Table 2.

Evidence-based pharmacogenomics and clinical implementation.

Associated drug	Genetic variant	Hypersensitivity	Ethnicity and Carriage rate (%)	Level of evidence	Stage of implementation
Abacavir	HLA-B*57:01	Hypersensitivity syndrome (NOT SJS/TEN) [2]	European (5~8%) African American (2–3%) Southeast Asian (<1%) Sub-Sahara African (<1%)	CPIC Level1- High PharmGKB Level2- 1A	U.S FDA3,4- PGx testing required Health Canada- PGx testing required EMA- PGx testing required PMDA- PGx testing required Singapore- PGx testing should be considered
Allopurinol	HLA-B*58:01	SJS/TEN and DRESS [5]	Southeast Asian (10–15%) Sub-Sahara African (10%)* European (1–6%)* African American (4%)	CPIC Level- High PharmGKB Level- 1A	American College of Rheumatology guideline- PGx testing recommended EMA- PGx testing recommended PMDA- Actionable PGx# TFDA- PGx testing recommended Singapore- PGx testing is not required as a standard of care
Carbamazepine	HLA-B*15:02	SJS/TEN [3,27,31]	Asian, particularly Han Chinese (10–15%) African (<1%) European (<0.1%)	CPIC Level- High PharmGKB Level- 1A	U.S FDA- PGx testing recommended Health Canada- PGx testing recommended EMA- PGx testing recommended PMDA- Actionable PGx TFDA- PGx testing required Singapore- PGx testing required
	HLA-A*31:01	SJS/TEN and DRESS and MPE [27,31]	European (≤6%) Korean (10%) Japanese (18%) Sub-Sahara African (<1%)	CPIC Level- High PharmGKB Level- 1A	U.S FDA- Actionable PGx Health Canada- PGx testing recommended EMA- PGx testing recommended PMDA- Actionable PGx
Dapsone	HLA-B*13:01	DRESS and SJS/TEN [4]	Southeast Asian (Chinese and Thai populations) (2–52%) European (Up to 4%)	CPIC Level- Low PharmGKB Level- 2A	Not available
Oxcarbazepine	HLA-B*15:02	SJS/TEN [29]	Asian, particularly Han Chinese (10–15%) African (<1%) European (<0.1%)	CPIC Level- High PharmGKB Level- 1A	U.S FDA- PGx testing recommended EMA- PGx testing recommended PMDA- Actionable PGx TFDA- PGx testing recommended
Phenytoin	CYP2C9*3	SJS/TEN and DRESS and MPE [28]	European (≤8%) Southeast Asian (≤5%) African (<1%)	CPIC Level- High PharmGKB Level- 1A	TFDA- Actionable PGx
	HLA-B*15:02	SJS/TEN and DRESS [28]	Asian, particularly Han Chinese (10–15%) African (<1%) European (<0.1%)	CPIC Level- High PharmGKB Level- 1A	U.S FDA- Actionable PGx Health Canada- PGx testing recommended TFDA- Actionable PGx
Vancomycin	HLA-A*32:01	DRESS [30]	European (6–7%) African American (3%)	Preliminary	Single allele testing methodology available

CPIC, Clinical Pharmacogenetics Implementation Consortium (https://cpicpgx.org); CYP, Cytochromes P450; DRESS, drug reaction with eosinophilia and systemic symptoms; EMA, European Medicines Agency; FDA, Food and Drug Administration; HLA, human leukocyte antigen; MPE, maculopapular eruption; PharmGKB, a pharmacogenomics knowledge resource (https://www.pharmgkb.org); PMDA, Pharmaceuticals and Medical Devices Agency in Japan; PGx, pharmacogenomics; SJS/TEN, Stevens-Johnson syndrome and toxic epidermal necrolysis; TFDA, Taiwan Food and Drug Administration.

¹The levels of evidence graded by the Clinical Pharmacogenetics Implementation Consortium as defined at https://cpicpgx.org/levels-of-evidence

²PharmGKB Clinical Annotation Levels of Evidence as defined at https://www.pharmgkb.org/page/clinAnnLevels

³PharmGKB Drug Label Annotations- https://www.pharmgkb.org/labelAnnotations

⁴U.S FDA Table of Pharmacogenomic Biomarkers in Drug Labeling- https://www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling; https://www.fda.gov/media/124784/download.

^*NPV of HLA-B*58:01 for SJS/TEN and DRESS and Africans and Europeans is lower than Southeast Asians (explains approximately 60% of disease).

^#Actionable PGx- Product labeling includes specific actions to be taken based on the biomarker information.