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.