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Review

An update on CYP2C9 polymorphisms and phenytoin metabolism: implications for adverse effects

ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Pages 723-734 | Received 08 Apr 2020, Accepted 05 Jun 2020, Published online: 16 Jul 2020

References

  • Merritt HH, Putnam TJ. Sodium diphenyl hydantoinate in the treatment of convulsive disorders. JAMA. 1984;251(8):1062–1067.
  • Friedlander WJ. Putnam, Merritt, and the discovery of Dilantin. Epilepsia. 1986;27(s3):S1–S20.
  • McCorry D, Chadwick D, Marson A. Current drug treatment of epilepsy in adults. Lancet Neurol. 2004;3(12):729–735.
  • Keppel Hesselink JM, Kopsky DJ. Phenytoin: 80 years young, from epilepsy to breast cancer, a remarkable molecule with multiple modes of action. Journal of Neurology. 2017;264(8):1617–1621.
  • World Health Organization. Epilepsy. 2019. [cited 2020 March 27]. Available from: https://www.who.int/news-room/fact-sheets/detail/epilepsy
  • Weston J, Greenhalgh J, Marson AG. Antiepileptic drugs as prophylaxis for post-craniotomy seizures. Cochrane Database Syst Rev. 2015;2015:CD007286.
  • Hung CC, Lin CJ, Chen CC, et al. Dosage recommendation of phenytoin for patients with epilepsy with different CYP2C9/CYP2C19 polymorphisms. Ther Drug Monit. 2004;26(5):534–540.
  • von Winckelmann SL, Spriet I, Willems L. Therapeutic drug monitoring of phenytoin in critically ill patients. Pharmacotherapy. 2008;28(11):1391–1400.
  • Yaari Y, Selzer ME, Pincus JH. Phenytoin: mechanisms of its anticonvulsant action. Ann Neurol. 1986;20(2):171–184.
  • Francis J, Burnham WM. [3H]Phenytoin identifies a novel anticonvulsant-binding domain on voltage-dependent sodium channels. Mol Pharmacol. 1992;42:1097–1103.
  • Ahn JE, Cloyd JC, Brundage RC, et al. Phenytoin half-life and clearance during maintenance therapy in adults and elderly patients with epilepsy. Neurology. 2008;71(1):38–43.
  • Bergen DC. Pharmacokinetics of phenytoin: reminders and discoveries. Epilepsy Curr. 2009;9(4):102–104.
  • Morita DA, Glauser TA. Phenytoin and fosphenytoin. In: Wyllie E, Princ E eds. Wyllie’s Treatment of Epilepsy, Principles and Practice 5th. Philadelphia, PA:Lippincott Williams and Wilkins. 2011. 630–647.
  • Ter Heine R, Kane SP, Huitema ADR, et al. Nonlinear protein binding of phenytoin in clinical practice: development and validation of a mechanistic prediction model. Br J Clin Pharmacol. 2019;85(10):2360–2368.
  • Patsalos PN, Spencer EP, Berry DJ. Therapeutic Drug Monitoring of Antiepileptic Drugs in Epilepsy: A 2018 Update. Ther Drug Monit. 2018;40(5):526–548.
  • Kang JS, Lee MH. Overview of therapeutic drug monitoring. Korean J Intern Med. 2009;24(1):1‐10.
  • Patsalos PN, Berry DJ. Therapeutic drug monitoring of antiepileptic drugs by use of saliva. Ther Drug Monit. 2013;35(1):4–29.
  • Thorn CF, Whirl-Carrillo M, Leeder JS, et al., PharmGKB summary: phenytoin pathway. Pharmacogenet Genomics. 22(6): 466–470. 2012. .
  • Martz F, Failinger C, Blake DA. Phenytoin teratogenesis: correlation between embryopathic effect and covalent binding of putative arene oxide metabolite in gestational tissue. J Pharmacol Exp Ther. 1977;203(1):231–239.
  • Komatsu T, Yamazaki H, Asahi S, et al. Formation of a dihydroxy metabolite of phenytoin in human liver microsomes/cytosol: roles of cytochromes P450 2C9, 2C19, and 3A4. Drug Metab Dispos. 2000;28(11):1361–1368.
  • Krauss G. Current understanding of delayed anticonvulsant hypersensitivity reactions. Epilepsy Curr. 2010;51(2):33–37.
