Sexual healthGuojun Liang, Hao Huang, Haokui Wang, Qiong Liu, Yang Song
BACKGROUND: Flibanserin, a centrally acting 5-HT1A agonist and 5-HT2A antagonist, is the first approved therapy for acquired, generalized hypoactive sexual desire disorder in premenopausal women. Despite its clinical availability, post-marketing data on real-world safety remain limited. METHODS: A retrospective pharmacovigilance analysis was conducted using the US Food and Drug Administration Adverse Event Reporting System from 2016 to 2025. Duplicate removal, data harmonization and standardized MedDRA coding were applied. Only reports in which flibanserin was designated as the primary suspect drug were included. Disproportionality analyses using proportional reporting ratio, reporting odds ratio, information component and empirical Bayes geometric mean algorithms identified flibanserin-associated safety signals. Sensitivity analyses were conducted according to recorded concomitant medication status. RESULTS: A total of 1702 adverse event reports were identified, with 95% involving women. Most events were non-serious and occurred within the first week of therapy (median onset: 3 days). Prominent signals were nervous system and psychiatric disorders, notably somnolence, dizziness, insomnia and fatigue. Additional signals included hypotension, orthostatic hypotension and product use in unapproved populations, suggesting off-label exposure. Central nervous system-related signals remained directionally consistent in flibanserin-only and concomitant-medication cohorts, whereas hypotension was prominent among reports with recorded concomitant medications. CONCLUSIONS: Flibanserin's real-world safety profile is largely consistent with preapproval data, dominated by early-onset, reversible central nervous system reactions linked to its serotonergic mechanism. However, persistent hypotension and off-label or product-use-related reports underscore the need for continued pharmacovigilance, clinician education, and strict adherence to Risk Evaluation and Mitigation Strategy requirements to maintain an optimal benefit-risk balance.
Bipolar disordersAdele C Viguera, Marlene P Freeman, Ella K Slaby, Ana M Manuelian, Peter Gaccione, David Chitayat, Sonia Hernández-Díaz, Lee S Cohen
OBJECTIVE: Systematically collected pregnancy safety data for cariprazine have been lacking, despite growing use of this medication across psychiatric indications. The goal of this analysis was to determine the risk of major malformations among infants of mothers with psychiatric illness who used cariprazine during the first trimester of pregnancy compared to unexposed controls. METHODS: The National Pregnancy Registry for Psychiatric Medications (NPRPM) is a prospective pharmacovigilance program in which pregnant women with psychiatric diagnoses are enrolled during pregnancy and followed through the postpartum period. Labor and delivery and pediatric medical records are reviewed for evidence of major malformations followed by final adjudication by a dysmorphologist blinded to medication exposure. Infants with first-trimester exposure to cariprazine were compared to controls not exposed to second-generation antipsychotic medications. RESULTS: As of September 9, 2025, N = 4,125 have enrolled in the study. Of those enrolled, 58 cariprazine-exposed infants and 2,098 infants in the comparison group were eligible for inclusion in this analysis. There were no major malformations in the cariprazine-exposed group (absolute risk 0.00%; 95% confidence interval, 0.00%-6.16%) compared to 32 infants with major malformations in the control group (1.53%; 1.05%-2.15%). CONCLUSIONS: In this prospective cohort, 0 of 58 infants exposed to cariprazine during the first trimester had major malformations, compared with 32 of 2,098 (1.53%) unexposed infants. Although these data are preliminary and cannot rule out modest teratogenic effects, they are nonetheless important to provide to health care providers and the public, as cariprazine use has been rising among women of reproductive age.
Basic & clinical pharmacology & toxicologyRonja Levomäki, Päivi Hirvensalo, Aleksi Tornio, Anne M Filppula
The 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor rosuvastatin is a substrate of breast cancer resistance protein (BCRP). BCRP inhibition increases rosuvastatin plasma concentrations and may result in concentration-dependent muscle toxicity, at worst rhabdomyolysis. We investigated if concomitant use of rosuvastatin and drugs identified as in vitro BCRP inhibitors shows an increased number of rhabdomyolysis events based on pharmacovigilance data. From reports in the US Food and Drug Administration Adverse Event Reporting System for patients using rosuvastatin, we formed interaction (rosuvastatin with inhibitor) and non-interaction (rosuvastatin without inhibitor) groups for 71 BCRP inhibitors. These groups were further divided into subgroups with or without rhabdomyolysis. For each inhibitor, we calculated reporting odds ratio (ROR) and 95% confidence intervals (CIs). We identified 9777 individual rosuvastatin-related reports during 2013-2023, including 815 rhabdomyolysis reports. Of the 71 inhibitors, 19 had enough reports for analysis. Significantly increased RORs were obtained for the clinical BCRP inhibitors febuxostat (ROR 2.47, 95% CI 1.38-4.43) and ticagrelor (ROR 4.15, 95% CI 3.32-5.20). Amiodarone, erlotinib and rifampicin showed significantly increased RORs. Our findings support known interactions involving febuxostat and ticagrelor and suggest that also other BCRP inhibitors may increase the risk of rosuvastatin-induced rhabdomyolysis.
