Carbamazepine: Dangerous & fatal skin reactions

admin December 14th, 2007

Carbamazepine’s propensity to skin rashes is well known, with 5-20% of patients developing skin rashes which can lead to drug withdrawal. It is also associated relatively rarely with more serious skin reactions such as exfoliative dermititis, Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The FDA have issued information about a genetic susceptibility, mainly present in patients with an Asian/South Asia ancestory, and are advise that patients with such ancestory should be screened prior to treatment.

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.

An example of toxic epidermal necrolysis (TEN).

Further details, and evidence, are available from the FDA website. The FDA have provided a list of areas with higher prevalences of HLA-B*1502 (although many regions of Asia have not been studied), although they suggest the following figures to be no more than a rough guide in deciding which patients to screen:

  • 10-15% or more of patients may carry the allele in parts of China, Thailand, Malaysia, Indonesia, the Philippines, and Taiwan.
  • South Asians, including Indians, appear to have intermediate prevalence of HLA-B*1502, averaging 2 to 4%, but higher in some groups.
  • HLA-B*1502 appears to be present at a low frequency, <1%, in Japan and Korea.

Bottom Line: Although SJS and TEN rarely occur (1 to 6 cases per 10,000 new users ) they can be permanently disabling, and even fatal. Asian patients, including South Asian Indians, appear to have a tenfold increased risk of such serious skin reactions, and testing provides an indication of this increased risk to aid in risk benefit decisions about the appropriateness of therapy. Patients who have already taken carbamazepine for a few months without skin reactions, are at low risk of such reactions.

  • FDA
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