Types of human leukocyte antigen
Thirteen drug label annotations contain information about various human leukocyte antigen (HLA) types. Some of the inconsistencies are reasonable because the frequencies of HLA types vary among different populations. For example, all agencies but the PMDA requires testing for HLA-B*5701 before therapy with abacavir. The information in the PMDA-approved label is informative because the prevalence of this allele is only 0.1% in the Japanese population.
For carbamazepine, while the FDA- and Swissmedic-approved labels require screening of patients with ancestry in line with genetically at-risk populations (individuals of Asian descent) for the presence of the HLA-B*1502 allele prior to treatment due to a high risk of serious, and sometimes fatal, dermatologic reactions, HCSC and TMMDA recommend testing. PMDA’s level of information is only actionable and states that the HLA-B*1502 allele was prevalent in nearly all of a group of Han Chinese patients who developed Steven–Johnsons Syndrome or toxic epidermal necrolysis (SJS/TEN). Swissmedic and HCSC also recommend testing for HLA-A*3101, which increases the risk of developing hypersensitivity reactions to carbamazepine. On the other hand, the FDA and PMDA levels of information are actionable for this allele, despite the fact that it appeared at a high frequency in Japanese patients. Similarly, for oxcarbamazepine, the Swissmedic-approved label requires testing for the HLA-B*1502 allele as due to the increased risk of SJS/TEN, the FDA and TMMDA recommend testing. Information is more variable in the case of phenytoin and HLA-B*15:02. The FDA and Swissmedic level of information is actionable and states the high risk of SJS/TEN in patients of Asian ancestry. The HCSC recommends testing and the TMMDA has an informative level of information for three of the five generic formulations. Although Han/Chinese descendants are rare in Turkey’s population, the inconsistency in different pharmaceutical/commercial forms is notable.