What is the dosage for allopurinol (xanthine oxidase inhibitor) in the treatment of gout?

From the Guidelines

The recommended starting dosage of allopurinol for gout is typically 100 mg daily, which is then gradually increased by 100 mg increments every 2-4 weeks until the target serum uric acid level of less than 6 mg/dL is achieved, as recommended by the 2020 American College of Rheumatology guideline for the management of gout 1.

Key Considerations

• The usual maintenance dose ranges from 300-600 mg daily, though some patients may require up to 800 mg daily.
• For patients with kidney impairment, lower doses are necessary, starting at 50 mg daily with careful monitoring, as suggested by the 2012 American College of Rheumatology guidelines for management of gout 1.
• Allopurinol should be taken with food to minimize gastrointestinal upset, and adequate hydration is important during treatment.
• The medication works by inhibiting xanthine oxidase, the enzyme responsible for converting xanthine to uric acid, thereby reducing uric acid production and preventing crystal formation in joints.

Important Recommendations

• Allopurinol is recommended as the first-line urate-lowering therapy (ULT) for gout, including for those with moderate-to-severe chronic kidney disease (CKD; stage ≥3) 1.
• A treat-to-target management strategy with ULT dose titration guided by serial serum urate measurements, with an SU target of <6 mg/dl, is strongly recommended 1.
• When initiating ULT, concomitant anti-inflammatory prophylaxis therapy for a duration of at least 3–6 months is strongly recommended to prevent acute gout attacks during the first few months of treatment 1.

Additional Guidance

• Prior to initiation of allopurinol, rapid, PCR-based HLA-B5801 screening should be considered as a risk management component in sub-populations where both HLA-B5801 allele frequency is elevated and the HLA-B*5801 positive subjects have a very high hazard ratio for severe allopurinol hypersensitivity reaction, as suggested by the 2012 American College of Rheumatology guidelines for management of gout 1.
• Combination oral ULT, with one xanthine oxidase inhibitor agent and one uricosuric agent, is appropriate when the serum urate target has not been met by appropriate dosing of an xanthine oxidase inhibitor, as recommended by the 2012 American College of Rheumatology guidelines for management of gout 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 average is 200 to 300 mg/day for patients with mild gout and 400 to 600 mg/day for those with moderately severe tophaceous gout The minimal effective dosage is 100 to 200 mg daily and the maximal recommended dosage is 800 mg daily To reduce the possibility of flare-up of acute gouty attacks, it is recommended that the patient start with a low dose of allopurinol tablets (100 mg daily) and increase at weekly intervals by 100 mg until a serum uric acid level of 6 mg/dL or less is attained but without exceeding the maximal recommended dosage.

The dosage for allopurinol in gout is:

• Minimal effective dosage: 100 to 200 mg daily
• Average dosage:
  • 200 to 300 mg/day for patients with mild gout
  • 400 to 600 mg/day for those with moderately severe tophaceous gout
• Maximal recommended dosage: 800 mg daily
• Initial dosage: 100 mg daily, increased at weekly intervals by 100 mg until a serum uric acid level of 6 mg/dL or less is attained 2

From the Research

Allopurinol Dosage in Gout

The dosage for allopurinol in gout is a crucial aspect of treatment, as it can impact the risk of adverse events such as allopurinol hypersensitivity syndrome (AHS).

• A study published in 2012 3 found that starting allopurinol at a dose of 1.5 mg per unit of estimated glomerular filtration rate (GFR) may be associated with a reduced risk of AHS.
• The study suggested that in patients who tolerate allopurinol, the dose can be gradually increased to achieve the target serum urate level.
• However, the optimal dosage for allopurinol in gout patients, particularly those with renal impairment, is still a topic of debate.
• Other studies have compared the efficacy and safety of allopurinol with febuxostat, another urate-lowering therapy, in patients with gout and hyperuricemia 4, 5, 6.
• A study published in 2020 6 found that febuxostat may be more renoprotective than allopurinol in patients with both hyperuricemia and chronic kidney disease (CKD).
• However, more research is needed to determine the optimal dosage for allopurinol in gout patients, particularly those with renal impairment.

Key Considerations

• The dosage of allopurinol should be adjusted based on the patient's renal function and tolerance.
• Patients with renal impairment may require lower doses of allopurinol to minimize the risk of AHS.
• The goal of treatment is to achieve a target serum urate level, which may require gradual increases in the dose of allopurinol.
• Further research is needed to determine the optimal dosage for allopurinol in gout patients, particularly those with renal impairment.