What is the appropriate dosing of Allopurinol (generic name) for a patient with Chronic Kidney Disease (CKD) stage 3, characterized by Impaired renal function?

From the Guidelines

For patients with chronic kidney disease stage 3 (CKD 3), the recommended starting dose of allopurinol is 50-100 mg once daily, with gradual titration based on serum uric acid levels and tolerability, as recommended by the 2020 American College of Rheumatology guideline for the management of gout 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, such as pruritis, rash, and elevated hepatic transaminases 1.
• Prior to initiation, consider HLA-B*5801 in selected patients, specifically in higher risk sub-populations for severe allopurinol hypersensitivity reaction, such as Koreans with stage 3 or worse CKD, and all those of Han Chinese and Thai descent 1.
• Dose adjustments should be made every 2-4 weeks with monitoring of serum uric acid levels, aiming for a target below 6 mg/dL, and regular monitoring of renal function, liver enzymes, and complete blood count is essential during therapy.

Monitoring and Titration

• Patients should be observed for hypersensitivity reactions, particularly in the first few weeks of treatment, and the dose reduction in CKD is necessary because allopurinol and its active metabolite oxypurinol are primarily eliminated by the kidneys, and accumulation can occur with reduced renal function, increasing the risk of toxicity and adverse effects.
• Starting with a low dose and gradually increasing helps minimize the risk of hypersensitivity reactions and other adverse effects while effectively managing hyperuricemia.

Additional Recommendations

• For allopurinol and febuxostat, starting at a low dose with subsequent dose titration to target over starting at a higher dose is strongly recommended, such as ≤100 mg/day (and lower in patients with CKD) for allopurinol or ≤40 mg/day for febuxostat 1.
• Concomitant antiinflammatory prophylaxis therapy, such as colchicine, NSAIDs, or prednisone/prednisolone, should be initiated when starting ULT, and continued for 3-6 months, with ongoing evaluation and continued prophylaxis as needed if the patient continues to experience flares 1.

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. The dosage for CKD 3 is not explicitly stated, but based on the information provided for creatinine clearance, CKD 3 typically corresponds to a creatinine clearance of 30-59 mL/min. However, the label only provides guidance for creatinine clearances of 10-20 mL/min and less than 10 mL/min. Given the available information, a conservative approach would be to consider a dose reduction for patients with CKD 3, but the exact dosage cannot be determined from the provided label information 2.

From the Research

Allopurinol Dosing for CKD 3

• The ideal dosing of allopurinol for patients with chronic kidney disease (CKD) stage 3 is not explicitly stated in the provided studies.
• However, a study published in the Iranian Journal of Kidney Diseases 3 used a daily dose of 100 mg of allopurinol for 12 months in patients with stages 3 and 4 CKD.
• The study found that allopurinol may slow down stage 3 CKD progression, particularly in patients with mild glomerular filtration rate (GFR) impairment.
• Another study published in Scientific Reports 4 compared febuxostat with allopurinol in patients with CKD, but did not specify the dosing of allopurinol used in the study.
• The study found that febuxostat was associated with a greater reduction in serum uric acid (SUA) level than allopurinol, but there was no significant difference in renal function changes between the two groups.
• A study published in the International Journal of Clinical Pharmacology and Therapeutics 5 compared the efficacy of allopurinol and febuxostat in patients with CKD and hyperuricemia, and found that febuxostat 40 mg was more effective than allopurinol 100 mg in reducing SUA levels.
• However, the study did not provide information on the optimal dosing of allopurinol for CKD 3 patients.

Key Findings

• Allopurinol may slow down stage 3 CKD progression, particularly in patients with mild GFR impairment 3.
• Febuxostat may be more effective than allopurinol in reducing SUA levels in patients with CKD and hyperuricemia 5, 4.
• The optimal dosing of allopurinol for CKD 3 patients is not explicitly stated in the provided studies.