Table 1.

Description of pharmacogenomic information in the five drug labels of the United States, European Union (EU) or the United Kingdom (UK), Canada, Australia, Singapore, and Japan.

Drugs	Biomarker	US	EU or UK	Canada	Australia	Singapore	Japan
Allopurinol	HLA-B*58:01	(Warnings) • This drug should be discontinued at the first appearance of skin rash or other signs which may indicate an allergic reaction. • In some instances a skin rash may be followed by more severe hypersensitivity reactions such as exfoliative, urticarial, and purpuric lesions, as well as SJS (erythema multiforme exudativum), DRESS and/or generalized vasculitis, irreversible hepatotoxicity, and, on rare occasions, death.	(EU, Special Warnings and Precautions for Use) • The HLA-B*5801 allele is reportedly associated with the risk of developing allopurinol related hypersensitivity syndrome and SJS/TEN. • Screening for HLA-B*5801 should be considered before starting treatment with allopurinol in patient subgroups where the prevalence of this allele is known to be high.	(Warnings) • Allopurinol should be discontinued immediately at the appearance of a skin rash, as the rash may be, in some instances, followed by a more severe hypersensitivity reaction, including SJS, DRESS, and TEN.	(Special Warnings and Precautions for Use) • The HLA-B*5801 allele is known to be associated with the risk of developing allopurinol related hypersensitivity syndrome and SJS/TEN. • Screening for HLA-B*5801 should be considered before starting treatment in patient subgroups where the prevalence of this allele is known to be high.	(Warnings and Precautions) • The HLA-B*5801 allele is reportedly associated with the risk of developing allopurinol related hypersensitivity syndrome and SJS/TEN. • Screening for HLA-B*5801 should be considered before starting treatment with allopurinol in patient subgroups where the prevalence of this allele is known to be high.	(Side Effects/Other Precautions) • A previous report has presented the association of HLA-B*5801 and SJS/TEN in Han Chinese, Japanese and European populations. • Allele frequency of HLA-B*5801 in Japanese and European population is very low (0.010–0.020) when compared with that in Han Chinese (0.20–0.30).
Carbamazepine	HLA-B*15:02	(Boxed Warnings) • HLA-B*1502 is found almost exclusively in patients with ancestry across broad areas of Asia. • Patients with ancestry in genetically at-risk populations should be screened for the presence of HLA-B*1502 prior to initiating treatment with carbamazepine. • Patients testing positive for the allele should not be treated with carbamazepine unless the benefit clearly outweighs the risk.	(EU, Special Warnings and Precautions for Use) • Whenever possible, these individuals should be screened for this allele before starting treatment with carbamazepine or chemically-related active substances. • If patients of these ethnic origins are tested positive for HLA-B*1502 allele, the use of eslicarbazepine acetate may be considered if the benefits are thought to exceed risks.	(Boxed Serious Warnings and Precautions) • The HLA-B*1502 allele is found almost exclusively in individuals with ancestry across broad areas of Asia. • Recommended that physicians consider HLA-B*1502 genotyping as a screening tool in genetically at-risk populations. • Until further information is available, the use of carbamazepine and other antiepileptic drugs associated with SJS/TEN should be avoided in patients who test positive for the HLA-B*1502 allele.	(Special Warnings and Precautions for Use) • Testing for the presence of HLA-B*1502 allele should be considered in patients with ancestry in genetically at-risk populations, prior to initiating treatment with carbamazepine. • The use of carbamazepine should be avoided in tested patients who are found to be positive for HLA-B*1502 unless the benefits clearly outweigh the risks.	(Warnings and Precautions) • Testing for the presence of HLA-B*1502 allele is highly recommended prior to the initiation of carbamazepine therapy in new patients of Asian ancestry. • The use of carbamazepine should be avoided in tested patients who are found to be positive for HLA-B*1502 unless the benefits clearly outweigh the risks.	(Side Effects/Other Precautions) • Citing a paper showing association of HLA-B*1502 and SJS/TEN in Han Chinese populations. • Allele frequency of HLA-B*1502 in Japanese population is very low (0.001) compared to that in Han Chinese (0.019–0.124)
