MedDRA Research Articles

Adverse event profile of albumin-bound paclitaxel: a real-world pharmacovigilance analysis

BackgroundAbraxane plays a crucial role in the treatment of various types of cancer, despite the considerable attention it has garnered for its adverse drug events (ADEs). Nevertheless, there is currently a significant lack of comprehensive real-world pharmacovigilance studies on the ADEs associated with Abraxane.MethodsWe conducted a retrospective analysis of ADEs associated with Abraxane using data mining from the FAERS database, analyzing data from 2005 to 2023. In a real-world setting, we quantified and visualized the signals of these ADEs using four pharmacovigilance algorithms.ResultsThe FAERS database identified a total of 10,230 adverse event reports associated with Abraxane. The study revealed that Abraxane-related adverse drug events involved 27 system organ classes (SOC), with the strongest signals associated with the lymphatic and hematological systems and hepatobiliary disorders. Additionally, we identified 70 significant Preferred Terms (PT) signals, which included some critical adverse events not highlighted in the product labeling, such as cystoid macular edema. Further analysis of the timing of adverse reactions showed a median onset time of 41 days. Most adverse events (AEs) occurred within the first month of using Abraxane (43.5%), although some were still possible 1 year after treatment (3.5%). Gender-specific analysis indicated that high-risk AEs differed between females (nausea, vomiting, and erythema) and males (febrile neutropenia, disseminated intravascular coagulation, and upper gastrointestinal bleeding).ConclusionThe examined results provide crucial recommendations for optimizing the administration of Abraxane, enhancing its effectiveness, and mitigating potential adverse effects. This knowledge will substantially facilitate the implementation of the substance in clinical settings.

Adverse events associated with parenteral nutrition support therapy: A pharmacovigilance study.

Parenteral nutrition (PN) plays a crucial role in nutrition support therapy, yet data on related adverse events (AEs) in practical settings are scarce. To address this, we analyzed AE signals associated with PN treatment from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. We extracted data from the FAERS database, covering the period from the first quarter (Q1) of 2004 to Q1 of 2024. Drug names and AEs were standardized. We then conducted disproportionality analyses using four different algorithms to evaluate the association between PN and its associated AEs. We collected a total of 48,890,925 reports from the FAERS database, of which 1642 involved PN-related AEs. After categorization, we identified 21 system organ classes (SOCs), and hepatobiliary disorders were the only significant SOC across all four algorithms. At the preferred term (PT) level, we identified 99 PTs that showed significant disproportionality in all four algorithms. Fat overload syndrome, fatty acid deficiency, parenteral nutrition-associated liver disease (PNALD), Malassezia infection, and Pantoea agglomerans infection were the most prominent PTs. In addition, several potential new AE signals included nervous, cardiac, immune, psychiatric, blood, renal, urinary, and eye disorders. Our study identified several common and rare PN-related AEs reported in the FAERS database. Patients and healthcare providers should remain vigilant about these AEs. Understanding the risks of PN therapy and establishing practical procedures can help reduce AEs.

Adverse events associated with tezepelumab: a safety analysis of clinical trials and a pharmacovigilance system

ABSTRACT Background Tezepelumab is the first asthma biologic approved by the FDA that is not restricted by biomarker phenotypes. To date, there have been no studies reporting adverse events (AEs) associated with the real-world use of tezepelumab. Research design and methods This study included a comprehensive evaluation of AE reports related to tezepelumab since its approval (4th quarter of 2021 to 1st quarter of 2024) using the FAERS database, and compared with the currently reported clinical trial results (ClinicalTrials.gov). Results A total of 2153 reports of tezepelumab-related AEs were extracted. 256 preferred terms (PTs) of adverse reactions involving 27 system organ classes were identified. Significant AEs that were not reported on the drug label, such as ‘dyspnea,’ ‘body temperature,’ and ‘tongue pruritus,’ were reported. The median time to onset (TTO) of tezepelumab-related AEs was 35 days.The most frequent AEs in different sexes were ‘arthralgia’ and ‘dyspnea,’ with differences in signal strength ranking between the sexes. Conclusions This study represents the largest report to date on tezepelumab-related AEs, providing valuable insights into the potential side effects of tezepelumab. This work is crucial for the broader clinical application of this novel biologic and improving outcomes for patients with severe asthma.

