Table 2.

Therapeutic recommendations where evidence exists for strong HLA associations for various adverse drug reaction phenotypes^†.

Medications	HLA	Phenotype	Populations studied	Therapeutic recommendation	Selected references
Abacavir	HLA-B*57:01	HSS	All	HLA-B*57:01 testing prior to abacavir prescription and avoid abacavir use in HLA-B*57:01 positive individuals	41,42,45–48
Carbamazepine	HLA-B*15:02§	SJS/TEN	Han Chinese (China, Hong Kong, Taiwan), Thai, Malaysian, Indian (South Asians)	Avoid carbamazepine in all HLA-B*15:02 positive individuals†† Screening currently recommended for at risk populations (Han Chinese, southeast and south Asians) or unknown ethnicity	51,58,64,167,168
Carbamazepine	HLA-A*31:01	DRESS/HSS>SJS/TEN	Han Chinese, Japanese, Korean, Caucasian	If alternative therapeutic agent exists, avoid carbamazepine in all carbamazepine naïve HLA-A*31:01 positive individuals	51,58,63,52,55,61,62,64
Allopurinol	HLA-B*58:01	DRESS/HSS and SJS/TEN	Han Chinese (China and Hong Kong), Thai, Korean, Japanese, European	Avoid allopurinol use in the setting of allopurinol naïve HLA-B*58:01 posivite individuals Widespread guidelines for screening prior to use have not been issued¶	54,66–74

SCAR: severe cutaneous adverse reactions, HLA: human leucocyte antigen, HSS: hypersensitivity syndrome, SJS: Stevens-Johnson syndrome, TEN: toxic epidermal necrolysis, DRESS: drug reaction with eosinophilia and systemic symptoms.

^†For any individual carrying an HLA risk allele, if they have already tolerated the drug for > 12 continuous weeks currently or in the past, then it is safe for them to continue the drug or for the drug to be reinstituted in the future.

^§Carbamazepine SJS/TEN is also associated with other B75 serotype HLA alleles such as HLA-B*15:21, B*15:08, B*15:11 and potentially B*15:30 and B*15:31, therefore additional caution should be exerted for carbamazepine use if these HLA types are identified.

^††Although a much weaker association exists between HLA-B*15:02 and other aromatic amine anticonvulsants, such as oxcarbamazepine, eslicarbamzepine, lamotrigine, phenytoin and fosphenytoin, consideration should be given to choosing an alternative non-aromatic anticonvulsant in the case of identified HLA-B*15:02+.

^¶The American College of Rheumatology Guidelines for Management of Gout (2012) have recommended HLA-B*58:01 testing prior to allopurinol prescription in specific popualtions including 1) those of increased risk (Southeast Asian) and 2) Subpopualtions with increase risk based on advanced chronic renal failure (stage 3).¹⁶⁹