Background: The Phosphoinositide 3-kinases (PI3Ks) family plays a crucial role in tumorigenesis. Alpelisib (inhibiting PI3Kα), copanlisib (inhibiting PI3Kα andPI3Kδ), duvelisib (inhibiting PI3Kδ and PI3Kγ), and idelalisib (inhibiting PI3Kδ) were developed to target the PI3K pathway. However, the toxicity limits their application to some extent. It's necessary to investigate the adverse effects (AEs) of these inhibitors.
Research design and methods: We conducted a comparative analysis of the safety signals of AEs in PI3K inhibitors using disproportionality analysis in the FDA Adverse Event Reporting System database(FAERS).
Results: Our study identified significant safety signals for metabolic disorders with all PI3K inhibitors. Notable safety signals for gastrointestinal disorders were observed with most PI3K inhibitors, with the exception of copanlisib. Common AEs shared among all PI3K inhibitors included colitis and dehydration. Alpelisib displayed unique AEs associated with metabolic disorders, whereas copanlisib exhibited idiosyncratic AEs linked to cardiac and vascular disorders. Stevens-Johnson syndrome emerged as a common severe adverse event (SAE) among alpelisib, copanlisib, and idelalisib, while febrile neutropenia was prevalent among copanlisib, duvelisib, and idelalisib. Intestinal perforation was solely associated with alpelisib.
Conclusions: The safety profiles of the five PI3K inhibitors vary concerning adverse events. These findings could guide drug selection and inform future prospective research.
{"title":"Post-marketing safety concern of PI3K inhibitors in the cancer therapies: an 8-year disproportionality analysis from the FDA Adverse Event Reporting System.","authors":"Xiaorong Lin, Yimin Zhang, Hongyan Huang, Wei Zhuang, Lisha Wu","doi":"10.1080/14740338.2024.2387317","DOIUrl":"10.1080/14740338.2024.2387317","url":null,"abstract":"<p><strong>Background: </strong>The Phosphoinositide 3-kinases (PI3Ks) family plays a crucial role in tumorigenesis. Alpelisib (inhibiting PI3Kα), copanlisib (inhibiting PI3Kα andPI3Kδ), duvelisib (inhibiting PI3Kδ and PI3Kγ), and idelalisib (inhibiting PI3Kδ) were developed to target the PI3K pathway. However, the toxicity limits their application to some extent. It's necessary to investigate the adverse effects (AEs) of these inhibitors.</p><p><strong>Research design and methods: </strong>We conducted a comparative analysis of the safety signals of AEs in PI3K inhibitors using disproportionality analysis in the FDA Adverse Event Reporting System database(FAERS).</p><p><strong>Results: </strong>Our study identified significant safety signals for metabolic disorders with all PI3K inhibitors. Notable safety signals for gastrointestinal disorders were observed with most PI3K inhibitors, with the exception of copanlisib. Common AEs shared among all PI3K inhibitors included colitis and dehydration. Alpelisib displayed unique AEs associated with metabolic disorders, whereas copanlisib exhibited idiosyncratic AEs linked to cardiac and vascular disorders. Stevens-Johnson syndrome emerged as a common severe adverse event (SAE) among alpelisib, copanlisib, and idelalisib, while febrile neutropenia was prevalent among copanlisib, duvelisib, and idelalisib. Intestinal perforation was solely associated with alpelisib.</p><p><strong>Conclusions: </strong>The safety profiles of the five PI3K inhibitors vary concerning adverse events. These findings could guide drug selection and inform future prospective research.</p>","PeriodicalId":12232,"journal":{"name":"Expert Opinion on Drug Safety","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1080/14740338.2024.2393269
Jie Zhou, Junchang Ye, Maohua Chen, Xinlei Zheng
Objective: Baloxavir marboxil (hereafter referred to as baloxavir) is the only cap-dependent endonuclease inhiabitor approved for the treatment and prevention of influenza. However, as a new drug marketed in 2018, the long-term safety of baloxavir in large sample population was unclear. This study aims to evaluate baloxavir-associated adverse events (AEs) through data mining of the international pharmacovigilance database of US FDA Adverse Event Reporting System (FAERS).
Methods: Disproportionality analysis was conducted to assess the association between baloxavir and its AEs. Data were collected from FAERS from March 2018 to June 2023. After standardizing the data, signal quantification techniques including ROR, PRR, BCPNN and MGPS were used for analysis.
