacks (≥2 per year), arthropathy, tophi, radiographic changes of gout, or history of nephrolithiasis. 1

First-Line Urate-Lowering Agent

• Allopurinol is the confirmed first-line urate-lowering therapy with proven long-term effectiveness (effect size 1.39). 1
• Start at 100 mg daily and titrate upward to achieve target serum uric acid <6.0 mg/dL (<357 µmol/L). 1, 6
• Allopurinol can be safely initiated during an acute gout attack without prolonging the attack, as long as appropriate anti-inflammatory therapy is provided. 7

Alternative Urate-Lowering Agents

• If allopurinol toxicity occurs, options include other xanthine oxidase inhibitors (febuxostat), allopurinol desensitization, or uricosuric agents. 1
• Benzbromarone is more effective than allopurinol (effect size 1.50) and can be used in mild to moderate renal insufficiency, but carries hepatotoxicity risk. 1
• Probenecid is reserved for allopurinol-allergic patients with normal renal function and no history of urolithiasis. 8

Prophylaxis During Urate-Lowering Therapy Initiation

An acute gout attack often occurs when starting urate-lowering therapy due to mobilization of urate from tissue deposits; therefore, prophylaxis is essential. 1, 5

Prophylaxis Options

• First-line: Colchicine 0.5-1 mg daily (0.6 mg once or twice daily in US) for at least 6 months after initiating urate-lowering therapy. 1, 5
• Duration should be at least 8 weeks, but preferably 3-6 months or longer until serum uric acid is at target and patient is flare-free. 1
• Second-line: Low-dose NSAID with gastroprotection if indicated, or low-dose prednisone (<10 mg/day) if colchicine and NSAIDs are contraindicated. 1, 2

Lifestyle Modifications

Non-pharmacological management is essential and includes weight loss if obese, reduced alcohol consumption (especially beer), low animal purine diet, and treatment of associated comorbidities. 1

• If gout is associated with diuretic use, discontinue the diuretic if possible. 1
• Encourage consumption of vegetables and low-fat dairy products. 9
• Avoid beverages sweetened with high-fructose corn syrup. 9

Critical Pitfalls to Avoid

• Never delay treatment beyond 24-36 hours of symptom onset—effectiveness drops significantly. 1, 4, 3
• Do not interrupt ongoing urate-lowering therapy during an acute attack; continue it while treating the acute inflammation. 2, 3
• Do not use the obsolete high-dose colchicine regimen (0.5 mg every 2 hours)—it causes severe diarrhea without additional benefit. 4
• Do not use high-dose prednisone (>10 mg/day) for prophylaxis during urate-lowering therapy initiation. 2, 3
• Do not start urate-lowering therapy without concurrent prophylaxis—this will trigger acute attacks. 1, 5