Age-Dependent Differences in Canakinumab Safety: A Comprehensive Pharmacovigilance Analysis Using the FAERS Database.

Despite the established use of both liposomal irinotecan and conventional irinotecan, a comparative analysis of their safety profiles is lacking. This study leverages the FDA Adverse Event Reporting System (FAERS) database to fill this gap by comparing their adverse events (AEs) to inform clinical practice. AEs were categorized by System Organ Class (SOC) and described using Preferred Terms (PTs) from the Medical Dictionary for Regulatory Activities (MedDRA, v26.1). The signals for liposomal irinotecan and irinotecan were quantified through disproportionality analysis, employing multiple algorithms: the reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma poisson shrinker (MGPS), and Bayesian confidence propagation neural network (BCPNN). A total of 934 and 10,362 AE reports were retrieved for liposomal irinotecan and irinotecan, respectively, with each drug involving 25 and 27 System Organ Class (SOC) categories. At the SOC level, both drugs have significant SOC-level signals value for "Gastrointestinal Disorders", "Neoplasms Benign, Malignant And Unspecified (Incl Cysts And Polyps)", "Blood And Lymphatic System Disorders", "Metabolism And Nutrition Disorders", "Hepatobiliary Disorders", and "Congenital, Familial And Genetic Disorders". For liposomal irinotecan, 61 effective PT-level signals were detected, dominated by gastrointestinal disorders (diarrhoea). For irinotecan, 431 effective PT-level signals were detected, dominated by gastrointestinal disorders (diarrhoea) and blood and lymphatic system disorders (neutropenia). Comparative analysis revealed distinct safety profiles between the two drugs. Irinotecan demonstrated a stronger association with hematological and gastrointestinal events, including neutropenia, febrile neutropenia, and diarrhea, as well as with decreased appetite. For patients treated with liposomal irinotecan and irinotecan, the majority of AEs manifested within 30days after the initiation of therapy. As the first FAERS-based study comparing liposomal irinotecan and irinotecan, this analysis provides crucial evidence for clinical decision-making. While the detected signals indicate statistical associations, further clinical studies are warranted to establish causality and strengthen drug safety evaluation.

IntroductionPacritinib, a selective Janus kinase (JAK) inhibitor, is approved for the treatment of myelofibrosis in adults with severe thrombocytopenia. However, its safety profile in real-world populations remains unclear. The aim of study is provided a comprehensive profile of pacritinib's safety by evaluating the adverse events (AEs) using a real-world pharmacovigilance database.MethodsData from the FDA Adverse Event Reporting System (FAERS) database, spanning from the first quarter of 2022 to the second quarter of 2024, served as the basis for this analysis. To identify potential AE risk signals, several disproportionality analysis methods were applied, including the reporting odds ratio, the proportional reporting ratio, the multi-item gamma Poisson shrinker, and the Bayesian confidence propagation neural network.ResultsA total of 4,304,335 AE reports were collected from the FAERS, with 1,940 reports identifying pacritinib as the primary suspect drug. Significant disproportionality was observed in the following system organ classes: gastrointestinal disorders, investigations, and surgical and medical procedures. Common preferred terms were identified, including diarrhea, fatigue, death, nausea, platelet count decreased, and hemoglobin decreased. Notably, 26 off­-label AEs were also identified.DiscussionOur study would provide valuable insights for the post-marketing safety surveillance and assessment of pacritinib, and guide its clinical practice.

This investigation leverages data derived from the United States Food and Drug Administration Adverse Event Reporting (FAERS) to real-world adverse reactions associated with Belimumab, with the intention of providing guidance for safe clinical pharmacotherapy. Data encompassing adverse drug event (ADE) reports relating to Belimumab from Q1 2011 to Q4 2023 within the FAERS were extracted and analyzed using methodologies such as the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). The study identified a total of 19 825 ADE reports where Belimumab was the primary suspect medication, with the United States constituting the majority of reporting countries (16 312 cases, or 82.28%). Patients aged 18 to 64.9 years accounted for the largest demographic (36.29%), while the proportion of female patients (77.91%) significantly surpassed that of male patients (5.03%). The analysis uncovered 184 unique Preferred Terms (PTs) across 21 System Organ Classes (SOCs). Following selection through ROR, the SOC signal strength was prioritized as follows: Systemic disorders and administration site conditions, infections and infestations, a variety of musculoskeletal and connective tissue disorders, and conditions related to pregnancy, puerperium, and the perinatal period. The top five PTs for ADE reports not included in the product's labeling were hypersensitivity reactions, immunosuppression, non-vascular diseases, herpes virus infections, and Sjögren's syndrome. The top five PTs for ADE signal strength not included in the labeling were disseminated cutaneous herpes zoster, herpes zoster meningitis, onycholysis, cyclothymic disorder, and mixed connective tissue disease. Based on pharmacovigilance research utilizing the FAERS database, it is recommended that clinical monitoring of Bevacizumab should be intensified to support effective pharmaceutical care and ensure rational clinical medication use.