Results: A total of 49 significant baloxavir-related preferred terms (PTs) in 20 system organ classes (SOCs) were identified in our data analysis. Compared to baloxavir's FDA label, some new PTs emerged, with the top 10 being pneumonia, loss of consciousness, rhabdomyolysis, seizure, altered state of consciousness, hepatic function abnormal, delirium, depressed level of consciousness, encephalopathy and cardio-respiratory arrest.
Conclusion: In clinical application of baloxavir, attention should be paid to the new AE signals in addition to the those recorded in the labels, so as to ensure the safety of the patients.
{"title":"A real-world disproportionality analysis of baloxavir marboxil: post-marketing pharmacovigilance data.","authors":"Jie Zhou, Junchang Ye, Maohua Chen, Xinlei Zheng","doi":"10.1080/14740338.2024.2393269","DOIUrl":"10.1080/14740338.2024.2393269","url":null,"abstract":"<p><strong>Objective: </strong>Baloxavir marboxil (hereafter referred to as baloxavir) is the only cap-dependent endonuclease inhiabitor approved for the treatment and prevention of influenza. However, as a new drug marketed in 2018, the long-term safety of baloxavir in large sample population was unclear. This study aims to evaluate baloxavir-associated adverse events (AEs) through data mining of the international pharmacovigilance database of US FDA Adverse Event Reporting System (FAERS).</p><p><strong>Methods: </strong>Disproportionality analysis was conducted to assess the association between baloxavir and its AEs. Data were collected from FAERS from March 2018 to June 2023. After standardizing the data, signal quantification techniques including ROR, PRR, BCPNN and MGPS were used for analysis.</p><p><strong>Results: </strong>A total of 49 significant baloxavir-related preferred terms (PTs) in 20 system organ classes (SOCs) were identified in our data analysis. Compared to baloxavir's FDA label, some new PTs emerged, with the top 10 being pneumonia, loss of consciousness, rhabdomyolysis, seizure, altered state of consciousness, hepatic function abnormal, delirium, depressed level of consciousness, encephalopathy and cardio-respiratory arrest.</p><p><strong>Conclusion: </strong>In clinical application of baloxavir, attention should be paid to the new AE signals in addition to the those recorded in the labels, so as to ensure the safety of the patients.</p>","PeriodicalId":12232,"journal":{"name":"Expert Opinion on Drug Safety","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.1080/14740338.2024.2405126
Fuchun Zheng, Fei Wang, Yuyang Yuan, Zhipeng Wang, Sheng Li, Bin Fu, Wei Liu
Drug-induced urinary retention (DIUR) can severely impact patient quality of life and complicate treatment. This study investigates the incidence and characteristics of DIUR using data from the FDA...
{"title":"Investigating drug-induced urinary retention: a pharmacovigilance analysis of FDA adverse event reports from 2004 to 2024","authors":"Fuchun Zheng, Fei Wang, Yuyang Yuan, Zhipeng Wang, Sheng Li, Bin Fu, Wei Liu","doi":"10.1080/14740338.2024.2405126","DOIUrl":"https://doi.org/10.1080/14740338.2024.2405126","url":null,"abstract":"Drug-induced urinary retention (DIUR) can severely impact patient quality of life and complicate treatment. This study investigates the incidence and characteristics of DIUR using data from the FDA...","PeriodicalId":12232,"journal":{"name":"Expert Opinion on Drug Safety","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1080/14740338.2024.2393268
Ying Zhang, Shengzhu Sun, Yuming Wang
Background: Migraine, a prevalent neurovascular disorder, can significantly disrupt an individual's daily life. Atogepant (AGN-241689), an orally administered small-molecule drug classified as a calcitonin gene-related peptide receptor antagonist, is utilized for prophylactic migraine treatment. The objective of this study was to investigate adverse events (AEs) associated with atogepant through data mining in the FDA Adverse Event Reporting System (FAERS) to enhance clinical safety.
Methods: Data for atogepant were obtained from the FAERS database covering Q3 2021 through Q4 2023. Disproportionality analysis was employed to quantify relevant AEs associated with atogepant. Reported Ratio of Ratios (ROR) was utilized for identifying risk signals within the FAERS data. This methodology relies on the System Organ Class (SOC) and Preferred Terminology (PT) of the Medical Dictionary for Regulatory Activities (MedDRA).
