Ohyama Katsuhiro, Kawakami Haruna, Inoue Michiko
Education Center for Experiential Pharmacy Practice, School of Pharmacy, Tokyo University of Pharmacy and Life Science.
Biol Pharm Bull. 2017;40(5):616-620. doi: 10.1248/bpb.b16-00848.
Topical prostaglandin F2α (PGF2α) analogs are widely used as the first line of therapy for glaucoma. Systemic PGF2α is suggested to increase blood pressure. Some ophthalmic formulations with β-receptor blocking or α-receptor stimulating actions are reported to cause systemic adverse events such as a decrease in heart rate and blood pressure. The objective of this study was to evaluate the association between topical PGF2α analogs and blood pressure elevation. We analyzed the reports obtained from the Food and Drug Administration Adverse Event Reporting System (FAERS) database from the first quarter of 2004 until the end of 2015 and the Japanese Adverse Drug Event Report (JADER) database from April 2004 to January 2016 for signal detection using reporting odds ratio (ROR), a method of disproportionality analyses. Signals are considered significant if the ROR estimates and lower bound of the 95% confidence interval (CI) exceed 1. Preferred terms in the Medical Dictionary for Regulatory Activities were utilized to define blood pressure elevation. A total of 6156081 reports from the FAERS and 351226 reports from the JADER were analyzed. The significant RORs with 95% CI were calculated to be 1.82 (95% CI: 1.55-2.13) for bimatoprost, 1.69 (95% CI: 1.53-1.85) for latanoprost, and 2.17 (95% CI: 1.82-2.59) for travoprost from the FAERS. From the JADER, 5.01 (95% CI: 1.59-15.8) was calculated for bimatoprost and 8.02 (95% CI: 2.94-21.9) for tafluprost. The resulting data suggest the necessity for further clinical research on blood pressure elevation associated with topical PGF2α analogs and close monitoring.
局部用前列腺素F2α（PGF2α）类似物被广泛用作青光眼的一线治疗药物。有研究表明，全身性PGF2α会使血压升高。据报道，一些具有β受体阻断或α受体刺激作用的眼科制剂会引发全身性不良事件，如心率和血压下降。本研究的目的是评估局部用PGF2α类似物与血压升高之间的关联。我们分析了从2004年第一季度至2015年底的美国食品药品监督管理局不良事件报告系统（FAERS）数据库以及2004年4月至2016年1月的日本药品不良事件报告（JADER）数据库中获取的报告，采用报告比值比（ROR）这一不成比例分析方法进行信号检测。如果ROR估计值和95%置信区间（CI）的下限超过1，则认为信号具有显著性。使用《监管活动医学词典》中的首选术语来定义血压升高。共分析了FAERS中的6156081份报告和JADER中的351226份报告。FAERS数据显示，比马前列素的显著ROR（95%CI）为1.82（95%CI：1.55 - 2.13），拉坦前列素为1.69（95%CI：1.53 - 1.85），曲伏前列素为2.17（95%CI：1.82 - 2.59）。从JADER数据来看，比马前列素为5.01（95%CI：1.59 - 15.8），他氟前列素为8.02（95%CI：2.94 - 21.9）。所得数据表明有必要对局部用PGF2α类似物相关的血压升高进行进一步临床研究并密切监测。
