Allopurinol Therapy and HLA-B*58:01 Genotype

Excerpt

Allopurinol (brand names Zyloprim, Aloprim) is a xanthine oxidase inhibitor that decreases the production of uric acid. It is most commonly used to manage gout, tumor lysis syndrome, and symptomatic hyperuricemia (high levels of uric acid). It is not indicated for use in asymptomatic hyperuricemia (1).

The human leukocyte antigen B (HLA-B) plays an important role in how the immune system recognizes and responds to pathogens. The variant HLA-B*58:01 allele is strongly associated with severe cutaneous adverse reactions (SCAR) during treatment with allopurinol. This allele is most common among Asian subpopulations, notably in individuals of Korean, Han-Chinese, or Thai descent.

At this time, the FDA-approved drug label for allopurinol does not discuss HLA-B genotype (Table 1) (1). However, the American College of Rheumatology (ACR) conditionally recommends testing HLA–B*5801 before starting allopurinol for individuals of Southeast-Asian descent (for example, Han-Chinese, Korean, Thai) and African-Americans (Table 2) (2). For individuals who are positive for the HLA-B*58:01 variant, an alternative drug is recommended by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG) (Table 3 and 4). While CPIC states allopurinol is contraindicated in carriers of HLA-B*58:01, both DPWG and ACR state that a possible option is allopurinol desensitization (3, 4, 5).