  • Liponi DF. Phenytoin therapy and toxicities. Ann Intern Med. 1984;101(4):568–569.
  • Pharmacogene Variation Consortium. CYP2C9. 2020. [cited 2020 Mar 27]. Available from: https://www.pharmvar.org/gene/CYP2C9.
  • Blaisdell J, Jorge-Nebert LF, Coulter S, et al. Discovery of new potentially defective alleles of human CYP2C9. Pharmacogenetics. 2004;14(8):527–537.
  • Wang B, Wang J, Huang S-Q, et al. Genetic Polymorphism of the Human Cytochrome P450 2C9 Gene and Its Clinical Significance. <![CDATA[Current Drug Metabolism]]>. 2009;10(7):781–834.
  • Kidd RS, Straughn AB, Meyer MC, et al. Pharmacokinetics of chlorpheniramine, phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C9*3 allele. Pharmacogenetics. 1999;9(1):71–80.
  • Kidd RS, Curry TB, Gallagher S, et al. Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin. Pharmacogenetics. 2001;11(9):803–808.
  • Mamiya K, Ieiri I, Shimamoto J, et al. The effects of genetic polymorphisms of CYP2C9 and CYP2C19 on phenytoin metabolism in Japanese adult patients with epilepsy: studies in stereoselective hydroxylation and population pharmacokinetics. Epilepsia. 1998;39(12):1317–1323.
  • Odani A, Hashimoto Y, Otsuki Y, et al. Genetic polymorphism of the CYP2C subfamily and its effect on the pharmacokinetics of phenytoin in Japanese patients with epilepsy. Clin Pharmacol Ther. 1997;62(3):287–292.
  • Aynacioglu AS, Brockmöller J, Bauer S, et al. Frequency of cytochrome P450 CYP2C9 variants in a Turkish population and functional relevance for phenytoin. Br J Clin Pharmacol. 1999;48(3):409–415.
  • Caraco Y, Muszkat M, Wood AJ. Phenytoin metabolic ratio: a putative marker of CYP2C9 activity in vivo. Pharmacogenetics. 2001;11(7):587–596.
  • Lee S-Y, Lee S-T, Kim J-W. Contributions of CYP2C9/CYP2C19 genotypes and drug interaction to the phenytoin treatment in the Korean epileptic patients in the clinical setting. J Biochem Mol Biol. 2007;40:448–452.
  • Caudle KE, Rettie AE, Whirl-Carrillo M, et al. Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing. Clinical Pharmacology & Therapeutics. 2014;96:542–548.
  • Tate SK, Depondt C, Sisodiya SM, et al. Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin. Proc Natl Acad Sci U S A. 2005;102(15):5507–5512.
  • Ramasamy K, Narayan SK, Chanolean S, et al. Severe phenytoin toxicity in a CYP2C9*3*3 homozygous mutant from India. Neurol India. 2007;55(4):408–409.
  • Depondt C, Godard P, Espel RS, et al. A candidate gene study of antiepileptic drug tolerability and efficacy identifies an association of CYP2C9 variants with phenytoin toxicity. Eur J Neurol. 2011;18(9):1159–1164.
  • Dagenais R, Wilby KJ, Elewa H, et al. Impact of Genetic Polymorphisms on Phenytoin Pharmacokinetics and Clinical Outcomes in the Middle East and North Africa Region. Drugs R D. 2013;13(3):341–361.
  • Silvado C, Terra VC, Twardowschy CA. CYP2C9 polymorphisms in epilepsy: influence on phenytoin treatment. Pharmgenomics Pers Med. 2018;11:51–58.
  • Franco V, Perucca E. CYP2C9 polymorphisms and phenytoin metabolism: implications for adverse effects. Expert Opin Drug Metab Toxicol. 2015;11(8):1269–1279.
  • Chadwick D, Shaw MD, Foy P, et al. Serum anticonvulsant concentrations and the risk of drug induced skin eruptions. J Neurol Neurosurg Psychiatry. 1984;9(6):642–644.
  • Leppik IE, Lapora J, Loewenson R. Seasonal incidence of phenytoin allergy unrelated to plasma levels. Arch Neurol. 1985;42(2):120–122.
  • Arif H, Buchsbaum R, Weintraub D, et al. Comparison and predictors of rash associated with 15 antiepileptic drugs. Neurology. 2007;68(20):1701–1709.
