A Canadian drug safety group has recommended genetic testing for gene variants associated with the risk of developing Stevens-Johnson syndrome, a serious, possibly fatal, skin reaction in patients taking the drug carbamazepine.
The Canadian Pharmacogenomics Network for Drug Safety (CPNDS) has recommended testing for the alleles HLA-B*15-02 and HLA-A*31:01 that affect histocompatibility before patients begin taking the anti-seizure medication carbamazepine. The study was published online March 5 in Epilepsia.
Carbamazepine – available under the brand names Tegretol, Tegretol XR, Carbatrol, Epitol, and Equetro – is prescribed for certain types of seizures (epilepsy), certain types of pain, and for bipolar disorder (manic-depressive illness), according to the Mayo Clinic.
CPNDS recommends testing for the two alleles, which are associated with severe, sometimes fatal, skin reactions that can develop in patients taking carbamazepine, Skin & Allergy News reports. Such reactions usually occur within the first three months of treatment. Dr. Ursula Amstutz of the University of British Columbia, Vancouver, one of the study’s authors, says HLA-B*15-02 is associated with Stevens-Johnson syndrome and toxic epidermal necrolysis, (TEN) and HLA-A*31:01 is associated with SJS, TEN, acute generalized exanthematous pustulosis, and less-severe skin reactions. HLA-B*15-02 is most common in patients of Chinese, Thai, Malaysian, and Indian descent and is strongly associated with Stevens-Johnson syndrome and toxic epidermal necrolysis in those taking carbamazepine. HLA-A*31:01 is found among white, Japanese, Korean, and Chinese patients, and people of mixed descent. It is found in most ethnic groups.
Stevens-Johnson syndrome – a serious disorder in which the skin and mucous membranes react severely to a medication or infection – often begins with flu-like symptoms, followed by a painful red or purplish rash that spreads and blisters, the Mayo Clinic says. The top layer of skin eventually dies and is shed. Patients have suffered sepsis, eye damage, damage to internal organs, and permanent skin damage. Stevens-Johnson syndrome is considered a medical emergency and treatment usually requires hospitalization, often in an intensive care or burn unit. In December 2013, the U.S. Food and Drug Administration (FDA) warned of an SJS risk with another anti-seizure drug, Onfi (clobazam), and the FDA revised the Onfi label and medication guide.
CPNDS recommends that genetic testing for the alleles be carried out before starting carbamazepine or within the first three months of starting treatment, Skin and Allergy News reports. If a patient has not had a reaction after at least three months of treatment, screening is not necessary. But any patient who has had a skin reaction while taking carbamazepine – for any length of time – should have genetic testing. Patients taking carbamazepine should watch for signs of a reaction, which is possible even after negative test results.