March 17, 2008
Dear Health Care Professional:
Subject: New Safety Information for the anti-epileptic drug TEGRETOL*
Novartis Pharmaceuticals Canada Inc., following discussion with Health Canada, would like to inform you about new safety information in the Product Monograph for TEGRETOL* (carbamazepine).
The TEGRETOL* Product Monograph has been revised to include the following safety information in the WARNINGS section:
Serious and sometimes fatal dermatologic reactions, including Toxic Epidermal Necrolysis (TEN) and Stevens-Johnson Syndrome (SJS), have been reported with TEGRETOL*. Should signs and symptoms suggest a serious skin reaction such as SJS or TEN, TEGRETOL* should be withdrawn at once and alternative therapy should be considered.
The risk of SJS and TEN exists in all patients, but these reactions are generally very rare. However, in some Asian countries the risk is estimated to be approximately 10 times higher than in Western countries.
In studies that included small samples of patients of Han Chinese ancestry a strong association was found between the risk of developing SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA-B gene.
The HLA-B*1502 allele is found almost exclusively in individuals with ancestry across broad areas of Asia. Therefore, physicians should consider HLA-B*1502 genotyping as a screening tool in genetically at-risk patients. HLA-B*1502 genotyping must never substitute for appropriate clinical vigilance and patient management.
Until further information is available, the use of TEGRETOL* and other anti-epileptic drugs associated with SJS/TEN should be avoided in patients who test positive for the HLA-B*1502 allele.Retrospective case-control studies in patients of Han Chinese ancestry have shown a strong association between the development of these severe skin reactions and the presence of HLA-B*1502, an inherited allelic variant of the HLA-B gene. The prevalence of this allele is negligible in Western Caucasian populations but is approximately 5-10% in Han Chinese, and ranges from <1% to over 15% in other Asian ethnic populations.