Severe cutaneous reactions requiring hospitalization in allopurinol initiators: A population-based cohort study.
ABSTRACT BACKGROUND: Rare but potentially life-threatening cutaneous adverse reactions have been associated with allopurinol, but population-based data on incidence and mortality of such reactions is scarce. METHODS: We conducted a propensity score-matched cohort study to evaluate incidence rate (IR) and in-hospital mortality of hospitalization for severe cutaneous adverse reactions (SCARs) in allopurinol initiators compared to non-allopurinol users, using data from five large Medicaid programs. The primary outcome was identified by the principal discharge diagnosis code 695.1. Cox proportional hazards model evaluated the relative risk of SCARs associated with use of allopurinol and determined the relative risk of SCARs associated with allopurinol dose. RESULTS: During a follow-up period of 65,625 person-years for allopurinol initiators, 45 were hospitalized with SCARs. The crude IR was 0.69 (95% CI 0.50-0.92) per 1,000 person-years. All 45 cases occurred within 365 days and 41 (91.1%) within 180 days after initiating treatment with allopurinol. Twelve (26.7%) patients died during the hospitalization. The crude IR in non-allopurinol users was 0.04 (95% CI 0.02-0.08) per 1,000 person-years. The risk of SCARs was increased in allopurinol initiators vs. non-users (HR 9.67, 95% CI 4.55-20.57). Among allopurinol initiators, the HR for the high- (>300mg/day) vs. low-dose allopurinol was 1.30 (95% CI 0.31-5.36) after adjusting for age, comorbidities and recent diuretic use. CONCLUSIONS: Among allopurinol initiators, SCARs were found to be rare but often fatal and occurred mostly in the first 180 days of treatment. The risk of SCARs was ten times as high in allopurinol initiators compared to allopurinol non-users.