Nakao Satoshi, Hatahira Haruna, Sasaoka Sayaka, Hasegawa Shiori, Motooka Yumi, Ueda Natsumi, Abe Junko, Fukuda Akiho, Naganuma Misa, Kanoh Hiroyuki, Seishima Mariko, Ishiguro Motoyuki, Kinosada Yasutomi, Nakamura Mitsuhiro
Laboratory of Drug Informatics, Gifu Pharmaceutical University.
Medical Database Co., Ltd.
Biol Pharm Bull. 2017;40(12):2158-2165. doi: 10.1248/bpb.b17-00561.
Drug-induced photosensitivity (DIP) refers to the development of cutaneous disorders caused by the combined effects of different medications and light. The aim of this study was to obtain new information on drug risk comparisons and on DIP onset profiles, including seasonal variations, for clinically used prescription drugs. We analyzed reports of DIP recorded in the Japanese Adverse Drug Event Report (JADER) database using a reporting odds ratio (ROR). We also used Weibull proportional-hazards models for each drug to examine the patterns of DIP. The JADER database contains 430587 reports recorded from April 2004 to November 2016. The ROR values (95% confidence interval [CI]) of losartan/hydrochlorothiazide (HCTZ), valsartan/HCTZ, and ketoprofen were 214.5 (162.1-283.9), 104.7 (66.3-165.5), and 117.9 (76.6-181.5), respectively. For time-to-onset analysis, the median durations (interquartile range) for DIP caused by losartan/HCTZ, valsartan/HCTZ, and ketoprofen were 56 (41-78), 49 (38-88), and 8 (2-14) days, respectively. The lower limit of the 95% CI for the Weibull shape parameter β value for losartan/HCTZ was greater than 1. More than half of the reports of DIP onset following the administration of ketoprofen were recorded within 10 d of treatment initiation. The seasonal variation of photosensitivity reactions was shown to follow an annual sinusoidal pattern with a peak in April and May. Based on the results, losartan/HCTZ, valsartan/HCTZ, and ketoprofen should be used carefully in clinical practice to avoid DIP.
药物性光敏反应（DIP）是指由不同药物和光线的联合作用引起的皮肤疾病。本研究的目的是获取有关临床使用的处方药的药物风险比较以及DIP发病情况（包括季节性变化）的新信息。我们使用报告比值比（ROR）分析了日本药品不良反应报告（JADER）数据库中记录的DIP报告。我们还对每种药物使用威布尔比例风险模型来研究DIP的发病模式。JADER数据库包含2004年4月至2016年11月记录的430587份报告。氯沙坦/氢氯噻嗪（HCTZ）、缬沙坦/HCTZ和酮洛芬的ROR值（95%置信区间[CI]）分别为214.5（162.1 - 283.9）、104.7（66.3 - 165.5）和117.9（76.6 - 181.5）。对于发病时间分析，氯沙坦/HCTZ、缬沙坦/HCTZ和酮洛芬引起的DIP的中位持续时间（四分位间距）分别为56（41 - 78）天、49（38 - 88）天和8（2 - 14）天。氯沙坦/HCTZ的威布尔形状参数β值的95%CI下限大于1。酮洛芬给药后DIP发病报告的一半以上是在治疗开始后10天内记录的。光敏反应的季节性变化呈年度正弦模式，4月和5月达到峰值。根据结果，在临床实践中应谨慎使用氯沙坦/HCTZ、缬沙坦/HCTZ和酮洛芬以避免DIP。
