What is the recommended acute and chronic management for an adult with gout, including medication choices, dosing, and lifestyle measures?

Gout Treatment: Acute and Chronic Management

Acute Gout Flare Management

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

First-Line Treatment Selection Algorithm

Step 1: Assess timing and contraindications

• If symptom onset >36 hours ago, do not use colchicine—select NSAID or corticosteroid instead 1, 2
• If eGFR <30 mL/min, use corticosteroids only; avoid NSAIDs and colchicine 1, 2
• If patient takes strong CYP3A4/P-glycoprotein inhibitors (clarithromycin, cyclosporine, ketoconazole, ritonavir, verapamil), colchicine is absolutely contraindicated 1, 2
• If heart failure, significant cardiovascular disease, cirrhosis, or active peptic ulcer present, avoid NSAIDs and use corticosteroids 1

Step 2: Choose agent based on patient factors

• NSAIDs: Naproxen 500 mg twice daily, indomethacin 50 mg three times daily, or sulindac 200 mg twice daily at full dose throughout entire attack 1
• Colchicine (if ≤36 hours from onset): 1.2 mg loading dose, then 0.6 mg one hour later (total 1.8 mg); after 12-hour pause, give 0.6 mg once or twice daily until resolution 1, 2
• Corticosteroids: Prednisone 30–35 mg daily for 5 days (no taper needed) or 0.5 mg/kg/day for 5–10 days 1, 2
• Intra-articular injection: For 1–2 large accessible joints, triamcinolone 40 mg (knee) or 20–30 mg (ankle) 1, 2

Combination Therapy for Severe Attacks

For polyarticular gout (≥4 joints) or multiple large joints, initiate combination therapy with colchicine + NSAID, oral corticosteroid + colchicine, or intra-articular steroid + any oral agent. 1, 2

• Avoid combining systemic NSAID with systemic corticosteroid due to synergistic gastrointestinal toxicity 1, 2

Critical Timing Considerations

• Maximum benefit occurs when treatment starts within 12–24 hours; delays beyond 24 hours markedly reduce effectiveness of all agents 1, 2
• Colchicine effectiveness drops sharply after 36 hours from symptom onset 1, 2

Common Pitfalls in Acute Management

• Do not taper NSAIDs early—maintain full dose throughout entire attack 1, 2
• Do not use obsolete high-dose colchicine regimens (0.5 mg every 2 hours); they cause severe diarrhea without added benefit 1, 2
• Do not stop existing urate-lowering therapy (allopurinol/febuxostat) during an acute flare 1, 2

---

Chronic Gout Management: Urate-Lowering Therapy

Indications to Initiate Urate-Lowering Therapy

Strong indications (start after first flare):

• Subcutaneous tophi present 1, 2
• Radiographic joint damage from gout 1, 2
• Chronic kidney disease stage ≥3 1, 3, 2

Conditional indications (consider after first flare):

• ≥2 gout attacks per year 1, 3
• Serum urate >9 mg/dL 1, 3
• Patient preference for early intervention 1, 2
• Age <40 years at disease onset 2
• Urolithiasis 3, 2

Do not initiate urate-lowering therapy after a single uncomplicated first attack in most patients. 1

Allopurinol: First-Line Urate-Lowering Agent

Initiation and titration protocol:

• Start at 100 mg daily (or 50 mg daily if CrCl 30–50 mL/min) 1, 4, 2
• Increase by 100 mg every 2–4 weeks until serum urate <6 mg/dL 1, 4, 2
• Typical maintenance dose: 300–600 mg daily; maximum 800 mg daily 4, 2
• Target serum urate: <6 mg/dL for all patients; <5 mg/dL for severe gout with tophi or chronic arthropathy 1, 2

Critical safety consideration: Starting allopurinol at high doses (e.g., 300 mg) significantly increases risk of acute flares and hypersensitivity syndrome 1, 2

Mandatory Flare Prophylaxis During Urate-Lowering Therapy Initiation

When starting allopurinol or febuxostat, provide colchicine 0.6 mg once or twice daily for at least 6 months to prevent acute flares. 1, 3, 2

• Duration: Continue for 3 months after achieving target urate if no tophi present; 6 months if tophi present 3, 2
• Evidence: Colchicine prophylaxis reduces flare rates from 77% to 33% during allopurinol initiation 2
• Alternative prophylaxis (if colchicine contraindicated): Low-dose NSAID with proton-pump inhibitor, or low-dose prednisone <10 mg/day 2

Alternative Urate-Lowering Agents

Febuxostat:

• Indicated when allopurinol fails to achieve target or is not tolerated 2, 5
• Start 40 mg daily, titrate to 80 mg (maximum 120 mg) to reach target 2
• Does not require renal dose adjustment in mild-to-moderate CKD 2

Probenecid (uricosuric):

• For patients with normal renal function and no urolithiasis history 1, 6
• Start 250 mg twice daily for one week, then 500 mg twice daily 6
• May increase by 500 mg every 4 weeks (maximum 2000 mg/day) 6
• Contraindicated if CrCl <30 mL/min 1, 6

Pegloticase:

• Reserved for severe, debilitating chronic tophaceous gout refractory to all other therapies at maximal doses 2, 7
• 8 mg IV every 2 weeks 7
• Requires premedication with antihistamines and corticosteroids; high anaphylaxis risk 7

---

Lifestyle and Non-Pharmacologic Measures

Dietary modifications (all patients):

• Limit: Alcohol (especially beer), sugar-sweetened beverages, high-fructose foods, organ meats, shellfish 1, 5
• Encourage: Low-fat dairy products, coffee, vegetables, cherries 1, 2
• Weight loss if obese and regular physical activity 1, 2

Medication review:

• Replace loop or thiazide diuretics when possible 1, 2
• Consider losartan for hypertension (increases uric acid excretion) 1, 5
• Use statins or fenofibrate for hyperlipidemia 2

Important caveat: Dietary modifications alone typically lower serum urate by only 10–18% and are insufficient as sole therapy for patients with frequent flares 3

---

Special Populations and Drug Interactions

Severe Renal Impairment (eGFR <30 mL/min)

• Acute flare: Use corticosteroids only; colchicine and NSAIDs contraindicated 1, 2
• Chronic management: Start allopurinol at 50 mg daily; titrate slowly with close monitoring 4, 2

Patients on Strong CYP3A4/P-glycoprotein Inhibitors

• Absolute contraindication to colchicine when combined with clarithromycin, erythromycin, cyclosporine, ketoconazole, ritonavir, or verapamil—especially with any renal or hepatic impairment 1, 2
• Risk of fatal colchicine toxicity, multiorgan failure, and death 2

Patients on Anticoagulation (e.g., Apixaban)

• Colchicine and allopurinol are safe with apixaban; no pharmacokinetic interaction 2
• Avoid NSAIDs due to additive bleeding risk 2
• Colchicine preferred for flare prophylaxis in anticoagulated patients 2

---

Monitoring and Long-Term Management

Serum urate monitoring:

• Check every 2–4 weeks while titrating allopurinol 2
• Consider discontinuing urate-lowering therapy if serum urate rises above 6 mg/dL on two consecutive measurements, particularly during pegloticase therapy 7

Duration of urate-lowering therapy:

• Continue indefinitely to maintain serum urate <6 mg/dL 1, 2
• After 6+ months without flares and normal urate levels, may cautiously reduce dose by 500 mg every 6 months, but do not allow urate to rise 6

Avoid maintaining serum urate <3 mg/dL long-term 2