Real-world pharmacovigilance investigation of imipenem/cilastatin: signal detection using the FDA Adverse Event Reporting System (FAERS) database

Peng Jia ¹ Yusen Zhou ² Yuan Gao ^1* Shangyu Wang ^1* Jiangliu Yin ² Yixiang Lian ^3* Quanyou Lai ^1*

• ¹ Department of Hepato-biliary and Pancreato-splenic Surgery, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi Province, China
• ² Department of Neurosurgery, Changsha Central Hospital, Changsha, Hunan Province, China
• ³ Department of Pathology, Changsha Central Hospital, Changsha, Hunan Province, China

Background: Although imipenem/cilastatin (IMI/CIL) has demonstrated favorable therapeutic efficacy against various infections, the incidence of potential adverse events (AEs) has escalated in parallel with its increased utilization and has been documented in clinical trials. However, a comprehensive understanding of real-world implications remains lacking. Methods: By conducting a comprehensive search in the FDA Adverse Event Reporting System (FAERS) database, AE reports associated with IMI/CIL as the primary suspect (PS) were selected for analysis, spanning from the first quarter of 2004 to the fourth quarter of 2023. Utilizing disproportionality analysis techniques, potential signals of AE s were identified through reported odds ratio (ROR), proportional report ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric mean (EBGM). The obtained results were systematically classified using Medical Dictionary for Regulatory Activities (MedDRA). Result: From the first quarter of 2004 to the fourth quarter of 2023, a total of 2574 reports documenting AEs associated with IMI/CIL were obtained, with more than half (n=1517, 58.94%) involving individuals aged over 60 years old. Descriptive analysis was conducted based on age groups and time to onset, revealing that the majority of AEs occurred within three days. Adverse drug reactions caused by IMI/CIL were classified into 24 system organ classes (SOCs) at the preferred term (PT) level. Furthermore, previously unreported and clinically significant AEs such as cerebral atrophy, and delirium were also identified at the PT level.This study offers a more comprehensive insight into the monitoring, supervision, and management of adverse drug reactions associated with IMI/CIL. Clinicians should pay further attention to the implications of numerous AEs and their corresponding signal intensities, as well as unrecorded signals of severe AEs. This holds significant value in enhancing the clinical safety profile of IMI/CIL.