{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:04:40Z","timestamp":1790805880366,"version":"4.1.0"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2021,1,3]],"date-time":"2021-01-03T00:00:00Z","timestamp":1609632000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,1,3]],"date-time":"2021-01-03T00:00:00Z","timestamp":1609632000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ther Innov Regul Sci"],"published-print":{"date-parts":[[2021,5]]},"DOI":"10.1007\/s43441-020-00245-w","type":"journal-article","created":{"date-parts":[[2021,1,3]],"date-time":"2021-01-03T19:03:06Z","timestamp":1609700586000},"page":"514-522","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Allopurinol-Induced Severe Cutaneous Adverse Drug Reactions: An Analysis of Spontaneous Reports in Malaysia (2000\u20132018)"],"prefix":"10.1007","volume":"55","author":[{"given":"Sing Chet","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wee Kee","family":"Wo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Sheong","family":"Yeoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norleen","family":"Mohamed Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0294-6070","authenticated-orcid":false,"given":"Vidhya","family":"Hariraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,3]]},"reference":[{"issue":"11","key":"245_CR1","doi-asserted-by":"publisher","first-page":"4134","DOI":"10.1073\/pnas.0409500102","volume":"102","author":"SI Hung","year":"2005","unstructured":"Hung SI, Chung WH, Liou LB, et al. HLA-B* 5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci. 2005;102(11):4134\u20139.","journal-title":"Proc Natl Acad Sci"},{"key":"245_CR2","doi-asserted-by":"publisher","DOI":"10.1002\/acr.24180","author":"JD FitzGerald","year":"2020","unstructured":"FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care Res. 2020. https:\/\/doi.org\/10.1002\/acr.24180.","journal-title":"Arthritis Care Res"},{"key":"245_CR3","unstructured":"Ministry of Health Malaysia. Clinical Practice Guidelines: Management of Gout. Putrajaya: The Ministry; 2008 Oct. 36 p. Report No.: MOH\/P\/PAK\/172.08 (GU)."},{"issue":"7","key":"245_CR4","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1093\/rheumatology\/kex156","volume":"56","author":"M Hui","year":"2017","unstructured":"Hui M, Carr A, Cameron S, et al. The British Society for Rheumatology guideline for the management of gout. Rheumatology. 2017;56(7):e1\u201320.","journal-title":"Rheumatology"},{"issue":"2","key":"245_CR5","first-page":"203","volume":"27","author":"JC Roujeau","year":"2009","unstructured":"Roujeau JC, Allanore L, Liss Y, et al. Severe cutaneous adverse reactions to drugs (SCAR): definitions, diagnostic criteria, genetic predisposition. Dermatol Sin. 2009;27(2):203\u20139.","journal-title":"Dermatol Sin"},{"issue":"10","key":"245_CR6","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1038\/gim.2014.195","volume":"17","author":"JW Jung","year":"2015","unstructured":"Jung JW, Kim DK, Park HW, et al. An effective strategy to prevent allopurinol-induced hypersensitivity by HLA typing. Genet Med. 2015;17(10):807\u201314.","journal-title":"Genet Med"},{"issue":"2","key":"245_CR7","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/clpt.2012.209","volume":"93","author":"MS Hershfield","year":"2013","unstructured":"Hershfield MS, Callaghan JT, Tassaneeyakul W, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for human leukocyte antigen-B genotype and allopurinol dosing. Clin Pharmacol Ther. 2013;93(2):153\u20138.","journal-title":"Clin Pharmacol Ther"},{"issue":"21","key":"245_CR8","doi-asserted-by":"publisher","first-page":"2231","DOI":"10.1001\/jama.2014.839","volume":"311","author":"Y Finkelstein","year":"2014","unstructured":"Finkelstein Y, Macdonald EM, Li P, et al. Recurrence and mortality