Comparative analysis of semaglutide induced adverse reactions: Insights from FAERS database and social media reviews with a focus on oral vs subcutaneous administration

BackgroundCompared to alternative weight-loss strategies and medications, semaglutide stands out for its convenience and efficacy, resulting in a significant increase in prescriptions and raising public safety concerns. Furthermore, the safety profiles of its oral and subcutaneous formulations require further examination.ObjectiveOur goal is to investigate the potential safety risks associated with semaglutide by analyzing data from the FAERS database and social media. Additionally, we aim to compare the adverse drug reaction (ADR) signals between the oral and subcutaneous administration routes of semaglutide.MethodsWe collected semaglutide-related reports from the FAERS database spanning Q1 2018 to Q2 2023, and patient reviews on WebMD and AskaPatient up to 20 July 2023. Following data extraction and cleansing, we conducted descriptive analyses of demographic characteristics. Subsequently, we calculated adverse drug reaction (ADR) signals using the reporting odds ratio (ROR).ResultsWe identified 19,289 and 422 semaglutide-related adverse drug events (ADEs) reported in the FAERS database and online patient reviews, respectively. Gastrointestinal disorders emerged as the most commonly reported System Organ Class (SOC) in both datasets. Predominant Preferred Terms (PTs) included nausea, vomiting, and diarrhea. Serious outcomes constituted 3.07% and 2.25% of all cases for oral and subcutaneous semaglutide, respectively. At the SOC level, gastrointestinal disorders accounted for 30.19% of total ADEs in oral semaglutide, slightly surpassing the 27.76% in subcutaneous semaglutide. The median onset for gastrointestinal PTs was 4 days in both oral (Q1: 1, Q3: 32) and subcutaneous (Q1: 1, Q3: 35) formulations. Noteworthy, new serious adverse event (AE) signals were identified, including hemorrhagic diarrhea (ROR: 3.69), hepatic pain (ROR: 4.20), abnormal hormone levels (ROR: 6.51), and pancreatic failure (ROR: 36.34) in subcutaneous semaglutide, and Dupuytren’s contracture (ROR: 46.85) in oral semaglutide.ConclusionOur study delineates the safety profile of semaglutide using data from the FAERS database and social media. And identified novel ADR signals specific to oral and subcutaneous forms of semaglutide.

Adverse drug reaction signals mining comparison of amiodarone and dronedarone: a pharmacovigilance study based on FAERS

BackgroundAmiodarone and dronedarone are both class III antiarrhythmic medications used to treat arrhythmias. The objective of this study was to enhance the current understanding of adverse drug reaction (ADR) associated with amiodarone and dronedarone by employing data mining methods on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), and providing a reference for safe and reasonable clinical use.MethodsThe ADR records were selected by searching the FAERS database from 2011 Q3 to 2023 Q3. The disproportionality analysis algorithms, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), were used to detect signals of amiodarone-related and dronedarone-related ADRs. The ADR profiles of amiodarone and dronedarone categorized by organ toxicity were compared through the Z-test and the Fisher exact test.Results9,295 reports specifically mentioned the use of amiodarone and 2,485 reports mentioned the use of dronedarone among 9,972,109 reports, with the majority of ADRs occurring in males over 60 years old. The United States was responsible for the highest proportion of reported ADRs. Significant system organ classes (SOC) for both included Cardiac disorders, Respiratory, thoracic and mediastinal disorders, and Investigations, etc. At the preferred terms (PTs) level, the more frequent ADR signals for amiodarone were drug interaction (n = 856), hyperthyroidism (n = 758), and dyspnoea (n = 607), while dronedarone were atrial fibrillation (n = 371), dyspnoea (n = 204), and blood creatinine increased (n = 123). Notably, unexpected ADRs, including electrocardiogram T wave alternans (n = 16; EBGM05 = 231.27), accessory cardiac pathway (n = 11; EBGM05 = 140), thyroiditis (n = 178; EBGM05 = 125.91) for amiodarone, and cardiac ablation (n = 11; EBGM05 = 31.86), cardioversion (n = 7; EBGM05 = 22.69), and dysphagia (n = 47; EBGM05 = 3.6) for dronedarone, were uncovered in the instructions. The analysis also revealed significant differences in the ADR profiles of amiodarone and dronedarone, with dronedarone showing higher proportions of cardiac toxicity but lower thyroid toxicity compared to amiodarone.ConclusionThese findings underscore the significance of vigilantly monitoring and comprehending the potential risks linked to the use of amiodarone and dronedarone. New ADRs discovered and clear ADR profiles of amiodarone and dronedarone enhance a thorough understanding of these drugs, which is essential for clinicians to ensure safe use of amiodarone and dronedarone.

