Serious dermatological reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in both children and adults in association with TRILEPTAL use. Such serious skin reactions may be life threatening, and some patients have required hospitalization with very rare reports of fatal outcome. The median time of onset for reported cases was 19 days after treatment initiation. Recurrence of the serious skin reactions following rechallenge with TRILEPTAL has also been reported.

The reporting rate of TEN and SJS associated with TRILEPTAL use, which is generally accepted to be an underestimate due to underreporting, exceeds the background incidence rate estimates by a factor of 3- to 10-fold. Estimates of the background incidence rate for these serious skin reactions in the general population range between 0.5 to 6 cases per million-person years. Therefore, if a patient develops a skin reaction while taking TRILEPTAL, consideration should be given to discontinuing TRILEPTAL use and prescribing another antiepileptic medication.

Association With HLA-B*1502

Patients carrying the HLA-B*1502 allele may be at increased risk for SJS/TEN with TRILEPTAL treatment. Human Leukocyte Antigen (HLA) allele B*1502 increases the risk for developing SJS/TEN in patients treated with carbamazepine. The chemical structure of TRILEPTAL is similar to that of carbamazepine. Available clinical evidence, and data from nonclinical studies showing a direct interaction between TRILEPTAL and HLA-B*1502 protein, suggest that the HLA-B*1502 allele may also increase the risk for SJS/TEN with TRILEPTAL. 

The frequency of HLA-B*1502 allele ranges from 2% to 12% in Han Chinese populations, is about 8% in Thai populations, and above 15% in the Philippines, and in some Malaysian populations. Allele frequencies up to about 2% and 6% have been reported in Korea and India, respectively. The frequency of the HLA-B*1502 allele is negligible in people from European descent, several African populations, indigenous peoples of the Americas, Hispanic populations, and in Japanese (< 1%). 

Testing for the presence of the HLA-B*1502 allele should be considered in patients with ancestry in genetically at-risk populations, prior to initiating treatment with TRILEPTAL. The use of TRILEPTAL should be avoided in patients positive for HLA-B*1502 unless the benefits clearly outweigh the risks. Consideration should also be given to avoid the use of other drugs associated with SJS/TEN in HLA-B*1502 positive patients, when alternative therapies are otherwise equally acceptable. Screening is not generally recommended in patients from populations in which the prevalence of HLA-B*1502 is low, or in current TRILEPTAL users, as the risk of SJS/TEN is largely confined to the first few months of therapy, regardless of HLA-B*1502 status. 

The use of HLA-B*1502 genotyping has important limitations, and must never substitute for appropriate clinical vigilance and patient management. The role of other possible factors in the development of, and morbidity from, SJS/TEN, such as AED dose, compliance, concomitant medications, comorbidities, and the level of dermatologic monitoring have not been well characterized.