following severe cutaneous adverse reactions. JAMA. 2014;311(21):2231\u20132.","journal-title":"JAMA"},{"issue":"1","key":"245_CR9","doi-asserted-by":"publisher","first-page":"195","DOI":"10.3904\/kjim.2015.365","volume":"34","author":"MS Yang","year":"2019","unstructured":"Yang MS, Kim JY, Kang MG, et al. Direct costs of severe cutaneous adverse reactions in a tertiary hospital in Korea. Korean J Intern Med. 2019;34(1):195.","journal-title":"Korean J Intern Med"},{"issue":"5","key":"245_CR10","doi-asserted-by":"publisher","first-page":"867","DOI":"10.3904\/kjim.2018.126","volume":"33","author":"JW Jung","year":"2018","unstructured":"Jung JW, Kim JY, Park IW, et al. Genetic markers of severe cutaneous adverse reactions. Korean J Intern Med. 2018;33(5):867.","journal-title":"Korean J Intern Med"},{"key":"245_CR11","unstructured":"World Health Organization-Uppsala Monitoring Centre (WHO-UMC). VigiLyze. https:\/\/vigilyze.who-umc.org\/."},{"key":"245_CR12","unstructured":"World Health Organization-Uppsala Monitoring Centre (WHO-UMC). The Use of the WHO-UMC System for Standardised Case Causality Assessment; 2005. https:\/\/www.who.int\/medicines\/areas\/quality_safety\/safety_efficacy\/WHOcausality_assessment.pdf."},{"key":"245_CR13","volume-title":"Men, Ageing and Health: Achieving Health Across the Life Span","author":"World Health Organization","year":"2001","unstructured":"World Health Organization. Men, Ageing and Health: Achieving Health Across the Life Span. Geneva: World Health Organization; 2001."},{"key":"245_CR14","unstructured":"Package Insert - Zyloric (Allopurinol). Selangor: Aspen Medical Products Malaysia; 2017."},{"issue":"1","key":"245_CR15","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1002\/art.1780290111","volume":"29","author":"JZ Singer","year":"1986","unstructured":"Singer JZ, Wallace SL. The allopurinol hypersensitivity syndrome. Unnecessary morbidity and mortality. Arthritis Rheum. 1986;29(1):82\u20137.","journal-title":"Arthritis Rheum"},{"issue":"9","key":"245_CR16","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1001\/jamainternmed.2015.3536","volume":"175","author":"CY Yang","year":"2015","unstructured":"Yang CY, Chen CH, Deng ST, et al. Allopurinol use and risk of fatal hypersensitivity reactions: a nationwide population-based study in Taiwan. JAMA Intern Med. 2015;175(9):1550\u20137.","journal-title":"JAMA Intern Med"},{"issue":"7","key":"245_CR17","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1097\/FPC.0000000000000285","volume":"27","author":"N Saksit","year":"2017","unstructured":"Saksit N, Tassaneeyakul W, Nakkam N, et al. Risk factors of allopurinol-induced severe cutaneous adverse reactions in a Thai population. Pharmacogenet Genom. 2017;27(7):255\u201363.","journal-title":"Pharmacogenet Genom"},{"issue":"8","key":"245_CR18","first-page":"1187","volume":"77","author":"SF Keller","year":"2018","unstructured":"Keller SF, Lu N, Blumenthal KG, et al. Racial\/ethnic variation and risk factors for allopurinol-associated severe cutaneous adverse reactions: a cohort study. Ann Rheum Dis. 2018;77(8):1187\u201393.","journal-title":"Ann Rheum Dis"},{"issue":"5","key":"245_CR19","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1111\/j.1365-2125.2010.03774.x","volume":"71","author":"BY Thong","year":"2011","unstructured":"Thong BY, Tan TC. Epidemiology and risk factors for drug allergy. Br J Clin Pharmacol. 