Allopurinol, Febuxostat Induce Hypersensitivity Similar to Colchicine

Compared with colchicine, allopurinol and febuxostat similarly increase the risk of hypersensitivity reactions, according to findings of a recent study.

To reach this conclusion, the researchers evaluated data from the 5% Medicare beneficiary sample (2006–2012) to identify people with a newly filled prescription for allopurinol, febuxostat, or colchicine.

Multivariable-adjusted Cox regression analyses were used to compare the hazard ratio (HR) of incident hypersensitivity reactions with allopurinol or febuxostat use vs colchicine use; separate analyses were also performed among those exposed to allopurinol. Propensity-matched analyses were used to compare HRs with allopurinol vs febuxostat use.

The crude incidence rate of hypersensitivity reactions was 23.7 per 1000 person-years for allopurinol; 30.7 per 1000 person-years for febuxostat; and 25.6 per 1000 person-years for colchicine. 

The use of allopurinol, febuxostat, and febuxostat plus colchicine were all associated with significantly higher HRs of hypersensitivity reactions compared with colchicine use. The HR of hypersensitivity reactions was 1.32 (95% CI, 1.10-1.60) for allopurinol; 1.54 (95% CI, 1.12-2.12) for febuxostat, and 2.17 (95% CI, 1.18-3.99) for febuxostat plus colchicine, respectively.

Febuxostat did not significantly differ from allopurinol, based on the propensity-matched analyses; the HR for hypersensitivity reactions was 1.25 (95% CI, 0.93-1.67). 

An allopurinol starting dose of 300 mg or higher per day, diabetes, and female sex were associated with significantly higher HRs of hypersensitivity reactions compared with an allopurinol starting dose of less than 200 mg per day.

Most hypersensitivity reactions (69%) occurred in the outpatient setting.

—Melinda Stevens


Singh JA, Cleveland JD. Hypersensitivity reactions with allopurinol and febuxostat: a study using the Medicare claims data [published online February 5, 2020]. Ann Rheum Dis. doi:10.1136/annrheumdis-2019-216917.