MedicineHeng Chen, Ju Hou, Lihui Ouyang, Gefei He, Juanjuan Huang
Cataracts are a leading cause of global blindness and visual impairment, with drug-induced cataracts emerging as a significant yet understudied contributor. This study aimed to comprehensively and systematically investigate medication-related cataract risk signals using data from the FDA Adverse Event Reporting System. We searched the FDA Adverse Event Reporting System database for all reported cases of medication-related cataracts from October 2014 to September 2024. Disproportionality analysis, employing the information component and reporting odds ratio, identified the medications most commonly associated with cataracts. Demographic characteristics, drug categories, and time-to-onset were also evaluated. After deduplication, 37,838 cataract-related reports were included. A total of 588 drugs were linked to cataracts. The top 50 medications with the highest signal association strength were identified based on information component values, including anti-cancer agents, immunomodulators, glucocorticoids, adrenergic medications, and anticholinergic medications. Mirvetuximab soravtansine, nitisinone, and belantamab mafodotin demonstrated the strongest signals. Most cases involved individuals over 60 years old, with females accounting for 68.7% of the reports. Significant variability in time-to-onset was also observed. In conclusion, this large-scale signal detection analysis utilizes real-world data to provide a comprehensive list of medications potentially associated with cataracts. Future research is required to validate these statistical associations.
Nafamostat is a broad-spectrum serine protease inhibitor approved for pancreatitis, disseminated intravascular coagulation, and extracorporeal circulation anticoagulation. It also showed potential anti-SARS-CoV-2 activity during the COVID-19 pandemic, leading to expanded clinical use. This study aimed to explore post-marketing adverse event (AE) signals of nafamostat based on the Japanese Adverse Drug Event Report database so as to provide evidence for clinical safety management. Retrospective analysis was performed on AE reports retrieved from the Japanese Adverse Drug Event Report database between Q1 2004 and Q3 2024. Four disproportionality analysis algorithms, including reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker, were adopted to detect AE signals. The distribution of AEs across system organ classes and preferred terms was summarized, and the time to onset was analyzed using the Weibull shape parameter test. A total of 2051 valid AE reports with nafamostat as the primary suspected drug were included, covering 20 system organ classes. The most prominent signals were observed in immune system disorders (n = 997) and vascular disorders (n = 370). Twenty-four preferred terms met the screening criteria of all 4 algorithms, among which anaphylactic shock (n = 746), shock (n = 341), and hyperkalemia (n = 200) were the most frequently reported. Six potential novel signals not recorded in the drug label were identified, namely acquired factor V deficiency, increased viral load, burning sensation, retroperitoneal hemorrhage, abdominal wall hematoma, and device-related thrombosis. Further bias analysis confirmed that 3 signals were false-positive results caused by confounding by indication or protopathic bias, while burning sensation had clear biological plausibility. The median time to onset was 1 day (interquartile range: 1-9 days); 58.55% of AEs occurred on the 1st day of administration, and 82.63% developed within 30 days. The Weibull test indicated that the AE risk peaked at the initial medication stage and gradually decreased over time. This real-world study clarified the safety profile of nafamostat, identifying severe allergic reactions and hyperkalemia as the main AEs. Of 6 initially detected unlabeled signals, 3 were confirmed as false-positive due to confounding bias, while the remaining 3 (bleeding complications and abnormal burning sensation) warrant clinical monitoring. Close monitoring within 24 hours after administration is highly recommended to reduce drug-related risks.
MedicineGuanbo Xie, Huili Weng, Jingxian Yu, Liqun Chi
Zuranolone and Brexanolone are Food and Drug Administration-approved novel agents for postpartum depression, yet real-world post-marketing safety data for the two drugs remain insufficient. This study aimed to systematically characterize their adverse event (AE) profiles via two authoritative pharmacovigilance databases, namely the Food and Drug Administration Adverse Event Reporting System (FAERS) and VigiAccess. FAERS data from Q1 2019 to Q3 2025 and VigiAccess data updated to November 2025 were extracted. Reporting odds ratio and proportional reporting ratio were adopted to screen and compare AE signals of the two drugs. A total of 631 primary suspect (PS) drug reports for Zuranolone and 102 for Brexanolone were extracted from FAERS, whereas 863 Zuranolone and 227 Brexanolone reports were obtained from VigiAccess. At the system organ class level, AEs associated with Zuranolone involved 22 SOCs in FAERS and 24 SOCs in VigiAccess, with the top three SOCs sorted by reported cases as follows: Nervous system disorders, Psychiatric disorders, and General disorders and administration site conditions (FAERS); Nervous system disorders, General disorders and administration site conditions, and Psychiatric disorders (VigiAccess). For Brexanolone, AEs retrieved from FAERS involved 16 SOCs, compared with 21 SOCs in VigiAccess; the top three SOCs by the number of reported cases were Injury, poisoning and procedural complications, General disorders and administration site conditions, and Psychiatric disorders. After signal screening in the FAERS database, a total of 78 positive signals (involving 9 SOCs) were identified for Zuranolone, whereas 10 positive signals (involving 4 SOCs) were detected for Brexanolone. Four SOCs were commonly implicated in the positive AE signals of both drugs, with the most commonly reported AEs including gait disturbance, exposure via breast milk, fatigue, and therapy cessation. Additionally, compared to Brexanolone, 5 SOCs were uniquely associated with Zuranolone, with the most commonly reported AEs such as vertigo, vision blurred, muscle twitching, somnolence, and loss of personal independence in daily activities. Zuranolone's AEs mainly involved nervous system disorders and Psychiatric disorders, while Brexanolone's primarily included Injury, poisoning and procedural complications, and Psychiatric disorders. This study would provide more safety reference data for the clinical use of two drugs.
