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Pharmacogenetics of allopurinol--making an old drug safer

May P S Lam1, Chi K Yeung, Bernard M Y Cheung

  • 1Department of Medicine, The University of Hong Kong, Hong Kong. maypslam@hku.hk

Journal of Clinical Pharmacology
|February 6, 2013
PubMed

Insights

Allopurinol can cause severe skin reactions. The HLA-B*58:01 genetic marker is linked to these reactions, but screening is not standard practice.

Area of Science:

  • Pharmacogenomics
  • Immunology
  • Dermatology

Background:

  • Allopurinol is a widely used medication for managing hyperuricemia in conditions like gout and tumor lysis syndrome.
  • Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are serious risks associated with allopurinol.
  • The human leukocyte antigen (HLA) B*58:01 allele has been identified as a significant genetic risk factor for allopurinol-induced SCARs.

Purpose of the Study:

  • To highlight the association between the HLA-B*58:01 allele and allopurinol-induced SCARs.
  • To emphasize the current lack of routine genetic screening for HLA-B*58:01 before allopurinol initiation.
  • To advocate for the development of accessible screening methods.

Main Methods:

  • Review of existing literature on allopurinol, SCARs, and HLA associations.
  • Comparison of current genetic screening practices for other drugs (e.g., abacavir, carbamazepine) with allopurinol.
  • Identification of barriers to genetic screening for allopurinol.

Main Results:

  • The HLA-B*58:01 allele is strongly associated with allopurinol-induced SCARs, potentially explaining ethnic variations in incidence.
  • Genetic screening is mandated for abacavir and carbamazepine to prevent SJS but not for allopurinol.
  • A key obstacle to allopurinol genetic screening is the lack of rapid, inexpensive tests for the HLA-B*58:01 allele.

Conclusions:

  • The association between HLA-B*58:01 and allopurinol-induced SCARs necessitates consideration for preemptive genetic screening.
  • The absence of routine screening for allopurinol contrasts with practices for other drugs with similar genetic risks.
  • There is a critical need for the development and implementation of cost-effective, rapid screening tests for the HLA-B*58:01 allele to improve patient safety.

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