Yang Yang, Cui Zhiwei, Feng Xiaoshan, Zou Fan, Wu Xiaoling
Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Shaanxi, 710004, People's Republic of China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
BMC Pharmacol Toxicol. 2025 Apr 22;26(1):91. doi: 10.1186/s40360-025-00920-4.
Ganirelix, a third-generation GnRH antagonist, is widely used in assisted reproductive technology (ART) for rapid pituitary suppression to prevent premature luteinizing hormone (LH) surges. Despite its extensive clinical use, real-world evidence on its safety in large populations remains scarce. This study aimed to evaluate the safety profile of ganirelix by comprehensively analyzing adverse drug events (ADEs) using real-world data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japan Adverse Drug Event Reporting (JADER) database.
We extracted ADE data from FAERS (Q1 2004-Q2 2024) and JADER (Q1 2009-Q1 2024). Disproportionality analyses, including reporting odds ratios (ROR), proportional reporting ratios (PRR), Bayesian Confidence Propagation Neural Networks (BCPNN), and Multi-item Gamma Poisson Shrinkage (MGPS), were employed to identify significant associations between ganirelix and ADEs.
In the FAERS database, we identified 1,096 ganirelix-related ADE reports, spanning 26 system organ classes (SOCs). A total of 65 positive signals were detected, including ADEs consistent with drug label such as ovarian hyperstimulation syndrome (OHSS) (n = 290, ROR 2462.76, PRR 2168.48, EBGM05 1655.59, IC025 9.18), injection site pain (n = 54, ROR 3.99, PRR 3.93, EBGM05 3.13, IC025 0.31), and fetal death (n = 6, ROR 21.05, PRR 21.00, EBGM05 10.72, IC025 2.72). Additionally, unexpected signals not listed in the drug label were identified, including ectopic pregnancy (n = 7, ROR 33.02, PRR 32.93, EBGM05 17.64, IC025 3.37), maternal exposure before pregnancy (n = 30, ROR 76.09, PRR 75.16, EBGM05 74.72, IC025 6.22), dermatitis allergic (n = 4, ROR 7.98, PRR 7.97, EBGM05 3.50, IC025 1.33), and bladder tamponade (n = 4, ROR 771.47, PRR 770.3, EBGM05 311.57, IC025 7.80). The median time to ADE onset was 13 days. External validation using the JADER database (62 ganirelix-related ADE reports) confirmed four signals, including abortion (n = 19), OHSS (n = 17), missed abortion (n = 9), and fetal death (n = 8), aligning with FAERS findings.
This study provides a robust real-world safety evaluation of ganirelix, with findings corroborated by two independent pharmacovigilance databases. While consistent with clinical observations, the identification of unexpected signals warrants further pharmacoepidemiological investigations to confirm these results.
第三代促性腺激素释放激素（GnRH）拮抗剂加尼瑞克广泛应用于辅助生殖技术（ART），用于快速抑制垂体，以防止促黄体生成素（LH）过早激增。尽管其在临床上广泛使用，但关于其在大量人群中的安全性的真实世界证据仍然稀缺。本研究旨在通过使用来自美国食品药品监督管理局不良事件报告系统（FAERS）和日本药品不良反应报告（JADER）数据库的真实世界数据，全面分析药物不良事件（ADEs），以评估加尼瑞克的安全性。
我们从FAERS（2004年第一季度至2024年第二季度）和JADER（2009年第一季度至2024年第一季度）中提取ADE数据。采用不成比例分析，包括报告比值比（ROR）、比例报告比值（PRR）、贝叶斯置信传播神经网络（BCPNN）和多项目伽马泊松收缩（MGPS），以确定加尼瑞克与ADEs之间的显著关联。
在FAERS数据库中，我们识别出1096份与加尼瑞克相关的ADE报告，涵盖26个系统器官类别（SOCs）。共检测到65个阳性信号，包括与药物标签一致的ADEs，如卵巢过度刺激综合征（OHSS）（n = 290，ROR 2462.76，PRR 2168.48，EBGM05 1655.59，IC025 9.18）、注射部位疼痛（n = 54，ROR 3.99，PRR 3.93，EBGM05 3.13，IC025 0.31）和胎儿死亡（n = 6，ROR 21.05，PRR 21.00，EBGM05 10.72，IC025 2.72）。此外，还识别出药物标签中未列出的意外信号，包括异位妊娠（n = 7，ROR 33.02，PRR 32.93，EBGM05 17.64，IC025 3.37）、妊娠前母亲暴露（n = 30，ROR 76.09，PRR 75.16，EBGM05 74.72，IC025 6.22）、过敏性皮炎（n = 4，ROR 7.98，PRR 7.97，EBGM05 3.50，IC025 1.33）和膀胱填塞（n = 4，ROR 771.47，PRR 770.3，EBGM05 311.57, IC025 7.80）。ADE发作的中位时间为13天。使用JADER数据库（62份与加尼瑞克相关的ADE报告）进行的外部验证确认了四个信号，包括流产（n = 19）、OHSS（n = 17）、稽留流产（n = 9）和胎儿死亡（n = 8），与FAERS的结果一致。
本研究对加尼瑞克进行了强有力的真实世界安全性评估，研究结果得到了两个独立的药物警戒数据库的证实。虽然与临床观察结果一致，但意外信号的识别值得进一步进行药物流行病学调查以确认这些结果。
