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Impact of baseline glucocorticoids (GCs) on cardiotoxic events and myocardial damage related to immune checkpoint inhibitors: a retrospective clinical research.
IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-14 DOI: 10.1080/14740338.2025.2467814
Qiaoyun Wang, Haixia Zhang, Yawen Chen, Xin Lv, Yanli Qiao, Qiaoling Zhu

Background: Immune checkpointinhibitors (ICIs)-associated cardiotoxic events (CEs) are of increasing concern.Existing research about glucocorticoids (GCs) on immunotherapy focused on ICIs'efficacy and patients' outcome. The influence of GCs on ICIs-associated CEs andmyocardial damage (MD) remains unknown.

Research design and methods: This single-centerretrospective study included patients treated with ICIs from 2018 to 2022, withfollow-up period ending on 30 June 2023. The incidence, risk factors of ICIs-associated CEs, especially MD were described.Additionally, the impact of baseline GCs was assessed by propensity scorematching (PSM) to mitigate intergroup differences and ensure comparability.

Results: Among 1018 patients, 204(20.04%) experienced ICIs-associated CEs, including 71 (6.97%) with MD. Themean follow-up time was 40.39 (95%CI 38.47-42.31) weeks. The median time toonset of MD was the shortest at 12.57 weeks (IQR 5.29-25.14). Tumor type,co-medication with platinum and angiogenesis inhibitors may beinfluential factors of MD. After PSM, the relative risks of CEs (OR 0.4625,95%CI 0.2514-0.7235, p = 0.0020) and MD (OR 0.3254, 95%CI 0.1190-0.8898, p = 0.0378)in GCs1 ≥ 20mggroup were both significantly lower than those in GCs1 < 20 mg.

Conclusion: GCs ≥20 mg during the first ICIstreatment cycle is significantly associated with the reduced risks of bothICIs-associated CEs and MD.

背景:免疫检查点抑制剂(ICIs)相关的心脏毒性事件(CEs)越来越受到关注。现有关于糖皮质激素(GCs)对免疫治疗的研究主要集中在ICIs的疗效和患者的预后上。GCs 对 ICIs 相关 CEs 和心肌损伤(MD)的影响仍然未知:这项单中心回顾性研究纳入了2018年至2022年接受ICIs治疗的患者,随访期截至2023年6月30日。研究描述了与 ICIs 相关的 CE,尤其是 MD 的发生率和风险因素。此外,研究还通过倾向评分匹配(PSM)评估了基线 GCs 的影响,以减少组间差异并确保可比性:在 1018 名患者中,204 人(20.04%)出现了 ICI 相关 CE,其中 71 人(6.97%)出现了 MD。中位随访时间为 40.39 周(95%CI 38.47-42.31 周)。MD 的中位发生时间最短,为 12.57 周(IQR 5.29-25.14)。肿瘤类型、联合使用铂类药物和血管生成抑制剂可能是导致 MD 的影响因素。PSM后,GCs1≥20mg组CEs(OR 0.4625,95%CI 0.2514-0.7235,p = 0.0020)和MD(OR 0.3254,95%CI 0.1190-0.8898,p = 0.0378)的相对风险均显著低于GCs1结论:第一个 ICI 治疗周期内 GCs≥20 毫克与 ICI 相关 CEs 和 MD 风险的降低明显相关。
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引用次数: 0
The impact of the COVID-19 pandemic on adverse events associated with ACEIs and ARBs: a real-world analysis using the FDA adverse event reporting system.
IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-13 DOI: 10.1080/14740338.2025.2465865
Hui Qiu, Li He, Jianzhu Zhou, Zeying Feng, Ling Ye, Tong Li, Xin Huang, Longjian Huang, Chengjun Guo, Shaojun Chen, Chengxian Guo

Background: During the 2019 coronavirus disease (COVID-19) pandemic, although patients were advised to continue using angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), it remains unclear whether the pandemic influenced the occurrence of adverse reactions to these drugs. This study aims to analyze and compare changes in ACEIs and ARBs adverse events before and during the COVID-19 pandemic, exploring its potential impact on the safety of these medications.