JMIR research protocolsMiki Ohta, Miki Ota, Mikihiko Ohta
BACKGROUND: Pharmacovigilance aims to protect patient safety by identifying and managing adverse events associated with pharmaceuticals. Determining the causality of these adverse events is central at both the individual case and population levels; however, it is increasingly challenging as the volume and complexity of safety data grow. Although AI and related technologies have been proposed to support causality assessment, limited research has examined how these methods are used, their information and quality requirements, or how associated risks are addressed. OBJECTIVE: This scoping review aims to determine the available evidence on AI-based methods for causality assessment in pharmacovigilance. The primary objective is to characterize how these methods are applied or proposed with a focus on their functional roles, reported data inputs and information needs, and associated risks. Secondary objectives include comparing applications at the individual case and population levels; describing the types of AI-based techniques and automation tools used in causality assessment workflows; and summarizing reported data quality considerations and governance mechanisms, including risk management approaches. METHODS: Sources describing or proposing AI-based approaches, including data-driven models (machine learning, natural language processing, knowledge graphs, and causal inference) and knowledge- or rule-based systems implementing causal assessment logic, will be eligible. Searches will be conducted in PubMed, Web of Science Core Collection, ProQuest, EBSCOhost, and Ichushi Web and will be restricted to English- and Japanese-language sources. Two reviewers will independently screen records and full-text articles, with disagreements resolved by a third reviewer. Data will be charted on use cases, information inputs, data quality dimensions, model characteristics, governance mechanisms, and identified risks. Synthesis will follow a reflexive thematic analysis approach and be reported in accordance with PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) guidelines informed by applicable PRISMA-S (Preferred Reporting Items for Systematic reviews and Meta-Analyses literature search extension) elements. RESULTS: This protocol was registered in the Open Science Framework platform on December 23, 2025. The registration was subsequently updated on May 19, 2026, to reflect an extension to the data collection period. A preliminary database search was conducted in December 2025, retrieving a total of 760 records, of which the preliminary title and abstract screening identified 196 (25.8%) articles for full-text review. Database searches are scheduled for July 2026. Data charting is scheduled for August 2026, and synthesis is scheduled for September 2026. Findings are expected to be submitted for publication by the end of December 2026. CONCLUSIONS: This review is expected to provide a structured map of AI-based applications for causality assessment in pharmacovigilance, clarify reported information inputs and data quality dimensions, and synthesize risk management and governance approaches. The findings are expected to inform methodological development, practical implementation, and the governance of AI-supported causality assessment. TRIAL REGISTRATION: Open Science Framework 10.17605/OSF.IO/QVF5C; https://osf.io/qvf5c/overview. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/101691.
PloS oneQian Chen, JinYue Li, Mao Zhang, XueDong Kang, LiZhu Han, Yuan Bian, HongLi Luo
OBJECTIVE: To systematically characterize the post-marketing safety signals of isotretinoin using real-world data from the U.S. FDA Adverse Event Reporting System (FAERS), with independent external validation in the European EudraVigilance (EV) database. METHODS: Adverse event (AE) reports in FAERS from 2004Q1 to 2024Q3 were analyzed. Signal detection was conducted using four complementary disproportionality algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS). Signals concurrently detected by all four methods were defined as robust. Key findings were subsequently examined in EV as an external reference. RESULTS: Among 50,519 patients contributing 142,160 isotretinoin-associated AE reports, 469 statistically robust signals were identified, spanning 25 system organ classes (SOCs). Signals were most concentrated in psychiatric disorders (75, 15.99%), gastrointestinal disorders (58, 12.37%), and congenital, familial, and genetic disorders (50, 10.66%). The strongest association was observed for inflammatory bowel disease (IBD; ROR = 579.14); however, temporal clustering and reporter-type profiling suggested substantial stimulated reporting, potentially driven by litigation, warranting cautious interpretation. Several high-ranking signals were not described in current product labeling, including nasal vestibulitis, hypertrophic anal papilla, and SAPHO syndrome. Pregnancy-related signals were prominent, with unintended pregnancy showing a strong signal (ROR = 91.39). External validation in EV demonstrated high concordance, supporting the robustness and reproducibility of the findings. CONCLUSIONS: Isotretinoin is associated with a broad spectrum of pharmacovigilance signals, with disproportionate representation of psychiatric, gastrointestinal, and pregnancy-related events. While multiple previously unlabelled signals emerged, their clinical relevance remains to be established. These findings underscore the need for strengthened clinical monitoring, rigorous pregnancy prevention strategies, and careful interpretation of spontaneous reporting data.
