From the Guidelines
Urate levels should be maintained below 6 mg/dL (360 mmol/L) to prevent gout attacks and complications, with a lower target of <5 mg/dL (300 mmol/L) for patients with severe gout, as recommended by the 2016 updated EULAR evidence-based recommendations for the management of gout 1. To manage high urate levels, lifestyle modifications are recommended, including:
- Limiting purine-rich foods (red meat, organ meats, seafood)
- Reducing alcohol consumption (especially beer)
- Maintaining a healthy weight
- Staying hydrated Medications to lower urate levels include:
- Allopurinol (starting at 100mg daily, gradually increasing to 300-600mg daily)
- Febuxostat (40-80mg daily)
- Probenecid (250mg twice daily, increasing to 500mg twice daily) During acute gout attacks, anti-inflammatory medications like colchicine (0.6mg once or twice daily), NSAIDs, or corticosteroids are used for symptom relief, as supported by high-strength evidence from the American College of Physicians clinical practice guideline 1. Regular monitoring of urate levels is essential to ensure treatment effectiveness and prevent complications like kidney stones and chronic kidney disease, with a treat-to-target strategy recommended to maintain urate levels below the saturation point for MSU to dissolve all crystal deposits 1. The use of prophylactic colchicine or NSAIDs for more than 8 weeks is also recommended to reduce the risk for acute gout attacks in patients initiating urate-lowering therapy, as supported by high-strength evidence from the American College of Physicians clinical practice guideline 1.
From the FDA Drug Label
It is an inhibitor of xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine and of xanthine to uric acid, the end product of purine metabolism in man. The etiology of this hyperuricemia is the overproduction of uric acid in relation to the patient's ability to excrete it Administration of allopurinol tablets generally results in a fall in both serum and urinary uric acid within 2 to 3 days. Allopurinol tablets reduce both the serum and urinary uric acid levels by inhibiting the formation of uric acid
- Urate levels are reduced by allopurinol through the inhibition of xanthine oxidase, an enzyme responsible for the conversion of hypoxanthine to xanthine and xanthine to uric acid.
- The reduction in urate levels occurs within 2 to 3 days of administration of allopurinol tablets and can be manipulated based on the dose.
- Allopurinol tablets can substantially reduce serum and urinary uric acid levels, even in patients with renal damage 2
From the Research
Urate Overview
- Urate is a key component in the development of gout, a common form of acute inflammatory arthritis caused by the deposition of monosodium urate crystals within the synovium of joints 3
- The goal of urate-lowering therapy is to prevent gout flares by reducing serum uric acid levels, with a target of less than 6 mg/dL 4
Urate-Lowering Therapies
- Xanthine-oxidase inhibitors, such as allopurinol and febuxostat, are commonly used to lower serum uric acid levels 3, 4
- Uricosuric agents, including probenecid, sulfinpyrazone, and benzbromarone, can also be used as adjuncts to xanthine-oxidase inhibitors 3, 5
- Febuxostat has been shown to be more effective than allopurinol in lowering serum uric acid levels, particularly in patients with renal dysfunction 4, 6
Treatment Outcomes
- Studies have demonstrated that febuxostat is a suitable pharmacological option for first-line treatment of gout, with established efficacy and safety 4, 6
- Allopurinol has been found to have worse persistence rates than febuxostat among patients with gout, suggesting that febuxostat may be a better option for long-term urate-lowering therapy 6
- The inhibition of xanthine oxidase overactivation has been shown to be an excellent therapeutic option to limit the harmful effects of excess urate and reactive oxygen species 7
Clinical Implications
- Early detection and careful management of hyperuricemia is required to prevent the development of gout and other systemic disorders, such as hypertension, obesity, and chronic kidney disease 7
- Urate-lowering therapy should be tailored to individual patient needs, taking into account comorbidities and patient preference 3, 5