Human Leukocyte Antigen (HLA) variants can be a risk factor for developing potentially fatal
drug hypersensitivity reactions. Our aim was to estimate the potential impact of genotyping for the HLA risk alleles incorporated in the Dutch Pharmacogenetics Working Group (DPWG) guidelines in The Netherlands. We estimated the number of
hypersensitivity reactions and associated deaths that can be avoided annually by genotyping for these HLA risk alleles. Additionally, the cost-effectiveness was estimated. Nationwide implementation of genotyping HLA risk alleles before initiating drugs with an actionable drug-gene interaction can potentially save the life of seven
allopurinol initiators and two
flucloxacillin initiators each year in The Netherlands. Besides these deaths, 28 cases of
abacavir hypersensitivity, 24 cases of
allopurinol induced
SCARs, 6 cases of
carbamazepine induced DRESS and 22 cases of
flucloxacillin induced DILI can be prevented. Genotyping
HLA-B*5701 in
abacavir initiators has a number needed to genotype of 31 to prevent one case of
abacavir hypersensitivity and is cost-saving. Genotyping
HLA-B*5801 in
allopurinol initiators has a number needed to genotype of 1149 to prevent one case of
SCAR but is still cost-effective. Genotyping before initiating
antiepileptic drugs or
flucloxacillin is not cost-effective. Our results confirm the need for mandatory testing of
HLA-B*5701 in
abacavir initiators, as indicated in the drug label, and show genotyping of
HLA-B*5801 in
allopurinol initiators should be considered.