European journal of pediatricsAnnelien Vantrappen, Nadir Yalcin, Karen van Hoeve, Pauline De Bruyne, Karel Allegaert
UNLABELLED: While drug-associated acute pancreatitis is proportionally more prevalent in children than adults, age-stratified pharmacovigilance data remain limited. This study analysed paediatric-specific signals to improve recognition and safety. This study aimed to identify drugs associated with acute pancreatitis in children compared with adults and explored age-related differences in patterns using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). A retrospective disproportionality analysis was conducted on 29,349 reports (November 1970-February 2026) from the FAERS. The dataset included 2138 (7.3%) paediatric cases (0-17 years). Suspected active pharmaceutical ingredients (APIs) were identified, and reporting patterns were compared between age groups (chi-squared, reporting odds ratio (ROR), proportional reporting ratio (PRR), multivariate regression analysis). The top ten suspected drugs in children were as follows: methotrexate, pegaspargase, asparaginase, dexamethasone, acetaminophen, prednisone, vincristine sulphate, cytarabine, valproic acid, and mercaptopurine. Paediatric cases were primarily linked to oncologic and immunomodulatory treatments, whereas adult reports were mainly linked to antidiabetic and cardiovascular agents. Seven APIs present in the top 25 list of children and adults (dexamethasone, acetaminophen, prednisone, tacrolimus, lamivudine, didanosine, furosemide) showed significantly higher reporting proportions in children (p < 0.01). Dexamethasone, tacrolimus, and didanosine showed positive interaction terms with serious outcomes in adjusted models. Serious outcome and consumer-reporting were more common in neonates and infants. CONCLUSION: Distinct age-dependent patterns were identified. These findings support paediatric-specific pharmacovigilance assessment and caution against direct extrapolation of adult spontaneous-reporting patterns to children. A clinically useful list of drugs with the highest reporting frequencies in children has been generated. WHAT IS KNOWN: • Drug-associated acute pancreatitis is proportionally more prevalent in children. • The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) can be used to analyse and explore age-dependent patterns. WHAT IS NEW: • The top ten suspected drugs in children were as follows: methotrexate, pegaspargase, asparaginase, dexamethasone, acetaminophen, prednisone, vincristine sulphate, cytarabine, valproic acid, and mercaptopurine, linked to oncology and immunomodulation. • Compared to adults, seven drugs (dexamethasone, acetaminophen, prednisone, tacrolimus, lamivudine, didanosine, furosemide) showed significantly higher reporting proportions in children. Dexamethasone, tacrolimus, and didanosine were associated with serious events.
Journal of medical Internet researchYoung Mi Ha, Minjung Kim, YoungIn Bang, Daejin Choi, Jae Hyun Kim, Sandy Jeong Rhie, Yoshihiro Noguchi, Myeong Gyu Kim
BACKGROUND: Causality assessment is central to pharmacovigilance but remains resource-intensive and subjective. The applicability of large language models (LLMs) to formal World Health Organization-Uppsala Monitoring Centre (WHO-UMC) drug-adverse event causality assessment has not been well established. OBJECTIVE: This study aims to evaluate the performance of LLMs in WHO-UMC causality assessment. METHODS: A curated set of 55 cases derived from the US Food and Drug Administration Adverse Event Reporting System, comprising 337 drug-level assessments, was constructed. Cases involving 2 to 11 suspected drugs were stratified by drug count, and 5 cases were sampled from each stratum. To ensure representation of rare but clinically important categories, 5 additional cases containing at least 1 "Certain" drug-adverse event pair were included. Case data were reorganized into a standardized semistructured format that preserved key elements required for WHO-UMC causality assessment. Domain experts conducted a pilot evaluation to align interpretation criteria prior to independently assessing the final dataset, yielding an interexpert agreement (Fleiss κ) of 0.762 across 337 drug-level assessments. Multiple prompting strategies, including standard prompting, chain-of-thought (CoT), CoT with self-consistency, few-shot, reasoning and acting, and tree-of-thought prompting, were applied across multiple LLMs, including GPT-5.4 and its mini variant and Gemini 2.5 Flash and Pro, via their respective application programming interfaces. Agreement with expert assessments was quantified using Cohen κ, weighted κ, and accuracy metrics. Internal consistency across repeated inferences was evaluated using Fleiss κ. RESULTS: Performance varied across models and prompting strategies. Cohen κ ranged from 0.368 to 0.641, weighted κ ranged from 0.641 to 0.821, accuracy ranged from 0.583 to 0.804, and