From the Guidelines
Allopurinol dosing should be reduced in patients with end-stage renal disease (ESRD), with a recommended starting dose of 100 mg orally every other day or 50 mg daily, and a maximum dose adjusted according to creatinine clearance. For patients on hemodialysis, a similar reduced dosing approach is appropriate, with allopurinol administered after hemodialysis sessions on dialysis days since approximately 20% of the drug is removed during dialysis 1. Dose adjustments should be made based on serum uric acid levels and clinical response, with gradual increases if needed. Monitoring for adverse effects is crucial, particularly hypersensitivity reactions which may be more common in patients with renal impairment. Regular monitoring of complete blood count, liver function tests, and serum uric acid levels is recommended. The dose reduction is necessary because allopurinol and its active metabolite oxypurinol are primarily eliminated by the kidneys, leading to accumulation and potential toxicity in patients with severely impaired renal function. This cautious approach helps maintain therapeutic efficacy while minimizing the risk of adverse effects in this vulnerable population.
Some key considerations in allopurinol dosing for ESRD patients include:
- Starting with a low dose and gradually increasing as needed and as tolerated 1
- Adjusting the dose based on creatinine clearance, as recommended by the task force 1
- Monitoring for signs of toxicity, such as hypersensitivity reactions, and adjusting the dose accordingly 1
- Considering alternative therapies, such as febuxostat, in patients who cannot tolerate allopurinol or who have severe renal impairment 1
It's also important to note that the 2017 EULAR guidelines recommend adjusting the allopurinol dosage according to creatinine clearance in patients with renal impairment 1, and the 2012 American College of Rheumatology guidelines recommend starting with a low dose and gradually increasing as needed and as tolerated 1. However, the most recent and highest quality study, the 2017 EULAR guidelines, should be prioritized in making treatment decisions 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. With extreme renal impairment (creatinine clearance less than 3 mL/min) the interval between doses may also need to be lengthened
The recommended dosing of allopurinol in patients with End-Stage Renal Disease (ESRD) is as follows:
- For patients with a creatinine clearance of 10 to 20 mL/min, a daily dosage of 200 mg is suitable.
- For patients with a creatinine clearance of less than 10 mL/min, the daily dosage should not exceed 100 mg.
- For patients with extreme renal impairment (creatinine clearance less than 3 mL/min), the interval between doses may also need to be lengthened 2.
From the Research
Allopurinol Dosing in ESRD
- There is limited information available on allopurinol dosing specifically in patients with End-Stage Renal Disease (ESRD) 3, 4, 5, 6, 7.
- However, studies suggest that febuxostat may be a more effective alternative to allopurinol in reducing serum uric acid levels and slowing the progression of renal disease in patients with chronic kidney disease (CKD) 3, 6, 7.
- One study found that febuxostat was more potent than allopurinol in lowering serum uric acid levels, and that patients who received febuxostat had a significantly lower risk of progressing to ESRD 6.
- Another study found that the long-term use of febuxostat may exert a protective effect on the kidneys, with a positive eGFR slope compared to a negative slope in patients treated with allopurinol 7.
- The optimal dosing of allopurinol in patients with ESRD is not well established, and further research is needed to determine the safest and most effective dosing regimen for these patients.
- It is essential to consider the potential benefits and risks of allopurinol treatment in patients with ESRD, and to monitor renal function and serum uric acid levels closely in these patients 4, 5.