Zhang Yanjing, Zhou Chunhua, Liu Yan, Hao Yupei, Wang Jing, Song Bingyu, Yu Jing
Department of Clinical Pharmacy, The First Hospital of Hebei Medical University, Shijiazhuang, China.
The Technology Innovation Center for Artificial Intelligence in Clinical Pharmacy of Hebei Province, The First Hospital of Hebei Medical University, Shijiazhuang, China.
Front Pharmacol. 2024 Sep 23;15:1472648. doi: 10.3389/fphar.2024.1472648. eCollection 2024.
Lumateperone has been approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia in adults since 2019, however, there is still a lack of data report on adverse reactions in real-world settings. Conducting data mining on adverse events (AEs) associated with Lumateperone and investigating the risk factors for serious AEs can provide valuable insights for its clinical practice.
AE reports in the FDA Adverse Event Reporting System (FAERS) from 2019 Q4 (FDA approval of Lumateperone) to 2024 Q1 were collected and analyzed. Disproportionality in Lumateperone-associated AEs was evaluated using the following parameters: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Univariate and multivariate logistic regression analyses were conducted to identify the risk factors for Lumateperone-induced severe AEs.
A total of 2,644 reports defined Lumateperone as the primary suspected drug was collected, including 739 reports classified as severe AEs and 1905 reports as non-severe AEs. The analysis revealed that 130 preferred terms (PTs) with significant disproportionality were based on the four algorithms, 67 (51.53%) of which were not included in the product labeling, affecting 6 systems and organs. In addition, dizziness (81 cases) was the most reported Lumateperone-associated severe AEs, and tardive dyskinesia showed the strongest signal (ROR = 186.24). Logistic regression analysis indicated that gender, bipolar II disorder, and concomitant drug use are independent risk factors for Lumateperone-associated severe AEs. Specifically, female patients had a 1.811-fold increased risk compared with male patients (OR = 1.811 [1.302, 2.519], = 0.000), while patients with bipolar II disorder had a 1.695-fold increased risk compared with patients diagnosed with bipolar disorder (OR = 1.695 [1.320, 2.178], = 0.000). Conversely, concomitant use of CYP3A4 inhibitors or drugs metabolized by CYP3A4 was associated with a decreased risk of severe AEs (OR = 0.524 [0.434, 0.633], = 0.000).
Collectively, this study provides critical insights into the safety profile of Lumateperone. It highlights the need for cautious use in high-risk populations, such as females and individuals with bipolar II disorder, and emphasizes the importance of monitoring for AEs, including dizziness and tardive dyskinesia. Healthcare also should remain alert to potential AEs not listed in the prescribing information to ensure medical safety.
自2019年以来，鲁马西平已获美国食品药品监督管理局（FDA）批准用于治疗成人精神分裂症，但在真实世界环境中关于不良反应的数据报告仍然缺乏。对与鲁马西平相关的不良事件（AE）进行数据挖掘并调查严重AE的风险因素可为其临床应用提供有价值的见解。
收集并分析FDA不良事件报告系统（FAERS）中2019年第四季度（鲁马西平获FDA批准）至2024年第一季度的AE报告。使用以下参数评估鲁马西平相关AE的不成比例性：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）和多项伽马泊松收缩器（MGPS）。进行单因素和多因素逻辑回归分析以确定鲁马西平诱发严重AE的风险因素。
共收集到2644份将鲁马西平定义为主要可疑药物的报告，其中739份被归类为严重AE报告，1905份为非严重AE报告。分析显示，基于四种算法有130个优先术语（PT）存在显著不成比例性，其中67个（51.53%）未包含在产品标签中，影响6个系统和器官。此外，头晕（81例）是报告最多的与鲁马西平相关的严重AE，迟发性运动障碍显示出最强信号（ROR = 186.24）。逻辑回归分析表明，性别、双相II型障碍和合并用药是鲁马西平相关严重AE的独立风险因素。具体而言，女性患者与男性患者相比风险增加1.811倍（OR = 1.811 [1.302, 2.519]，P = 0.000），而双相II型障碍患者与诊断为双相I型障碍的患者相比风险增加1.695倍（OR = 1.695 [1.320, 2.178]，P = 0.000）。相反，合并使用CYP3A4抑制剂或由CYP3A4代谢的药物与严重AE风险降低相关（OR = 0.524 [0.434, 0.633]，P = 0.000）。
总体而言，本研究为鲁马西平的安全性概况提供了关键见解。它强调在高危人群（如女性和双相II型障碍患者）中谨慎使用的必要性，并强调监测AE（包括头晕和迟发性运动障碍）的重要性。医疗保健人员还应警惕处方信息中未列出的潜在AE，以确保医疗安全。