balanced accuracy ranged from 0.513 to 0.735. Fleiss κ ranged from 0.730 to 0.915, corresponding to substantial to almost perfect agreement. The highest Cohen κ was observed for Gemini 2.5 Flash with CoT prompting (0.641). Gemini 2.5 Flash with CoT-self-consistency prompting showed a Cohen κ of 0.640 and achieved the highest observed point estimates for weighted κ (0.821), accuracy (0.804), and Fleiss κ (0.915), although the gains over other prompting strategies were modest. Category-level performance for this model showed higher performance for "Certain" (F1-score=0.793), "Probable/Likely" (F1-score=0.794), and "Unlikely" (F1-score=0.898), whereas performance for "Possible" remained substantially lower (F1-score=0.293), reflecting the difficulty of intermediate causality assessment. CONCLUSIONS: LLMs demonstrated moderate to substantial agreement in WHO-UMC causality assessment, indicating meaningful but still limited performance relative to expert judgment. Although LLMs are not suitable for independent decision-making, they may serve as supportive tools in pharmacovigilance workflows, particularly for preliminary case triage. Further studies using larger and more diverse datasets and evaluating performance on raw narrative reports are warranted.
Medical science monitor : international medical journal of experimental and clinical researchLiang Tian, Shanshan Xu, Hui Guo
BACKGROUND Levofloxacin is a fluoroquinolone antibiotic that can cause a range of dermatological adverse drug reactions (ADRs), including rashes, phototoxicity, and hyperpigmentation, as well as severe conditions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. The China National Adverse Drug Reaction Monitoring System (CADRMS) is an online pharmacovigilance network that includes data from patient medical records. This study evaluated 35 patients with levofloxacin-induced cutaneous ADRs reported to CADRMS in 2021. MATERIAL AND METHODS Individual case safety reports involving levofloxacin-associated cutaneous ADRs in 2021 were retrieved from CADRMS. After excluding duplicates and cases with insufficient details or alternative causative drugs, 35 cases with probable/possible causality were included. Key variables (demographics, administration route/dose, comorbidities, polypharmacy, ADR manifestations, onset, severity, and outcomes) were descriptively analyzed. RESULTS Among 35 patients (mean age 43.7±17.6 years; 60% male), 80% received intravenous levofloxacin (71% at 500 mg/day), primarily as inpatients (77%) for respiratory (43%) or urinary (37%) infections. Polypharmacy was common (89%), and all had comorbidities. Cutaneous manifestations were predominantly mild (89%), including maculopapular rash (37%), pruritus (20%), urticaria (14%), erythema (11%), and photosensitive dermatitis (9%). Onset was rapid (89% within 24 hours). One severe case (3%; exfoliative dermatitis) occurred. All reactions resolved fully after drug discontinuation and supportive therapy (antihistamines in 37%; corticosteroids in a few cases). CONCLUSIONS Levofloxacin-induced cutaneous ADRs are typically mild, immediate-onset, and reversible with prompt discontinuation and anti-allergic treatment. Rational prescribing should emphasize allergy history screening, close monitoring during initial intravenous administration, and cautious use in comorbid or polypharmacy settings to minimize risks while preserving clinical utility.
The Journal of international medical researchYantian Wang, Anqi Li, Jiafu Wang, Min Xie
ObjectiveThis study aimed to evaluate the association between hormonal therapies and bone adverse events using the Food & Drug Administration Adverse Event Reporting System (FAERS) and to explore possible molecular mechanisms.MethodsFAERS data were analyzed for adverse events related to five hormonal therapy drug categories, and disproportionality analysis was used to identify significant adverse events. Transcriptomic data from Gene Expression Omnibus datasets (GSE147271 and GSE20181) were analyzed to identify bone-related pathways and differentially expressed genes.ResultsOverall, 57 significant bone-related signals, including 22 Important Medical Events, were identified, most commonly fractures at various sites, osteoporosis, and bone metastases associated with estrogen receptor-targeted drugs and aromatase inhibitors. Estrogen-related adverse events typically occurred after 6 months, whereas androgen-related events appeared earlier. Transcriptomic analysis identified FOS, JUN, COL1A1, and IGF1 as key genes, implicating the Janus kinase signaling pathway in bone injury.ConclusionThis study demonstrates a strong association between hormonal therapy drugs and bone-related adverse events, particularly fractures and bone cancers. It emphasizes the importance of monitoring bone health and suggests the Janus kinase signaling pathway as a potential therapeutic target for mitigating bone-related adverse events.
