What is the dosing for allopurinol (xanthine oxidase inhibitor) in the treatment of hyperuricemia?

From the Guidelines

The recommended starting dose of allopurinol for hyperuricemia is 100 mg daily, which should be gradually increased by 100 mg every 2-5 weeks until the target serum uric acid level is achieved, as recommended by the 2012 American College of Rheumatology guidelines 1.

Key Considerations

• The dose can be raised above 300 mg daily, even with renal impairment, as long as this is accompanied by adequate patient education and monitoring for drug toxicity 1.
• Prior to initiation, consider HLA-B*5801 in selected patients, specifically in higher risk sub-populations for severe allopurinol hypersensitivity reaction 1.
• For patients with stage 4 or worse CKD, the starting dose should be 50 mg/day 1.

Monitoring and Adjustments

• Patients should be monitored for side effects including rash, which can indicate hypersensitivity, and liver function tests and complete blood counts should be performed periodically.
• The dose should be adjusted based on the patient's response and tolerance, with a goal of achieving the target serum uric acid level.

Comparison with Other Guidelines

• The 2017 EULAR guidelines also recommend adjusting the allopurinol dosage according to the creatinine clearance, and suggest that febuxostat may be a suitable alternative for patients with CKD 1.
• The 2006 EULAR guidelines recommend a starting dose of 100 mg daily, with gradual increases of 100 mg every 2-4 weeks until the target serum uric acid level is achieved 1.

From the FDA Drug Label

The dosage of allopurinol tablets to accomplish full control of gout and to lower serum uric acid to normal or near-normal levels varies with the severity of the disease. The minimal effective dosage is 100 to 200 mg daily and the maximal recommended dosage is 800 mg daily For the prevention of uric acid nephropathy during the vigorous therapy of neoplastic disease, treatment with 600 to 800 mg daily for 2 or 3 days is advisable together with a high fluid intake 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 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 dosing for allopurinol for hyperuricemia is as follows:

• Adults: 100 to 800 mg daily, with an average dose of 200 to 300 mg/day for mild cases and 400 to 600 mg/day for moderately severe cases
• Children 6 to 10 years: 300 mg daily for secondary hyperuricemia associated with malignancies
• Children under 6 years: 150 mg daily for secondary hyperuricemia associated with malignancies
• Renal impairment: dose reduction is necessary, with a daily dosage of 200 mg for creatinine clearance of 10 to 20 mL/min, and not exceeding 100 mg for creatinine clearance less than 10 mL/min 2 2

From the Research

Allopurinol Dosing for Hyperuricemia

• The dosing for allopurinol in patients with hyperuricemia varies depending on the patient's renal function and the severity of the condition 3, 4.
• A study published in 2013 found that most patients with gout attained target serum uric acid levels (<360 mmol/L) at a dose of 300 mg/day, but 30% of patients required further dose escalation up to 600 mg/day 3.
• Another study published in 2007 suggested that allopurinol dose reduction is necessary in patients with renal impairment to prevent adverse events, but also noted that this may lead to under-treatment of hyperuricemia 4.
• A study published in 2007 found that treatment with 300 mg/day allopurinol for three months significantly improved serum uric acid levels, glomerular filtration rate, and blood pressure in patients with hyperuricemia and normal renal function 5.

Factors Affecting Allopurinol Dosing

• Renal function is an important factor in determining the appropriate dose of allopurinol, as patients with impaired renal function may require lower doses to prevent adverse events 4.
• The presence of gout or other conditions that affect uric acid metabolism may also impact the dosing of allopurinol 3, 6.
• Comparison with other urate-lowering therapies, such as febuxostat, may also be necessary to determine the most effective treatment for individual patients 6, 7.

Comparison with Other Urate-Lowering Therapies

• A study published in 2018 found that febuxostat was effective in lowering serum uric acid levels in patients with chronic kidney disease who were refractory to allopurinol treatment 6.
• Another study published in 2017 found that febuxostat was more effective than allopurinol in achieving target serum uric acid levels in patients with gout and hyperuricemia 7.