{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T01:39:28Z","timestamp":1793410768516,"version":"4.5.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T00:00:00Z","timestamp":1766793600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T00:00:00Z","timestamp":1766793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ther Innov Regul Sci"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    To verify safety profiles of generic statins in a real-world setting, the risk of liver dysfunction as a common adverse event was compared between generic and brand drugs. A new user cohort design was employed in which patients prescribed one of six statins (atorvastatin, simvastatin, pitavastatin, pravastatin, fluvastatin, or rosuvastatin) in Japan between January 1, 2014 and March 31, 2022 were identified in the MID-NET\n                    <jats:sup>\u00ae<\/jats:sup>\n                    database. Adjusted hazard ratios (aHRs) for generic drugs compared with their corresponding brand drug for the occurrence of first liver dysfunction were estimated using high-dimensional propensity score-weighted Cox models. Among the six statins, no increased trends in aHRs were observed in the primary analysis, except for atorvastatin. The primary analysis showed an aHR of 2.08 (95% confidence interval [CI]: 1.20\u20133.63) for atorvastatin. In an additional analysis with shorter follow-up periods, aHRs for atorvastatin gradually approached 1.00 (1.74 [95% CI: 0.94\u20133.22] within 360\u00a0days, 1.65 [95% CI: 0.84\u20133.25] within 180\u00a0days, 1.49 [95% CI: 0.73\u20133.01] within 90\u00a0days, and 1.33 [95% CI: 0.60\u20132.96] within 30\u00a0days). Results suggest that risks of liver dysfunction by generic statins are similar to those for brand drugs, facilitating our understanding about the safety of generic drugs. The aHR for atorvastatin was inconsistent between the primary and additional analyses, which suggests that the observed increased risk of generic atorvastatin may be affected by other factors and does not necessarily indicate a different safety profile between generic and brand drugs.\n                  <\/jats:p>","DOI":"10.1007\/s43441-025-00904-w","type":"journal-article","created":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T20:51:23Z","timestamp":1766868683000},"page":"336-345","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Safety Comparison of Risk of Liver Dysfunction between Generic and Brand Statin Drugs Marketed in Japan: A Cohort Study Using MID-NET\u00ae"],"prefix":"10.1007","volume":"60","author":[{"given":"Hotaka","family":"Maruyama","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kinoshita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Okui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maki","family":"Komamine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Kajiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Horiuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Uyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,27]]},"reference":[{"issue":"5","key":"904_CR1","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1208\/s12248-015-9777-x","volume":"17","author":"R Kuribayashi","year":"2015","unstructured":"Kuribayashi R, Matsuhama M, Mikami K. Regulation of generic drugs in Japan: the current situation and future prospects. AAPS J. 2015;17(5):1312\u20136.","journal-title":"AAPS J"},{"key":"904_CR2","unstructured":"Ministry of Health, Labour and Welfare. Promotion of use of generic drugs [in Japanese] [Available from: http:\/\/www.mhlw.go.jp\/stf\/seisakunitsuite\/bunya\/kenkou_iryou\/iryou\/kouhatu-iyaku\/] Accessed 26 June 2025."},{"issue":"6","key":"904_CR3","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1002\/cpt.1342","volume":"105","author":"A Takami","year":"2019","unstructured":"Takami A, Hirata K, Ishiguro C, et al. Lower proportion of spontaneous adverse event reports for generic drugs by comparison with original branded drugs at the postmarket stage in Japan. Clin Pharmacol Ther. 2019;105(6):1471\u20136.","journal-title":"Clin Pharmacol Ther"},{"key":"904_CR4","unstructured":"Ministry of Health, Labour and Welfare. The Administrative disposition of Kobayashi Kako Co., ltd. was executed by Fukui prefecture [in Japanese] [Available from: https:\/\/www.mhlw.go.jp\/content\/11126000\/000735984.pdf] Accessed 26 June 2025."},{"key":"904_CR5","unstructured":"Ministry of Health, Labour and Welfare. Draft survey report on the impact and implementation of measures to promote the use of generic drugs [in Japanese] [Available from: https:\/\/www.mhlw.go.jp\/content\/12404000\/001165883.pdf] Accessed 26 June 2025."},{"issue":"4","key":"904_CR6","first-page":"210","volume":"5","author":"VL Serebruany","year":"2019","unstructured":"Serebruany VL, Hall TS, Atar D, et al. Mortality and adverse events with brand and generic clopidogrel in the US Food and Drug Administration Adverse Event Reporting System. 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The e-labeling of Lipitor Tablet 5mg and 10mg [in Japanese] [Available from: https:\/\/www.pmda.go.jp\/PmdaSearch\/iyakuDetail\/ResultDataSetPDF\/671450_2189015F1023_2_05] Accessed 26 June 2025."},{"key":"904_CR20","unstructured":"Pharmaceuticals and Medical Devices Agency. The e-labeling of CRESTOR Tablets 2.5mg and 5mg & OD Tablets 2.5mg and 5mg [in Japanese] [Available from: https:\/\/www.pmda.go.jp\/PmdaSearch\/iyakuDetail\/ResultDataSetPDF\/670227_2189017F1022_1_32] Accessed 26 June 2025."},{"key":"904_CR21","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1002\/pds.4879","volume":"28","author":"M Yamaguchi","year":"2019","unstructured":"Yamaguchi M, Inomata S, Harada S, et al. Establishment of the MID-NET\u00ae medical information database network as a reliable and valuable database for drug safety assessments in Japan. 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