Methods: We used real-world data to explore the impact of the COVID-19 pandemic on adverse events related to ACEIs and ARBs.

Results: During the pandemic, ACEI-related adverse events (70 cases) and ARB-related adverse events (7 cases) showed increased reporting rates and RORs, with a notable rise in ACEI-related ear and labyrinth disorders. Additionally, 170 new adverse event signals were detected for ACEIs (8 with significantly increased risk) and 191 signals for ARBs (2 with significantly increased risk).

Conclusions: This study, based on real-world data, revealed significant signals indicating that ACEI use during the COVID-19 pandemic may have increased the risk of renal adverse events and ear labyrinth diseases. The study emphasized the need for increased caution when using ACEIs and ARBs during the pandemic.

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引用次数: 0
Cardiovascular toxicities of hypoxia-inducible factor prolyl hydroxylase inhibitors: a disproportionality analysis based on JADER database.
IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-13 DOI: 10.1080/14740338.2025.2465873
Danna Wu, Ting Xie, Shuxin Jiao, Peitao Xie, Hongru Lin, Guo Yu

Background: Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have shown promising prospects as novel therapeutic agents in renal anemia, but their potential cardiovascular toxicities have raised widespread concern. This study aim to explore the cardiovascular toxicities associated with HIF-PHIs through real-world long-term safety data.

Research design and methods: A disproportionality analysis was employed by calculating the reporting odds ratios (ROR), information component (IC), and their 95% credibility intervals (CrI) in Japan Adverse Drug Event Report (JADER) database from 1 January 2020, to 30 September 2023.

Results: From Q1 2020 to Q3 2023, 253,599 adverse events (AEs) cases were extracted from the JADER database, including 4,015 cases related to HIF-PHIs and 1,537 (38.28%) cases of cardiovascular toxicities. Embolic and thrombotic events (ROR = 6.66, IC = 2.74), cardiac failure (ROR = 3.86, IC = 1.95), and ischemic heart disease (ROR = 3.37, IC = 1.75) indicated positive signals in HIF-PHIs. The median time to onset (TTO) of hypertension for HIF-PHIs was noted to be the earliest at 15.50 days.

Conclusion: HIF-PHIs are related to multiple cardiovascular toxicities. Although disproportionality analysis is a hypothesis-driven method, improving the surveillance of these toxicities related to HIF-PHIs used in managing renal anemia is still crucial.

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引用次数: 0
Safety concerns associated with BACE1 inhibitors - past, present and future.
IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-13 DOI: 10.1080/14740338.2025.2467811
Aniketh Naidu, Bret Silverglate, Mary Silverglate, George T Grossberg

Introduction: BACE1 (beta-site amyloid precursor protein cleaving enzyme 1) inhibitors have shown promise in treating Alzheimer's disease (AD) by reducing amyloid-beta (Aβ) production. However, clinical trials of inhibitors like atabecestat, verubecestat, and lanabecestat have faced challenges, including limited efficacy and significant adverse effects.

Areas covered: This narrative review discusses randomized-controlled trials of BACE1 inhibitors. Literature searches were conducted using PubMed and Web of Science for studies from 2010 to 2024. Association with BACE1's widespread expression beyond the brain shows adverse effects such as anxiety, depressive symptoms, and hepatotoxicity.

Expert opinion: The trial results underscore the need for CNS-specific BACE1 inhibitors to reduce adverse effects. Future research should focus on optimizing drug design and identifying additional therapeutic avenues, such as prostate cancer and insulin resistance.

