What is the recommended dosing of allopurinol in patients with impaired renal function?

From the Guidelines

Allopurinol dosing in patients with impaired renal function should start at a low dose, with a maximum starting dose of 100 mg/day for any patient, and 50 mg/day in stage 4 or worse CKD, with gradual titration upwards every 2–5 weeks to achieve the target serum uric acid level. The dosing of allopurinol in patients with impaired renal function is crucial to prevent toxicity and ensure effective management of gout. According to the 2012 American College of Rheumatology guidelines 1, the starting dose should be no greater than 100 mg/day for any patient, and 50 mg/day in stage 4 or worse CKD. 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. Key considerations in allopurinol dosing include:

• Starting with a low dose and gradually titrating upwards to achieve the target serum uric acid level
• Monitoring for adverse effects, particularly during the first few months of treatment
• Regular monitoring of renal function, liver enzymes, and complete blood count during dose adjustments and periodically thereafter
• Considering HLA-B*5801 in selected patients, specifically in higher risk sub-populations for severe allopurinol hypersensitivity reaction The 2017 updated EULAR evidence-based recommendations for the management of gout 1 also support starting allopurinol at a low dose and titrating upwards to achieve the target serum uric acid level, with a goal of maintaining serum urate below 6 mg/dL. In patients with renal impairment, the allopurinol maximum dosage should be adjusted to creatinine clearance, and if the target serum uric acid level cannot be achieved, consideration should be given to switching to febuxostat or adding a uricosuric. Overall, the key to effective and safe allopurinol dosing in patients with impaired renal function is careful monitoring and gradual titration to achieve the target serum uric acid level, while minimizing the risk of toxicity.

From the FDA Drug Label

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. When the creatinine clearance is less than 10 mL/min, the daily dosage should not exceed 100 mg. In patients with severely impaired renal function or decreased urate clearance, the half-life of oxipurinol in the plasma is greatly prolonged. Therefore, a dose of 100 mg per day or 300 mg twice a week, or perhaps less, may be sufficient to maintain adequate xanthine oxidase inhibition to reduce serum urate levels Patients with decreased renal function require lower doses of allopurinol tablets than those with normal renal function. Lower than recommended doses should be used to initiate therapy in any patients with decreased renal function and they should be observed closely during the early stages of administration of allopurinol tablets

The recommended dosing of allopurinol in patients with impaired renal function is as follows:

• Creatinine clearance of 10 to 20 mL/min: 200 mg daily
• Creatinine clearance less than 10 mL/min: not more than 100 mg daily
• Severely impaired renal function: 100 mg per day or 300 mg twice a week, or perhaps less 2, 2

From the Research

Allopurinol Dosing in Renal Impairment

• The recommended dosing of allopurinol in patients with impaired renal function is a topic of ongoing debate 3.
• Guidelines advocate for allopurinol dose reduction according to creatinine clearance in patients with renal impairment, but recent studies suggest that this may lead to under-treatment of hyperuricemia 3.
• A study found that low-dose allopurinol (100 mg daily) promoted greater serum urate lowering in gout patients with chronic kidney disease (CKD) compared to those with normal kidney function 4.
• However, another study suggested that febuxostat, a novel xanthine oxidase inhibitor, may be more effective in reducing serum uric acid levels and slowing the progression of renal disease in CKD patients compared to allopurinol 5.

Renal Function and Allopurinol Dosing

• The dose of allopurinol required to achieve target serum urate levels may vary according to renal function, with patients with severe renal impairment requiring lower doses 6.
• A systematic review found that febuxostat may be more renoprotective than allopurinol in patients with hyperuricemia and CKD, but the evidence is limited by serious risk of bias 7.
• Further studies are needed to determine the optimal dosing of allopurinol in patients with impaired renal function and to compare the long-term renal outcomes of allopurinol and febuxostat in this population 3, 7.

Key Considerations

• Patients with renal impairment are at increased risk of allopurinol hypersensitivity syndrome, and dose reduction may be necessary to minimize this risk 3.
• Close monitoring of serum uric acid concentrations and renal function is essential in patients with impaired renal function receiving allopurinol 3.
• The choice of urate-lowering therapy (allopurinol or febuxostat) should be individualized based on patient factors, including renal function, and careful consideration of the potential benefits and risks of each therapy 5, 7.