What is the appropriate allopurinol (Zyloprim) dosage for a patient with impaired renal function, specifically a glomerular filtration rate (GFR) of 30?

From the Guidelines

For a patient with a GFR of 30 mL/min, the starting dose of allopurinol should be no greater than 50 mg/day, as recommended for stage 4 or worse CKD. This dose can be gradually titrated upwards every 2–5 weeks to achieve the desired serum uric acid (SUA) target, while closely monitoring for signs of drug toxicity, such as pruritis, rash, and elevated hepatic transaminases 1. The dose can be raised above 300 mg daily, even with renal impairment, as long as the patient is adequately educated and monitored for potential adverse effects. Prior to initiation, it is essential to consider HLA-B*5801 testing in selected patients, particularly those in higher risk sub-populations for severe allopurinol hypersensitivity reaction, such as Koreans with stage 3 or worse CKD, and Han Chinese and Thai patients, irrespective of renal function 1. Key considerations in managing patients with renal impairment include:

• Starting with a low dose and gradually increasing as needed and tolerated
• Regular monitoring of serum uric acid levels to ensure the dose is effective
• Periodic reassessment of renal function to guide potential dose adjustments
• Vigilant monitoring for potential adverse effects, including rash, liver function abnormalities, and hypersensitivity reactions
• Ensuring adequate hydration to reduce the risk of kidney stones and maintain renal function.

From the FDA Drug Label

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 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 dosage of allopurinol for a patient with a GFR of 30 is not explicitly stated, but based on the information provided for creatinine clearance, a dose of 200 mg per day may be suitable, as a GFR of 30 is roughly equivalent to a creatinine clearance of 30 mL/min, which falls within the 10 to 20 mL/min range for a daily dosage of 200 mg of allopurinol tablets 2. However, it is crucial to monitor the patient closely and adjust the dosage as needed to maintain adequate xanthine oxidase inhibition and reduce serum urate levels 2.

From the Research

Allopurinol Dosage Adjustment in Patients with Reduced Kidney Function

• The dosage of allopurinol may need to be adjusted in patients with reduced kidney function, as it is excreted by the kidneys 3.
• The estimated glomerular filtration rate (eGFR) can be used to guide dose adjustment in patients with stable kidney function 3.
• For patients with an eGFR of 30, the dosage of allopurinol may need to be reduced to avoid toxicity 3.

Comparison of Allopurinol and Febuxostat in Patients with Chronic Kidney Disease

• Febuxostat has been shown to be more effective than allopurinol in reducing serum uric acid levels in patients with chronic kidney disease (CKD) 4, 5, 6.
• Febuxostat may also have a protective effect on the kidneys, as it has been shown to slow the progression of renal disease in patients with CKD 4, 5.
• However, the choice of urate-lowering therapy (ULT) should be individualized based on patient characteristics and kidney function 6.

Considerations for Drug Dose Adjustment in Patients with Reduced Kidney Function

• The choice of equation used to estimate kidney function, such as the Cockcroft-Gault or MDRD equation, can affect the estimated glomerular filtration rate (eGFR) and subsequent drug dose adjustment 7.
• Different literature references may recommend different drug dose adjustments for patients with reduced kidney function, highlighting the need for standardized methods 7.
• Close monitoring of drug effect and toxicity is necessary in patients with reduced kidney function, and therapeutic drug monitoring may be useful in some cases 3.