Allopurinol is the most commonly used drug for the treatment of hyperuricemia and gout. However, allopurinol is also one of the most common causes of severe cutaneous adverse reactions (SCARs), which include drug hypersensitivity syndrome, Stevens–Johnson syndrome, and toxic epidermal necrolysis. A variant allele of the human leukocyte antigen (HLA)-B, HLA-B*58:01, associates strongly with allopurinol-induced SCAR. We have summarized the evidence from the published literature and developed peer-reviewed guidelines for allopurinol use based on HLA-B genotype.
The aim of this article is to provide pharmacogenetic information relevant to the clinical use of HLA-B*58:01 genotyping results in patients with indications for allopurinol use. On the basis of this information, a guideline is recommended for the use of allopurinol when HLA-B*58:01 genotyping results are available. Other areas are beyond the scope of this guideline, including the selection of an alternative to allopurinol or the use of other tests, such as an intradermal skin test and cost effectiveness analyses. The Clinical Pharmacogenetics Implementation Consortium (CPIC) publishes a series of guidelines aimed at incorporating pharmacogenetics into clinical decisions. These guidelines are updated periodically on www.pharmgkb.org based on new developments in the field.