Allopurinol doses exceeding 100 mg/d may induce severe cutaneous reactions in older patients with nondialysis-dependent chronic kidney disease (CKD), a new study confirms.

Initiating allopurinol, a xanthine oxidase inhibitor, at a starting dose of more than 100 mg/d (vs 100 mg/d or less) was significantly associated with a 2.3-fold increased risk of a severe cutaneous reaction within 180 days (0.40% vs 0.18%), Lavanya Bathini, MD, and colleagues from ICES Western in Ontario, Canada, reported in the American Journal of Kidney Diseases. In subgroup analyses of patients with CKD and diagnosed gout, a higher allopurinol dose was significantly associated with a 2.8-fold increased risk of severe cutaneous reactions (0.42% vs 0.15%). A severe cutaneous reaction was defined as a hospital visit with a main diagnosis of a generalized or localized skin eruption due to drugs, erythematous conditions, exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis. The risk of a severe cutaneous reaction did not appear to differ among patients who either maintained or increased their dose after tolerating an initial allopurinol prescription of less than 100 mg/d. The databases lacked information on ethnicity and the HLA–B*5801 genotype, which are known risk factors for severe cutaneous reactions.

Starting allopurinol at a dose exceeding 100 mg/d was significantly associated with a 7% increased risk of all-cause hospitalization, Dr Bathini’s team reported.

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The findings were from a population-based study of 47,315 patients in Ontario, Canada aged 66 years and older with an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2 who did not receive renal replacement therapy. Of the CKD cohort, 55% were prescribed allopurinol at a dose exceeding 100 mg/d.

According to Dr Bathini’s team, the findings support current recommendations from the American College of Rheumatology to initiate allopurinol at a dose of 100 mg/d or less in patients with CKD.

The study was underpowered to detect risk differences by eGFR categories less than 60 mL/min/1.73 m2. Future research is needed to understand the benefit-risk profile of allopurinol to treat gout in patients with CKD while minimizing adverse effects.


Bathini L, Garg AX, Sontrop JM, et al. Initiation dose of allopurinol and the risk of severe cutaneous reactions in older adults with CKD: a population-based cohort study. Am J Kidney Dis. Published online May 26, 2022. doi:10.1053/j.ajkd.2022.04.006