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Consider genotyping before carbamazepine use.

Before carbamazepine is prescribed, screening patients for the presence of the HLA-B*1502 and the HLA-A*3101 alleles will identify those most likely to develop potentially lethal hypersensitivity reactions, according to two separate reports.

In the first report, researchers identified 8% of 4,855 Taiwanese patients as carriers of the HLA-B*1502 allele, preventing 10 cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) that would have developed if no screening had taken place.

In the second report, Northern European carriers of the HLA-A*3101 allele were found to have a probability of 26% for developing hypersensitivity reactions to carbamazepine, compared with 3.8% fore those who did not carry the allele.

Both reports suggest that genetic screening for these alleles before prescribing carbamazepine is now warranted, the investigators said.

In the first study, Pei Chen, Ph.D., of Academia Sinica, Taipei, and associates gave prescriptions for carbamazepine during a 3-year period at 23 hospitals throughout Taiwan.

Of the 4,855 subjects, 372 (8%) were positive for HLA-B*1502 and did not take carbamazepine. Some HLA-B*1502-positive patients were given alternative therapies, while those negative for the allele were started on carbamazepine and closely monitored for 2 months.

No patients developed SJS or TEN, the most serious adverse reactions associated with carbamazepine. In contrast, at least 10 cases of SJS or TEN would be expected to develop in an unscreened population of this size, the researchers said (N. Engl. J. Med. 2011;364:1126-33).

Adverse cutaneous reactions that did occur were described as "mild, localized, and transient."

In the second report, Mr. Mark McCormack of the Royal College of Surgeons in Ireland, Dublin, and his associates genotyped 22 patients of northern European ancestry who developed carbamazepine-induced hypersensitivity syndrome and compared the results with those from 2,691 healthy controls in a blood-sample database. They found a strong association between the hypersensitivity syndrome and carriage of the HLA-A*3101 allele.

In a separate genomewide association study, the researchers compared samples from 106 patients with carbamazepine-induced maculopapular exanthema and 1,553 control subjects. They found a strong association between carbamazepine-induced maculopapular exanthema and the HLA-A*3101 allele.

The investigators then searched for the HLA-A*3101 allele in samples from 12 patients who had carbamazepine-induced SJS or TEN. Five (42%) of the affected subjects carried the allele, compared with 10 (4%) of 257 control subjects.

On this basis, "we calculated that the presence of HLA-A*3101 had a sensitivity of 26% and a specificity of 96% as a predictor of carbamazepine-associated hypersensitivity" in patients of northern European descent, Mr. McCormack and his colleagues wrote (N. Engl. J. Med. 2011;364:1134-43).

Assuming that hypersensitivity to carbamazepine in the general U.K. population is approximately 5%, "the presence of the HLA-A*3101 allele increases the [absolute] risk of hypersensitivity to 26%, whereas its absence reduces the [absolute] risk to 3.8%."

Dr. McCormack and his associates suggested that "consideration be given to adding the association with HLA-A*3101 to the drug label for carbamazepine."

Dr. Chen's study was funded by the National Science Council of Taiwan, the Taiwan Drug Relief Foundation, and the Academy-Industry Collaboration Program. Some of Dr. Chen's associates reported ties to Pharmigene Inc., and some reported filing a patent for a risk assessment tool for adverse drug reactions. Dr. McCormack's study was funded by the U.K. Department of Health, the Wellcome Trust, Brainwave-the Irish Epilepsy Association, and several other sources. Dr. McCormack's associates reported ties to numerous industry sources.


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Title Annotation:NEUROLOGY
Author:Moon, Mary Ann
Publication:Internal Medicine News
Date:Apr 15, 2011
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