Initiation dose of allopurinol and the risk of severe cutaneous reactions in older adults with CKD: a population-based cohort study

Rationale and Objective — Allopurinol should be started at lower doses in patients with chronic kidney disease (CKD) to avoid adverse effects. We examined the risk of severe cutaneous reactions in older adults with CKD who were newly prescribed allopurinol at varied doses.

Design — Population-based cohort study using linked healthcare databases.

Setting and Participants — Patients in Ontario, Canada (2008-2019) aged >66 years, with an eGFR <60 mL/min/1.73m2, and who were new users of allopurinol.

Exposure — A new prescription for allopurinol >100 mg/d versus a dose ≤100 mg/d.

Outcome — The primary outcome was a hospital visit with a severe cutaneous reaction within 180 days of starting allopurinol. Secondary outcomes included all-cause hospitalization and all-cause mortality.

Analytical Approach — The exposure and referent groups were balanced on indicators of baseline health using inverse probability of treatment weighting on the propensity score. Weighted risk ratios (RR) were obtained using modified Poisson regression and weighted risk differences (RD) using binomial regression.

Results — Of 47,315 patients (median age 76; eGFR 45 mL/min/1.73m2), 55% started allopurinol at >100 mg/d. Starting allopurinol at >100 versus ≤100 mg/d was associated with an increased risk of a severe cutaneous reaction: number of events (weighted), 103/25,802 (0.40%) versus 46/25,816 (0.18%), respectively (weighted RR, 2.25 [95% CI, 1.50 to 3.37]; weighted RD, 0.22% [95% CI, 0.12% to 0.32%]. Starting allopurinol at >100 versus ≤100 mg/d was associated with an increased risk of all-cause hospitalization, but not with all-cause mortality.

Limitations — This study was underpowered to detect risk differences in the association of allopurinol dose across eGFR categories (i.e., 45–59, 30–44, and <30 ml/min/1.73m2).

Conclusion — Older patients with CKD who started allopurinol at >100 mg/d versus ≤100 mg/d were twice as likely to visit a hospital with a severe cutaneous reaction in the next 180 days.