What is the recommended dose of allopurinol (xanthine oxidase inhibitor) for an 80-year-old male with impaired renal function (Blood Urea Nitrogen (BUN) of 35, creatinine of 1.58, and Glomerular Filtration Rate (GFR) of 44)?

From the Guidelines

For an 80-year-old male with impaired renal function (BUN 35, creatinine 1.58, GFR 44), the recommended starting dose of allopurinol is 100 mg daily, as indicated by the most recent guidelines 1. This approach is supported by the 2016 updated EULAR evidence-based recommendations for the management of gout, which emphasize adjusting the allopurinol dosage according to the creatinine clearance to minimize the risk of severe cutaneous adverse reactions (SCARs) 1. Given the patient's moderate renal impairment, with a GFR of 44 ml/min indicating stage 3B chronic kidney disease, standard doses could lead to accumulation of oxypurinol and increased risk of adverse effects, particularly hypersensitivity reactions. After initiating treatment, the dose can be gradually increased by 100 mg increments every 2-4 weeks while monitoring serum uric acid levels, with a target of achieving uric acid levels below 6 mg/dL, as suggested by previous guidelines 1. Regular monitoring of renal function, liver enzymes, and complete blood count is essential during dose adjustments. The maximum daily dose should generally not exceed 300 mg in patients with this level of renal impairment, although some guidelines suggest that doses can be raised above 300 mg daily with careful monitoring for drug toxicity 1. Additionally, the patient should be advised to maintain adequate hydration to reduce the risk of kidney stones and to report any skin rashes immediately, as this could indicate a serious hypersensitivity reaction to allopurinol. Some key points to consider in the management of this patient include:

• Starting with a low dose of allopurinol and gradually increasing as needed and tolerated
• Monitoring for signs of hypersensitivity reactions, which can be severe and life-threatening
• Adjusting the dose based on renal function to minimize the risk of adverse effects
• Considering alternative urate-lowering therapies if allopurinol is not tolerated or effective
• Maintaining adequate hydration and monitoring for kidney stones
• Regularly reviewing and adjusting the treatment plan as necessary to achieve optimal control of uric acid levels and prevent gout flares.

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 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 patient has a GFR of 44, which indicates impaired renal function.

• The recommended dose for a patient with a creatinine clearance of 10 to 20 mL/min is 200 mg daily.
• However, the patient's GFR is 44, which is higher than 10 to 20 mL/min but still indicates impaired renal function.
• A dose of 200 mg daily or perhaps less may be sufficient to maintain adequate xanthine oxidase inhibition to reduce serum urate levels, but the patient should be observed closely during the early stages of administration of allopurinol tablets.
• It is recommended to start with a low dose of allopurinol (100 mg daily) and increase at weekly intervals by 100 mg until a serum uric acid level of 6 mg/dL or less is attained but without exceeding the maximal recommended dosage 2.
• The dose should be adjusted based on the patient's renal function and serum uric acid levels 2.

From the Research

Renal Dose of Allopurinol

To determine the recommended dose of allopurinol for an 80-year-old male with impaired renal function, we need to consider the patient's Blood Urea Nitrogen (BUN) of 35, creatinine of 1.58, and Glomerular Filtration Rate (GFR) of 44.

Factors Affecting Allopurinol Dosing

• The patient's renal function, as indicated by the GFR of 44, is impaired, which requires careful consideration when dosing allopurinol 3, 4, 5.
• The risk of allopurinol hypersensitivity syndrome (AHS) is increased with higher starting doses, particularly in patients with renal impairment 5.
• The goal of allopurinol therapy is to reduce serum uric acid levels while minimizing the risk of adverse effects.

Recommended Dosing

• A study published in 2012 suggested that starting allopurinol at a dose of 1.5 mg per unit of estimated GFR may be associated with a reduced risk of AHS 5.
• For a patient with a GFR of 44, the estimated starting dose would be approximately 66 mg/day (1.5 mg/unit x 44 units).
• However, the optimal dose may need to be adjusted based on the patient's response to therapy and tolerance of the medication.

Considerations

• The patient's age and renal function should be closely monitored during allopurinol therapy, and the dose adjusted as needed to minimize the risk of adverse effects 3, 4, 6.
• Alternative therapies, such as febuxostat, may be considered in patients with severe renal impairment or those who are intolerant of allopurinol 4, 7.