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

Toh DS1, Tan LL1, Aw DC2, Pang SM3, Lim SH4, Thirumoorthy T3, Lee HY3, Tay YK5, Tan SK6, Vasudevan A7, Lateef A8, Chong YY9, Chan YC10, Loke C1,Chan CL1, Koay ES11, Ren EC12, Lee EJ13, Sung C14.

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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.The Pharmacogenomics Journal advance online publication, 7 January 2014; doi:10.1038/tpj.2013.46.