People of Asian ancestry should take a genetic test before they are treated with drugs containing carbamazepine, the FDA announced on Dec. 12.
Drugs that contain the active ingredient are used to treat epilepsy, bipolar disorder, and neuropathic pain and are sold under brand names Tergretol, Equetro, and Carbatrol.
The prescribing information for these drugs already warn about the risk for developing rare but sometimes life-threatening skin reactions. The drug's makers, however, will now add the FDA's recommendation on genetic testing to their labeling. The reactions include toxic epidermal necrolysis and Stevens-Johnson syndrome, which can cause multiple skin lesions, blisters, fever, itching, and other symptoms.
Studies have reported that an inherited variant of the immune system gene HLA-B* 1502, which is found almost exclusively in people with Asian ancestry, is associated with a higher risk for developing these skin reactions. For example, a study in Taiwan found that 59 out of 60 patients who had developed skin disorders after taking carbamazepine tested positive for the gene. On the other hand, the incidence of HLA-B* 1502 amongst the carbamazepine-tolerant controls was only 4 percent, as reported in an April 2006 study in Pharmacogenetic Genomics.
The FDA noted that in countries with mainly white populations, the risk of these reactions is estimated to be about one to six per 10,000 new users of the drug, according to 1997 and 2005 studies in Neurology. But according to post-marketing adverse events reported to the World Health Organization, the risk is estimated to be about 10 times higher in some Asian countries.
So what's the take-home message for neurologists? According to the FDA, people who test positive for this gene shouldn't be treated with carbamazepine unless the benefit of the drug clearly outweighs the increased risk of these skin reactions.
Cynthia L. Harden, MD, director of Research and Program Development of the Comprehensive Epilepsy Center at the Weill Medical College of Cornell University in New York City, said she won't be taking any of her epilepsy patients off carbamazepine since any allergic reactions would occur in the first few months of taking the drug. For new patients, though, she will first consider other drugs.
“I think it's wonderful that we have this pharmaco-genomic information that can help us treat patients more safely but I think there should be an effort to more widely distribute this information,” she said.
FDA spokesperson Karen Mahoney said physicians will need to find a lab that does HLA typing. Many blood collection facilities and facilities with bone marrow and cord blood programs can do the test, she said. To find manufacturers of HLA test kits visit the FDA's products Web site: http://www.fda.gov/cber/efoi/510k.htm.
• Shuen-Iu H, Wen-Hung C, Yuan-Tsong C, et al. Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. Pharmacogenet Genomics
•Tennis P, Stern RS. Risk of serious cutaneous disorders after initiation of use of phenytoin, carbamazepine, or sodium valproate: A record linkage study. Neurology
•Mockenhaupt M, Messenheimer J, Schlingmann J. Risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in new users of antiepileptics. Neurology