{"title":"Safety concerns associated with BACE1 inhibitors - past, present and future.","authors":"Aniketh Naidu, Bret Silverglate, Mary Silverglate, George T Grossberg","doi":"10.1080/14740338.2025.2467811","DOIUrl":"https://doi.org/10.1080/14740338.2025.2467811","url":null,"abstract":"<p><strong>Introduction: </strong>BACE1 (beta-site amyloid precursor protein cleaving enzyme 1) inhibitors have shown promise in treating Alzheimer's disease (AD) by reducing amyloid-beta (Aβ) production. However, clinical trials of inhibitors like atabecestat, verubecestat, and lanabecestat have faced challenges, including limited efficacy and significant adverse effects.</p><p><strong>Areas covered: </strong>This narrative review discusses randomized-controlled trials of BACE1 inhibitors. Literature searches were conducted using PubMed and Web of Science for studies from 2010 to 2024. Association with BACE1's widespread expression beyond the brain shows adverse effects such as anxiety, depressive symptoms, and hepatotoxicity.</p><p><strong>Expert opinion: </strong>The trial results underscore the need for CNS-specific BACE1 inhibitors to reduce adverse effects. Future research should focus on optimizing drug design and identifying additional therapeutic avenues, such as prostate cancer and insulin resistance.</p>","PeriodicalId":12232,"journal":{"name":"Expert Opinion on Drug Safety","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413807","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}
引用次数: 0
Use of signal detection methods to identify associations between prenatal medication exposure and subsequent childhood cancers: a Nordic hypothesis-generating registry-based study.
IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-12 DOI: 10.1080/14740338.2025.2461204
Hannah Johnson, Sarah Hjorth, Joan Morris, Anton Pottegård, Maarit Leinonen, Ulrika Norby, Hedvig Nordeng

Background: Childhood cancer is an important contributor to childhood mortality in high-income countries. Information on associations between childhood cancer and in-utero exposure is absent or limited for most medications. Signal detection methods identify medications where research should be focused but have not been applied to datasets containing prenatal medication exposures and childhood cancers.

Research design and methods: The aim of this study was to apply and evaluate four signal detection methods - odds ratios (OR), the information component (IC), sequential probability ratio testing (SPRT), and Bayesian hierarchical models (BHM) - for identification of associations between medications dispensed during pregnancy and subsequent, incident diagnosis of childhood cancer <10 years, using linked Nordic registry data. Signal detection results were compared to propensity score adjusted odds ratios from generalized linear models.

Results: Analysis was performed for 117 medication-cancer pairs with 5 or more observations. The OR had the greatest sensitivity (0.75). The IC had a greater specificity (0.98) than the OR (0.95).

Conclusions: The IC may be the most appropriate method for identifying signals within this type of data. Reported signals should not be considered sufficient evidence of causal association and must be followed-up by tailored investigations that consider confounding by indication.

{"title":"Use of signal detection methods to identify associations between prenatal medication exposure and subsequent childhood cancers: a Nordic hypothesis-generating registry-based study.","authors":"Hannah Johnson, Sarah Hjorth, Joan Morris, Anton Pottegård, Maarit Leinonen, Ulrika Norby, Hedvig Nordeng","doi":"10.1080/14740338.2025.2461204","DOIUrl":"10.1080/14740338.2025.2461204","url":null,"abstract":"<p><strong>Background: </strong>Childhood cancer is an important contributor to childhood mortality in high-income countries. Information on associations between childhood cancer and in-utero exposure is absent or limited for most medications. Signal detection methods identify medications where research should be focused but have not been applied to datasets containing prenatal medication exposures and childhood cancers.</p><p><strong>Research design and methods: </strong>The aim of this study was to apply and evaluate four signal detection methods - odds ratios (OR), the information component (IC), sequential probability ratio testing (SPRT), and Bayesian hierarchical models (BHM) - for identification of associations between medications dispensed during pregnancy and subsequent, incident diagnosis of childhood cancer <10 years, using linked Nordic registry data. Signal detection results were compared to propensity score adjusted odds ratios from generalized linear models.</p><p><strong>Results: </strong>Analysis was performed for 117 medication-cancer pairs with 5 or more observations. The OR had the greatest sensitivity (0.75). The IC had a greater specificity (0.98) than the OR (0.95).</p><p><strong>Conclusions: </strong>The IC may be the most appropriate method for identifying signals within this type of data. Reported signals should not be considered sufficient evidence of causal association and must be followed-up by tailored investigations that consider confounding by indication.</p>","PeriodicalId":12232,"journal":{"name":"Expert Opinion on Drug Safety","volume":" ","pages":"1-12"},"PeriodicalIF":3.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382033","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}
引用次数: 0
A drug safety evaluation of dapagliflozin for diabetic nephropathies in patients with cardiovascular risk.
IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-12 DOI: 10.1080/14740338.2025.2462671
Aayushi Sood, Aanchal Sawhney, Benjamin Borokhovsky, Apurva V Vyas, Rahul Gupta

