Safrina Dewi Ratnaningrum
  MNJ, pp. 40-46  


Carbamazepine as an antiepileptic drug that is used widely and was known can cause severe cutaneous adverse drug reactions like SJS-TEN. These adverse drug reactions is known to be associated with some specific HLA polymorphism in European populations (HLA-A*31: 01), China (HLA-A*31: 01; HLA-B*15: 02), Japan (HLA-A*31 : 01; HLA-B*15: 11), Korea HLA-A*31: 01; HLA-B*15: 02; HLA-B*15: 11), India (HLA-B*15: 02), Thailand (HLA-B*15: 02), and Malaysia (HLA-B*15: 02). Information related to certain HLA polymorphism is important to prevent adverse drug reaction but there is no sufficient data on the population of Indonesia.


Carbamazepine; Human Leukocyte Antigen (HLA); Steven-Johnson Syndrome (SJS); Toxic Epidermal Necrolysis (TEN)

Full Text:



Patsalos PN. Antiepileptic drug interactions: a clinical guide, 2nd ed. Springer, London. 2013.p437.

Thorn CF, Leckband SG, Kelsoe J, Leeder JS, Muller DJ, Klein TE, Altman RB. PharmGKB summary: carbamazepine pathway. Pharmacog Genom. 2011;21(12):906-10.

Montegazza M, Curia G, Biagini G, Ragsdale DS, Avoli M. Voltage-gated sodium channels as therapeutic target in epilepsy and other neurological disorders. Lancet Neurol. 2010;9:413-24.

Zeng K, Wang X, Xi Z, Yan Y. Adverse effects of carbamazepine, phenytoin, valproate and lamotrigine monotherapy in epileptic adult Chinese patients. Clin Neurol Neurosurg. 2010;112:291-5.

Bolognia JL, Jorizzo JL, Schaffer JV. Dermatology, 3rd ed. Elsevier Limited. 2012.p319-33.

Merk HF, Baron JM, Neis MM, Obrigkeit DH, Karlberg AT. Skin: Major target organ of allergic reactions to small molecular weight compounds. Toxicol App Pharmacol. 2007;224:313-317.

Fourie L, Breytenbach JC, Plessis JD, Goosen C, Swart H, Hadgraft J. Percutaneous delivery of carbamazepine and selected N-alkyl and N-hydroxyalkyl analogues. Int J Pharmaceutics. 2004;279:59-66.

Sharma VK, Sethuraman G, Minz A. Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and SJS-TEN overlap: A retrospective study of causative drugs and clinical outcome. Indian J Dermatol Venereol Leprol. 2008;74(8):238-40.

Berita MESO. Laporan kasus di Indonesia: carbamazepine. MESO. 2007;25(2):5.

Roujeau JC, Kelly JP, Naldi L, Rzany B, Stern RS, Anderson T, et al. Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. NEJM. 1995;333(24):1600-7.

Berita MESO. Laporan kasus (case reports): risiko efek samping carbamazepine dan profil laporan efek samping obat tahun 2008. MESO. 2009;27(1):4-5.

Berita MESO. Profil pelaporan efek samping obat yang diterima oleh Pusat Farmakovigilans Nasional Badan POM RI pada tahun 2011. MESO. 2012;30(1):6.

McCormack M, Alfirevic A, Bourgeois S, Farrel JJ, Kasperaviciute D, Carrington M, et all. HLAA*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med. 2011;364:1134-43.

Mehta TY, Prajapati LM, Mittal B, Joshi CG, Sheth JJ, Pattel DB, Dave DM, Goyal RK. Association of HLA-B*15:02 allele and carbamazepine-induced Stevens-Johnsons syndrome among Indians. Indian J Dermatol Venereol Leprol. 2009;75(6):579-82.

Wang Q, Zhou J, Zhou L, Chen Z, Fang Z, Chen S, et all. Association between HLA-B*1502 allele and carbamazepine-induced severe cutaneous adverse reactions in Han people of southern China mainland. Seizure. 2011;20:446-8.

