Table 3.

CPIC (2016) Recommendations for Carbamazepine Therapy based on HLA-B and HLA-A Genotype.

GenotypeaImplicationTherapeutic recommendationClassification of recommendationsConsiderations for other aromatic anticonvulsants
HLA-B*15:02 negative and HLA-A*31:01 negativeNormal risk of carbamazepine-induced SJS/TEN, DRESS, and MPEUse carbamazepine per standard dosing guidelines.bStrongN/A
HLA-B*15:02 negative and HLA-A*31:01 positiveGreater risk of carbamazepine-induced SJS/TEN, DRESS, and MPEIf patient is carbamazepine-naïve and alternative agents are available, do not use carbamazepine.StrongOther aromatic anticonvulsantsd have very limited evidence, if any, linking SJS/ TEN, DRESS, and/or MPE with the HLA-A*31:01 allele, and thus no recommendation can be made with respect to choosing another aromatic anticonvulsant as an alternative agent.
If patient is carbamazepine-naïve and alternative agents are not available, consider the use of carbamazepine with increased frequency of clinical monitoring. Discontinue therapy at first evidence of a cutaneous adverse reaction.OptionalN/A
The latency period for cutaneous adverse drug reactions is variable depending on phenotype; however, all usually occur within three months of regular dosing. Therefore, if the patient has previously used carbamazepine consistently for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of carbamazepine.OptionalPrevious tolerance of carbamazepine is not indicative of tolerance to other aromatic anticonvulsants.d
HLA-B*15:02 positivec and any HLA-A*31:01 genotype (or HLA-A*31:01 genotype unknown)Greater risk of carbamazepine-induced SJS/TENIf patient is carbamazepine-naïve, do not use carbamazepine.StrongOther aromatic anticonvulsantsd have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent.
The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (4-28 days), and cases usually occur within three months of dosing; therefore, if the patient has previously used carbamazepine consistently for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of carbamazepine in the future.OptionalPrevious tolerance of carbamazepine is not indicative of tolerance to other aromatic anticonvulsants.d

DRESS, drug reaction with eosinophilia and systemic symptoms; MPE, maculopapular exanthema; N/A, not applicable; SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis.
aIf only HLA-B*15:02 was tested, assume HLA-A*31:01 is negative and vice versa.
bHLA-B*15:02 has a 100% negative predictive value for carbamazepine-induced SJS/ TEN, and its use is currently recommended to guide the use of carbamazepine and oxcarbazepine only. Because there is a much weaker association and less than 100% negative predictive value of HLA-B*15:02 for SJS/TEN associated with other aromatic anticonvulsants, using these drugs instead of carbamazepine or oxcarbazepine in the setting of a negative HLA-B*15:02 test in Southeast Asians will not result in prevention of anticonvulsant-associated SJS/TEN.
cIn addition to HLA-B*15:02, the risk for carbamazepine-induced SJS/TEN has been reported in association with the most common B75 serotype alleles in Southeast Asia, HLA-B*15:08, HLA-B*15:11, and HLA- B*15:21. Although not described, the possibility of carbamazepine-induced SJS/TEN in association with less frequently carried B75 serotype alleles, such as HLA- B*15:30 and HLA-B*15:31, should also be considered.
dAromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital.

This table is adapted from Phillips EJ, Sukasem C, Whirl-Carrillo M, Müller DJ, Dunnenberger HM, Chantratita W, Goldspiel B, Chen YT, Carleton BC, George ALJ, Mushiroda T, Klein T, Gammal RS, and Pirmohamed M. Clinical Pharmacogenetics Implementation Consortium Guideline for HLA Genotype and Use of Carbamazepine and Oxcarbazepine: 2017 Update. Clinical pharmacology and therapeutics (4).

From: Carbamazepine Therapy and HLA Genotype

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