Building pharmacogenetics into a pharmacovigilance program in Singapore: using serious skin rash as a pilot study

Pharmacogenomics J. 2014 Aug;14(4):316-21. doi: 10.1038/tpj.2013.46. Epub 2014 Jan 7.

Abstract

To study the possible genetic associations with adverse drug reactions (ADR), the Singapore Health Sciences Authority (HSA) has piloted a program to collect DNA and phenotype data of ADR cases as part of its pharmacovigilance program. Between 2009 and 2012, HSA screened 158 cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). To assess the association between HLA-B*1502 and carbamazepine (CBZ)-induced SJS/TEN, 13 cases and 26 drug-tolerant controls were analyzed. All 13 CBZ-SJS/TEN cases and 3/26 controls were HLA-B*1502 positive (odds ratio 181, 95% confidence interval: 8.7-3785, P=6.9 × 10(-8)). Discussions of the finding with the Ministry of Health and an expert panel led to the decision to make HLA-B*1502 testing the standard of care prior to first use of CBZ in Asians and to subsidize the genotyping test at public hospitals. This program illustrates the role of a regulatory authority in advancing the use of pharmacogenetics for drug safety.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Carbamazepine / adverse effects*
  • Case-Control Studies
  • Exanthema / chemically induced*
  • Genotype
  • HLA-B Antigens / genetics
  • Humans
  • Middle Aged
  • Pharmacogenetics* / methods
  • Pharmacovigilance*
  • Pilot Projects
  • Singapore
  • Stevens-Johnson Syndrome / etiology

Substances

  • HLA-B Antigens
  • Carbamazepine