What is the use of Allopurinol (Zyloprim)?

From the Guidelines

Allopurinol is recommended as a first-line treatment for gout, starting at a low dose of 100 mg daily and increasing by 100 mg increments every 2-4 weeks if required, to reach the uricaemic target of <6 mg/dL. This recommendation is based on the 2020 American College of Rheumatology guideline for the management of gout 1. The guideline suggests that allopurinol is the preferred first-line urate-lowering therapy (ULT), including for patients with moderate-to-severe chronic kidney disease (CKD).

Key Considerations

• The starting dose of allopurinol should be no greater than 100 mg daily, and start at 50 mg daily in patients with stage 4 or worse CKD 1.
• Allopurinol can be advanced above 300 mg daily to achieve the serum urate target, including in patients with CKD, with appropriate risk management 1.
• Patients should be educated on the potential risks of allopurinol, including the risk of severe hypersensitivity reaction, and monitored for drug toxicity 1.
• Regular monitoring of liver and kidney function is recommended during treatment with allopurinol 1.

Management of Gout

• Gout patients should receive full information and be fully involved in decision-making concerning the use of ULT 1.
• A treat-to-target strategy should be used, with ULT dose titration guided by serial serum urate measurements, and a target serum urate level of <6 mg/dL 1.
• Patients with severe gout, such as those with tophi or chronic arthropathy, may require a lower serum urate target of <5 mg/dL to achieve better disease control 1.

Side Effects and Interactions

• Common side effects of allopurinol include rash, nausea, and diarrhea 1.
• Rarely, a severe hypersensitivity reaction called allopurinol hypersensitivity syndrome can occur, particularly in patients with renal impairment or those taking thiazide diuretics 1.
• Allopurinol should be used with caution in patients with renal impairment, and the dose should be adjusted according to creatinine clearance 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 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 daily uric acid excretion It is not recommended for the treatment of asymptomatic hyperuricemia 2 2

From the Research

Allopurinol Efficacy and Tolerability

• Allopurinol is still the drug of choice for the long-term control of hyperuricemia in patients with gout 3.
• A study found that 70.4% of patients reached the treatment target using allopurinol 300 mg/day, and 92.5% reached the target after dose escalation up to 600 mg/day 3.
• The mean serum uric acid (SUc) reduction was significant at both 300 mg/day and 600 mg/day doses 3.

Comparison with Febuxostat

• Febuxostat was more effective than allopurinol in lowering serum urate levels in patients with gout 4.
• A study found that febuxostat reduced serum uric acid levels and slowed the progression of renal disease in patients with chronic kidney disease (CKD) compared to allopurinol 5.
• Another study found that febuxostat was associated with greater reduction in serum uric acid levels than allopurinol in patients with CKD, but showed no difference in renal function changes 6.

Dose Adjustment and Renal Function

• Published guidelines recommend adjusting allopurinol doses according to creatinine clearance, but a study found that this may not provide adequate control of hyperuricemia in patients with gout 7.
• A study found that switching from allopurinol to febuxostat was significantly associated with changes in estimated glomerular filtration rate (eGFR) in patients with CKD 5.
• Another study found that febuxostat and allopurinol showed no difference in renal function changes during study follow-up in patients with CKD 6.