Results: From the FAERS database, a collection of 7,991,243 reports was obtained. Among these reports, a subset of 3015 was identified as 'primary suspected (PS)' AEs specifically related to atogepant. AEs induced by atogepant were observed across 27 organ systems. A total of 48 significantly disproportionate Preferred Terminologies (PTs) meeting all four algorithms were identified.
Conclusion: Our study has identified adverse events (AEs) associated with atogepant, potentially providing crucial support for the clinical monitoring and risk identification of atogepant.
{"title":"Adverse events associated with Atogepant: a FAERS-based pharmacovigilance analysis.","authors":"Ying Zhang, Shengzhu Sun, Yuming Wang","doi":"10.1080/14740338.2024.2393268","DOIUrl":"10.1080/14740338.2024.2393268","url":null,"abstract":"<p><strong>Background: </strong>Migraine, a prevalent neurovascular disorder, can significantly disrupt an individual's daily life. Atogepant (AGN-241689), an orally administered small-molecule drug classified as a calcitonin gene-related peptide receptor antagonist, is utilized for prophylactic migraine treatment. The objective of this study was to investigate adverse events (AEs) associated with atogepant through data mining in the FDA Adverse Event Reporting System (FAERS) to enhance clinical safety.</p><p><strong>Methods: </strong>Data for atogepant were obtained from the FAERS database covering Q3 2021 through Q4 2023. Disproportionality analysis was employed to quantify relevant AEs associated with atogepant. Reported Ratio of Ratios (ROR) was utilized for identifying risk signals within the FAERS data. This methodology relies on the System Organ Class (SOC) and Preferred Terminology (PT) of the Medical Dictionary for Regulatory Activities (MedDRA).</p><p><strong>Results: </strong>From the FAERS database, a collection of 7,991,243 reports was obtained. Among these reports, a subset of 3015 was identified as 'primary suspected (PS)' AEs specifically related to atogepant. AEs induced by atogepant were observed across 27 organ systems. A total of 48 significantly disproportionate Preferred Terminologies (PTs) meeting all four algorithms were identified.</p><p><strong>Conclusion: </strong>Our study has identified adverse events (AEs) associated with atogepant, potentially providing crucial support for the clinical monitoring and risk identification of atogepant.</p>","PeriodicalId":12232,"journal":{"name":"Expert Opinion on Drug Safety","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1080/14740338.2024.2401025
Zicheng Yu, Haibin Zhu, Xiaolan Liao
Background: Interstitial lung diseases (ILD) is a serious adverse event (AE) associated with antibody-drug conjugates (ADCs). This study aims to delve deeply into the signals of AE associated with ILD linked to ADCs.
Research design and methods: The AE reports were extracted from the first quarter of 2004 to the fourth quarter of 2023 based on the FDA Adverse Event Reporting System (FAERS) database. Signal mining was performed using the reporting odds ratio (ROR) method and the multi-item gamma Poisson shrinker (MGPS) method. Data management, analysis, and visualization were carried out using Python, R software, and MySQL.
Results: A total of 1389 AE reports related to ILD with 11 types of ADCs as the primary suspected drugs were obtained. The age groups most represented were 61-80 age group. ILD-related AE signals were detected for 11 ADCs in the study. Trastuzumab deruxtecan showed the strongest signals in both for ROR and MGPS methods. The median onset time vary from 8 days to 207 days.
Conclusions: The signals of ILD AE associated with ADCs are notably strong. ILD should be closely monitored and assessed in the clinical use of ADCs taking full account of the efficacy and risks of these drugs.