Introduction: Diabetic nephropathy is a significant concern for patients with cardiovascular disease. Dapagliflozin, an SGLT2 inhibitor, has emerged as a promising therapeutic approach to managing diabetic nephropathy and reducing cardiovascular risk.

Areas covered: This review encompasses the research and literature search methodology, including clinical trials and real-world evidence, assessing the safety profile of Dapagliflozin in patients with diabetic nephropathy and cardiovascular risk.

Expert opinion: Dapagliflozin, an SGLT2 inhibitor, has redefined patient-centric care by simultaneously improving glycemic control, cardiovascular health, and renal outcomes in individuals with type 2 diabetes, cardiovascular disease, and nephropathy.

{"title":"A drug safety evaluation of dapagliflozin for diabetic nephropathies in patients with cardiovascular risk.","authors":"Aayushi Sood, Aanchal Sawhney, Benjamin Borokhovsky, Apurva V Vyas, Rahul Gupta","doi":"10.1080/14740338.2025.2462671","DOIUrl":"10.1080/14740338.2025.2462671","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetic nephropathy is a significant concern for patients with cardiovascular disease. Dapagliflozin, an SGLT2 inhibitor, has emerged as a promising therapeutic approach to managing diabetic nephropathy and reducing cardiovascular risk.</p><p><strong>Areas covered: </strong>This review encompasses the research and literature search methodology, including clinical trials and real-world evidence, assessing the safety profile of Dapagliflozin in patients with diabetic nephropathy and cardiovascular risk.</p><p><strong>Expert opinion: </strong>Dapagliflozin, an SGLT2 inhibitor, has redefined patient-centric care by simultaneously improving glycemic control, cardiovascular health, and renal outcomes in individuals with type 2 diabetes, cardiovascular disease, and nephropathy.</p>","PeriodicalId":12232,"journal":{"name":"Expert Opinion on Drug Safety","volume":" ","pages":"1-10"},"PeriodicalIF":3.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079142","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}
引用次数: 0
Post-marketing safety evaluation of zanubrutinib: a real-world pharmacovigilance analysis based on the FAERS database.
IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-12 DOI: 10.1080/14740338.2025.2465872
Xiaolu Chen, Biao Zhang, Yajiao Huang, Yan Chen, Yuanrong Yang

Background: Zanubrutinib has been demonstrated to have significant response rates and promising survival data in clinical trials. However, real-world adverse events still need to be ameliorated to facilitate rational clinical drug use.

Research design and methods: Adverse incident reports from October 2019 to March 2024 were extracted from the FDA's Adverse Event Reporting System (FAERS) database. Zanubrutinib-related adverse events were obtained after data cleaning and analysis with SAS 9.4. Four methods were utilized to calculate disproportionality and evaluate AE signals of zanubrutinib.

Result: At the system organ class (SOC) level, one SOC met the criteria of the four algorithms. At the preferred term (PT) level, most AEs are those already included in the product monograph, and no unexpected safety signals have been identified. Furthermore, the average time to onset of adverse events was 134.8 days, with a median time of 16.5 days. Adverse events occurred in 57.96% of cases within 1 month.

Conclusion: Compared to the adverse events reported in clinical trials and drug labels, no unreported signals were identified. This finding will provide clinicians with a more comprehensive understanding of the clinical application of zanubrutinib and provide valuable insights for future investigations.

