What is the appropriate allopurinol dose for gout in a patient with hyperuricemia (uric acid 6.7) and impaired renal function (Glomerular Filtration Rate (GFR) 48)?

From the Guidelines

For a patient with gout, uric acid level of 6.7 mg/dL, and reduced kidney function (GFR 48 mL/min), I recommend starting allopurinol at a reduced dose of 100 mg daily, as suggested by the 2020 American College of Rheumatology guideline for the management of gout 1. This lower starting dose is necessary due to the moderate kidney impairment, as allopurinol and its active metabolite oxypurinol are primarily eliminated through the kidneys. After starting treatment, monitor uric acid levels monthly and kidney function every 3 months. The dose can be gradually increased by 100 mg increments every 2-4 weeks as needed to reach a target uric acid level below 6 mg/dL, with a maximum dose of 300 mg daily for this level of kidney function. Some key points to consider when managing gout include:

• Using a treat-to-target management strategy with ULT dose titration guided by serial serum urate measurements, with an SU target of <6 mg/dl 1
• Concomitant antiinflammatory prophylaxis therapy for a duration of at least 3–6 months when initiating ULT 1
• Lifestyle modifications, such as weight loss, avoidance of alcohol and sugar-sweetened drinks, and regular exercise, can also help reduce uric acid levels and prevent gout flares 1 Watch for side effects including rash, which could signal allopurinol hypersensitivity syndrome. Ensure adequate hydration and consider prescribing colchicine 0.6 mg daily for the first 3-6 months of allopurinol therapy to prevent gout flares that commonly occur when initiating urate-lowering therapy. Allopurinol works by inhibiting xanthine oxidase, the enzyme responsible for converting xanthine to uric acid, thereby reducing uric acid production and allowing existing urate crystals to dissolve over time. It is also important to note that the 2016 updated EULAR evidence-based recommendations for the management of gout suggest that allopurinol should be started at a low dose and then titrated upwards until the SUA target is reached, and that the maximum dosage should be adjusted to creatinine clearance in patients with renal impairment 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 Since allopurinol tablets and its metabolites are primarily eliminated only by the kidney, accumulation of the drug can occur in renal failure, and the dose of allopurinol tablets should consequently be reduced With a creatinine clearance of 10 to 20 mL/min, a daily dosage of 200 mg of allopurinol tablets is suitable.

The patient has a GFR of 48, which indicates renal impairment. The recommended dose for patients with mild gout is 200 to 300 mg/day. Considering the patient's renal impairment, a dose of 200 mg/day or less may be suitable, and the dose should be adjusted based on the patient's serum uric acid level.

• The patient's uric acid level is 6.7, which is slightly elevated.
• The goal is to reduce the uric acid level to 6 mg/dL or less.
• The patient should start with a low dose of 100 mg daily and increase at weekly intervals by 100 mg until the desired uric acid level is attained. 2

From the Research

Uric Acid and GFR Considerations

• The patient has a uric acid level of 6.7 mg/dL and a GFR of 48, indicating impaired kidney function.
• According to the studies, the target serum uric acid level for gout management is <6 mg/dL, or even lower (≤5 mg/dL) in patients with severe gout 3, 4.

Allopurinol Dosing for Gout

• Allopurinol is a commonly used urate-lowering therapy for gout, but its efficacy and safety compared to febuxostat are debated 3, 5, 6, 7, 4.
• The initial dose of allopurinol is typically 100 mg daily, with titration up to 800 mg daily as needed to achieve target serum uric acid levels 6.
• However, in patients with impaired kidney function, such as the one described (GFR 48), the dose of allopurinol may need to be adjusted to avoid adverse effects 6, 7.

Comparison with Febuxostat

• Febuxostat is another urate-lowering therapy that has been shown to be effective in reducing serum uric acid levels and preventing gout flares 3, 6, 7, 4.
• Studies have compared the efficacy and safety of febuxostat and allopurinol, with some suggesting that febuxostat may be more effective in achieving target serum uric acid levels, particularly in patients with impaired kidney function 3, 6, 7, 4.
• However, the choice between allopurinol and febuxostat should be individualized based on patient factors, such as kidney function, and clinical judgment 6, 7.