{"title":"Antibody-drug conjugates-related interstitial lung diseases: data mining of the FAERS database.","authors":"Zicheng Yu, Haibin Zhu, Xiaolan Liao","doi":"10.1080/14740338.2024.2401025","DOIUrl":"10.1080/14740338.2024.2401025","url":null,"abstract":"<p><strong>Background: </strong>Interstitial lung diseases (ILD) is a serious adverse event (AE) associated with antibody-drug conjugates (ADCs). This study aims to delve deeply into the signals of AE associated with ILD linked to ADCs.</p><p><strong>Research design and methods: </strong>The AE reports were extracted from the first quarter of 2004 to the fourth quarter of 2023 based on the FDA Adverse Event Reporting System (FAERS) database. Signal mining was performed using the reporting odds ratio (ROR) method and the multi-item gamma Poisson shrinker (MGPS) method. Data management, analysis, and visualization were carried out using Python, R software, and MySQL.</p><p><strong>Results: </strong>A total of 1389 AE reports related to ILD with 11 types of ADCs as the primary suspected drugs were obtained. The age groups most represented were 61-80 age group. ILD-related AE signals were detected for 11 ADCs in the study. Trastuzumab deruxtecan showed the strongest signals in both for ROR and MGPS methods. The median onset time vary from 8 days to 207 days.</p><p><strong>Conclusions: </strong>The signals of ILD AE associated with ADCs are notably strong. ILD should be closely monitored and assessed in the clinical use of ADCs taking full account of the efficacy and risks of these drugs.</p>","PeriodicalId":12232,"journal":{"name":"Expert Opinion on Drug Safety","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1080/14740338.2024.2396410
Shengjun Chai,Haiming Xu,Guocai Xu,Chunmei Cai
BACKGROUNDORENITRAM, an oral treprostinil formulation, was approved in 2013 for pulmonary arterial hypertension (PAH) treatment, necessitating ongoing safety monitoring.RESEARCH DESIGN AND METHODSThis retrospective analysis used FDA Adverse Event Reporting System data from Q4 2013 to Q4 2023, employing disproportionality analysis and the reporting odds ratio (ROR) to identify adverse events (AEs) linked with ORENITRAM.RESULTSOut of 15,660,695 reports, ORENITRAM was the primary suspect in 10,125 cases. We identified 174 significant adverse events across 27 organ systems, with notable issues like pulmonary edema, ascites, and ventricular fibrillation. Females reported more AEs (75.6%) than males (24.0%), suggesting potential metabolic differences. AEs were most common within 30 days of starting treatment or after one year.CONCLUSIONSThe study indicates significant safety issues with ORENITRAM, including serious unexpected events such as pulmonary edema, ascites, and ventricular fibrillation. These findings highlight the necessity for careful clinical monitoring and effective risk management, particularly with observed gender differences in AE profiles. The study's retrospective nature and reliance on spontaneous reports may affect result generalizability.
{"title":"ORENITRAM's decadal journey: unveiling safety profiles and adverse event through a real-world pharmacovigilance study of FAERS events.","authors":"Shengjun Chai,Haiming Xu,Guocai Xu,Chunmei Cai","doi":"10.1080/14740338.2024.2396410","DOIUrl":"https://doi.org/10.1080/14740338.2024.2396410","url":null,"abstract":"BACKGROUNDORENITRAM, an oral treprostinil formulation, was approved in 2013 for pulmonary arterial hypertension (PAH) treatment, necessitating ongoing safety monitoring.RESEARCH DESIGN AND METHODSThis retrospective analysis used FDA Adverse Event Reporting System data from Q4 2013 to Q4 2023, employing disproportionality analysis and the reporting odds ratio (ROR) to identify adverse events (AEs) linked with ORENITRAM.RESULTSOut of 15,660,695 reports, ORENITRAM was the primary suspect in 10,125 cases. We identified 174 significant adverse events across 27 organ systems, with notable issues like pulmonary edema, ascites, and ventricular fibrillation. Females reported more AEs (75.6%) than males (24.0%), suggesting potential metabolic differences. AEs were most common within 30 days of starting treatment or after one year.CONCLUSIONSThe study indicates significant safety issues with ORENITRAM, including serious unexpected events such as pulmonary edema, ascites, and ventricular fibrillation. These findings highlight the necessity for careful clinical monitoring and effective risk management, particularly with observed gender differences in AE profiles. The study's retrospective nature and reliance on spontaneous reports may affect result generalizability.","PeriodicalId":12232,"journal":{"name":"Expert Opinion on Drug Safety","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142191198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1080/14740338.2024.2399082
Wenjie Li,Ruxue Lv,Wei Wang
BACKGROUNDOngoing studies are evaluating the efficacy and toxicity profiles of combining epidermal growth factor receptor inhibitors (EGFR-TKIs) with antiangiogenic agents in non-small cell lung cancer (NSCLC). However, the complete toxicity profiles remain elusive.RESEARCH DESIGN AND METHODSThis study conducted an extensive pharmacovigilance analysis utilizing the FDA Adverse Event Reporting System database. The analysis focused on identifying and characterizing adverse events (AEs) associated with the concurrent use of EGFR-TKIs and antiangiogenic inhibitors in patients with NSCLC.RESULTSThe study identified significant occurrences of AEs linked to the combination therapy, particularly impacting general disorders, skin and subcutaneous tissue conditions, and vascular disorders. Frequently reported AEs included rash, diarrhea, fatigue, nausea, decreased appetite, and anemia. Notably, the combination of EGFR-TKIs with antiangiogenic inhibitors resulted in an increased incidence of AEs across multiple organ systems compared to EGFR-TKIs alone, with some adverse effects, such as anemia, arrhythmia, and ulcerative keratitis, persisting beyond one year in a subset of patients.CONCLUSIONSThe combination of EGFR-TKIs and antiangiogenic inhibitors in NSCLC treatment presents a distinct and substantial AE profile, often with delayed onset. This finding underscores the necessity for rigorous and ongoing monitoring protocols to mitigate potential long-term adverse effects.
