i=rsjrsj/\/\5 ESTABLISHED INNOVATIONS IN DIAGNOSTICS Carbamazepine HypersensitivityReal-time PCR assays for HLA-A*31:01 and HLA-B*15:02 to minimize the risk of oarbamazepine-induoed hypersensitivity reactions Carbamazepine, adverse reactions and HLA alleles Carbamazepine is an anticonvulsant commonly prescribed for the treatment of epilepsy, bipolar disorder and trigeminal neuralgia. Up to 10% of patients show cutaneous adverse reactions ranging from relatively mild maculopapular exanthema (MPE) to severe drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Although rare, DRESS, SJS and TEN show a high mortality rate of 10% to 50%. The human leukocyte antigen allele HLA-A*31:01 is predominantly associated with carbamazepine-induced MPE, DRESS and SJS/TEN in Europeans and Japanese. Also in Chinese, the allele is a risk factor for MPE and DRESS. Another HLA allele, HLA-B*15:02, is strongly associated with carbamazepine-induced SJS/TEN in many Asian populations, where the prevalence of the allele can be up to 25%. According to the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, patients positive for HLA-A*31:01 or HLA-B*15:02 should not be treated with carbamazepine. Thus, testing of patients prior to starting therapy will significantly reduce the incidence of severe hypersensitivity reactions. ViennaLab HLA-A3101 and HLA-B1502 RealFast™ Assays • Single reaction per sample (PCR control included) • Easy interpretation of results: signal for HLA-A*31:01 or HLA-B*15:02 present or absent • Positive and negative controls supplied with the kit • Compatible with ViennaLab D2PCR™ Buffer for rapid DNA isolation • Compatible with a wide range of real-time PCR instruments C € IIVDl REF: • HLA-A3101 RealFast™ Assay: 7-640/7-643 (100/32 reactions) • HLA-B1502 RealFast™ Assay: 7-630/7-633 (100/32 reactions)

i=rsjrsj/\/\5 ESTABLISHED INNOVATIONS IN DIAGNOSTICS Carbamazepine (CBZ) hypersensitivity in different populations HLA allele Abbreviations: MPE, maculopapular exanthema; DRESS, severe drug reaction with eosinophilia and systemic symptoms; SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis D2PCR™ Buffer for an even faster workflow of RealFast™ Assays The D2PCR™ Buffer is designed to offer a rapid and simple protocol for generating ready-to-use PCR templates. These templates can be directly used for the subsequent PCR without any further processing of the DNA. The D2PCR™ Buffer is...