MedicineYe Zhang, Mengnan Shuai, Dan Huang, Minghua Yang, Shengfeng Wang
Vinorelbine is a widely used vinca alkaloid chemotherapeutic agent. Although its hematologic and gastrointestinal toxicities are well characterized, its cardiopulmonary safety profile remains insufficiently defined, and evidence in pediatric populations is limited. This study aimed to systematically evaluate vinorelbine-associated adverse events (AEs) using the FDA Adverse Event Reporting System (FAERS) and WHO VigiBase databases, with particular focus on cardiopulmonary events and pediatric safety. AEs from FAERS (2004 Q1-2024 Q4) and VigiBase (up to 2024 Q4) were analyzed using disproportionality methods, including reporting odds ratio (ROR) and Bayesian confidence propagation neural network to identify potential safety signals. Among 1712 FAERS and 16,175 VigiBase reports listing vinorelbine as the primary suspected drug, 210 significant signals were detected across multiple system organ classes. Strong associations were found not only with hematologic toxicities but also with respiratory, thoracic, and cardiac disorders (notable cardiopulmonary signals), with most AEs occurring within 30 days of administration. In pediatric patients, vinorelbine showed a significant association with endocrine disorders. These findings highlight the importance of enhanced monitoring of cardiopulmonary effects during vinorelbine treatment, particularly during combination therapy, and heightened vigilance for endocrine-related AEs in pediatric patients. As a retrospective observational study based on spontaneous reporting databases, underreporting and unmeasured confounders may affect the interpretation of results.
Experimental dermatologyKe Gan, Jie Liu, Jianjiang Shen, Lu Lu, Ruiyang Xu, Zenan Xu, Jianmei Chen, Yan Lu
This study aims to assess the adverse event profile of apremilast using FDA Adverse Event Reporting System (FAERS) data to identify potential safety risks and support clinical use. FAERS data from Q1 2014 to Q1 2024 were analysed. Adverse drug events (ADEs) related to apremilast were extracted and evaluated using four signal detection methods: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). A total of 122 287 apremilast-related AE reports, encompassing 238 215 adverse reactions across 24 System Organ Classes (SOCs) and 60 apremilast-induced AE signals, were identified. Gastrointestinal disorders, skin and subcutaneous tissue disorders, and musculoskeletal and connective tissue disorders were the most frequently reported SOCs. Common Preferred Terms (PTs) included diarrhoea, nausea, and headache. Notably, some adverse effects not listed in the drug package insert were found, such as multiple allergic reactions and tumour signals. This study identified significant disproportionality signals for ADEs reported with apremilast, particularly concerning gastrointestinal reactions, psychiatric disorders, and infections. While these findings do not establish causality, they offer valuable real-world insights that underscore the importance of continued clinical monitoring and warrant further pharmacoepidemiologic investigation.
BACKGROUND: Veterinary pharmaceuticals often enter into ecosystems through the disposal of unused and expired medicines and animal excreta. Consequently, these substances are emerging as a global threat, posing risks to ecosystems, biodiversity and public health. However, despite the increasing concerns attributed to veterinary pharmaceuticals, there is a lack of empirical data regarding awareness and practices related to ecopharmacovigilance (EPV) among veterinary professionals in Ethiopia. EPV is an emerging discipline focused on the detection, evaluation, understanding and the prevention of the environmental impacts of pharmaceuticals. This knowledge gap highlights the need for evidence-based assessment of veterinary professionals' awareness and practices of EPV in Ethiopia. Therefore, this study aimed to assess veterinary professionals' knowledge, attitudes and practices (KAP) regarding EPV and pharmaceutical waste management. METHODS: A cross-sectional survey was conducted between January 2024 and May 2025 among 37 veterinary healthcare providers in and around Gondar City. The data were collected using a structured, self-administered questionnaire. Data were analysed using SPSS version 25 through descriptive statistics and chi-square tests to identify associations between socio-demographic characteristics and KAP indicators. RESULTS: The study found that 73% of respondents had never heard of EPV, 78.4% had not received relevant training, and 67.6% reported the absence of pharmaceutical disposal guidelines in their facilities. Although 94.6% acknowledged the harmful effects of improper drug disposal on human and environmental health, only 16.2% were familiar with the term EPV. Knowledge was marginally associated with reading scientific literature (p = 0.084), whereas attitudes were significantly related to prior knowledge (p = 0.001), training (p = 0.001) and reviewing related reports (p = 0.001). Practices were influenced by prior knowledge (p = 0.023) and engagement with literature (p = 0.032). About 40.5% of participants disposed of pharmaceuticals in regular trash, and only 27% returned unused drugs to appropriate authorities. Overall, 62.8% of respondent's demonstrated poor knowledge, 56.8% held negative attitudes, and practices were inadequate. CONCLUSION: This baseline study reveals low awareness of EPV and poor waste management practices among veterinary healthcare providers. The study shows the urgent need for targeted training, policy enforcement and the integration of environmental education into veterinary curricula in Ethiopia. This is necessary to promote responsible pharmaceutical stewardship and safeguard the environment and public health.