背景正在进行的研究评估了表皮生长因子受体抑制剂(EGFR-TKIs)与抗血管生成药物联合治疗非小细胞肺癌(NSCLC)的疗效和毒性概况。本研究利用 FDA 不良事件报告系统数据库进行了广泛的药物警戒分析。结果本研究发现了与联合治疗相关的大量不良事件,尤其是影响全身疾病、皮肤和皮下组织状况以及血管疾病的不良事件。经常报告的不良反应包括皮疹、腹泻、疲劳、恶心、食欲下降和贫血。值得注意的是,与单用 EGFR-TKIs 相比,EGFR-TKIs 与抗血管生成抑制剂联用会导致多个器官系统的 AEs 发生率增加,部分患者的某些不良反应(如贫血、心律失常和溃疡性角膜炎)会持续一年以上。这一发现突出表明,有必要制定严格、持续的监测方案,以减轻潜在的长期不良反应。
{"title":"Toxicity profiles associated with EGFR-TKIs combined with angiogenesis inhibitors in non-small cell lung cancer: an epidemiological surveillance analysis of the FDA adverse event reporting system.","authors":"Wenjie Li,Ruxue Lv,Wei Wang","doi":"10.1080/14740338.2024.2399082","DOIUrl":"https://doi.org/10.1080/14740338.2024.2399082","url":null,"abstract":"BACKGROUNDOngoing studies are evaluating the efficacy and toxicity profiles of combining epidermal growth factor receptor inhibitors (EGFR-TKIs) with antiangiogenic agents in non-small cell lung cancer (NSCLC). However, the complete toxicity profiles remain elusive.RESEARCH DESIGN AND METHODSThis study conducted an extensive pharmacovigilance analysis utilizing the FDA Adverse Event Reporting System database. The analysis focused on identifying and characterizing adverse events (AEs) associated with the concurrent use of EGFR-TKIs and antiangiogenic inhibitors in patients with NSCLC.RESULTSThe study identified significant occurrences of AEs linked to the combination therapy, particularly impacting general disorders, skin and subcutaneous tissue conditions, and vascular disorders. Frequently reported AEs included rash, diarrhea, fatigue, nausea, decreased appetite, and anemia. Notably, the combination of EGFR-TKIs with antiangiogenic inhibitors resulted in an increased incidence of AEs across multiple organ systems compared to EGFR-TKIs alone, with some adverse effects, such as anemia, arrhythmia, and ulcerative keratitis, persisting beyond one year in a subset of patients.CONCLUSIONSThe combination of EGFR-TKIs and antiangiogenic inhibitors in NSCLC treatment presents a distinct and substantial AE profile, often with delayed onset. This finding underscores the necessity for rigorous and ongoing monitoring protocols to mitigate potential long-term adverse effects.","PeriodicalId":12232,"journal":{"name":"Expert Opinion on Drug Safety","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142191200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1080/14740338.2024.2399094
Carlos De Las Cuevas, Victoria C de Leon, Hilario Blasco-Fontecilla, Enrique Baca-García, Marina Sagud, Emilio J Sanz, Jose de Leon
Background: In the United States, clozapine was first approved for treatment-resistant schizophrenia and then for suicidality in schizophrenia psychoses. Systematic reviews support clozapine's anti-suicidal effect, but the forensic literature stresses its lethality during overdoses.