  • Hirsch LJ, Arif H, Nahm EA, et al. Cross-sensitivity of skin rashes with antiepileptic drug use. Neurology. 2008;71(19):1527–1534.
  • Saltzstein SL, Ackerman LV. Lymphadenopathy induced by anticonvulsant drugs and mimicking clinically pathologically malignant lymphomas. Cancer. 1959;12(1):164–182.
  • Roujeau J-C, Kelly JP, Naldi L, et al. Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med. 1995;333(24):1600–1608.
  • Kardaun SH, Sidoroff A, Valeyrie-Allanore L, et al. Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a DRESS syndrome really exist? Br J Dermatol. 2007;156(3):609–611.
  • Cacoub P, Musette P, Descamps V, et al. The DRESS syndrome: a literature review. Am J Med. 2011;124(7):588–597.
  • Husain Z, Reddy BY, Schwartz RA. DRESS syndrome: part I. Clinical perspectives. J Am Acad Dermatol. 2013;68(5):709.e1-709.e9. 693.e1-14..
  • Kardaun SH, Sekula P, Valeyrie-Allanore L, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction Results from the prospective RegiSCAR study. . Br J Dermatol. 2013;169:1071–1080.
  • Roujeau JC, Stern RS. Severe adverse cutaneous reactions to drugs. N Engl J Med. 1994;331(19):1272–1285.
  • Roujeau JC. The spectrum of Stevens-Johnson syndrome and toxic epidermal necrolysis: a clinical classification. J Invest Dermatol. 1994;102(6):28S–30S.
  • Sassolas B, Haddad C, Mockenhaupt M, et al. ALDEN, an algorithm for assessment of drug causality in Stevens-Johnson Syndrome and toxic epidermal necrolysis: comparison with case-control analysis. Clin Pharmacol Ther. 2010;88(1):60–68.
  • Stern RS. Exanthematous drug eruptions. N Engl J Med. 2012;366(26):2492–2501.
  • White KD, Abe R, Ardern-Jones M, et al. SJS/TEN 2017: building Multidisciplinary Networks to Drive Science and Translation. The Journal of Allergy and Clinical Immunology: In Practice. 2018;6(1):38–69.
  • Chang WC, Abe R, Anderson P, et al. SJS/TEN 2019: from science to translation. J Dermatol Sci. 2020;98(1):2‐12.
  • Mockenhaupt M, Messenheimer J, Tennis P, et al. Risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in new users of antiepileptics. Neurology. 2005;64(7):1134–1138.
  • Knowles SR, Dewhurst N, Shear NH. Anticonvulsant hypersensitivity syndrome: an update. Expert Opin Drug Saf. 2012;11(5):767–778.
  • Mockenhaupt M, Viboud C, Dunant A, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. Journal of Investigative Dermatology. 2008;128(1):35–44.
  • Wang Y-H, Chen C-B, Tassaneeyakul W, et al. The Medication Risk of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Asians: the Major Drug Causality and Comparison With the US FDA Label. Clin Pharmacol Ther. 2019;105(1):112–120.
  • Zaccara G, Franciotta D, Perucca E. Idiosyncratic Adverse Reactions to Antiepileptic Drugs. Epilepsia. 2007;48(7):1223–1244.
  • Ghannam M, Mansour S, Nabulsi A, et al. Anticonvulsant hypersensitivity syndrome after phenytoin administration in an adolescent patient: a case report and review of literature. Clin Mol Allergy. 2017;15(1):14.
  • Lee A-Y, Kim M-J, Chey W-Y, et al. Genetic polymorphism of cytochrome P450 2C9 in diphenylhydantoin-induced cutaneous adverse drug reactions. Eur J Clin Pharmacol. 2004;60(3):155–159.
  • Chung W-H, Chang W-C, Lee Y-S, et al., Genetic variants associated with phenytoin-related severe cutaneous adverse reactions. JAMA. 312(5): 525–534. 2014. .
  • Suvichapanich S, Jittikoon J, Wichukchinda N, et al., Association analysis of CYP2C9*3 and phenytoin-induced severe cutaneous adverse reactions (SCARs) in Thai epilepsy children. J Hum Genet. 2015;60(8): 413–417.
  • Su S-C, Chen C-B, Chang W-C, et al. HLA Alleles and CYP 2C9*3 as Predictors of Phenytoin Hypersensitivity in East Asians. Clin Pharmacol Ther. 2019;105(2):476–485.
