What is the use of allopurinol (Zyloprim) in the treatment of hyperuricemia?

From the Guidelines

Allopurinol should be started at a low dose of 100 mg daily and titrated upward to achieve a serum urate target of less than 6 mg/dL, with dose adjustments based on creatinine clearance in patients with renal impairment, as recommended by the 2016 updated EULAR evidence-based recommendations for the management of gout 1. The standard starting dose of allopurinol is typically 100 mg daily, which can be gradually increased to 300-600 mg daily depending on uric acid levels and clinical response.

• For patients with kidney impairment, lower doses are recommended, with the maximum dose adjusted to creatinine clearance.
• Allopurinol should be taken with food to minimize stomach upset, and patients should drink plenty of fluids while taking this medication.
• Common side effects include rash, stomach upset, and liver function abnormalities.
• Rarely, a severe hypersensitivity reaction called allopurinol hypersensitivity syndrome can occur, characterized by fever, rash, and organ damage.
• This medication is also used to prevent tumor lysis syndrome in patients undergoing chemotherapy and to prevent recurrent kidney stones caused by high uric acid.
• When starting allopurinol, patients may experience an initial increase in gout attacks, so colchicine or an anti-inflammatory medication is often prescribed concurrently for the first few months of therapy. The 2016 updated EULAR evidence-based recommendations for the management of gout also recommend that allopurinol be used as first-line therapy in patients with normal kidney function, with febuxostat or a uricosuric as alternative options if allopurinol is not tolerated or if the serum urate target cannot be achieved 1. In patients with renal impairment, the maximum dose of allopurinol should be adjusted to creatinine clearance, and febuxostat or benzbromarone may be considered as alternative options if the serum urate target cannot be achieved with allopurinol alone 1.

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

Allopurinol is used to treat conditions such as gout, leukemia, lymphoma, and malignancies that cause high levels of uric acid. It works by reducing serum and urinary uric acid concentrations. The use of allopurinol should be individualized for each patient and requires an understanding of its mode of action and pharmacokinetics.

• Key Indications:
  • Primary or secondary gout
  • Leukemia, lymphoma, and malignancies with elevated uric acid levels
  • Recurrent calcium oxalate calculi with high uric acid excretion 2 2

From the Research

Allopurinol Overview

• Allopurinol is a commonly used urate-lowering therapy in gout treatment 3
• It works by reducing serum urate levels, which can help prevent gout attacks and other related complications

Dosage and Safety

• The starting dose of allopurinol is a risk factor for allopurinol hypersensitivity syndrome (AHS), a rare but potentially fatal adverse event 3
• A proposed safe starting dose of allopurinol is 1.5 mg per unit of estimated glomerular filtration rate (eGFR) 3
• Increasing the dose of allopurinol above the proposed creatinine clearance-based dose can be effective and safe in patients with chronic gout, including those with renal impairment 4

Comparison with Febuxostat

• Allopurinol and febuxostat are both effective in achieving serum urate goals in patients with gout 5
• Allopurinol was found to be noninferior to febuxostat in controlling flares in a 72-week trial 5
• Switching from allopurinol to febuxostat can reduce serum uric acid levels and slow the progression of renal disease in patients with chronic kidney disease 6

Effect on Renal Function

• Allopurinol treatment can improve kidney function in hyperuricemic patients, especially those with higher initial eGFR 7
• A retrospective cohort study found that allopurinol treatment resulted in a significant improvement in kidney function over an average of 3.4 years 7