Research design and methods: Clozapine reports to the international pharmacovigilance database (VigiBase) were analyzed for suicidal ideation, suicide attempts, intentional overdose, and completed suicides from introduction to 1 January 2024. VigiBase uses the information component (IC) as a disproportionality analysis.
Results: The clozapine ICs (range: other antipsychotics) were: 1) suicidal ideation IC = 0.570 with IC025 = 0.454 to IC975 = 0.680 (IC = 3.568 for aripiprazole and 1.729 for risperidone), 2) suicide attempt IC = 1.428 with IC025 = 1.323 to IC975 = 1.529 (IC = 4.150 for quetiapine and 2.968 for risperidone), 3) intentional overdose: IC = 0.995 with IC025 = 0.864 to IC975 = 1.120 (IC = 4.080 for quetiapine and 1.957 for aripiprazole), and 4) completed suicide IC = 1.133 with IC025 = 1.026 to IC975 = 1.235 (IC = 4.648 for quetiapine and 2.160 for risperidone). In summary, all clozapine ICs were significantly lower. We found 2391 clozapine-treated patients on the suicidality spectrum (627 cases with suicidal ideation, 752 with suicide attempt, 488 with intentional overdose, and 731 with completed suicide) but many were taking other antipsychotics. The most frequent reporting countries were the United States, the United Kingdom, and Croatia.
Conclusion: This pharmacovigilance study, with all its inherent limitations, provides independent proof, not overlapping with prior literature, that clozapine may have specific strong anti-suicidal effects that do not appear to be present in other antipsychotics. Further VigiBase studies are needed to compare the lethality of an intentional overdose of clozapine (14.3%) with other antipsychotics.
背景:在美国,氯氮平首先被批准用于治疗耐药性精神分裂症,然后被批准用于治疗精神分裂症精神病患者的自杀倾向。系统综述支持氯氮平的抗自杀作用,但法医文献强调其在过量用药时的致命性:对国际药物警戒数据库(VigiBase)中的氯氮平报告进行分析,以了解从引入到 2024 年 1 月 1 日期间的自杀意念、自杀未遂、故意用药过量和自杀完成情况。VigiBase 使用信息成分(IC)进行比例失调分析:结果:氯氮平的 IC(范围:其他抗精神病药物)为1)自杀意念 IC = 0.570,IC025 = 0.454 至 IC975 = 0.680(阿立哌唑的 IC = 3.568,利培酮的 IC = 1.729);2)自杀未遂 IC = 1.428,IC025 = 1.323 至 IC975 = 1.529(喹硫平的 IC = 4.150,利培酮的 IC = 2.968);3)自杀倾向 IC = 0.570,IC025 = 0.454 至 IC975 = 0.680(阿立哌唑的 IC = 3.568,利培酮的 IC = 1.729)。3) 故意用药过量:IC = 0.995,IC025 = 0.864 至 IC975 = 1.120(喹硫平的 IC = 4.080,阿立哌唑的 IC = 1.957),以及 4) 完成自杀:IC = 1.133,IC025 = 1.026 至 IC975 = 1.235(喹硫平的 IC = 4.648,利培酮的 IC = 2.160)。总之,所有氯氮平的 IC 均显著降低。我们发现有 2391 例接受氯氮平治疗的患者有自杀倾向(627 例有自杀意念,752 例自杀未遂,488 例故意用药过量,731 例自杀完成),但其中许多人正在服用其他抗精神病药物。报告最多的国家是美国、英国和克罗地亚:这项药物警戒研究虽然有其固有的局限性,但它提供了独立的证据,证明氯氮平可能具有其他抗精神病药物所不具有的特殊的强烈抗自杀作用。还需要进一步开展 VigiBase 研究,以比较故意过量服用氯氮平(14.3%)与其他抗精神病药物的致死率。
{"title":"Clozapine may consistently protect from suicidal behaviors while other antipsychotics may lack a specific protective effect: a comprehensive VigiBase study interpreted in the context of the prior literature.","authors":"Carlos De Las Cuevas, Victoria C de Leon, Hilario Blasco-Fontecilla, Enrique Baca-García, Marina Sagud, Emilio J Sanz, Jose de Leon","doi":"10.1080/14740338.2024.2399094","DOIUrl":"10.1080/14740338.2024.2399094","url":null,"abstract":"<p><strong>Background: </strong>In the United States, clozapine was first approved for treatment-resistant schizophrenia and then for suicidality in schizophrenia psychoses. Systematic reviews support clozapine's anti-suicidal effect, but the forensic literature stresses its lethality during overdoses.