BackgroundAducanumab, a monoclonal antibody targeting amyloid-beta plaques, has been introduced as a pivotal therapeutic agent for Alzheimer’s disease (AD). Although it offers promising benefits in the treatment of early-stage Alzheimer’s disease, a thorough evaluation of its safety profile and potential adverse events (AEs) is essential to ensure patient safety.MethodsThis retrospective pharmacovigilance study analyzed data from the FDA Adverse Event Reporting System (FAERS) database to evaluate AEs associated with Aducanumab. Employing a case/non-case methodology, the study utilized signal detection algorithms, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS), to identify AEs signals related to Aducanumab use.ResultsThe study encompassed a total of 11517459 reports, with 431 specifically citing Aducanumab. A substantial number of AEs were identified, particularly among the elderly population and those with pre-existing neurological conditions. The most frequently reported AEs were related to the nervous system, including “amyloid-related imaging abnormalities” such as edema/effusion and microhemorrhages. Other affected system organ classes (SOCs) included psychiatric disorders and general disorders and administration site conditions. Specific preferred terms (PTs) linked with Aducanumab included “confusional state,” “disorientation,” and “cerebral microhemorrhage.” Unexpected AEs such as “subdural hematoma” and “head injury” were also noted, indicating a broader safety profile that requires further investigation.ConclusionsThe study’s findings underscore the necessity for close monitoring of Aducanumab use, especially in elderly patients with AD. The identification of both expected and unexpected AEs emphasizes the need for ongoing pharmacovigilance and additional research to fully understand the safety profile of Aducanumab in clinical practice.Strengths and limitations of this studyStrength: Utilized multiple signal detection algorithms (ROR, PRR, BCPNN, MGPS) to enhance robustness of pharmacovigilance findings. Limitation: Reliance on spontaneous FAERS reports, which are prone to underreporting, overreporting, and reporting bias.

The study was based on the FDA Adverse Event Reporting System (FAERS) database, with the objective of analysing the actual safety of Neulasta® (pegfilgrastim) in patients with solid tumours. This study also sought to provide a reference for the use of clinical drugs. For patients with solid tumors, data on adverse events (AEs) related to Neulasta® (pegfilgrastim) applications between the first quarter of 2004 and the fourth quarter of 2024 were collected and standardized. Subsequently, an analysis of the signal quantization technique was conducted. The following methods are included: Reporting Odds Ratio (ROR) method, proportional reporting ratio (PRR) method, Bayesian Confidence Propagation Neural Network (BCPNN) method, and Multi-Item Gamma Poisson Shrinker (MGPS) method. A total of 193,534 reports were retrieved, encompassing 6,380 Adverse Drug Event (ADE) reports in patients diagnosed with solid tumors, with Neulasta® (pegfilgrastim) identified as the primary suspected pharmaceutical agent. Following the incorporation of duplicate PRIMARYID, the study comprised a total of 2,428 patients. At the level of system organ classes (SOCs), four SOCs were positive in the four signal quantification techniques, including musculoskeletal and connective tissue disorders, general disorders and administration site conditions, blood and lymphatic system disorders, injury, poisoning, and procedural complications. At the preferred term (PTs) level, 251 PTs were found from 26 SOCs, including febrile neutropenia, leukocytosis, eye swelling, lip swelling, swollen tongue, influenza-like illness, application site hemorrhage, injection site pain, application site pain, swelling face, hypersensitivity, lower respiratory tract infection, wrong technique in product usage process, unintentional medical device removal, accidental exposure to product, device use error, drug dose omission by device, intercepted product preparation error, product preparation error, device placement issue, underdose, abnormal white blood cell count, abnormal neutrophil count, increased white blood cell count, bone pain, myalgia, decreased mobility, pelvic pain, urticaria, and hyperhidrosis. These findings, while hypothesis-generating, require validation through controlled epidemiological studies due to the inherent limitations of spontaneous reporting databases. Neulasta® (pegfilgrastim) is a promising treatment option for patients with solid tumors. This study focused on the population of solid tumors, providing more references and support for the FDA-approved labeling regarding the drug-related adverse reactions of Neulasta® (pegfilgrastim) in the population with solid tumors.

