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Background: Several type B adverse drug reactions (ADRs), especially severe cutaneous adverse reactions (SCARs), are associated with particular human leukocyte antigen (HLA) genotypes. However, pre‐stored HLA information obtained from other clinical workups has not been used to prevent ADRs. We aimed to simulate the preemptive use of pre‐stored HLA information in electronic medical records to evaluate whether this information can prevent ADRs. Methods: We analyzed the incidence and the risk of ADRs for selected HLA alleles (HLA‐B*57:01, HLA‐B*58:01, HLA‐A*31:01, HLA‐B*15:02, HLA‐B*15:11, HLA‐B*13:01, HLA‐B*59:01, and HLA‐A*32:01) and seven drugs (abacavir, allopurinol, carbamazepine, oxcarbazepine, dapsone, methazolamide, and vancomycin) using pre‐stored HLA information of transplant patients based on the Pharmacogenomics Knowledge Base guidelines and experts' consensus. Results: Among 11,988 HLA‐tested transplant patients, 4092 (34.1%) had high‐risk HLA alleles, 4583 (38.2%) were prescribed risk drugs, and 580 (4.8%) experienced type B ADRs. Patients with HLA‐B*58:01 had a significantly higher incidence of type B ADR and SCARs associated with allopurinol use than that of patients without HLA‐B*58:01 (17.2% vs. 11.9%, odds ratio [OR] 1.53 [95% confidence interval {CI} 1.09–2.13], p = 0.001, 2.3% versus 0.3%, OR 7.13 [95% CI 2.19–22.69], p < 0.001). Higher risks of type B ADR and SCARs were observed in patients taking carbamazepine or oxcarbazepine if they had one of HLA‐A*31:01, HLA‐B*15:02, or HLA‐B*15:11 alleles. Vancomycin and dapsone use in HLA‐A*32:01 and HLA‐B*13:01 carriers, respectively, showed trends toward increased risk of type B ADRs. Conclusion: Utilization of pre‐stored HLA data can prevent type B ADRs including SCARs by screening high‐risk patients. [ABSTRACT FROM AUTHOR]

Summary: Background: Although the US FDA recommends screening for HLA-B*1502 allele in most of Asian ancestry before initiating carbamazepine therapy, the HLA associations with carbamazepine hypersensitivity in non-Chinese Asian populations remain unclear. This study investigated the association between the HLA class I genotype and carbamazepine-induced severe cutaneous adverse reaction (SCAR) in Koreans. Methods: Twenty-four patients who had developed carbamazepine-induced SCAR (7 Stevens–Johnson syndrome (SJS), 17 drug hypersensitivity syndrome (HSS)), 50 carbamazepine-tolerant controls from the Korean Pharmacogenetic Adverse Drug Reaction Research Network and data of 485 Korean general population from a previously published study were recruited. HLA-A, -B, and -C genotyping was performed by direct DNA sequence analysis. Results: Only one of the seven SJS patients was positive for the B*1502 allele, but the frequency of B*1511 was much higher in the patients with CBZ-SJS than in the CBZ-tolerant control patients (P =0.011, P c =not significant; OR=18.0(2.3–141.2)). The frequencies of A*3101 in carbamazepine-induced HSS and SCAR were significantly higher than those in carbamazepine-tolerant controls (P c =0.011, OR=8.8(2.5–30.7) and P c =0.013, OR=7.3(2.3–22.5), respectively). The frequencies of B*1511 in carbamazepine-SJS and A*3101 in carbamazepine-HSS/SCAR were significantly higher than those in the general population. Conclusions: HLA-B*1502 does not seem to be an effective predictive marker for carbamazepine-induced SCAR, while HLA-B*1511 and A*3101 was associated with carbamazepine-induced SJS and HSS/SCAR respectively in the Korean population. [ABSTRACT FROM AUTHOR]