title: Building pharmacogenetics into a pharmacovigilance program in Singapore: using serious skin rash as a pilot study.
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.
authors.affiliation: Vigilance Branch, Health Sciences Authority, Singapore.
authors.forename: D S L
authors.initials: DS
authors.lastname: Toh
authors.affiliation: Vigilance Branch, Health Sciences Authority, Singapore.
authors.forename: L L
authors.initials: LL
authors.lastname: Tan
authors.affiliation: Dermatology Department, National University Hospital, Singapore.
authors.forename: D C W
authors.initials: DC
authors.lastname: Aw
authors.affiliation: Dermatology Department, Singapore General Hospital, Singapore.
authors.forename: S M
authors.initials: SM
authors.lastname: Pang
authors.affiliation: 1] Neurology Department, Singapore General Hospital, Singapore [2] Duke-NUS Graduate Medical School, Singapore.
authors.forename: S H
authors.initials: SH
authors.lastname: Lim
authors.affiliation: Dermatology Department, Singapore General Hospital, Singapore.
authors.forename: T
authors.initials: T
authors.lastname: Thirumoorthy
authors.affiliation: Dermatology Department, Singapore General Hospital, Singapore.
authors.forename: H Y
authors.initials: HY
authors.lastname: Lee
authors.affiliation: 1] Dermatology Department, Changi General Hospital, Singapore [2] Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Y K
authors.initials: YK
authors.lastname: Tay
authors.affiliation: Dermatology Department, Changi General Hospital, Singapore.
authors.forename: S K
authors.initials: SK
authors.lastname: Tan
authors.affiliation: Rheumatology Department, Changi General Hospital, Singapore.
authors.forename: A
authors.initials: A
authors.lastname: Vasudevan
authors.affiliation: Rheumatology Department, National University Hospital, Singapore.
authors.forename: A
authors.initials: A
authors.lastname: Lateef
authors.affiliation: Rheumatology and Immunology Department, Singapore General Hospital, Singapore.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Chong
authors.affiliation: 1] Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore [2] Neurology Department, National University Hospital, Singapore.
authors.forename: Y C
authors.initials: YC
authors.lastname: Chan
authors.affiliation: Vigilance Branch, Health Sciences Authority, Singapore.
authors.forename: C
authors.initials: C
authors.lastname: Loke
authors.affiliation: Vigilance Branch, Health Sciences Authority, Singapore.
authors.forename: C L
authors.initials: CL
authors.lastname: Chan
authors.affiliation: 1] Molecular Diagnosis Centre, National University Hospital, Singapore [2] Pathology Department, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: E S C
authors.initials: ES
authors.lastname: Koay
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
authors.forename: E C
authors.initials: EC
authors.lastname: Ren
authors.affiliation: Pharmacology Department, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: E J D
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: 1] Vigilance Branch, Health Sciences Authority, Singapore [2] Duke-NUS Graduate Medical School, Singapore.
authors.forename: C
authors.initials: C
authors.lastname: Sung
mesh_terms: D000328:Adult; D000483:Alleles; D002220:Carbamazepine / Q000009:adverse effects*; D016022:Case-Control Studies; D005076:Exanthema / Q000139:chemically induced*; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D010597:Pharmacogenetics / Q000379:methods; D060735:Pharmacovigilance; D010865:Pilot Projects; D012846:Singapore; D013262:Stevens-Johnson Syndrome / Q000209:etiology
chemical_list: D015235:HLA-B Antigens; D002220:Carbamazepine