Carbamazepine

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Patients carrying HLA-B*15:02 are at strongly increased risk for carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). HLA-B*1502-positive patients with CBZ-SJS/TEN have been reported from Asian countries: including China, Thailand, Malaysia, Indonesia, and India. HLA-B*1502 is rare among Caucasians or Japanese. 'Patients who test positive for HLA-B*1502 should not be treated with carbamazepine unless the expected benefit clearly outweighs the increased risk of SJS/TEN' (FDA ALERT 12/12/2007).

Guidelines USA: Patients with ancestry in Asia should be screened for the HLA-B*1502 allele prior to starting carbamazepine. 'Due to wide variability in rates of HLA-B*1502 even within ethnic groups, the difficulty in ascertaining ethnic ancestry, and the likelihood of mixed ancestry, screening for HLA-B*1502 should be performed for most patients of Asian ancestry' (12/12/2007).

Guidelines Netherlands: Genetic screening test for HLA-B*1502 is required before carbamazepine is administered to Han-Chinese and patients from Thailand.Consider genetic screening as well for patient originating from Malaysia, the Phillipines and India (Farmacotherapeutisch Kompas, 2016).

See also: Special topics: Carbamazepine-induced SJS/TEN

Singapore

Patients from Singapore have increased rates of carrying HLA-B*1502. Patients carrying HLA-B*1502 are at strongly increased risk for carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). Odds Ratio for SJS/TEN (Stevens Johnson Syndrome (SJS) and Toxic Epidermolytic Necrolysis (TEN)) in HLA-B*1502-positive patients relative to that in HLA-B*1502-negative patients was estimated by exact logistic regression to be 27.20 (95% CI 2.67 to 8).HLA-B*1502 positivity increases the odds of carbamazepine-induced severe adverse cutaneous drug reactions (SCDR) in Singapore children of Chinese and Malay ethnicity. Adverse drug reactions to carbamazepine occurred within 2 weeks and at low doses.(Chong, 2014).

The population mean value of carbamazepine clearance obtained in epileptic patients living in Singapore (mostly Chinese), was similar to that previously reported for patients with a very different ethnic (Caucasians and Blacks) or geographical background (South Africa, Europe and USA) (Chan,2001).

See also: special topics.

Thailand

There is a strong relationship between the HLA-B*1502 allele and carbamazepine-induced Stevens-Johnson syndrome in the Thai population.
The odds ratio (relationship between the presence of HLA-B*1502 in at least 1 allele and carbamazepine-induced Stevens-Johnson syndrome) according to the meta-analysis of Tangamornsuksan et al (2013) is 54.43 (95%CI: 16.28-181.96).
HLA-B*1502 was present in 100% (4 of 4) of the patients with carbamazepine-induced Stevens-Johnson syndrome and 19% (8 of 42) of the carbamazepine-tolerant patients in this study. This revealed a 100% (95% CI: 61%–100%) sensitivity and 75% (95% CI: 67%–90%) specificity of HLA-B*1502 as a test for CBZ-SJS in the Thai population.
(N=31 Thai epileptic patients, King Chulalongkorn Memorial Hospital, Bangkok), (Locharernkul et al. 2008).