  • Tassaneeyakul W, Prabmeechai N, Sukasem C, et al. Associations between HLA class I and cytochrome P450 2C9 genetic polymorphisms and phenytoin-related severe cutaneous adverse reactions in a Thai population. Pharmacogenet Genomics. 2016;26(5):225–234.
  • Yampayon K, Sukasem C, Limwongse C, et al. Influence of genetic and non-genetic factors on phenytoin-induced severe cutaneous adverse drug reactions. Eur J Clin Pharmacol. 2017;73(7):855–865.
  • Sukasem C, Sririttha S, Tempark T, et al. Genetic and clinical risk factors associated with phenytoin-induced cutaneous adverse drug reactions in Thai population. Pharmacoepidemiol Drug Saf. 2020;29(5):565‐574.
  • Hikino K, Ozeki T, Koido M, et al. HLA-B*51:01 and CYP2C9*3 Are Risk Factors for Phenytoin-Induced Eruption in the Japanese Population: analysis of Data From the Biobank Japan Project. Clin Pharmacol Ther. 2020;107(5):1170‐1178.
  • Robinson J, Halliwell JA, Hayhurst JH, et al. The IPD and IMGT/HLA database: allele variant databases. Nucleic Acids Res. 2015;43(D1):D423–431.
  • The IPD and IMGT/HLA database. HLA alleles numbers. [cited 2020 Mar 27]. Available from http://hla.alleles.org/nomenclature/stats.html
  • Chung W-H, Hung S-I, Hong H-S, et al., Medical genetics: a marker for Stevens-Johnson syndrome. Nature. 428(6982): 486. 2004. .
  • Hung S-I, Chung W-H, Liu Z-S, et al. Common risk allele in aromatic antiepileptic-drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese. Pharmacogenomics. 2010;11(3):349–356.
  • Locharernkul C, Loplumlert J, Limotai C, et al. Carbamazepine and phenytoin induced Stevens-Johnson syndrome is associated with HLA-B*1502 allele in Thai population. Epilepsia. 2008;49(12):2087–2091.
  • Chang -C-C, Ng -C-C, Too C-L, et al. Association of HLA-B*15:13 and HLA-B*15:02 with phenytoin-induced severe cutaneous adverse reactions in a Malay population. Pharmacogenomics J. 2017;17(2):170–173.
  • Cheung Y-K, Cheng S-H, Chan EJM, et al. HLA-B alleles associated with severe cutaneous reactions to antiepileptic drugs in Han Chinese. Epilepsia. 2013;54(7):1307–1314.
  • González-Galarza FF, Takeshita LYC, Santos EJM, et al. Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations. Nucleic Acids Res. 2015;43(D1):D784–D788.
  • Allele Frequency Net Database. [cited 2020 Mar 27]. Available from: http://www.allelefrequencies.net
  • Puangpetch A, Koomdee N, Chamnanphol M, et al. HLA-B allele and haplotype diversity among Thai patients identified by PCR-SSOP: evidence for high risk of drug-induced hypersensitivity. Front Genet. 2015;5:478.
  • Satapornpong P, Jinda P, Jantararoungtong T, et al. Genetic Diversity of HLA Class I and Class II Alleles in Thai Populations: contribution to Genotype-Guided Therapeutics. Front Pharmacol. 2020;11:78.
  • McCormack M, Alfirevic A, Bourgeois S, et al. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med. 2011;364(12):1134–1143.
  • Ozeki T, Mushiroda T, Yowang A, et al. 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 Genet. 2011;20(5):1034–1041.
  • Zhang FR, Liu H, Irwanto A, et al. HLA-B*13:01 and the Dapsone Hypersensitivity Syndrome. N Engl J Med. 2013;369(17):1620‐1628.
  • Tempark T, Satapornpong P, Rerknimitr P, et al. Dapsone-induced severe cutaneous adverse drug reactions are strongly linked with HLA-B*13:01 allele in the Thai population. Pharmacogenet Genomics. 2017;27(12):429‐437.
  • Liu H, Wang Z, Bao F, et al. Evaluation of Prospective HLA-B*13:01 Screening to Prevent Dapsone Hypersensitivity Syndrome in Patients With Leprosy. JAMA Dermatology. 2019;155(6):666‐672.