Serious adverse events following immunization with COVID-19 vaccines in Lebanon: a retrospective analysis of the National Pharmacovigilance Database

Continuous surveillance and risk assessment of inactivated Coronavirus Disease 2019 (COVID-19)) vaccines provide an understanding of their safety profiles, guide vaccination strategy and public health policy. This study aims to analyze the characteristics and prevalence of officially reported serious adverse events following immunization (AEFIs) with inactivated COVID-19 vaccines by System Organ Class (SOC), age, and sex.To achieve this aim, a retrospective observational study was conducted between February 14th, 2021, and June 30th, 2022. Reported AEFIs were evaluated for data completeness. Causality assessment adhered to the World Health Organization guidelines.Findings revealed that the AEFIs occurrence did not significantly differ between vaccines used (ChAdOx1 vs. BNT162b2), sex, or SOC. The most prevalent AEFIs were vascular disorders (37%), followed by cardiac (25%) and nervous system disorders (14%). The adverse events were predominantly reported post-vaccination with the BNT162b2 vaccine, mainly after the first dose. The mean age was highest for miscellaneous disorders (70 ± 21.7 years) and the lowest for nervous system (46 ± 22 years) and immune system disorders (45 ± 19 years). Age differences were statistically different for vascular disorders (p = 0.003) and immune system disorders (p = 0.012).In conclusion, ongoing surveillance and risk assessment of the vaccine’s safety profile is crucial for detecting potential safety signals. Active surveillance of the reported serious AEFIs is highly needed to support evidence-based vaccination strategies and maintain public confidence in immunization programs,

A Retrospective Observational Study of Adverse Drug Reactions (ADR) Reported to ADR Monitoring Centre from 2010 to 2020.

Adverse Drug Reactions (ADR) are one of the essential causes of hospital admissions and pose a significant clinical and economic burden on the healthcare system. The Adverse Drug Reaction Monitoring Centre (AMC) in JIPMER functioning under the Pharmacovigilance Programme of India (PvPI) plays a vital role in ensuring medication safety by routinely detecting and monitoring ADRs. Hence, this study aimed to assess the characteristics of ADR reported from 2010 to 2020 in AMC JIPMER and to detect signals, if any. To study the characteristics of Adverse Drug Reactions (ADR) reported to a regional ADR monitoring center from 2010 to 2020 and to detect signals of disproportionate reporting (SDRs) if any from the reported ADRs. A total of 6007 ADR reports with a single suspect drug were included for analysis from 2010 to 2020. The characteristics of these reports, including patient's age and gender, Number and percentage of ADRs, the causality of ADR using WHO UMC (World Health Organization-Uppsala Monitoring Scale), the seriousness of the ADR, and outcome were collected from the ADR reports. MedDRA (Medical Dictionary for Regulatory Activities) Preferred Terms (PT) were used to classify adverse drug reactions. Causality analysis using the Naranjo Algorithm and Preventability using Modified Schumock and Thornton criteria were performed for the ADRs. The number and percentage of severe ADRs were analyzed. The System Organ class of all the ADRs was enumerated. ADRs not mentioned in the US FDA (United States Food and Drug Administration) product label (unlabelled reactions) were documented. Unlabeled reactions with ≥3 ADR reports were included for signal detection by disproportionality analysis. Antineoplastic drugs, followed by antimicrobials, anticonvulsants, Anti snake venom, and NSAID were the most common drugs implicated in ADRs. Skin and subcutaneous tissue disorders were the most common System Organ Class (SOC) involved in the ADRs. Among the 6007 reports, 19.2% were serious ADRs. Most of the ADR reports were of possible causality followed by probable and certain as per WHO UMC and Naranjo causality scales. Only ten ADRs were preventable and one reaction (Tamoxifen-induced neuropathy) was eligible for signal detection. Disproportionality analysis using a 2x2 contingency table showed insignificant signal detection using the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR). Analysis of ADRs from an ADR Monitoring center functioning in a tertiary care hospital shows antineoplastic drugs to be the most common drugs associated with adverse drug reactions, with rash being the most common adverse effect. The majority of the ADRs were not preventable. No Signals of Disproportionate Reporting (SDR) were detected in our study.

