Is allopurinol 300 mg safe with Impaired renal function (GFR 28)?

From the Guidelines

Allopurinol Dosage in Impaired Renal Function

Allopurinol 300 mg is not safe for patients with impaired renal function, specifically those with a GFR of 28 mL/min, without careful consideration and monitoring.

• The starting dose of allopurinol should be no greater than 100 mg/day for any patient, and even lower (50 mg/day) in stage 4 or worse CKD 1.
• While the dose can be raised above 300 mg daily, even with renal impairment, this should be accompanied by adequate patient education and monitoring for drug toxicity 1.
• For patients with renal impairment, the allopurinol maximum dosage should be adjusted to creatinine clearance, and if the SUA target cannot be achieved at this dose, alternative treatments such as febuxostat should be considered, especially in patients with eGFR <30 mL/min 1.
• A dose of 100-200 mg per day is often considered for patients with decreased renal function, rather than the standard 300 mg per day, to minimize the risk of adverse effects.
• The exact dose and duration of allopurinol therapy should be individualized and monitored closely by a healthcare provider to ensure safe and effective management of hyperuricemia or gout.
• It is crucial to monitor the patient's renal function and adjust the dose accordingly to prevent potential toxicity.
• Regular monitoring of SUA levels is also necessary to ensure that the target level is achieved and maintained, which is typically <6 mg/dL for most patients with gout 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

The recommended dose for patients with severely impaired renal function is 100 mg per day or 300 mg twice a week, which is lower than the standard dose of 300 mg per day. For a patient with a GFR of 28, which indicates severely impaired renal function, a dose of 300 mg per day may be too high. A more suitable dose would be 100 mg per day or 300 mg twice a week to minimize the risk of adverse effects 2.

From the Research

Allopurinol Safety with Impaired Renal Function

• The safety of allopurinol 300 mg with impaired renal function (GFR 28) is a concern due to the potential for adverse effects in patients with reduced kidney function.
• A study published in the Journal of clinical rheumatology 3 found that allopurinol treatment resulted in a significant improvement of kidney function in patients with hyperuricemia, with an average increase in GFR of 11.9 mL/min.
• Another study published in the Iranian journal of kidney diseases 4 found that allopurinol may slow down stage 3 chronic kidney disease progression, but its effectiveness in patients with severe GFR impairment (GFR < 30 mL/min/1.73 m2) is limited.
• A study published in the Journal of the Medical Association of Thailand 5 found that allopurinol treatment resulted in significant improvements in blood pressure and estimated GFR in patients with early stage chronic kidney disease.
• However, a study published in Basic & clinical pharmacology & toxicology 6 found that patients with impaired renal function may still be exposed to inappropriate drug use, including allopurinol, despite the use of electronic prescribing and automated reporting of estimated glomerular filtration rate.

Dosing Considerations

• The dosing of allopurinol in patients with impaired renal function is crucial to minimize the risk of adverse effects.
• The study published in the Iranian journal of kidney diseases 4 used a dose of 100 mg daily, while the study published in the Journal of the Medical Association of Thailand 5 used a dose of 50 mg once daily.
• The study published in Basic & clinical pharmacology & toxicology 6 highlighted the importance of adhering to clinical prescribing recommendations to minimize the risk of adverse effects in patients with impaired renal function.

Clinical Guidelines

• The expert consensus for the diagnosis and treatment of patients with renal impairment of multiple myeloma published in Zhonghua nei ke za zhi 7 recommends evaluating the estimated glomerular filtration rate (eGFR) using creatinine-based formula and staging the renal injuries according to the 2013 Kidney Disease Improving Global Outcomes (KDIGO) CKD guidelines.
• The guidelines also recommend considering the treatment of multiple myeloma with bortizomib-based regimen, which does not require dosage adjustment in patients with dialysis or renal insufficiency.