FDA Warns of HLA Allele Linked to Skin Reaction with Carbamazepine

Marianne Mattera
ROCKVILLE, Md., Dec. 12 -- Stevens Johnson syndrome or related toxic epidermal necrolysis may be caused by carbamazepine therapy, especially in patients of Asian ancestry with a particular HLA allele, according to an FDA safety alert.
The HLA-B*1502 allele is found almost exclusively in patients of Asian ancestry and is particularly prevalent in China, Thailand, Malaysia, Indonesia, the Philippines, and Taiwan, and to a lesser degree in South Asia, including India.
The agency recommended genetic testing for the HLA-B*1502 allele before prescribing carbamazepine for most patients of Asian ancestry. Carbamazepine is FDA-approved for treatment of epilepsy, mania/bipolar disorder, and neuropathic pain.
If patients test positive, carbamazepine should not be started unless the expected benefit clearly outweighs the increased risk of serious skin reactions, said the FDA. If patients test negative, they have a low risk, but dangerous skin reactions can still rarely occur.
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, the agency added.
Post-marketing adverse events reported to the World Health Organization and carbamazepine manufacturers pointed to a rate of the skin conditions that is about 10 times higher in Asian countries than in mainly Caucasian populations.
One study pointed to 5% absolute risk of Stevens Johnson syndrome and toxic epidermal necrolysis in HLA-B*1502-positive patients exposed to carbamazepine.
Revised product information will indicate the association of carbamazepine with the two skin disorders, the FDA said.
Stevens Johnson syndrome and toxic epidermal necrolysis are blistering reactions of the skin and mucous membranes that can be permanently disabling or fatal. The rash, which is often preceded by flu-like symptoms, usually appears across the face or trunk, and may spread to other parts of the body.