IntroductionPexidartinib, an oral selective colony-stimulating factor 1 receptor (CSF1R) inhibitor, is the only systemic therapy approved by the U.S. Food and Drug Administration (FDA) for tenosynovial giant cell tumor (TGCT). While clinical trials have defined its initial safety profile, their limited sample sizes and short follow-up restrict the detection of rare or delayed adverse events (AEs), underscoring the need for real-world pharmacovigilance.MethodsUsing the FDA Adverse Event Reporting System (FAERS) database, we conducted a disproportionality analysis to characterize the post-approval safety profile of pexidartinib and identify unlabeled AEs, applying reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) methods.ResultsAmong 7,168,342 FAERS reports, 668 implicated pexidartinib as the primary suspect, with AEs reported across 26 organ systems. Sixty-seven preferred terms met the criteria of all four signal detection methods, including 16 not listed in the FDA-approved label.DiscussionThe overall safety profile was largely consistent with clinical trial findings, while newly detected AEs suggest possible rare or delayed toxicities in broader patient populations. These results highlight the importance of continuous post-marketing surveillance and support the need for prospective studies to clarify causal relationships.

To date, only two drugs, pirfenidone and nintedanib, are approved for the treatment of patients with idiopathic pulmonary fibrosis (IPF). In addition, very few studies have reported on the safety profile of either drug in large populations. This study aims to identify and compare adverse drug events (ADEs) associated with pirfenidone and nintedanib in real-world settings by analyzing data from the US Food and Drug Administration Adverse Event Reporting System (FAERS). In addition, we utilized data from the Japanese Adverse Drug Event Report (JADER) database for external validation. The ADE reports on both drugs from 2014 Q3 to 2024 Q2 in FAERS and from 2008 Q1 to 2024 Q1 in JADER were collected. After deduplication, Bayesian and non-Bayesian methods for disproportionality analysis, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multiple Gamma Poisson Shrinkers (MGPS), were used for signal detection. Additionally, time to onset (TTO) analysis were performed. In total, 35,804 and 20,486 ADE reports were identified from the FAERS database for pirfenidone and nintedanib, respectively. At the system organ class (SOC) level, both drugs have a positive signal value for "gastrointestinal disorders," "respiratory, thoracic, and mediastinal disorders," and "metabolism and nutrition disorders." Other positive signals for pirfenidone include "general disorders and administration site conditions," and "skin and subcutaneous tissue disorders," while for nintedanib, they were "investigations," "infections and infestations," and "hepatobiliary disorders." Some positive signals were consistent with the drug labels, including nausea, decreased appetite, and weight decreased identified in pirfenidone, as well as diarrhea, decreased appetite, abdominal pain upper, and epistaxis identified in nintedanib. We also identified unexpected signals not listed on the drug label, such as decreased gastric pH, and pneumothorax for pirfenidone, and constipation, flatulence for nintedanib. The median onset time for ADEs was 146 days for pirfenidone and 45 days for nintedanib, respectively. Although the two antifibrotics differed in the proportion of periods in which the ADEs occurred, these ADEs were likely to continue even after a year of treatment. In the external validation of JADER, the number of reports for pirfenidone and nintedanib were 265, and 1,327, respectively. The disproportionality analysis at the SOC and preferred term (PT) levels supports the FAERS results. This study systematically investigates and compares the ADEs and their onset times at the SOC and specific PT levels for pirfenidone and nintedanib. Our results provide valuable pharmacological insights for the similarities and differences between the safety profiles of the two drugs and highlight the importance of monitoring and managing the toxicity profile associated with antifibrotic drugs.

