Carbamazepine Label Gets Warning for Asian Patients

Article excerpt

Patients of Asian ancestry are at significantly increased risk for fatal skin reactions when treated with carbamazepine and should first undergo genetic testing to assess their risk before initiating therapy, according to an alert issued by the Food and Drug Administration.

People found to carry the human leukocyte antigen--B*1502 allele should forgo treatment with carbamazepine, unless the expected benefit clearly outweighs the risk, according to the FDA's alert. The fatal skin reactions, which include Stevens-Johnson syndrome and toxic epidermal necrolysis, occur more commonly in patients with the human leukocyte antigen--B*1502 allele. People with ancestry across broad areas of Asia, including South Asian Indians, account for almost all carriers of this allele.

The test for the allele is commercially available.

The prevalence of the HLA-B*1502 allele may be 10%-15% of the populations of China, Taiwan, Thailand, Malaysia, Indonesia, and the Philippines. In South Asia, including India, the prevalence is thought to be 2%-4%, according to a new boxed warning added to carbamazepine labeling.

The prevalence of the allele in patients of Japanese and Korean descent is thought to be less than 1%.

Overall, the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis associated with carbamazepine use is thought to be 1 patient to 6 patients per 10,000 users in countries with a primarily white population. However, the rate may be 10 times higher in Asian countries, according to the FDA.

One case-control study from Taiwan reported that 59 of 60 patients who developed Stevens-Johnson syndrome or toxic epidermal necrolysis associated with carbamazepine had the allele. That compared with a 4% incidence of the allele in patients who tolerated carbamazepine. The findings suggested an absolute risk of 5% in persons positive for the allele (Pharmacogenet. …