	HLA-A*31:01	(Warning) • The risks and benefits of carbamazepine therapy should be weighed before considering carbamazepine in patients known to be positive for HLA-A*3101.	(EU, Special Warnings and Precautions for Use) • There are insufficient data supporting a recommendation for HLA-A*3101 screening before starting carbamazepine or chemically-related compounds treatment. • If patients of European descent or Japanese origin are known to be positive for HLA-A*3101 allele, the use of carbamazepine or chemically-related compounds may be considered if the benefits are thought to exceed risks.	(Boxed Serious Warnings and Precautions) • Recommending that physicians consider HLA-A*3101 genotyping as a screening tool in genetically at-risk populations. • Until further information is available, the use of carbamazepine and other antiepileptic drugs associated with SJS/TEN should be avoided in patients who test positive for the HLA-A*3101 allele.	(Special Warnings and Precautions for Use) • Testing for the presence of HLA-A*3101 allele should be considered in patients with ancestry in genetically at-risk populations, prior to initiating treatment with carbamazepine. • The use of carbamazepine should be avoided in patients who are found to be positive for HLA-A*3101, unless the benefits clearly outweigh the risks.	(Warnings and Precautions) • Testing for the presence of HLA-A*3101 allele should be considered in patients with ancestry in genetically at-risk populations prior to initiating treatment with carbamazepine. • The use of carbamazepine should be avoided in patients who are found to be positive for HLA-A*3101, unless the benefits clearly outweigh the risks.	(Side Effects/Other Precautions) • Citing a paper showing association of HLA-A*3101 and severe cutameous adverse reactions in Japanese. • Allele frequency of HLA-A*3101 in Japanese population is relatively high (0.071–0.120).
Oxcarbazepine	HLA-B*15:02	(Warnings) • Patients who have had hypersensitivity reactions to carbamazepine should be informed that approximately 25–30% patients with reactions are known to experience hypersensitivity reactions with oxcarbazepine. • If signs or symptoms of hypersensitivity develop, oxcarbazepine should be discontinued immediately.	(UK, Warnings and Precautions) • The risk of serious skin reactions in patients of Han Chinese or Thai origin associated with carbamazepine or chemically-related compounds may be predicted by testing a blood sample from these patients. • Your doctor should be able to advise if a blood test is necessary before taking oxcarbazepine.	(Boxed Warnings and Precautions) • The HLA-B*1502 allele is found almost exclusively in individuals with ancestry across broad areas of Asia. • It is therefore, recommended that physicians consider HLA-B*1502 genotyping as a screening tool in genetically at-risk populations. • Until further information is available, the use of oxcarbazepine and other anti-epileptic drugs associated with SJS/TEN should be avoided in patients who test positive for the HLA-B*1502 allele.	(Special Warnings and Precautions for Use) • As the chemical structure of oxcarbazepine is similar to that of carbamazepine, there is a possibility that patients carrying the HLA-B*1502 allele also have an increased risk of SJS/TEN skin reactions with oxcarbazepine. • Testing for the presence of the HLA-B*1502 allele should be considered in patients with an ancestry of genetically at-risk populations, prior to initiating treatment with oxcarbazepine. • The use of oxcarbazepine should be avoided in tested patients who are found to be positive for HLA-B*1502 unless the benefits clearly outweigh the risks.	Not approved	(Boxed Warnings/Side Effects/Other Precautions) • Patients treated with oxcarbazepine may present the appearance of severe cutaneous adverse reactions such as TEN, SJS, and DIHS. • A report showing allele frequency of HLA-B*1502 and HLA-A*3101 in Japanese population.