Capecitabine, a prodrug of 5-fluorouracil, is extensively utilized for the treatment of metastatic breast cancer, colorectal cancer, and gastric cancer. Nevertheless, there exist limitations in comprehending adverse reactions (AEs) in clinical practice. In this study, we investigated the distribution of AEs associated with capecitabine and explored potential rare adverse reactions by mining the Food and Drug Administration Adverse Event Reporting System (FAERS). Our research aimed to explore the spectrum of AEs associated with capecitabine, including both documented and potential events, to provide a comprehensive understanding of the drug's safety profile and guide clinical practice. At the same time, it provides a new direction for further research on AEs associated with capecitabine in the future. We collected capecitabine-related adverse reactions from the FAERS and standardized the classification of AEs using the Medical Dictionary for Regulatory Activities 26.0. Four statistical schemes were used to analyze the obtained standardized signals. We collected AEs reported for capecitabine from the FAERS between 2004 and 2023. To ensure standardized data, the collected reports related to capecitabine-associated adverse events were categorized using the preferred terms (PTs) and system organ classes (SOCs) classifications provided by the Medical Dictionary for Regulatory Activities 26.0. Statistical analysis involved the utilization of reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker. Four statistical schemes were employed to analyze the adverse reactions associated with capecitabine. A positive signal was considered when all four schemes indicated an association with the adverse event. We collected a total of 45,011 AEs associated with the use of capecitabine from the database, covering 27 SOCs from 2004 to 2023. The nine SOC categories with the highest number of events were identified, which include gastrointestinal disorders; general disorders and administration site conditions; skin and subcutaneous tissue disorders; nervous system disorders; investigations, injury, poisoning, and procedural complications; blood and lymphatic system disorders; metabolism and nutrition disorders; infections and infestations; and neoplasms benign, malignant, and unspecified (including cysts and polyps). Among these 27 SOCs, we identified seven SOCs that met the signal value criteria. Notably, we discovered AEs not mentioned in the instructions, including intestinal obstruction in gastrointestinal disorders, penetrating aortic ulcer in cardiac disorders, and non-cirrhotic portal hypertension in hepatobiliary disorders, all of which exhibited signals. Furthermore, 40.1% of AEs associated with the use of capecitabine occurred within the first 30 days. Our study conducted a comprehensive analysis of capecitabine's AEs using the FAERS database. We identified previously unreported AEs, mitigating the risk for patients and ensuring safe drug administration.

Comprehensive Pharmacovigilance Assessment of Pegvisomant-Associated Adverse Events Using the FDA Adverse Event Reporting Systemand World Health Organization VigiAccess Databases.

This study aims to evaluate the adverse drug reactions associated with imiglucerase in the treatment of Gaucher disease by analyzing data from the FDA Adverse Event Reporting System (FAERS) database. A comprehensive analysis was conducted on 166,800,135 adverse event reports from the FAERS database, covering the period from the first quarter of 2004 to the fourth quarter of 2023. The data were processed using R software and analyzed using multiple disproportionality methods, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS). These methodologies were applied to identify significant adverse reaction signals across various System Organ Classes (SOCs) and Preferred Terms (PTs). The analysis revealed significant adverse reaction signals in multiple SOCs, including general disorders and administration site conditions, injury, poisoning and procedural complications, infections and infestations, and nervous system disorders. Notably, general disorders and injury-related conditions had the highest number of reports. At the PT level, the term "Gaucher disease" yielded the highest statistical signal. This was identified as a critical reporting artifact, likely representing perceived treatment failure or disease progression, rather than a true adverse reaction. After accounting for this artifact, other significant adverse event signals included increased chitotriosidase, elevated acid phosphatase, and bone infarction, with musculoskeletal and connective tissue disorders being a key area of concern. A comparative analysis against other Gaucher therapies suggests this strong skeletal signal likely reflects confounding by indication rather than a drug-specific risk. The findings underscore the importance of ongoing pharmacovigilance to monitor the safety of imiglucerase, especially among vulnerable populations such as pregnant women, long-term users, and those with comorbid hepatobiliary or skeletal conditions.

ObjectiveLubiprostone is a selective intestinal chloride channel activator approved for treating chronic idiopathic constipation and constipation-predominant irritable bowel syndrome in adults. However, real-world data on its long-term safety, particularly regarding adverse events necessitating ongoing supplementation, remain limited.MethodsData from the FDA Adverse Event Reporting System (FAERS) database were collected from the second quarter of 2006 to the fourth quarter of 2023. The data was normalized, and various signal quantification techniques such as Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS) were used for analysis.ResultsA total of 1436 adverse event reports associated with lubiprostone were extracted from the FAERS database. These reports indicated a higher proportion of female patients compared to male patients (65.39% vs. 21.10%). Among those with explicit age data, the largest proportion of patients were 45–65 years old (20.6% of reports), followed by those ≥ 75 (19.9%), 18–45 (14.8%), and 65–75 years (10.1%). Adverse events induced by lubiprostone were observed in 24 System Organ Classes (SOCs), including common gastrointestinal disorders, general disorders, administration site conditions, as well as respiratory, thoracic, and mediastinal disorders, consistent with findings from clinical trials. Applying four algorithms simultaneously, 22 SOCS were detected, revealing a total of 57 positive response items, including 22 related to the digestive system. The most stringent algorithm, empirical Bayesian geometric mean (EBGM), highlighted severe gastrointestinal adverse reactions like gastric fistula (n = 5, ROR = 150.03, PRR = 149.87, IC = 7.21, EBGM = 147.71) and ischemic colitis (n = 19, ROR = 36.78, PRR = 36.63, IC = 5.19, EBGM = 36.51), which were not listed in the drug insert. This suggests the need for heightened vigilance towards these potential adverse reactions during clinical use.ConclusionsOur study comprehensively evaluated the safety of lubiprostone in the post-marketing setting. Despite its therapeutic advantages, there is a potential for various systemic adverse effects. In addition to adverse events consistent with information from existing clinical trials and the insert, we discovered several serious localized adverse reactions and previously unreported systemic adverse reactions. These may be potentially associated with lubiprostone, but are not confirmed adverse effects. This will provide valuable evidence for future studies and further prospective clinical trials to confirm these results and elucidate the relationship between them, thus better guiding the clinical practice of lubiprostone.

