How can I lower my uric acid levels?

How to Lower Uric Acid Levels

For symptomatic hyperuricemia (gout), initiate urate-lowering therapy with allopurinol starting at 100 mg daily, titrating by 100 mg every 2-4 weeks until serum uric acid is below 6 mg/dL, combined with dietary modifications including limiting alcohol, red meat, and high-fructose corn syrup. 1, 2

When to Treat Elevated Uric Acid

Treat symptomatic hyperuricemia (gout) but not asymptomatic hyperuricemia:

• Initiate urate-lowering therapy after the first gout episode, particularly when serum uric acid is >9 mg/dL or there is no avoidable precipitant 1
• Mandatory treatment for patients with ≥2 gout attacks per year, tophi, chronic gouty arthropathy, radiographic changes, or uric acid kidney stones 2, 3
• Do NOT use uric acid-lowering agents in asymptomatic hyperuricemia to delay CKD progression 1

Pharmacological Approach

First-Line: Xanthine Oxidase Inhibitors

Allopurinol is the preferred first-line agent:

• Start at 100 mg daily and increase by 100 mg every 2-4 weeks until target achieved 2, 4
• Target serum uric acid <6 mg/dL for most patients; <5 mg/dL for severe gout with tophi 2, 3
• Average maintenance dose: 200-300 mg/day for mild gout, 400-600 mg/day for moderately severe tophaceous gout 4
• Maximum dose: 800 mg daily 4
• Critical adjustment in renal impairment: With creatinine clearance 10-20 mL/min use 200 mg daily; <10 mL/min use maximum 100 mg daily 4

Febuxostat as alternative:

• Switch to febuxostat if allopurinol is not tolerated or ineffective 1, 2
• The STOP-Gout trial showed allopurinol was noninferior to febuxostat in stage 3 CKD patients 1

Second-Line Options

• Uricosuric agents can be used if xanthine oxidase inhibitors are contraindicated, though xanthine oxidase inhibitors are preferred in CKD 1
• Combination therapy: Add a uricosuric agent to allopurinol/febuxostat for patients not reaching target on monotherapy 2

Preventing Acute Flares During Treatment

Prophylaxis is essential when starting urate-lowering therapy:

• Use colchicine 0.5-1 mg daily for the first 6 months of urate-lowering therapy 2, 3
• Alternative: Low-dose NSAIDs with gastroprotection 2
• Critical pitfall: Discontinuing therapy after symptom improvement leads to recurrence in 87% of patients within 5 years 3

Colchicine Dosing and Drug Interactions

• For acute flares: FDA-approved dosing is 1.2 mg followed by 0.6 mg one hour later 1
• Avoid concurrent use with potent CYP3A4 inhibitors (macrolide antibiotics, diltiazem, verapamil, itraconazole, ketoconazole, cyclosporine, ritonavir/nirmatrelvir) due to increased toxicity risk 1

Dietary and Lifestyle Modifications

Non-pharmacological interventions are foundational:

• Limit: Alcohol consumption, red meat, organ meats, high-fructose corn syrup, and sugar-sweetened beverages 1, 5
• Encourage: Low-fat dairy products, coffee, cherries, vegetables, nuts, legumes, whole grains 6, 5
• Weight reduction with daily exercise reduces uric acid levels and insulin resistance 5
• Maintain fluid intake sufficient for at least 2 liters daily urinary output 4

Addressing Comorbidities

Select medications with uricosuric properties when treating comorbidities:

• For hypertension: Consider losartan (has modest uricosuric effect) 6, 7
• For hyperlipidemia: Consider fenofibrate (has modest uricosuric effect) 6, 7
• Vitamin C supplementation may lower urate levels 5

Monitoring Strategy

Systematic monitoring ensures target achievement:

• Check serum uric acid every 2-4 weeks during dose titration 6
• Once stable, monitor regularly to maintain target <6 mg/dL (or <5 mg/dL for severe gout) 2, 6
• Monitor for acute flares and adverse effects throughout treatment 6
• Continue colchicine/anti-inflammatory prophylaxis until serum uric acid normalized and freedom from attacks for several months 4

Special Populations

CKD patients require specific considerations:

• Prefer xanthine oxidase inhibitors over uricosuric agents 1
• Adjust allopurinol dose based on creatinine clearance 4
• For acute flares in CKD: Use low-dose colchicine, intra-articular/oral glucocorticoids rather than NSAIDs 1
• Consider rheumatology co-management for acute and recurrent symptomatic gout 1