Carbamazepine
Carbamazepine is a drug used to treat epilepsy, bipolar disorder, and certain types of nerve pain. It is a generic, sold under the trade names Carbatrol, Tegretol, or Equetro. Based on an adverse side effect predominantly affecting carriers of an HLA-B*1502 allele, which primarily occurs in Asians, the FDA released the following recommendation regarding having a "black box warning" for carbamazepine:
FDA ALERT [12/12/2007]: Dangerous or even fatal skin reactions (Stevens Johnson syndrome and toxic epidermal necrolysis), that can be caused by carbamazepine therapy, are significantly more common in patients with a particular human leukocyte antigen (HLA) allele, HLA-B*1502. This allele occurs almost exclusively in patients with ancestry across broad areas of Asia, including South Asian Indians. Genetic tests for HLA-B*1502 are already available. Patients with ancestry from areas in which HLA-B*1502 is present should be screened for the HLA-B*1502 allele before starting treatment with carbamazepine. If they test positive, carbamazepine should not be started unless the expected benefit clearly outweighs the increased risk of serious skin reactions. Patients who have been taking carbamazepine for more than a few months without developing skin reactions are at low risk of these events ever developing from carbamazepine. This is true for patients of any ethnicity or genotype, including patients positive for HLA-B*1502. This new safety information will be reflected in updated product labeling.
Full details are on the related FDA webpage.
SNPs that tag HLA-B*1502 include rs3909184 and rs2844682.
In Europeans, the HLA-A*3101 allele, found in about 2 - 5% of Northern Europeans, is significantly associated with the carbamazepine hypersensitivity syndrome, with odds ratios above 10. The presence of this HLA allele increases the risk from 5% to 26%, whereas its absence reduces the risk from 5% to 4%.[PMID 21428769]
A SNP that reliably serves as a proxy for the HLA-A*3101 allele, at least in populations of European descent, is rs1061235.[PMID 16998491]
Other SNPs influencing adverse drug reactions to carbamazepine include:
