Genetic testing for alleles that affect histocompatibility should be the rule for patients who initiate the drug carbamazepine, according to new recommendations issued by the Canadian Pharmacogenomics Network for Drug Safety.
Two variants are associated with the severe, sometimes deadly, skin reactions that carbamazepine can bring on, usually within the first 3 months of therapy. One (HLA-B*15-02) is a particularly high-risk allele that is not uncommon in patients of Chinese, Thai, Malaysian, and Indian descent. It’s strongly associated with Stevens-Johnson syndrome and toxic epidermal necrolysis in those taking carbamazepine.
HLA-A*31:01 has been found among white, Japanese, Korean, and Chinese patients; in fact, it is somewhat common in most ethnic groups and people of mixed descent. This allele is associated with Stevens-Johnson, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis, as well as some of the less-severe skin reactions, said Dr. Ursula Amstutz of the University of British Columbia, Vancouver, and her colleagues in the Network’s clinical recommendation group (Epilepsia 2014 March 5 [doi:10.1111/epi.12564]).
Genetic testing for the variants should be carried out before initiating treatment or within the first 3 months of treatment. But patients who have not had a reaction after at least 3 months’ treatment don’t need to be screened, advised the group, which used a systematic review of the literature to develop an expert consensus on the recommendations.
The group’s other recommendations include:
• Testing for HLA-B*15-02 should be done in all patients of the susceptible ethnic groups before treatment begins. It’s optional in groups where it is uncommon, but all drug-naïve patients should probably undergo the test.
• All patients, regardless of ethnicity, should undergo testing for HLA-A*31:01.
• Genetic testing should be done in patients who have previously experienced a skin reaction while taking carbamazepine, regardless of how long they have taken it.
• Negative tests don’t entirely rule out the possibility of a reaction, so patients, families, and physicians should still be alert for any early signs that one could develop.
One author was been a paid consultant for Novartis in legal cases relevant to carbamazepine-induced hypersensitivity. The others reported no relevant financial conflicts.
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