Journal of the American College of Clinical Pharmacy : JACCPSuol Thanh Pham, Thang Nguyen, Ngoc Van Pham, Hao Yen Tran
BACKGROUND: Under-reporting of adverse drug reactions (ADRs) limits medication-safety learning in provincial hospitals, where dedicated pharmacovigilance infrastructure and personnel are often constrained. The objective of this study was to evaluate a clinical pharmacy-led multifaceted intervention to improve healthcare professionals' knowledge, attitudes, and reporting practices and to strengthen hospital pharmacovigilance performance. METHODS: We conducted a multicenter pre-post evaluation in three provincial hospitals in Ca Mau province, Vietnam (January 1, 2022-June 30, 2025). Repeated cross-sectional surveys were administered before and after a 6-month intervention (July-December 2023) (n = 372 each round). All spontaneous ADR reports submitted to the national pharmacovigilance center and archived at hospital pharmacies were retrospectively reviewed. Report completeness was assessed using VigiGrade (well documented ≥ 0.8), and organizational capacity was assessed using the Indicator-based Pharmacovigilance Assessment Tool (IPAT). RESULTS: Adequate knowledge increased from 2.7% (10/372) preintervention to 29.8% (111/372) postintervention. Adequate attitudes increased from 57.5% to 64.2%, and adequate self-reported practices from 47.8% to 55.6%. Among professionals who had encountered suspected ADRs, ever-reporting increased from 46/308 (14.9%) to 75/334 (22.5%) (p = 0.015). Spontaneous ADR reports increased from 26 preintervention to 144 postintervention while maintaining high completeness (VigiGrade ≥ 0.8: 96.2% vs. 97.9%; p = 0.419). IPAT performance improved across domains, with the largest gains in monitoring and reporting activities. CONCLUSIONS: A pragmatic, pharmacy-coordinated multifaceted intervention was associated with increased ADR reporting participation and volume without compromising documentation completeness and with strengthened organizational pharmacovigilance performance. This model appears feasible for resource-limited provincial hospitals, but the outcomes should be interpreted as improvements in reporting processes rather than direct evidence of reduced patient harm.
OBJECTIVES: To characterise post-marketing adverse event (AE) reporting patterns associated with CD3×CD20 bispecific antibodies (BsAbs) using multi-method disproportionality analysis and to identify potential safety signals warranting further investigation. DESIGN: Retrospective pharmacovigilance study using disproportionality analysis with multiple complementary methods. SETTING: Food and Drug Administration Adverse Event Reporting System database. PARTICIPANTS: A total of 2237 AE reports associated with CD3×CD20 BsAbs (1135 for epcoritamab, 673 for glofitamab and 429 for mosunetuzumab) were submitted from the fourth quarter of 2022 to the first quarter of 2025. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes included identification of statistically significant AE signals using reporting odds ratio (ROR) and Bayesian confidence propagation neural network with information component as the principal signal detection methods, while proportional reporting ratio was only used as a supplementary measure to enhance the robustness of signal detection. Secondary outcomes included subgroup analyses by sex and age, analysis of fatal outcomes and time-to-onset patterns using Kaplan-Meier analysis and Weibull distribution. RESULTS: A total of 93 AE signals were identified for epcoritamab, 65 for glofitamab and 41 for mosunetuzumab. The three disproportionality methods showed near-complete agreement (>98% concordance) in signal detection. Signals were detected for several AEs not currently listed in product labelling. For epcoritamab, unlabelled signals included progressive multifocal leukoencephalopathy (ROR (95% CI) 13.28 (5.51 to 31.97)), haemophagocytic lymphohistiocytosis (ROR (95% CI) 18.19 (10.75 to 30.79)) and disseminated intravascular coagulation (ROR (95% CI) 8.76 (3.28 to 23.39)). For glofitamab, unlabelled signals included disseminated tuberculosis (ROR (95% CI) 53.30 (17.10 to 166.13)) and cerebral haemorrhage (ROR (95% CI) 6.08 (2.28 to 16.22)). For mosunetuzumab, tumour lysis syndrome (ROR (95% CI) 29.91 (11.19 to 79.97)) and uveitis (ROR (95% CI) 10.75 (3.46 to 33.41)) were detected. With respect to patient characteristics, cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were more frequently reported in younger patients treated with epcoritamab, while pyrexia was more commonly reported among elderly patients receiving glofitamab or mosunetuzumab. Among reports with available dates, Kaplan-Meier analysis showed that most reported onset times fell within the first month following treatment initiation. In the indication-restricted sensitivity analysis, most signals remained detectable, whereas certain signals, including haemophagocytic lymphohistiocytosis with epcoritamab, were sensitive to comparator selection. CONCLUSIONS: This study provides a systematic characterisation of post-marketing AE reporting patterns for CD3×CD20 BsAbs, identifying several signals for AEs not currently listed in product labelling. However, disproportionality signals do not establish causality, and clinical correlation is essential. These findings may help inform post-marketing pharmacovigilance and prioritise signals for further clinical and epidemiological validation.
