In the U.S., rheumatologists treat more challenging and advanced gout patients, says Dr. Choi. He points out that this information about SJS/TEN risk among Asian and black patients is also “highly relevant” to primary care physicians who manage about 90% of the nation’s gout cases.
Other medical specialists and researchers use allopurinol to treat certain conditions other than gout. It is also prescribed for kidney stones, particularly those composed of uric acid, and tumor lysis syndrome in cancer patients. Some studies are investigating allopurinol’s potential therapeutic impact in cardiovascular-renal patients, even those without gout, such as those with asymptomatic hyperuricemia. Kidney function is closely related to allopurinol hypersensitivity, and epidemiological studies have suggested that gout might lead to cardiovascular and renal conditions, Dr. Choi adds.
Screening to stratify risk in patients taking allopurinol may also be helpful in countries known to have frequency of HLA-B*5801 carriage even higher than the rate among U.S. blacks. In the U.S., the rate of HLA-B*5801 allele frequency is 4% for blacks and 1% for Caucasians, while it is up to 10% in Kenya and 8% in South Africa. The risk of allopurinol hypersensitivity syndrome among patients in these countries “would be higher than what we have observed in the U.S.,” Dr. Choi notes.
Adverse reactions are not a practical concern in patients who have been tolerating allopurinol well for several months, Dr. Choi points out. “It should also be noted that our findings apply almost exclusively to patients who are starting allopurinol, since nearly all of these severe adverse events occur during the first three to six months of treatment,” he explains.
Allopurinol Alternatives
Other drugs that lower urate levels in the blood are available for patients at risk of SJS/TEN and allopurinol hypersensitivity syndrome. An alternative is febuxostat, which was approved by the U.S. Food and Drug Administration (FDA) in 2009. Like allopurinol, febuxostat is an inhibitor of xanthine oxidase, an enzyme involved in purine metabolism.
Recently, the Taiwanese Food and Drug Administration adopted febuxostat as an alternative first-line drug for patients with chronic kidney disease to help reduce allopurinol-associated SJS/TEN. A 2015 JAMA Internal Medicine study that involved a retrospective analysis of Taiwan National Health Insurance Research Database information collected between 2005 and 2011 found that use of allopurinol in patients with asymptomatic hyperuricemia and renal or cardiovascular diseases significantly increased the risk of allopurinol hypersensitivity reactions. That study advised caution when prescribing allopurinol to high-risk populations and urged practitioners to consider the potential risk of fatal adverse reactions.3