  • Shi Y-W, Min F-L, Zhou D, et al. HLA-A*24:02 as a common risk factor for antiepileptic drug-induced cutaneous adverse reactions. Neurology. 2017;88(23):2183–2191.
  • Ramírez E, Bellón T, Tong HY, et al. Significant HLA class I type associations with aromatic antiepileptic drug (AED)-induced SJS/TEN are different from those found for the same AED-induced DRESS in the Spanish population. Pharmacol Res. 2017;115:168–178.
  • Ihtisham K, Ramanujam B, Srivastava S, et al. Association of cutaneous adverse drug reactions due to antiepileptic drugs with HLA alleles in a North Indian population. Seizure. 2019;66:99–103.
  • McCormack M, Gui H, Ingason A, et al. Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients. Neurology. 2018;90(4):e332–e341.
  • Skerka C, Chen Q, Fremeaux-Bacchi V, et al. Complement factor H related proteins (CFHRs). Mol Immunol. 2013;56(3):170–180.
  • Auton A, Abecasis GR, Altshuler DM, et al. A global reference for human genetic variation. Nature. 2015;526:68–74.
  • Mockenhaupt M. Epidemiology of cutaneous adverse drug reactions. Allergologie Select. 2017;1(1):96‐108.
  • Frey N, Jossi J, Bodmer M, et al. The Epidemiology of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in the UK. J Invest Dermatol. 2017;137(6):1240‐1247.
  • Chung WH, Chang WC, Stocker SL, et al. Insights into the poor prognosis of allopurinol-induced severe cutaneous adverse reactions: the impact of renal insufficiency, high plasma levels of oxypurinol and granulysin. Ann Rheum Dis. 2015;74:2157‐2164.
  • Saksit N, Tassaneeyakul W, Nakkam N, et al. Risk factors of allopurinol-induced severe cutaneous adverse reactions in a Thai population. Pharmacogenet Genomics. 2017;27(7):255‐263.
  • Cheng FJ, Syu FK, Lee KH, et al. Correlation between drug-drug interaction-induced Stevens-Johnson syndrome and related deaths in Taiwan. J Food Drug Anal. 2016;24(2):427‐432.
  • Knowles SR, Shapiro LE, Shear NH. Anticonvulsant hypersensitivity syndrome: incidence, prevention and management. Drug Saf. 1999;21(6):489–501.
  • Hyson C, Sadler M. Cross sensitivity of skin rashes with antiepileptic drugs. Can J Neurol Sci. 1997;24:245–249.
  • Shi YW, Min FL, Qin B, et al. Association between HLA and Stevens-Johnson syndrome induced by carbamazepine in Southern Han Chinese: genetic markers besides B*1502? Basic Clin Pharmacol Toxicol. 2012;111(1):58–64.
  • Hung SI, Chung WH, Jee SH, et al. Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. PharmacogenetGenomics. 2006;16(4):297–306.
  • Wu XT, Hu FY, An DM, et al. Association between carbamazepine-induced cutaneous adverse drug reactions and the HLA-B*1502 allele among patients in central China. Epilepsy Behav. 2010;19(3):405–408.
  • Zhang Y, Wang J, Zhao LM, et al. Strong association between HLA-B*1502 and carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in mainland Han Chinese patients. Eur J Clin Pharmacol. 2011;67(9):885–887.
  • Wang W, Hu FY, Wu XT, et al. Genetic predictors of Stevens-Johnson syndrome and toxic epidermal necrolysis induced by aromatic antiepileptic drugs among the Chinese Han population. Epilepsy Behav. 2014;37:16–19.
  • Tassaneeyakul W, Tiamkao S, Jantararoungtong T, et al. Association between HLA-B*1502 and carbamazepine-induced severe cutaneous adverse drug reactions in a Thai population. Epilepsia. 2010;51(5):926–930.
  • Sukasem C, Chaichan C, Nakkrut T, et al. Association between HLA-B Alleles and Carbamazepine-Induced Maculopapular Exanthema and Severe Cutaneous Reactions in Thai Patients. J Immunol Res. 2018;2018:2780272.
  • Mehta TY, Prajapati LM, Mittal B, et al. Association of HLA-BFNx011502 allele and carbamazepine-induced Stevens-Johnson syndrome among Indians. Indian J Dermatol Venereol Leprol. 2009;75(6):579–582.
  • Kim SH, Lee KW, Song WJ, et al. Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans. Epilepsy Res. 2011;97:190–197.