{"title":"Post-marketing safety evaluation of zanubrutinib: a real-world pharmacovigilance analysis based on the FAERS database.","authors":"Xiaolu Chen, Biao Zhang, Yajiao Huang, Yan Chen, Yuanrong Yang","doi":"10.1080/14740338.2025.2465872","DOIUrl":"10.1080/14740338.2025.2465872","url":null,"abstract":"<p><strong>Background: </strong>Zanubrutinib has been demonstrated to have significant response rates and promising survival data in clinical trials. However, real-world adverse events still need to be ameliorated to facilitate rational clinical drug use.</p><p><strong>Research design and methods: </strong>Adverse incident reports from October 2019 to March 2024 were extracted from the FDA's Adverse Event Reporting System (FAERS) database. Zanubrutinib-related adverse events were obtained after data cleaning and analysis with SAS 9.4. Four methods were utilized to calculate disproportionality and evaluate AE signals of zanubrutinib.</p><p><strong>Result: </strong>At the system organ class (SOC) level, one SOC met the criteria of the four algorithms. At the preferred term (PT) level, most AEs are those already included in the product monograph, and no unexpected safety signals have been identified. Furthermore, the average time to onset of adverse events was 134.8 days, with a median time of 16.5 days. Adverse events occurred in 57.96% of cases within 1 month.</p><p><strong>Conclusion: </strong>Compared to the adverse events reported in clinical trials and drug labels, no unreported signals were identified. This finding will provide clinicians with a more comprehensive understanding of the clinical application of zanubrutinib and provide valuable insights for future investigations.</p>","PeriodicalId":12232,"journal":{"name":"Expert Opinion on Drug Safety","volume":" ","pages":"1-10"},"PeriodicalIF":3.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382027","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}
引用次数: 0
Adverse event profile of setmelanotide in obesity: an integrated assessment and systematic review using disproportionality analysis, case reports and meta-analysis.
IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-12 DOI: 10.1080/14740338.2025.2465880
Kannan Sridharan, Gowri Sivaramakrishnan

Background: Setmelanotide is approved for genetically determined obesity. While clinical trials and clinical evidence and practice provide some insights, a comprehensive assessment of its adverse event profile is needed that led to carrying out an assessment of reported adverse events in the USFDA Adverse Event Reporting System database, case reports and clinical trials.

Research design and methods: Multi-faceted analyses were carried out as follows: disproportionality measures employing frequentist and Bayesian methods; systematic review and meta-analysis (Medline, Cochrane CENTRAL and Google Scholar) generated-pooled estimates [proportion with 95% confidence intervals (CI)]; and published reports with adverse events to setmelanotide.

Results: The disproportionality analysis (n = 228) identified skin hyperpigmentation, injection-site reactions, nausea, melanocytic nevus and ephelides as key safety signals. Meta-analysis (seven trials; n = 185) confirmed high rates of injection-site reactions (96%; 95% CI: 89, 100), skin hyperpigmentation (62%; 95% CI: 43, 78), nausea (36%; 95% CI: 24, 49), vomiting (26%; 95% CI: 18, 34), and diarrhea (21%; 95% CI: 14, 29). Individual case reports corroborated these findings.

Conclusion: This study provides a detailed overview of setmelanotide's adverse event profile, highlighting the need for careful patient monitoring, emphasizing the importance of ongoing safety surveillance for at least 1.5 years, and further research to refine patient management strategies.