</p><p><strong>Research design and methods: </strong>Clozapine reports to the international pharmacovigilance database (VigiBase) were analyzed for suicidal ideation, suicide attempts, intentional overdose, and completed suicides from introduction to 1 January 2024. VigiBase uses the information component (IC) as a disproportionality analysis.</p><p><strong>Results: </strong>The clozapine ICs (range: other antipsychotics) were: 1) suicidal ideation IC = 0.570 with IC<sub>025</sub> = 0.454 to IC<sub>975</sub> = 0.680 (IC = 3.568 for aripiprazole and 1.729 for risperidone), 2) suicide attempt IC = 1.428 with IC<sub>025</sub> = 1.323 to IC<sub>975</sub> = 1.529 (IC = 4.150 for quetiapine and 2.968 for risperidone), 3) intentional overdose: IC = 0.995 with IC<sub>025</sub> = 0.864 to IC<sub>975</sub> = 1.120 (IC = 4.080 for quetiapine and 1.957 for aripiprazole), and 4) completed suicide IC = 1.133 with IC<sub>025</sub> = 1.026 to IC<sub>975</sub> = 1.235 (IC = 4.648 for quetiapine and 2.160 for risperidone). In summary, all clozapine ICs were significantly lower. We found 2391 clozapine-treated patients on the suicidality spectrum (627 cases with suicidal ideation, 752 with suicide attempt, 488 with intentional overdose, and 731 with completed suicide) but many were taking other antipsychotics. The most frequent reporting countries were the United States, the United Kingdom, and Croatia.</p><p><strong>Conclusion: </strong>This pharmacovigilance study, with all its inherent limitations, provides independent proof, not overlapping with prior literature, that clozapine may have specific strong anti-suicidal effects that do not appear to be present in other antipsychotics. Further VigiBase studies are needed to compare the lethality of an intentional overdose of clozapine (14.3%) with other antipsychotics.</p>","PeriodicalId":12232,"journal":{"name":"Expert Opinion on Drug Safety","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1080/14740338.2024.2386365
Dima L Diab,Nelson B Watts
INTRODUCTIONDenosumab (Prolia) is a fully human monoclonal antibody against the receptor activator of the nuclear factor kappaB ligand. It is a potent antiresorptive agent that reduces osteoclastogenesis.AREAS COVEREDDenosumab has been shown to improve bone mineral density and reduce the incidence of new fractures in postmenopausal women and men. It is also used in the treatment of glucocorticoid-induced osteoporosis, as well as for the prevention of bone loss and reduction of fracture risk in men receiving androgen deprivation therapy for non-metastatic prostate cancer and women receiving adjuvant aromatase inhibitor therapy for breast cancer. Initial safety concerns included infections, cancer, skin reactions, cardiovascular disease, hypocalcemia, osteonecrosis of the jaw, and atypical femur fractures; however, further study and experience provide reassurance on these issues. Anecdotal reports have raised concerns about an increased risk of multiple vertebral fractures following discontinuation of denosumab.EXPERT OPINIONAlthough bisphosphonates are often selected as initial therapy for osteoporosis, denosumab may be an appropriate initial therapy in patients at high risk for fracture, including older patients who have difficulty with the dosing requirements of oral bisphosphonates, as well as patients who are intolerant of, unresponsive to, or have contraindications to other therapies. Additional data is needed to address questions regarding treatment duration and discontinuation.