	HLA-A*31:01	• Included in the above section.	• Included in the above section.	(Boxed Warnings and Precautions) • Retrospective genome-wide studies in Japanese and Northern European populations reported an association between severe skin reactions (SJS, TEN, DRESS, AGEP, and maculopapular rash) associated with carbamazepine use and the presence of the HLA-A*3101 allele in these patients.	(Special Warnings and Precautions for Use) • As the chemical structure of oxcarbazepine is similar to that of carbamazepine, there is a possibility that patients carrying the HLA-A*3101 allele also have an increased risk of SJS/TEN skin reactions with oxcarbazepine.		• Included in the above section.
Phenytoin	HLA-B*15:02	(Warnings and Precautions) • HLA-B*1502 may be a risk factor for the development of SJS/TEN in patients of Asian ancestry taking other antiepileptic drugs associated with SJS/TEN, including phenytoin. • Consideration should be given to avoiding phenytoin as an alternative for carbamazepine in patients positive for HLA-B*1502.	(UK, Special Warnings and Precautions for Use) • HLA-B* 1502 may be a risk factor for the development of SJS/TEN in patients of Asian ancestry taking drugs associated with SJS/TEN, including phenytoin. • Consideration should be given to avoiding the use of drugs associated with SJS/TEN, including phenytoin, in HLA-B*1502 positive patients when alternative therapies are otherwise equally available.	(Warnings and Precautions) • The HLA-B*1502 allele is found almost exclusively in individuals with ancestry across broad areas of Asia. • Physicians should consider HLA-B *1502 genotyping as a screening tool in these patients. • The use of phenytoin and other anti-epileptic drugs associated with SJS/TEN should also be avoided in patients who test positive for the HLA-B*1502 allele.	(Special Warnings and Precautions for Use) • HLA-B*1502 may be a risk factor for developing SJS/TEN in patients of Asian ancestry taking drugs associated with SJS/TEN, including phenytoin. • Consideration should be given to avoiding the use of drugs associated with SJS/TEN, including phenytoin, in HLA-B*1502-positive patients when alternative therapies are otherwise equally available.	(Special Warnings and Precautions for Use) • HLA-B*1502 may be a risk factor for the development of SJS/TEN in patients of Asian ancestry taking drugs associated with SJS/TEN, including phenytoin. • Consideration should be given to avoiding the use of drugs associated with SJS/TEN, including phenytoin, in HLA-B*1502-positive patients when alternative therapies are otherwise equally available.	(Side Effects) • Patients treated with phenytoin may present the appearance of severe cutaneous adverse reactions such as TEN and SJS.
Fosphenytoin	HLA-B*15:02	(Warnings and Precautions) • Consider avoiding fosphenytoin as an alternative to carbamazepine in patients who are positive for HLA-B*1502 or in CYP2C9*3 carriers. • Fosphenytoin should be utilized for CYP2C9*3 carriers; consider starting at the lower end of the dosage range.	(UK, Special Warnings and Precautions for Use) • Fosphenytoin can cause SCARs such as AGEP, exfoliative dermatitis, SJS, TEN and DRESS which can be fatal. • Limited evidence suggests that HLA-B*1502 may be a risk factor for the development of SJS/TEN in patients of Asian ancestry taking drugs associated with SJS/TEN, including phenytoin.	(Warnings) • The HLA-B*1502 allele is found almost exclusively in individuals with ancestry across broad areas of Asia. • Physicians should consider HLA-B *1502 genotyping as a screening tool in these patients. • Until further information is available, the use of fosphenytoin and other anti-epileptic drugs associated with SJS/TEN should also be avoided in patients who test positive for the HLA-B*1502 allele.	Not approved	Not approved	(Side Effects) • Patients treated with fosphenytoin may present the appearance of severe cutaneous adverse reactions such as TEN and SJS.

AGEP, acute generalized exanthematous pustulosis; DIHS, drug-induced hypersensitivity syndrome; DRESS, drug reaction with eosinophilia and systemic symptoms; SCAR, severe cutaneous adverse reactions; SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis.