Mining of risk signals for thromboembolism and hepatotoxicity related to thrombopoietin receptor agonist based on the US FDA Adverse Event Reporting System database
10.3760/cma.j.cn11401-20230306-00155
- VernacularTitle:基于美国FDA不良事件报告系统数据库的血小板生成素受体激动剂血栓栓塞和肝毒性风险信号挖掘
- Author:
Cuilyu LIANG
1
;
Yin ZHANG
1
Author Information
1. 福建医科大学附属第二医院药学部，泉州 362000
- Publication Type:Journal Article
- Keywords:
Receptors, thrombopoietin;
Thromboembolism;
Chemical and drug induced liver injury;
Adverse reaction signal detection;
Eltrombopag;
Romiplostim;
Avatrombopa
- From:
Adverse Drug Reactions Journal
2024;26(1):38-43
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To mine the risk signals of thromboembolism and hepatotoxicity related to thrombopoietin receptor agonists (TPO-RAs) and provide references for safe use of these drugs in clinic.Methods:Adverse event (AE) reports on eltrombopag, romiplostim, and avatrombopag from October 2009 to September 2023 were collected by searching US FDA Adverse Event Reporting System database. AEs were classified and standardized according to the systematic organ class (SOC) and preferred terms (PT) of Medical Dictionary for Regulatory Activities version 25.0. The AE risk signals of thromboembolism and hepatotoxicity related to the 3 TPO-RAs were mined using reporting odds ratio (ROR) method. An AE with reports ≥3 and the lower limit of the 95% confidence interval of ROR >1 was defined as a risk signal. Results:The number of AE reports with eltrombopag, romiplostim and avatrombopag as the primary suspect drugs were 25 215, 18 762, and 1 204, respectively. Fifty-two, 51, and 9 PTs of thromboembolic events (TEEs) related to eltrombopag, romiplostim and avatrombopag were mined, respectively. The top 5 PTs in the signal strength of eltrombopag were renal embolism, portal vein thrombosis, splenic thrombosis, splenic vein thrombosis and hepatic artery thrombosis. The top 5 PTs in the signal strength of romiplostim were embolism arterial, cerebral vascular occlusion, vertebral artery occlusion, portal vein thrombosis, and thrombosis mesenteric vessel. The top 5 PTs in the signal strength of avatrombopag were renal vein thrombosis, portal vein thrombosis, cerebral venous sinus thrombosis, embolism, and deep vein thrombosis. In addition, 25, 14 and 4 PTs of hepatotoxicity related to eltrombopag, romiplostim, and avatrombopag were mined, respectively. The top 5 PTs in the signal strength of eltrombopag were portal vein dilatation, portal vein thrombosis, hepatic artery thrombosis, indirect bilirubin increase, and chronic hepatic failure. The top 5 PTs in the signal strength of romiplostim were portal vein thrombosis, chronic hepatic failure, alcoholic liver disease, hepatic haematoma, and hepatic cirrhosis. The PTs in the signal strength of avatrombopag were portal vein thrombosis, liver function test abnormality, hepatic function abnormality, and hepatic enzyme increase. A total of 24 PTs not recorded in drug labels of the 3 TPO-RAs were mined. The top 5 PTs in the signal strength were portal vein dilatation, chronic hepatic failure, liver function test abnormality, alcoholic liver disease, and ocular icterus.Conclusions:TEEs and hepatotoxicity are common adverse reactions of the 3 TPO-RAs. The coagulation function and liver function of patients should be monitored before and after application of TPO-RAs. It should be alert for the adverse reactions not recorded in the drug labels.