A Real-World Disproportionality Analysis of FDA Adverse Event Reporting System(FAERS) Event for Belatacept.

Faricimab is the first and only bispecific antibody approved by the U.S. Food and Drug Administration (FDA) for intravitreal injection. Given its increasingly widespread use in retinal vascular diseases, understanding its adverse events (AEs) in real-world settings is crucial. This study employed the FDA Adverse Event Reporting System (FAERS) database to investigate potential safety concerns, with the aim of providing new insights for clinical practice. This study conducted a disproportionality analysis of adverse event data from the FAERS database, in which faricimab was identified as the primary suspect, covering the period from the first quarter of 2022 to the second quarter of 2024. To ensure the accuracy and reliability of the study, we employed four types of disproportionality analyses: the reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), and Bayesian confidence propagation neural network (BCPNN). Additionally, the Weibull distribution was utilized to model the risk of adverse events over time. A total of 2,735 adverse reaction reports, in which faricimab was identified as the primary suspect, were retrieved from the FAERS database. The analysis showed that faricimab-induced AEs occurred across 25 system organ classes (SOCs), with eye disorders meeting the positive threshold for all four algorithms. Significant AEs were mapped to preferred terms (PT), identifying the adverse reactions listed on the drug label: endophthalmitis, elevated intraocular pressure, cataract, retinal pigment epithelial tear, vitreous floaters, retinal vasculitis, retinal artery occlusion, and retinal vein occlusion. In addition to the AEs listed on the drug label, several previously unreported AEs were identified, including blindness, cerebral infarction, retinal hemorrhage, retinal occlusive vasculitis, glaucoma, dry eye, metamorphopsia, and unilateral blindness. This study provided valuable evidence on the real-world safety of faricimab, suggesting that clinicians should place greater emphasis on monitoring its adverse effects during use.

BackgroundTo explore and analyze post-marketing adverse drug event (ADE) signals for voriconazole, posaconazole, and isavuconazole, and to compare the safety differences among the three drugs, aiming to provide insights for rational clinical use.MethodsUsing the Open Vigil 2.1 online tool, extract adverse drug event (ADE) report data for voriconazole, posaconazole, and isavuconazole from the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) database from the time the drugs were marketed up to the third quarter of 2023. Employ the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) methods for data mining. Filter out ADE signals detected by both the ROR and PRR methods, and categorize these ADE signals by System Organ Class (SOC) according to the Medical Dictionary for Regulatory Activities (MedDRA 26.0).ResultsA total of 8,898 ADE reports with voriconazole as the primary suspect drug were retrieved, 1,948 for posaconazole, and 944 for isavuconazole. From the basic analysis of the adverse event reports, male patients (50.31%) outnumber female patients (32.11%). In terms of age, the majority of patients are over 45 years old (52.72%). The reports primarily come from the United States, Japan, France, China, and other countries. A total of 607 ADE signals were identified, with 402 for voriconazole, 159 for posaconazole, and 46 for isavuconazole. Voriconazole ADEs primarily involved the following SOCs: Investigations (9.45%), Eye Disorders (8.46%), and Nervous System Disorders (7.21%); Posaconazole ADEs primarily involved the following SOCs: Investigations (13.84%), General Disorders and Administration Site Conditions (11.95%), and Nervous System Disorders (6.29%); Isavuconazole ADEs primarily involved the following SOCs: General Disorders and Administration Site Conditions (15.22%), Hepatobiliary Disorders (10.87%), and Blood and Lymphatic System Disorders (10.87%).ConclusionVoriconazole, posaconazole, and isavuconazole all potentially pose safety risks related to hepatobiliary disorders and cardiac disorders. Additionally, voriconazole carries a higher safety risk for eye disorders and nervous system disorders. Newly discovered ADE signals not mentioned in the drug package inserts include voriconazole-induced rhabdomyolysis, posaconazole-induced peripheral neuropathy, and isavuconazole-induced visual impairment and mental confusion. These findings are significant for guiding rational clinical use of these medications.

Adverse events reported with eltrombopag and romiplostim: Faers database