{"title":"The use of denosumab in osteoporosis - an update on efficacy and drug safety.","authors":"Dima L Diab,Nelson B Watts","doi":"10.1080/14740338.2024.2386365","DOIUrl":"https://doi.org/10.1080/14740338.2024.2386365","url":null,"abstract":"INTRODUCTIONDenosumab (Prolia) is a fully human monoclonal antibody against the receptor activator of the nuclear factor kappaB ligand. It is a potent antiresorptive agent that reduces osteoclastogenesis.AREAS COVEREDDenosumab has been shown to improve bone mineral density and reduce the incidence of new fractures in postmenopausal women and men. It is also used in the treatment of glucocorticoid-induced osteoporosis, as well as for the prevention of bone loss and reduction of fracture risk in men receiving androgen deprivation therapy for non-metastatic prostate cancer and women receiving adjuvant aromatase inhibitor therapy for breast cancer. Initial safety concerns included infections, cancer, skin reactions, cardiovascular disease, hypocalcemia, osteonecrosis of the jaw, and atypical femur fractures; however, further study and experience provide reassurance on these issues. Anecdotal reports have raised concerns about an increased risk of multiple vertebral fractures following discontinuation of denosumab.EXPERT OPINIONAlthough bisphosphonates are often selected as initial therapy for osteoporosis, denosumab may be an appropriate initial therapy in patients at high risk for fracture, including older patients who have difficulty with the dosing requirements of oral bisphosphonates, as well as patients who are intolerant of, unresponsive to, or have contraindications to other therapies. Additional data is needed to address questions regarding treatment duration and discontinuation.","PeriodicalId":12232,"journal":{"name":"Expert Opinion on Drug Safety","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142191199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1080/14740338.2024.2401024
Estefania Zapata-Bravo,Antonios Douros,Oriana Hoi Yun Yu,Kristian B Filion
INTRODUCTIONGlucose-lowering drugs pose a potential infection risk among individuals with type 2 diabetes. The U.S. Food and Drug Administration has issued safety warnings regarding increased risks of urinary tract infections (UTIs) and genital infections with sodium-glucose cotransporter 2 (SGLT2) inhibitors. However, the infection risk associated with other glucose-lowering drugs remains unclear. We conducted a PubMed database search to review the infection risk of glucose-lowering drugs, focusing on meta-analysis of randomized controlled trials.AREAS COVEREDWe described the infection risks associated with SGLT2 inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucose-like peptide-1 receptor agonists, metformin, and thiazolidinediones, covering infections of the genitourinary, respiratory, and gastrointestinal systems, including skin and soft tissue infections (SSTIs).EXPERT OPINIONSGLT2 inhibitors are associated with a higher genital infection risk, while their UTI risk remains inconclusive. DPP-4 inhibitors could be a treatment option for those intolerant to SGLT2 inhibitors, given their lower genital infection risk compared to placebo. Uncertainty persists regarding the risks of respiratory infections, gastroenteritis, and SSTIs with SGLT2 inhibitors. Limited evidence is available regarding the impact of DPP-4 inhibitors on respiratory infections. Additional research is needed to determine the comparative infection risk of other glucose-lowering drugs.
{"title":"Comparative risk of infection of medications used for type 2 diabetes.","authors":"Estefania Zapata-Bravo,Antonios Douros,Oriana Hoi Yun Yu,Kristian B Filion","doi":"10.1080/14740338.2024.2401024","DOIUrl":"https://doi.org/10.1080/14740338.2024.2401024","url":null,"abstract":"INTRODUCTIONGlucose-lowering drugs pose a potential infection risk among individuals with type 2 diabetes. The U.S. Food and Drug Administration has issued safety warnings regarding increased risks of urinary tract infections (UTIs) and genital infections with sodium-glucose cotransporter 2 (SGLT2) inhibitors. However, the infection risk associated with other glucose-lowering drugs remains unclear. We conducted a PubMed database search to review the infection risk of glucose-lowering drugs, focusing on meta-analysis of randomized controlled trials.AREAS COVEREDWe described the infection risks associated with SGLT2 inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucose-like peptide-1 receptor agonists, metformin, and thiazolidinediones, covering infections of the genitourinary, respiratory, and gastrointestinal systems, including skin and soft tissue infections (SSTIs).EXPERT OPINIONSGLT2 inhibitors are associated with a higher genital infection risk, while their UTI risk remains inconclusive. DPP-4 inhibitors could be a treatment option for those intolerant to SGLT2 inhibitors, given their lower genital infection risk compared to placebo. Uncertainty persists regarding the risks of respiratory infections, gastroenteritis, and SSTIs with SGLT2 inhibitors. Limited evidence is available regarding the impact of DPP-4 inhibitors on respiratory infections. Additional research is needed to determine the comparative infection risk of other glucose-lowering drugs.","PeriodicalId":12232,"journal":{"name":"Expert Opinion on Drug Safety","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142191201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}