{"title":"Adverse event profile of setmelanotide in obesity: an integrated assessment and systematic review using disproportionality analysis, case reports and meta-analysis.","authors":"Kannan Sridharan, Gowri Sivaramakrishnan","doi":"10.1080/14740338.2025.2465880","DOIUrl":"10.1080/14740338.2025.2465880","url":null,"abstract":"<p><strong>Background: </strong>Setmelanotide is approved for genetically determined obesity. While clinical trials and clinical evidence and practice provide some insights, a comprehensive assessment of its adverse event profile is needed that led to carrying out an assessment of reported adverse events in the USFDA Adverse Event Reporting System database, case reports and clinical trials.</p><p><strong>Research design and methods: </strong>Multi-faceted analyses were carried out as follows: disproportionality measures employing frequentist and Bayesian methods; systematic review and meta-analysis (Medline, Cochrane CENTRAL and Google Scholar) generated-pooled estimates [proportion with 95% confidence intervals (CI)]; and published reports with adverse events to setmelanotide.</p><p><strong>Results: </strong>The disproportionality analysis (<i>n</i> = 228) identified skin hyperpigmentation, injection-site reactions, nausea, melanocytic nevus and ephelides as key safety signals. Meta-analysis (seven trials; <i>n</i> = 185) confirmed high rates of injection-site reactions (96%; 95% CI: 89, 100), skin hyperpigmentation (62%; 95% CI: 43, 78), nausea (36%; 95% CI: 24, 49), vomiting (26%; 95% CI: 18, 34), and diarrhea (21%; 95% CI: 14, 29). Individual case reports corroborated these findings.</p><p><strong>Conclusion: </strong>This study provides a detailed overview of setmelanotide's adverse event profile, highlighting the need for careful patient monitoring, emphasizing the importance of ongoing safety surveillance for at least 1.5 years, and further research to refine patient management strategies.</p>","PeriodicalId":12232,"journal":{"name":"Expert Opinion on Drug Safety","volume":" ","pages":"1-10"},"PeriodicalIF":3.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382082","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}
引用次数: 0
Adverse drug event profile of pharmacotherapies for alcohol use disorder: a retrospective pharmacovigilance disproportionality analysis study.
IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-12 DOI: 10.1080/14740338.2025.2464896
Kannan Sridharan

Background: Alcohol Use Disorder (AUD) significantly affects global health, leading to physical deterioration and impacting personal and social relationships. This study aims to evaluate the adverse event profiles (AEP) of three USFDA-approved medications for AUD, acamprosate, disulfiram, and naltrexone, using data from the USFDA Adverse Event Reporting System (AERS).

Research designs and methods: Reports related to acamprosate, disulfiram, and naltrexone from March 2004 to March 2024 were extracted from the USFDA AERS database. Data were verified, and disproportionality analysis was conducted using frequentist and Bayesian methods. Adverse events were assessed based on reporting odds ratio, proportional reporting ratio, and Bayesian measures. Outcomes such as death, life-threatening events, and hospitalization were also analyzed.

Results: A total of 19,177 unique reports were analyzed (naltrexone: n = 18,544; acamprosate: n = 249; disulfiram: n = 384). Common adverse events included hepatobiliary, nervous system, and psychiatric disorders. Disulfiram was associated with coagulopathy and drug interactions, while naltrexone was linked to injection site reactions and hypersensitivity. Naltrexone had higher mortality reports, and disulfiram had more hospitalizations.

Conclusion: The study underscores the diverse AEPs of these medications, highlighting the need for careful monitoring and individualized treatment to ensure safety and efficacy in managing AUD.

