Allopurinol is contraindicated in individuals with the HLA-B*58:01 variant allele ("HLA-B*58:01-positive") due to significantly increased risk of allopurinol-induced SCAR.
Please see below for full details of these guidelines, with supporting evidence and disclaimers.
Guidelines regarding the use of pharmacogenomic tests in dosing for allopurinol have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).
Excerpt from the allopurinol dosing guidelines:
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 (SCAR), which includes drug hypersensitivity syndrome, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). A variant allele of the human leukocyte antigen-B, HLA-B*5801, associates strongly with allopurinol-induced SCAR. We have summarized evidence from the published literatures and develop peer-reviewed guidelines for allopurinol use based on HLA-B genotype.
Table 1: Recommended therapeutic use of allopurinol based on HLA-B genotype
|Likely phenotype||Genotypes||Examples of diplotypes||Implications for phenotypic measures||Recommendations for allopurinol therapy||Classification of recommendation for allopurinol therapy a|
|Low or reduced risk of allopurinol SCAR||Absence of *58:01 alleles (reported as "negative" on a genotyping test)||*X/*X b||Low or reduced risk of allopurinol SCAR||Use allopurinol per standard dosing guidelines||Strong|
|Significantly increased risk of allopurinol SCAR||Presence of at least one *58:01 allele (reported as "positive" on a genotyping test)||*58:01/*X b *58:01/*58:01||Significantly increased risk of allopurinol SCAR||Allopurinol is contraindicated||Strong|
a Rating scheme described in the supplementary data
b *X = any HLA-B genotype other than *58:01.
HLA-B = human leukocyte antigen B