What is the appropriate dosing of allopurinol for a patient with impaired renal function, specifically an estimated Glomerular Filtration Rate (eGFR) of 19 and a creatinine clearance rate (CrCl) of 18.5?

From the Guidelines

For a patient with an eGFR of 19 mL/min/1.73m² and creatinine clearance of 18.5 mL/min, the recommended allopurinol dose is 50 mg once daily, as starting with a higher dose may increase the risk of adverse effects, particularly in patients with severe renal impairment 1.

Key Considerations

• The dose should be gradually titrated upwards every 2–5 weeks to achieve the desired serum uric acid level, while closely monitoring for signs of toxicity, such as rash, pruritis, or elevated hepatic transaminases 1.
• Patients with renal impairment are at increased risk of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome and toxic epidermal necrolysis, which can be fatal 1.
• Regular monitoring of complete blood count, liver function, and renal function is essential during treatment, and patients should be advised to maintain adequate hydration and report any skin reactions, joint pain, or fever immediately.

Dose Adjustment and Monitoring

• Dose adjustments should be based on serum uric acid levels and clinical response, with the goal of maintaining uric acid below 6 mg/dL.
• Concurrent use of thiazide diuretics or ACE inhibitors may require additional dose adjustments due to potential interactions affecting renal function.
• The use of febuxostat or other uricosuric agents may be considered as alternative treatments, especially in patients who cannot tolerate allopurinol or have inadequate response to treatment 1.

From the FDA Drug Label

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

For a patient with an eGFR of 19 and a CrCl of 18.5, the recommended dose of allopurinol is likely to be 100 mg per day or 300 mg twice a week, or perhaps less 2, 2.

• The patient should be closely monitored during the early stages of administration.
• Dose adjustment may be necessary based on the patient's response to therapy and renal function.
• It is essential to periodically assess renal function and adjust the dosage accordingly.

From the Research

Allopurinol Dosing for eGFR of 19, CrCl of 18.5

• The provided studies do not directly address the dosing of allopurinol for a patient with an eGFR of 19 and a CrCl of 18.5 3, 4, 5, 6, 7.
• However, it is known that allopurinol dosage needs to be adjusted in patients with renal impairment, as it is primarily excreted by the kidneys 3, 4.
• A study comparing the efficacy and safety of febuxostat and allopurinol in patients with chronic kidney disease found that febuxostat was more effective in reducing serum uric acid levels and slowing the progression of renal disease 4.
• Another study found that febuxostat caused a more rapid decline in serum uric acid levels compared to allopurinol in early post-renal transplant recipients with new onset of hyperuricemia 5.
• The Cockcroft-Gault equation, which is commonly used to estimate CrCl, may not be accurate in patients with renal impairment, and other methods such as the Modification of Diet in Renal Disease (MDRD) or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations may be more reliable 6.
• A 13-year inception cohort study found that febuxostat and benzbromarone may be more effective than allopurinol in reducing the risk of progression to dialysis and lowering serum uric acid levels in patients with chronic kidney disease and hyperuricemia 7.

Considerations for Dosing

• The dosing of allopurinol in patients with renal impairment should be carefully considered, taking into account the patient's eGFR and CrCl 3, 4.
• The use of alternative urate-lowering therapies such as febuxostat or benzbromarone may be considered in patients with chronic kidney disease and hyperuricemia 4, 5, 7.