2011;71(5):684\u2013700.","journal-title":"Br J Clin Pharmacol"},{"issue":"10","key":"245_CR20","doi-asserted-by":"publisher","first-page":"577","DOI":"10.5414\/CP201514","volume":"49","author":"C Hofer-Dueckelmann","year":"2011","unstructured":"Hofer-Dueckelmann C, Prinz E, Beindl W, et al. Adverse drug reactions (ADRs) associated with hospital admission\u2014elderly female patients are at highest risk. Int J Clin Pharmacol Ther. 2011;49(10):577.","journal-title":"Int J Clin Pharmacol Ther"},{"issue":"1","key":"245_CR21","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1111\/j.1365-2125.2010.03811.x","volume":"71","author":"EM Rodenburg","year":"2011","unstructured":"Rodenburg EM, Stricker BH, Visser LE. Sex-related differences in hospital admissions attributed to adverse drug reactions in the Netherlands. Br J Clin Pharmacol. 2011;71(1):95\u2013104.","journal-title":"Br J Clin Pharmacol"},{"issue":"10","key":"245_CR22","doi-asserted-by":"publisher","first-page":"1368","DOI":"10.1136\/ard.2006.051649","volume":"65","author":"LR Harrold","year":"2006","unstructured":"Harrold LR, Yood RA, Mikuls TR, et al. Sex differences in gout epidemiology: evaluation and treatment. Ann Rheum Dis. 2006;65(10):1368\u201372.","journal-title":"Ann Rheum Dis"},{"issue":"1","key":"245_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13075-020-02273-1","volume":"22","author":"MD Do","year":"2020","unstructured":"Do MD, Mai TP, Do AD, et al. Risk factors for cutaneous reactions to allopurinol in Kinh Vietnamese: results from a case-control study. Arthritis Res Ther. 2020;22(1):1.","journal-title":"Arthritis Res Ther"},{"issue":"4","key":"245_CR24","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1111\/j.1365-2710.2005.00670.x","volume":"30","author":"M Takada","year":"2005","unstructured":"Takada M, Okada H, Kotake T, et al. Appropriate dosing regimen of allopurinol in Japanese patients 1. J Clin Pharm Ther. 2005;30(4):407\u201312.","journal-title":"J Clin Pharm Ther"},{"issue":"12","key":"245_CR25","doi-asserted-by":"publisher","first-page":"2157","DOI":"10.1136\/annrheumdis-2014-205577","volume":"74","author":"WH Chung","year":"2015","unstructured":"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(12):2157\u201364.","journal-title":"Ann Rheum Dis"},{"issue":"11","key":"245_CR26","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1111\/cea.12184","volume":"43","author":"J Yun","year":"2013","unstructured":"Yun J, Mattsson J, Schnyder K, et al. Allopurinol hypersensitivity is primarily mediated by dose-dependent oxypurinol-specific T cell response. Clin Exp Allergy. 2013;43(11):1246\u201355.","journal-title":"Clin Exp Allergy"},{"issue":"3","key":"245_CR27","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/nrneph.2017.181","volume":"14","author":"JJ Carrero","year":"2018","unstructured":"Carrero JJ, Hecking M, Chesnaye NC, et al. Sex and gender disparities in the epidemiology and outcomes of chronic kidney disease. Nat Rev Nephrol. 2018;14(3):151.","journal-title":"Nat Rev Nephrol"},{"issue":"2","key":"245_CR28","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1681\/ASN.V112319","volume":"11","author":"J Neugarten","year":"2000","unstructured":"Neugarten J, Acharya A, Silbiger SR. Effect of gender on the progression of nondiabetic renal disease: a meta-analysis. J Am Soc Nephrol. 2000;11(2):319\u201329.","journal-title":"J Am Soc Nephrol"},{"issue":"3","key":"245_CR29","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/0002-9343(87)90441-4","volume":"82","author":"EW Campion","year":"1987","unstructured":"Campion EW, Glynn RJ, Delabry LO. Asymptomatic hyperuricemia. Risks and consequences in the Normative Aging Study. Am J Med. 1987;82(3):421\u20136.","journal-title":"Am J Med"},{"issue":"2","key":"245_CR30","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1046\/j.1523-1747.2000.00061.x","volume":"115","author":"N Fouchard","year":"2000","unstructured":"Fouchard N, Bertocchi M, Roujeau JC, et al. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. J Investig Dermatol. 