What is the use of Allopurinol (Zyloprim)?

From the Guidelines

Allopurinol is the preferred first-line treatment for gout, with a starting dose of 100 mg daily, which can be gradually increased to 300-600 mg daily depending on uric acid levels and kidney function, as recommended by the 2020 American College of Rheumatology guideline for the management of gout 1.

Key Points

• Allopurinol works by reducing the production of uric acid in the body by inhibiting the enzyme xanthine oxidase.
• The goal of treatment is to lower serum urate levels to <6 mg/dL, with a target of <5 mg/dL in some cases.
• Patients should be aware that allopurinol may temporarily increase gout flares, so colchicine or an anti-inflammatory medication is often prescribed concurrently for the first 3-6 months.
• Common side effects include rash, gastrointestinal upset, and headache, while rare but severe hypersensitivity reactions can occur, particularly in patients with certain genetic markers (HLA-B*5801) more common in Asian populations.

Important Considerations

• Dose adjustments are necessary for those with kidney impairment, with a starting dose of less than 100 mg daily in moderate to severe chronic kidney disease (CKD) 1.
• Regular monitoring of uric acid levels and liver and kidney function is recommended during treatment.
• Allopurinol should be taken with food to minimize stomach upset, and patients should maintain adequate hydration.

Alternative Treatments

• Febuxostat is an alternative treatment option for patients who are intolerant or unresponsive to allopurinol, with a starting dose of 40 mg daily and a maximum dose of 120 mg daily 1.
• Uricosurics, such as benzbromarone, may be used in combination with allopurinol or as an alternative treatment option in some cases.

From the FDA Drug Label

THIS IS NOT AN INNOCUOUS DRUG. IT IS NOT RECOMMENDED FOR THE TREATMENT OF ASYMPTOMATIC HYPERURICEMIA. Allopurinol tablets reduce serum and urinary uric acid concentrations. 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 Asymptomatic hyperuricemia is not an indication for treatment with allopurinol tablets

The primary use of allopurinol is for the management of patients with:

• Gout (primary or secondary)
• Leukemia, lymphoma, and malignancies with elevated uric acid levels
• Recurrent calcium oxalate calculi with high uric acid excretion It is not recommended for the treatment of asymptomatic hyperuricemia 2 2

From the Research

Allopurinol Overview

• Allopurinol is a commonly used medication for the treatment of gout and hyperuricemia.
• It works by reducing the production of uric acid in the body, which can help to prevent the formation of urate crystals and reduce the risk of gout attacks.

Efficacy and Safety

• A study published in 2011 found that increasing the dose of allopurinol above the recommended dose based on creatinine clearance was effective and safe in patients with chronic gout, including those with renal impairment 3.
• Another study published in 2017 compared the efficacy of allopurinol and febuxostat in lowering serum uric acid levels in patients with gout and found that febuxostat was more effective than allopurinol in achieving target serum urate levels 4.
• A systematic review published in 2020 found that febuxostat may be more renoprotective than allopurinol in patients with hyperuricemia and chronic kidney disease, but the evidence was limited by the small number of studies and the risk of bias 5.

Comparative Effectiveness

• A double-blind noninferiority trial published in 2022 found that allopurinol was noninferior to febuxostat in controlling gout flares and achieving target serum urate levels in patients with gout, including those with stage 3 chronic kidney disease 6.
• A review article published in 2015 discussed the advances in pharmacotherapy for the treatment of gout, including the use of allopurinol, febuxostat, and other medications, and highlighted the importance of achieving a therapeutic serum urate target for effective gout management 7.

Renal Impairment

• The study published in 2011 found that increasing the dose of allopurinol above the recommended dose based on creatinine clearance was safe and effective in patients with renal impairment 3.
• The systematic review published in 2020 found that febuxostat may be more renoprotective than allopurinol in patients with hyperuricemia and chronic kidney disease, but the evidence was limited by the small number of studies and the risk of bias 5.
• The double-blind noninferiority trial published in 2022 found that allopurinol was noninferior to febuxostat in controlling gout flares and achieving target serum urate levels in patients with gout, including those with stage 3 chronic kidney disease 6.