What are the indications for using allopurinol (Zyloprim) in patients with hyperuricemia?

From the Guidelines

Allopurinol is indicated for patients with recurrent gout attacks, tophi, joint damage, or kidney stones caused by uric acid, as well as for those with hyperuricemia secondary to blood cancers or chemotherapy. The primary indications for allopurinol use include:

• Recurrent gout attacks (typically two or more attacks per year) 1
• Tophi 1
• Joint damage attributable to gout 1
• Kidney stones caused by uric acid 1
• Hyperuricemia secondary to blood cancers or chemotherapy (tumor lysis syndrome)
• Recurrent uric acid kidney stones even without gout

According to the 2020 American College of Rheumatology guideline for the management of gout 1, allopurinol is recommended for patients with:

• Frequent gout flares (≥2/year)
• Radiographic damage attributable to gout
• 1 or more subcutaneous tophi
• CKD stage ≥3, SU >9 mg/dl, or urolithiasis, even after the first flare

The typical starting dose of allopurinol is 100 mg daily, gradually increasing to 300-600 mg daily based on serum uric acid levels, with a target level below 6 mg/dL 1. Patients with renal impairment require dose reduction. Treatment is generally lifelong for gout patients. Allopurinol works by inhibiting xanthine oxidase, the enzyme responsible for converting xanthine to uric acid, thereby reducing uric acid production. Patients should be warned that allopurinol can initially increase gout flares, so prophylaxis with colchicine or NSAIDs is recommended during the first 3-6 months of therapy. Regular monitoring of liver and kidney function is necessary, and patients should be screened for HLA-B*5801 before starting therapy, particularly in high-risk populations, to prevent severe hypersensitivity reactions.

From the FDA Drug Label

Allopurinol tablets are indicated in:

1. the management of patients with signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis, and/or nephropathy).
2. the management of patients with leukemia, lymphoma and malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels
3. the management of patients with recurrent calcium oxalate calculi whose daily uric acid excretion exceeds 800 mg/day in male patients and 750 mg/day in female patients

The indications to use allopurinol are:

• Management of patients with signs and symptoms of primary or secondary gout
• Management of patients with leukemia, lymphoma, and malignancies who are receiving cancer therapy that causes elevations of serum and urinary uric acid levels
• Management of patients with recurrent calcium oxalate calculi whose daily uric acid excretion exceeds 800 mg/day in male patients and 750 mg/day in female patients 2

From the Research

Indications for Allopurinol Use

• Allopurinol is indicated for the treatment of hyperuricemia in gout, with a recommended dose of up to 800 mg/d 3
• It is considered a first-line drug for serum urate-lowering therapy in gout 3
• Allopurinol is effective in reducing the frequency of acute gout attacks and achieving target serum urate levels 4
• It is also used in patients with chronic kidney disease, although the long-term safety of elevating allopurinol dosages in these patients requires further study 3

Comparison with Other Urate-Lowering Drugs

• Allopurinol has been compared with febuxostat, benzbromarone, and probenecid in several studies, with similar efficacy and safety profiles 4, 5, 6
• Febuxostat may be more effective than allopurinol in achieving target serum urate levels, but allopurinol is noninferior to febuxostat in controlling flares 5
• Allopurinol has a similar incidence of adverse events compared to febuxostat, with a combined risk of adverse events of RR = 1.04 (95% CI 0.98,1.11) 6

Safety and Efficacy

• Allopurinol is generally well-tolerated, with a low risk of severe adverse reactions 7
• However, severe allopurinol hypersensitivity reactions can occur, and patients with a history of these reactions may require alternative treatments 7
• Allopurinol is safe and effective in patients with gout and hyperuricemia, including those with chronic kidney disease 5, 6