What is the appropriate dosing for Allopurinol?

From the Guidelines

Allopurinol dosing should start at a low dose, typically 100 mg daily, and be gradually increased to an effective dose, usually between 300-600 mg daily, taken orally in single or divided doses, with adjustments based on serum uric acid levels and renal function, as recommended by the most recent guidelines 1.

Initial Dosing

• Start with 100 mg once daily
• Increase by 100 mg every 2-5 weeks as needed, as suggested by the 2012 American College of Rheumatology guidelines 1
• Maximum dose: above 300 mg daily, even with renal impairment, as long as accompanied by adequate patient education and monitoring for drug toxicity 1

Adjusting Dosing

• Adjust dosing based on serum uric acid levels, aiming for a target <6 mg/dL
• Lower starting doses (50 mg daily) are recommended for patients with stage 4 or worse CKD, as indicated by the 2012 American College of Rheumatology guidelines 1

Important Considerations

• Take with food to reduce gastrointestinal upset
• Ensure adequate hydration to prevent uric acid crystallization
• Monitor liver and renal function regularly
• Be aware of potential drug interactions, especially with azathioprine and mercaptopurine
• Prior to initiation, consider HLA-B*5801 in selected patients, specifically in higher risk sub-populations for severe allopurinol hypersensitivity reaction, as recommended by the 2012 American College of Rheumatology guidelines 1 Allopurinol works by inhibiting xanthine oxidase, the enzyme responsible for uric acid production. Gradual dose escalation helps minimize the risk of acute gout flares that can occur when uric acid levels change rapidly. The medication may take several weeks to months to reach full effectiveness in lowering uric acid levels. Although other studies, such as the 2017 EULAR evidence-based recommendations for the management of gout 1 and the 2014 multinational evidence-based recommendations for the diagnosis and management of gout 1, provide additional guidance on gout management, the 2012 American College of Rheumatology guidelines 1 provide the most specific and relevant recommendations for allopurinol dosing.

From the FDA Drug Label

The dose of allopurinol tablets recommended for management of recurrent calcium oxalate stones in hyperuricosuric patients is 200 to 300 mg/day in divided doses or as the single equivalent With a creatinine clearance of 10 to 20 mL/min, a daily dosage of 200 mg of allopurinol tablets is suitable. When the creatinine clearance is less than 10 mL/min, the daily dosage should not exceed 100 mg. Children, 6 to 10 years of age, with secondary hyperuricemia associated with malignancies may be given 300 mg allopurinol tablets daily while those under 6 years are generally given 150 mg daily.

The appropriate dosing for Allopurinol is as follows:

• Adults: 200 to 300 mg/day in divided doses for hyperuricosuric patients, with adjustments based on serum uric acid levels and renal function.
• Renal impairment:
  • Creatinine clearance 10 to 20 mL/min: 200 mg daily
  • Creatinine clearance less than 10 mL/min: not to exceed 100 mg daily
• Children:
  • 6 to 10 years: 300 mg daily for secondary hyperuricemia associated with malignancies
  • Under 6 years: 150 mg daily for secondary hyperuricemia associated with malignancies 2

From the Research

Allopurinol Dosing

The appropriate dosing for Allopurinol can vary depending on several factors, including renal function and the presence of chronic kidney disease (CKD).

• The initial dose of Allopurinol is typically 100 mg/day, which can be increased by 100 mg every four weeks until the therapeutic goal is achieved or adverse effects occur 3.
• For patients with normal renal function, a dose of 300 mg/day is often sufficient to achieve the target serum uric acid concentration (SUc) of <6 mg/dl (360 micromol/L) 3.
• However, in patients with CKD, lower doses of Allopurinol may be more effective in achieving serum urate lowering, and the dose should be adjusted based on creatinine clearance rather than plasma creatinine levels 4, 5.
• Starting Allopurinol at a dose of 1.5 mg per unit of estimated GFR may be associated with a reduced risk of Allopurinol hypersensitivity syndrome (AHS) 6.
• Higher plasma oxypurinol concentrations may be required to achieve the therapeutic goal in patients with CKD, and doses up to 600 mg/day may be necessary in some cases 7.

Dosing Considerations

When determining the appropriate dose of Allopurinol, the following factors should be considered:

• Renal function: Patients with CKD may require lower doses of Allopurinol, and the dose should be adjusted based on creatinine clearance rather than plasma creatinine levels 4, 5.
• Serum uric acid levels: The dose of Allopurinol should be titrated to achieve the target SUc of <6 mg/dl (360 micromol/L) 3.
• Presence of AHS: Starting Allopurinol at a dose of 1.5 mg per unit of estimated GFR may be associated with a reduced risk of AHS 6.
• Tolerability: The dose of Allopurinol should be increased gradually to minimize the risk of adverse effects, such as gouty flares 3.