PMID- 37957717 OWN - NLM STAT- MEDLINE DCOM- 20231115 LR - 20231120 IS - 2050-6511 (Electronic) IS - 2050-6511 (Linking) VI - 24 IP - 1 DP - 2023 Nov 13 TI - A disproportionality analysis of adverse events associated to pertuzumab in the FDA Adverse Event Reporting System (FAERS). PG - 62 LID - 10.1186/s40360-023-00702-w [doi] LID - 62 AB - BACKGROUND: Pertuzumab is widely used for the treatment of HER2 + breast cancer. But its safety in the real world should be continuously monitored. So, we evaluated the safety of pertuzumab by pharmacovigilance analyze based on related adverse events (AEs) from the FDA Adverse Event Reporting System (FAERS) and find whether potential or uncertain adverse events were present. METHODS: In disproportionality analysis, four algorithms were employed to detect the signals of pertuzumab from the FAERS between 2012 and 2022. In addition, we also used MYSQL 8.0, Navicat Premium 15, and Microsoft EXCEL 2019 to analyze the potential and high-ROR (reporting odds ratio) signals of pertuzumab. We also collected the onset times of pertuzumab-associated AEs. RESULTS: From January 2012 to December 2022, there are 39,190,598 AEs reported from the FAERS database, of which 14,707 AEs listed pertuzumab as the 'primary suspected (PS)' drug. A total of 115 (46 potential) significant disproportionality preferred terms (PTs) conforming to the four algorithms were retained. Finally, we detected that the pertuzumab-induced AEs occurred in 12 organ systems. For pertuzumab, unexpected and significant PTs of AEs were found, including but not limited to below PTs: haematotoxicity, cardiotoxicity, cardiomyopathy, mitral valve incompetence, tachycardia, intestinal perforation, hemorrhoids, erysipelas, dehydration, pneumonitis, skin toxicity, onychomadesis, cyanosis, and circulatory collapse. We found there were 9 strong signals (5 potential safety signals) and 68 medium intensity signals (21 potential safety signals) according to IC(025) (information component). The potential strong signals (IC(025) > 3.0) were myelosuppression, cardiotoxicity, cardiac dysfunction, ejection fraction decreased, interstitial lung disease, and onychomadesis. Excluding unreported or unreasonable onset time reports, a total of 2016 AEs reported onset time and the median onset time was 117 days (4, 96), as median (Q1, Q3). Notably, most of the all AEs (n = 1133, 56%) and cardiac-related events (n = 405, 53%) all occurred within one month after pertuzumab therapy. CONCLUSION: Analysis of FAERS data identified pertuzumab-associated AEs, and our findings supported continuous clinical monitoring, pharmacovigilance, and further studies of pertuzumab. A significant association was detected between pertuzumab and some potential adverse events which should be regarded with some care. We have to pay attention to the first month after pertuzumab therapy and prepare emergency measures, especially for the elderly and patients with cardiovascular diseases. CI - (c) 2023. The Author(s). FAU - Zou, Shu-Peng AU - Zou SP AD - Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Wuhan, Hubei Province, 430000, China. FAU - Yang, Hai-Yun AU - Yang HY AD - School of Pharmacy, Lanzhou University, Lanzhou, Gansu Province, 730000, China. FAU - Ouyang, Meng-Ling AU - Ouyang ML AD - Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Wuhan, Hubei Province, 430000, China. FAU - Cheng, Qian AU - Cheng Q AD - Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Wuhan, Hubei Province, 430000, China. FAU - Shi, Xuan AU - Shi X AD - Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Wuhan, Hubei Province, 430000, China. FAU - Sun, Ming-Hui AU - Sun MH AD - Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Wuhan, Hubei Province, 430000, China. smh007tj@163.com. LA - eng PT - Journal Article DEP - 20231113 PL - England TA - BMC Pharmacol Toxicol JT - BMC pharmacology & toxicology JID - 101590449 RN - K16AIQ8CTM (pertuzumab) RN - 0 (Antibodies, Monoclonal, Humanized) SB - IM MH - Humans MH - Aged MH - Female MH - *Cardiotoxicity MH - Adverse Drug Reaction Reporting Systems MH - Antibodies, Monoclonal, Humanized/adverse effects MH - Pharmacovigilance MH - *Breast Neoplasms/drug therapy PMC - PMC10642055 OTO - NOTNLM OT - Adverse events OT - FAERS OT - Pertuzumab OT - Pharmacovigilance COIS- The authors declare no competing interests. EDAT- 2023/11/14 06:42 MHDA- 2023/11/15 06:42 PMCR- 2023/11/13 CRDT- 2023/11/14 00:14 PHST- 2023/06/27 00:00 [received] PHST- 2023/10/31 00:00 [accepted] PHST- 2023/11/15 06:42 [medline] PHST- 2023/11/14 06:42 [pubmed] PHST- 2023/11/14 00:14 [entrez] PHST- 2023/11/13 00:00 [pmc-release] AID - 10.1186/s40360-023-00702-w [pii] AID - 702 [pii] AID - 10.1186/s40360-023-00702-w [doi] PST - epublish SO - BMC Pharmacol Toxicol. 2023 Nov 13;24(1):62. doi: 10.1186/s40360-023-00702-w.