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Hypersensitivity reactions with allopurinol and febuxostat: a study using the Medicare claims data


Ann Rheum Dis. 2020 Apr;79(4):529-535. doi: 10.1136/annrheumdis-2019-216917.Epub 2020 Feb 5.

Jasvinder A Singh 1 2, John D Cleveland 3

Author Information

1 Departments of Medicine and Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA jasvinder.md@gmail.com.

2 Medicine Service, Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, USA.

3 Departments of Medicine and Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.


Objective: To assess the risk of hypersensitivity reactions (HSRs) with allopurinol and febuxostat in a population-based study.

Methods: We used the 5% Medicare beneficiary sample (≥65 years) from 2006 to 2012 to identify people with a newly filled prescription for allopurinol, febuxostat or colchicine. We used multivariable-adjusted Cox regression analyses to compare the hazard ratio (HR) of incident HSRs with allopurinol or febuxostat use versus colchicine use; separate analyses were done in people exposed to allopurinol. Propensity-matched analyses (5:1) compared hazards with allopurinol versus febuxostat.

Results: Crude incidence rates of HSRs were as follows: allopurinol, 23.7; febuxostat, 30.7; and colchicine, 25.6 per 1000 person-years. Compared with colchicine, allopurinol, febuxostat and febuxostat+colchicine were associated with significantly higher HRs of HSRs, 1.32 (95% CI: 1.10 to 1.60) and 1.54 (95% CI: 1.12 to 2.12) and 2.17 (95% CI: 1.18 to 3.99), respectively. In propensity-matched analyses, febuxostat did not significantly differ from allopurinol; HR for HSRs was 1.25 (95% CI: 0.93 to 1.67). Compared with allopurinol start dose <200 mg/day, allopurinol start dose ≥300 mg/day, diabetes and female sex were associated with significantly higher hazard of HSRs, 1.27 (95% CI: 1.12 to 1.44), 1.21 (95% CI: 1.00 to 1.45) and 1.32 (95% CI: 1.17 to 1.48), respectively. The majority (69%) of HSRs occurred in the outpatient setting.

Conclusions: Compared with colchicine, allopurinol and febuxostat similarly increased the risk of HSRs. Allopurinol and febuxostat did not differ from each other. In allopurinol users, starting dose, female sex and diabetes increased this risk, findings that need further study.