2000;115(2):149\u201353.","journal-title":"J Investig Dermatol"},{"issue":"4","key":"245_CR31","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1002\/acr.21817","volume":"65","author":"SC Kim","year":"2013","unstructured":"Kim SC, Newcomb C, Margolis D, et al. Severe cutaneous reactions requiring hospitalization in allopurinol initiators: a population-based cohort study. Arthritis Care Res. 2013;65(4):578\u201384.","journal-title":"Arthritis Care Res"},{"issue":"suppl_1","key":"245_CR32","doi-asserted-by":"publisher","first-page":"i35","DOI":"10.1093\/rheumatology\/kex422","volume":"57","author":"LK Stamp","year":"2018","unstructured":"Stamp LK, Barclay ML. How to prevent allopurinol hypersensitivity reactions? Rheumatology. 2018;57(suppl_1):i35\u201341.","journal-title":"Rheumatology"},{"issue":"4","key":"245_CR33","doi-asserted-by":"publisher","first-page":"319","DOI":"10.2165\/11588460-000000000-00000","volume":"34","author":"TF Butt","year":"2011","unstructured":"Butt TF, Cox AR, Lewis H, et al. Patient experiences of serious adverse drug reactions and their attitudes to medicines. Drug Saf. 2011;34(4):319\u201328.","journal-title":"Drug Saf"},{"key":"245_CR34","doi-asserted-by":"publisher","first-page":"204209862093859","DOI":"10.1177\/2042098620938595","volume":"11","author":"M Alomar","year":"2020","unstructured":"Alomar M, Tawfiq AM, Hassan N, et al. Post marketing surveillance of suspected adverse drug reactions through spontaneous reporting: current status, challenges and the future. Ther Adv Drug Saf. 2020;11:2042098620938595.","journal-title":"Ther Adv Drug Saf"},{"issue":"2","key":"245_CR35","doi-asserted-by":"publisher","first-page":"208","DOI":"10.3349\/ymj.2019.60.2.208","volume":"60","author":"MG Kang","year":"2019","unstructured":"Kang MG, Sohn KH, Kang DY, et al. Analysis of individual case safety reports of severe cutaneous adverse reactions in Korea. Yonsei Med J. 2019;60(2):208\u201315.","journal-title":"Yonsei Med J"},{"issue":"1","key":"245_CR36","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1007\/s40801-019-00174-7","volume":"7","author":"C Scavone","year":"2020","unstructured":"Scavone C, Di Mauro C, Ruggiero R, et al. Severe cutaneous adverse drug reactions associated with allopurinol: an analysis of spontaneous reporting system in Southern Italy. Drugs-Real World Outcomes. 2020;7(1):41\u201351.","journal-title":"Drugs-Real World Outcomes"},{"issue":"4","key":"245_CR37","doi-asserted-by":"publisher","first-page":"e94294","DOI":"10.1371\/journal.pone.0094294","volume":"9","author":"S Saokaew","year":"2014","unstructured":"Saokaew S, Tassaneeyakul W, Maenthaisong R, et al. Cost-effectiveness analysis of HLA-B* 5801 testing in preventing allopurinol-induced SJS\/TEN in Thai population. PLoS ONE. 2014;9(4):e94294.","journal-title":"PLoS ONE"}],"container-title":["Therapeutic Innovation & Regulatory Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s43441-020-00245-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s43441-020-00245-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s43441-020-00245-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,10]],"date-time":"2022-12-10T08:52:54Z","timestamp":1670662374000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s43441-020-00245-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,3]]},"references-count":37,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["245"],"URL":"https:\/\/doi.org\/10.1007\/s43441-020-00245-w","relation":{},"ISSN":["2168-4790","2168-4804"],"issn-type":[{"value":"2168-4790","type":"print"},{"value":"2168-4804","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,3]]},"assertion":[{"value":"9 September 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 November 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"The authors declared no potential conflicting interests in respect to the research, authorship, and\/or publication of this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}