Gout patients taking febuxostat (Uloric), allopurinol (Zyloprim) and colchicine (Colcrys) all face a similar risk for hypersensitivity reactions, according to a study published in the February 5 issue of Annals of the Rheumatic Diseases.
A hypersensitivity reaction is a condition where the normally protective immune system has an abnormal reaction, possibly harming the human body. Allopurinol hypersensitivity syndrome is characterized by a rash that looks like measles, and in rarer and more severe cases, DRESS syndrome, Stevens Johnson syndrome or toxic epidermal necrolysis.
“Compared with colchicine, allopurinol and febuxostat similarly increased the risk of [hypersensitivity reactions],” the study said.
“There are many gaps in our knowledge regarding the rare hypersensitivity drug reactions with allopurinol vs. other alternative medications used for the treatment of gout,” said Jasvinder A. Singh, MD of the University of Alabama at Birmingham. “While every patient and physician fears the allopurinol hypersensitivity syndrome, also called AHS, which is a rarely-occurring major drug reaction with allopurinol, our study examined all hypersensitivity drug reactions, major or minor, with allopurinol vs. other drugs in the elderly.”
“Very few published studies and data are available that provide any population-level comparative data of the risk of hypersensitivity reactions associated with allopurinol and febuxostat,” Singh said. “Our study attempted to fill this knowledge gap, using data from the U.S. Medicare.”
The study used a 5% Medicare beneficiary sample of patients, age 65 or older, from 2006 to 2012 to identify people with newly filled allopurinol, febuxostat or colchicine prescriptions. 1,038 hypersensitivity reactions occurred amongst the 39,261 cases and 66,178 new prescriptions for allopurinol, febuxostat or colchicine. The rates of hypersensitivity reactions were 30.7, 25.6 and 23.7 per 1,000 person-years for febuxostat, colchicine and allopurinol, respectively.
Combinations of the medications significantly raised the risk of hypersensitivity reactions. Febuxostat plus colchicine resulted in a reaction rate of 56.8 per 1,000 person-years. A combination of all three drugs resulted in a reaction rate of 89.1 per 1,000 person-years.
A study completed in 2017 linked febuxostat to an increased risk of death from heart-related or cardiovascular causes. The FDA concluded in February 2019 that Uloric’s risk of death was higher than allopurinol’s. The FDA added a Boxed Warning to Uloric’s label as a result of this conclusion. The FDA said that 15 deaths per 1,000 person-years occurred in Uloric patients compared to 11 deaths per 1,000 person-years in allopurinol patients.