Hsiao YH, Hui RCY, Wu T, Chang WC, Hsih MS, Yang CH, et all. Genotype-phenotype association between HLA and carbamazepine induced hypersensitivity reactions: strength and clinical correlation. J Dermatol Sci. 2014;73:101-9.

Wu XT, Hu FY, An DM, Yan B, Jiang X, Kwan P, et all. Association between carbamazepineinduced cutaneous adverse drug reactions and the HLA-B*1502 allele among patients in central China. Epi Behav. 2010;19:405-8.

Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC. A marker for Stevens-Johnsons syndrome. Nature. 2004;p428:486.

Hung SI, Chung WH, Jee SH, Chen WC, Chang YT, Lee WR, et all. Genetic susceptibility to carbamazepine-induced cutaneous drug reactions. Pharmacogenetics & genomics. 2006;16(4):297-306.

Kaniwa N, Saito Y, Aihara M, Matsunaga K, Tohkin M, Kurose K, et all. HLA-B*1511 is a risk factor for carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patient. Epilepsia. 2010;51(12):2461-5.

Ozeki T, Mushiroda T, Yowang A, Takahashi A, Kubo M, Shirakata Y, et all. Genome-wide association study identifies HLA-A*3101 allele as a genetic risk factor for carbamazepine induced cutaneous adverse drug reactions in Japanese population. Hum Mol Gen. 2011;20(5):1034-41.

Kim SH, Lee KW, Song WJ, Kim SH, Jee YK, Lee SM, et all. Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans. Epilepsy Res. 2011;.97:190-7.

Tessaneeyakul W, Tiamkao S, Jantararoungtong T, Chen P, Lin SY, Chen WH, et all. Association between HLA-B*1502 and carbamazepine-induced severe cutaneous adverse drug reactions in a Thai population. Epilepsia. 2010;51(5):926-30.

Kulkantrakorn K, Tassaneeyakul W, Tiamkao S, Jantararoungtong T, Prabmechai N, Vannaprasaht S, et all. HLA-B*1502 strongly predicts carbamazepine- P induced Stevens Johnson syndrome and toxic epidermal necrolysis in Thai patients with neuropathic pain. Pain Practice. 2011;12(3):202-8.

Locharernkul C, Loplumlert J, Limotai C, Korkij W, Desudchit T, Tongkobpetch S, et all. Carbamazepine and phenytoin induced Stevens-Johnson syndrome is associated with HLA-B*1502 allele in Thai population. Epilepsia.2008;49(12):2087-91.

Then SM, Rani ZZ, AA, Ratnaningrum S, Jamal R. Frequency of the HLA-B*1502 allele contributing to carbamazepine-induced hypersensitivity reactions in a cohort of Malaysian epilepsy patients. Asian Pac J Allergy Immunol. 2011;29:290-3.

Middleton D, Menchaca L, Rood H, Komerofsky R. New allele frequency database: Tissue Antigens. 2003.61:403-7.

Lonjou C, Thomas L, Borot N, Ledger N, de Toma C, et all. A marker for Stevens-Johnson syndrome…: ethnicity matters. The Pharmacogenomics J. 2006;6:265-8.

Dong D, Sung C, Finkelstein EA. Costeffectiveness of HLA-B*1502 genotyping in adult patients with newly diagnosed epilepsy in Singapore. Neurology. 2012;79:1259-67.

Tiamkao S, Jitpimorlard J, Sawanyawisuth K, Jitpimolmard S. Cost minimization of HLAB*1502 screening before prescribing carbamazepine in Thailand. Int J Clin Pharm. 2013;35:608-12.

Yuliwulandari R, Kashiwase K, Nakajima H, Uddin J, Susmiarsih TP, Sofro ASM, Tokunaga K. Polymorphisms of HLA genes in Western Javanese (Indonesia): close affinities to Southeast Asian populations. Tissue Antigens. 2008;73:46-53.

Berita MESO. Laporan kasus di Indonesia: carbamazepine. MESO. 2007;25(2):5.


  • There are currently no refbacks.