Correction of allopurinol dosing should be based on clearance of creatinine, but not plasma creatinine levels - Another insight to allopurinol-related toxicity

Background: Dosing of allopurinol should be corrected depending on renal function, but corrections based on either plasma creatinine (Per) or creatinine clearance (CrCl) have been suggested to be minimal standards of care. Methods: Data from a cohort database of 484 gouty patients were used to calculate estimated allopurinol doses using CrCl and estimation of the clearance of creatinine using the equation of Cockroft and Gault (CrCl-CG) if, as a hypothesis, a dosage of 300 mg/d would be prescribed in any patient with Per < 2.0 mg/dL. Also, allopurinol-related toxicity previous to rheumatologic consultation, during previous allopurinol therapy, and the relationship between both and estimated allopurinol doses were reviewed. Results: The cutoff point of plasma creatinine < 2 showed 13% sensitivity and 100% specificity to detect CrCl < 50 mL/min. Correlation and agreement between CrCl and CrCl-CG were good, as was the correlation between corrected doses using CrCl and CrCl-CG. One third of patients with Per 1.0-1.5 mg/dL and 90% of those with Per 1.5-2.0 mg/dL would receive estimated doses over 400 mg/dL/d CrCl. Also, 10% and 34% would receive estimated doses over 600 mg/dL/d CrCl, respectively. Allopurinol-related toxicity previous to consultation (11%) was associated with estimated doses over 400 mg/dL/d CrCl and severe toxicity with estimated doses over 600 mg/dL/d CrCl. When patients were given doses corrected on CrCl, few side effects were observed during follow up (6.7%), and the only severe one was associated with corrected dose over 600 mg/d. Conclusions: Dosage adjustment of allopurinol should be based on clearance of creatinine or estimation of glomerular filtration using the Cockcroft-Gault equation. Per is insensitive enough to detect renal function impairment so that patients may be placed at risk for overdosing side effects. Corrected doses over 600 mg/dL/d CrCl may be associated with increased risk of severe toxicity.