  • Amstutz U, Ross CJ, Castro-Pastrana LI, et al. HLA-A 31:01 and HLA-B 15:02 as genetic markers for carbamazepine hypersensitivity in children. Clin Pharmacol Ther. 2013;94(1):142–149.
  • Nguyen DV, Chu HC, Nguyen DV, et al. HLA-B*1502 and carbamazepine-induced severe cutaneous adverse drug reactions in Vietnamese. Asia Pac Allergy. 2015;5(2):68–77.
  • Khor AH, Lim KS, Tan CT, et al. HLA-A*31: 01 and HLA-B*15:02 association with Stevens-Johnson syndrome and toxic epidermal necrolysis to carbamazepine in a multiethnic Malaysian population. Pharmacogenet Genomics. 2017;27(7):275–278.
  • Hu FY, Wu XT, An DM, et al. Pilot association study of oxcarbazepine-induced mild cutaneous adverse reactions with HLA-B*1502 allele in Chinese Han population. Seizure. 2011;20(2):160–162.
  • Chen CB, Hsiao YH, Wu T, et al. Risk and association of HLA with oxcarbazepine-induced cutaneous adverse reactions in Asians. Neurology. 2017;3(88):78–86.
  • An DM, Wu XT, Hu FY, et al. Association study of lamotrigine-induced cutaneous adverse reactions and HLA-B*1502 in a Han Chinese population. Epilepsy Res. 2010;92(2–3):226–230.
  • Moon J, Park HK, Chu K, et al. The HLA-A*2402/Cw*0102 haplotype is associated with lamotrigine-induced maculopapular eruption in the Korean population. Epilepsia. 2015;56(10):e161–e167.
  • Koomdee N, Pratoomwun J, Jantararoungtong T, et al. Association of HLA-A and HLA-B Alleles with Lamotrigine-Induced Cutaneous Adverse Drug Reactions in the Thai Population. Front Pharmacol. 2017;29;8:879.
  • Lv YD, Min FL, Liao WP, et al. The association between oxcarbazepine-induced maculopapular eruption and HLA-B alleles in a northern Han Chinese population. BMC Neurol. 2013;13(1):75. 13.
  • Kaniwa N, Sugiyama E, Saito Y, et al. Specific HLA types are associated with antiepileptic drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese subjects. Pharmacogenomics. 2013;14(15):1821–1831.
  • Chen P, Lin JJ, Lu CS, et al. Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan. N Engl J Med. 2011;364(12):1126–1133.
  • Chen Z, Liew D, Kwan P. Effects of a HLA-B*15:02 screening policy on antiepileptic drug use and severe skin reactions. Neurology. 2014;83(22):2077–2084.
  • Ferrell PB, McLeod HL. Carbamazepine, HLA-B*1502 and risk of Stevens–Johnson syndrome and toxic epidermal necrolysis: US FDA recommendations. Pharmacogenomics. 2008;9(10):1543–1546.
  • Swen JJ, Nijenhuis M, De Boer A, et al., Pharmacogenetics: from bench to byte - an update of guidelines. Clin Pharmacol Ther. 89(5): 662–673. 2011. .
  • Amstutz U, Shear NH, Rieder MJ, et al. Recommendations for HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions. Epilepsia. 2014;55(4):496–506.
  • Phillips EJ, Sukasem C, Whirl-Carrillo M, et al. Clinical Pharmacogenetics Implementation Consortium Guideline for HLA Genotype and Use of Carbamazepine and Oxcarbazepine: 2017 Update. Clin Pharmacol Ther. 2018;103(4):574–581.
  • Thong BY-H. Stevens-Johnson syndrome/toxic epidermal necrolysis: an Asia-Pacific perspective. Asia Pac Allergy. 2013;3(4):215.
  • Pan R-Y, Dao R-L, Hung S-I, et al. Pharmacogenomic Advances in the Prediction and Prevention of Cutaneous Idiosyncratic Drug Reactions. Clin Pharmacol Ther. 2017;102(1):86–97.
  • Lin CW, Huang WI, Chao PH, et al. Temporal trends and patterns in carbamazepine use, related severe cutaneous adverse reactions, and HLA-B*15:02 screening: A nationwide study. Epilepsia. 2018;59(12):2325–2339.
  • Hung S-I, Chung W-H, Liou L-B, et al. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A. 2005;102(11):4134–4139.

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