Revista da Sociedade Brasileira de Medicina TropicalMárcia Paulliny Soares Bahia, Silon de Souza Gomes Junior, Argus Leão Araújo, Hoberdan Oliveira Pereira, José Geraldo Leite Ribeiro, Alexandre Sampaio Moura
BACKGROUND: A national dengue vaccination campaign using TAK-003 was launched in 2024, targeting adolescents. Post-licensure surveillance suggested higher-than-expected hypersensitivity reactions. METHODS: We conducted a descriptive study using vaccine adverse event data and vaccination records from Belo Horizonte among individuals aged 6-14 years. RESULTS: Of the 146,115 doses administered, 28 hypersensitivity reactions were reported (191.6 per million), including nine cases of anaphylaxis and two of anaphylactic shock. All events followed the first dose. Mean age was 9.4 years, and mean time to symptom onset was 31 minutes. CONCLUSIONS: Hypersensitivity rates exceeded expected vaccine-associated levels, reinforcing the need for continued pharmacovigilance.
International journal of medical informaticsAna Carolina Jacoby, Mell Amisa Matsuda, Carine Raquel Blatt, Sílvio César Cazella
BACKGROUND: Pharmacovigilance is dedicated to the identification, evaluation, and prevention of adverse effects associated with the use of medicines after their commercialization. In this context, data mining techniques have been widely employed for the detection of safety signals. Although machine learning algorithms show potential to identify complex patterns and improve the prediction of adverse drug reactions, their application in pharmacovigilance databases remains limited. OBJECTIVE: To map the computational approaches used in pharmacovigilance, to identify the prevalence of traditional statistical methods and data mining techniques, and to assess the role of machine learning algorithms. METHODS: This scoping review followed PRISMA‑ScR guidelines (protocol registered on OSF: https://doi.org/10.17605/OSF.IO/KZJDT). We searched PubMed, Scopus, Embase, and Web of Science for English primary studies published from 2015 to July 2025 that applied data mining techniques to pharmacovigilance databases. Data extraction used a standardized form. RESULTS: The search identified 1,468 records, of which 162 studies were included after screening and eligibility assessment. Traditional disproportionality methods, such as Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR), were used in 87.7% of the studies, whereas 12.3% applied machine learning or deep learning techniques, mainly in classification tasks, with logistic regression being the most frequently employed algorithm. The most investigated drugs included immune checkpoint inhibitors, such as nivolumab, pembrolizumab, atezolizumab, and durvalumab. The most studied therapeutic classes were antineoplastic agents, immunosuppressants, and psycholeptics. CONCLUSION: Signal detection in pharmacovigilance remains predominantly based on classical statistical methods. Progress in the field is still constrained by the slow incorporation of advanced machine learning techniques and the limited public availability of datasets used in analyses.
In vivo (Athens, Greece)Kousuke Hosonaka, Kenta Yamaoka, Mayako Uchida, Yoshihiro Uesawa, Kazushige Takahashi, Tadashi Shimizu
BACKGROUND/AIM: Anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates have incompletely characterized safety profiles. Therefore, we compared the adverse events for trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) using the Japanese Adverse Drug Event Report (JADER) database and U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). PATIENTS AND METHODS: We analyzed the JADER (April 2004-April 2025) and FAERS (Q1 1997-Q1 2025) databases for the target drugs T-DM1 and T-DXd, with trastuzumab and pertuzumab as comparators. All reported cases were included regardless of severity grade. RESULTS: Hepatobiliary disorder signals were detected for T-DM1, whereas hematotoxicity- and infection-related signals were prominent for T-DXd, including sepsis and Pneumocystis jirovecii pneumonia (PJP). Interstitial lung disease was observed for both agents. Signals for cardiac disorders were detected for trastuzumab, pertuzumab and T-DM1, but not for T-DXd. T-DXd-associated nausea and myelosuppression were frequently reported within 40 days of treatment initiation, whereas PJP was reported later, with a median time to onset of 90 days. CONCLUSION: Analyses using JADER and FAERS revealed the adverse event profiles of HER2 antibody-drug conjugates. Hepatobiliary disorders were characteristic of T-DM1, whereas hematotoxicity and infection-related events were characteristic of T-DXd. Interstitial lung disease was detected for both agents. These findings were consistent with those of clinical trials. Infection-related events associated with T-DXd were identified as potential signals, highlighting the clinical relevance of PJP, with a median time to onset of approximately 90 days.