{"title":"Adverse drug event profile of pharmacotherapies for alcohol use disorder: a retrospective pharmacovigilance disproportionality analysis study.","authors":"Kannan Sridharan","doi":"10.1080/14740338.2025.2464896","DOIUrl":"10.1080/14740338.2025.2464896","url":null,"abstract":"<p><strong>Background: </strong>Alcohol Use Disorder (AUD) significantly affects global health, leading to physical deterioration and impacting personal and social relationships. This study aims to evaluate the adverse event profiles (AEP) of three USFDA-approved medications for AUD, acamprosate, disulfiram, and naltrexone, using data from the USFDA Adverse Event Reporting System (AERS).</p><p><strong>Research designs and methods: </strong>Reports related to acamprosate, disulfiram, and naltrexone from March 2004 to March 2024 were extracted from the USFDA AERS database. Data were verified, and disproportionality analysis was conducted using frequentist and Bayesian methods. Adverse events were assessed based on reporting odds ratio, proportional reporting ratio, and Bayesian measures. Outcomes such as death, life-threatening events, and hospitalization were also analyzed.</p><p><strong>Results: </strong>A total of 19,177 unique reports were analyzed (naltrexone: <i>n</i> = 18,544; acamprosate: <i>n</i> = 249; disulfiram: <i>n</i> = 384). Common adverse events included hepatobiliary, nervous system, and psychiatric disorders. Disulfiram was associated with coagulopathy and drug interactions, while naltrexone was linked to injection site reactions and hypersensitivity. Naltrexone had higher mortality reports, and disulfiram had more hospitalizations.</p><p><strong>Conclusion: </strong>The study underscores the diverse AEPs of these medications, highlighting the need for careful monitoring and individualized treatment to ensure safety and efficacy in managing AUD.</p>","PeriodicalId":12232,"journal":{"name":"Expert Opinion on Drug Safety","volume":" ","pages":"1-16"},"PeriodicalIF":3.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370727","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}
引用次数: 0
A real-world pharmacovigilance study of sacubitrilvalsartan in older people: data mining of the FDA adverse event reporting system.
IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-11 DOI: 10.1080/14740338.2025.2464888
Zheng Kuai, Quan Li, Xiaoyi Zhang, Guowen Tang, Yangli Ye, Yu Hu

Background: Sacubitrilvalsartan is widely used in the clinical management of heart failure with reduced ejection fraction and hypertension. This study aims to systematically investigate and quantify the safety signals and potential risks associated with sacubitrilvalsartan in individuals aged 65 and older, leveraging data from the FAERS database to provide insights into its real-world safety profile.

Methods: Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms, were employed to quantify the signals of Sacubitrilvalsartan-associated AEs in elderly.

Results: The search retrieved 94,210 sacubitrilvalsartan-associated cases within the reporting period; 86 PTs with significant disproportionality were retained in 65 + . Reports emerged for several cognitive-related AEs and several fragility acceleration AEs, which were rare. Unexpected safety signals such as 'Injury, poisoning, and procedural complications' were only detected in 65 + . Most of the cases occurred within the first month after sacubitrilvalsartan initiation, and this was consistent across age groups.

Conclusions: Our study found potential new AEs signals and might provide important support for clinical monitoring and risk identification of Sacubitrilvalsartan in elderly.

{"title":"A real-world pharmacovigilance study of sacubitrilvalsartan in older people: data mining of the FDA adverse event reporting system.","authors":"Zheng Kuai, Quan Li, Xiaoyi Zhang, Guowen Tang, Yangli Ye, Yu Hu","doi":"10.1080/14740338.2025.2464888","DOIUrl":"10.1080/14740338.2025.2464888","url":null,"abstract":"<p><strong>Background: </strong>Sacubitrilvalsartan is widely used in the clinical management of heart failure with reduced ejection fraction and hypertension. This study aims to systematically investigate and quantify the safety signals and potential risks associated with sacubitrilvalsartan in individuals aged 65 and older, leveraging data from the FAERS database to provide insights into its real-world safety profile.</p><p><strong>Methods: </strong>Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms, were employed to quantify the signals of Sacubitrilvalsartan-associated AEs in elderly.</p><p><strong>Results: </strong>The search retrieved 94,210 sacubitrilvalsartan-associated cases within the reporting period; 86 PTs with significant disproportionality were retained in 65 + . Reports emerged for several cognitive-related AEs and several fragility acceleration AEs, which were rare. Unexpected safety signals such as 'Injury, poisoning, and procedural complications' were only detected in 65 + . Most of the cases occurred within the first month after sacubitrilvalsartan initiation, and this was consistent across age groups.</p><p><strong>Conclusions: </strong>Our study found potential new AEs signals and might provide important support for clinical monitoring and risk identification of Sacubitrilvalsartan in elderly.</p>","PeriodicalId":12232,"journal":{"name":"Expert Opinion on Drug Safety","volume":" ","pages":"1-9"},"PeriodicalIF":3.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363814","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}
引用次数: 0
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Expert Opinion on Drug Safety
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