FDA Warns of Genetic Link to Carbamazepine Skin Reactions

Yael Waknine

December 13, 2007

December 13, 2007 — Patients with Asian ancestry should be screened for the human leukocyte antigen (HLA) allele HLA-B*1502 before receiving carbamazepine therapy, the US Food and Drug Administration (FDA) warned healthcare professionals yesterday.

A revised boxed warning for the product states that patients with this allele are at increased risk for Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), according to an alert sent from MedWatch, the FDA's safety information and adverse event reporting program.

HLA-B*1502 occurs almost exclusively in patients with Asian ancestry, and its incidence is highest (10% — 15%) in those individuals from parts of China, Thailand, Malaysia, Indonesia, the Philippines, and Taiwan. South Asians, including Indians, are at moderate risk (2% — 4%, but it may be higher in some groups), whereas patients with Japanese or Korean ancestry are at low risk (<1%).

In countries with mainly white populations, the overall rate of carbamazepine-related SJS/TEN is fairly low, estimated to be 1 to 6 per 10,000 newly exposed patients. Data recently reported to the World Health Organization and carbamazepine manufacturers suggest that this rate is 10-fold higher in some Asian countries.

Carbamazepine and other antiepileptic drugs associated with SJS/TEN should not be used in HLA-B*1502-positive patients unless the expected benefit clearly outweighs the increased risk for serious skin reactions.

The FDA notes that patients who have taken carbamazepine for more than a few months are at low risk for these events, including those who are positive for the HLA allele. However, SJS/TEN can still occur in patients who have negative test results.

Carbamazepine is indicated for the treatment of epilepsy, mania/bipolar disorder, and neuropathic pain. It is marketed under the brand names Carbatrol (Shire Development, Inc), Equetro (Validus Pharmaceutical, Inc), and Tegretol (Novartis Pharmaceuticals Corp) and is also available in generic formulations from several manufacturers.

Adverse events related to use of carbamazepine should be communicated to the FDA's MedWatch reporting program by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at https://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, Maryland 20852-9787.


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