The Food and Drug Administration (FDA) recently issued a warning about the use of carbamazepine (Carbatrol, Equetro, Tegretol, Tegretol XR and generic formulations) in patients who have a very specific type of an HLA gene. Patients with HLA-B*1502 (an inherited variant of the HLA-B gene) are at substantially increased risk of developing serious, potentially life threatening skin reactions called toxic epidermal necrolysis and Stevens-Johnson syndrome, characterized by multiple skin lesions, blisters, fever, itching and other symptoms, compared to people without this gene.

About the gene: This gene is found almost exclusively in patients with Asian ancestry. While it appears that patients with ancestry from many parts of Asia, including South Asian Indians may have an increased chance of having this gene, the exact frequency for various specific ethnic groups is still somewhat unclear. It is believed that as many as 10-15% of patients from China, Taiwan, Thailand, the Philippines, Malaysia and Indonesia may test positive for this gene. Japanese and Korean patients may have a lower frequency, less than 1 percent, of carrying this gene.

Prior testing: Until more is known, the FDA is advising that patients of Asian descent, including those of mixed ancestry, undergo a blood test prior to starting carbamazepine treatment. Testing for HLA-B*1502 is a commonly performed blood test in patients prior to having organ transplants, in order to determine tissue compatibility. It is important to recognize that testing positive for this gene is not abnormal, and there are no other known medical risks associated with having it other than an increased risk of serious rash from carbamazepine.

Should you avoid the drug? Those patients who test positive for the specific type of HLA gene should discuss with their doctor whether the possible benefits outweigh the risks and whether there are any other options besides carbamazepine. In addition, although it is not clear what (if any) additional risks there might be, FDA is suggesting that physicians may want to avoid starting treatment with any antiepileptic drugs that have been associated with Stevens Johnson Syndrome as well.

About the syndrome: It is also important for patients to know that the vast majority of patients who do develop a serious skin rash, will do so within the first few months of treatment. So patients (including those testing positive for HLA-B*1502), who have been taking carbamazepine for more than several months are at very low risk of developing these serious rashes.

The full FDA article is available at:
http://www.fda.gov/cder/drug/InfoSheets/HCP/carbamazepineHCP.htm

Dr. Gidal, a member of the epilepsy.com board is a Professor at the University of Wisconsin School of Pharmacy and Department of Neurology, and Dr. Hayney is an Associate Professor at the University of Wisconsin, School of Pharmacy.

Edited by Steven C. Schachter, MD