Clinical Review, Adverse Events
Clinical Review, Adverse Events Drug: Carbamazepine NDA: 16-608, Tegretol 20-712, Carbatrol 21-710, Equetro Adverse Event: Stevens-Johnson Syndrome Reviewer: Ronald Farkas, MD, PhD Medical Reviewer, DNP, ODE I 1. Executive Summary 1.1 Background Carbamazepine (CBZ) is an anticonvulsant with FDA-approved indications in epilepsy, bipolar disorder and neuropathic pain. CBZ is associated with Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), closely related serious cutaneous adverse drug reactions that can be permanently disabling or fatal. Other anticonvulsants, including phenytoin, phenobarbital, and lamotrigine are also associated with SJS/TEN, as are members of a variety of other drug classes, including nonsteriodal anti-inflammatory drugs and sulfa drugs. The incidence of CBZ-associated SJS/TEN has been considered “extremely rare,” as noted in current U.S. drug labeling. However, recent publications and postmarketing data suggest that CBZ- associated SJS/TEN occurs at a much higher rate in some Asian populations, about 2.5 cases per 1,000 new exposures, and that most of this increased risk is in individuals carrying a specific human leukocyte antigen (HLA) allele, HLA-B*1502. This HLA-B allele is present in about 5- to 20% of many, but not all, Asian populations, and is also present in about 2- to 4% of South Asians/Indians. The allele is also present at a lower frequency, < 1%, in several other ethnic groups around the world (although likely due to distant Asian ancestry). About 10% of U.S. Asians carry HLA-B*1502. HLA-B*1502 is generally not present in the U.S.
[Show full text]