title: Analysis of Stevens-Johnson syndrome and toxic epidermal necrolysis using the Japanese Adverse Drug Event Report database.
abstract: BACKGROUND
  Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions associated with fatal disorders. Although many causes of SJS/TEN have been proposed, the time-to-onset for SJS/TEN and the relationship between aging and SJS/TEN are still not clear. Therefore, the aim of this study was to determine the relationship between aging and SJS/TEN using the Japanese Adverse Drug Event Report (JADER) database and analyze the time-to-onset profile of SJS/TEN.
  
  
  METHODS
  We analyzed reports of SJS/TEN recorded in the JADER database between 2004 and 2015 using an adjusted reporting odds ratio (ROR). We also used Weibull proportional hazards models for each drug to examine the expression patterns of SJS/TEN. We selected the drugs according to the number of the reports associated with SJS/TEN.
  
  
  RESULTS
  The JADER contained 330,686 reports from April 2004 to April 2015. The adjusted RORs for patients in the 0-19-, 20-39-, 60-79-, and ≥ 80-year-old groups from all data extracted from the JADER database were 1.33 (95 % confidence interval [CI], 1.21-1.45), 1.78 (95 % CI, 1.65-1.93), 0.71 (95 % CI, 0.66-0.75), and 0.72 (95 % CI, 0.66-0.79), respectively. The adjusted ROR tended to be higher in patients aged 0-19 years, particularly in patients using antipyretic analgesics, such as loxoprofen or acetaminophen. More than half of the cases of SJS/TEN onset following administration of loxoprofen and acetaminophen occurred within 4 days of the initiation of treatment. The median times-to-onset were 3 days for loxoprofen and 2 days for acetaminophen. The scale parameter α values of loxoprofen and acetaminophen were 9.44 and 6.17, respectively. The upper 95 % CIs of shape parameter β values for the drugs were all less than 1, with the exceptions of those for carbamazepine, ACE inhibitors, and corticosteroids.
  
  
  CONCLUSIONS
  Our results suggested that monitoring of younger patients who frequently use antipyretic analgesics is important. These drugs should be used and monitored within the first 2-3 days of treatment in the Japanese population.
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196 Japan ; Medical Database Co., Ltd, 3-11-10 Higashi, Shibuya-ku, Tokyo 150-0011 Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Abe
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196 Japan ; Clinical Research, Innovation and Education Center, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba Ward, Sendai, Miyagi 980-8574 Japan.
authors.forename: Ryogo
authors.initials: R
authors.lastname: Umetsu
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196 Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Mataki
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196 Japan.
authors.forename: Yamato
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196 Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Ueda
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196 Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakayama
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196 Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Hane
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196 Japan.
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Matsui
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196 Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Hatahira
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196 Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Sasaoka
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196 Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Motooka
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196 Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
authors.affiliation: Department of Pediatrics, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194 Japan ; United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu, 501-1194 Japan.
authors.forename: Zenichiro
authors.initials: Z
authors.lastname: Kato
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu, 501-1194 Japan.
authors.forename: Yasutomi
authors.initials: Y
authors.lastname: Kinosada
authors.affiliation: Laboratory of Pharmacology, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196 Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Inagaki
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196 Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Nakamura
keywords: Japanese Adverse Drug Event Report; Stevens-Johnson syndrome; Toxic epidermal necrolysis