Adverse events associated with herbal medicine products reported in the Korea Adverse Event Reporting System from 2012 to 2021

IntroductionSystematic collection of diverse adverse events during herbal medicine administration is crucial. The Korea Adverse Event Reporting System (KAERS) compiles spontaneously reported adverse event data for medicinal products including herbal medicines. This study focused on extracting and analyzing adverse event data specifically related to herbal medicine products from the KAERS database.MethodsIndividual case safety reports (ICSRs) encompassing 84 types of herbal medicine products, identified by item codes from 2012 to 2021, were extracted from the KAERS database. Descriptive statistics were employed to analyze the characteristics of the extracted reports, and adverse event information was systematically categorized and analyzed based on the MedDRA System Organ Class and preferred term classification.ResultsIn total, 1,054 ICSRs were extracted, with some documenting multiple adverse events in a single ICSR, resulting in 1,629 extracted adverse events. When categorized by the MedDRA System Organ Class, gastrointestinal disorders were the most prevalent (28.7%), followed by skin and subcutaneous tissue disorders (20.1%). Based on the preferred terms, the most frequently reported adverse events were diarrhea (5.8%), urticaria (5.3%), pruritus (4.7%), rash (4.4%), and abdominal discomfort (4.2%). The most frequently reported herbal medicines were Bangpungtongseong-san (297 cases), Kyeongok-go (144 cases), and Eunkyo-san (108 cases).ConclusionSpontaneously reported adverse events associated with herbal medicine products were systematically documented using the KAERS database. This study, which focused on voluntarily reported adverse reactions, underscores the need for additional research to estimate the incidence rate of adverse events and assess causality.

Mining and analysis of adverse event signals for alendronate based on the real-world data of FDA adverse event reporting system database

ABSTRACT Objective Our study aims to assess alendronate-related adverse events (AEs) from the US FDA adverse event reporting system database. Methods The AE data associated with alendronate between the first quarter of 2004 and the first quarter of 2024 were selected. Various signal quantification methods, including the ROR, PRR, BCPNN, and EBGM, were applied for analysis. Results In 34,943 reports where alendronate was the primary suspected drug for the AE, 24 affected system organ classes and 1046 significant preferred terms were identified in this study. Several significant AEs beyond drug instructions with strong signals were determined, including low turnover osteopathy, fracture delayed union, fracture nonunion, loss of anatomical alignment after fracture reduction, fracture malunion, periprosthetic fracture, carotid bruit, oral fibroma, traumatic occlusion, and phlebolith. The median time to onset of alendronate-related AEs was 306 days (interquartile range [IQR] 12–1,461 days), and the majority of cases occurred 2 years later (18.80%) and within 30 days (14.49%). Conclusions The current study detected multiple potential new AE signals for alendronate, and more clinical researches are required to further validate our results and clarify their associations.

A real-world adverse events study of rimegepant from the FAERS database

ABSTRACT Background The primary objective of this research is to conduct an exhaustive evaluation of rimegepant with the Food and Drug Administration Adverse Event Reporting System (FAERS) repository. Research design and methods This study downloaded the reporting files related to rimegepant from the second quarter of 2020 to the first quarter of 2024. Disproportionality analysis was utilized to explore the relationship between rimegepant and adverse drug events (ADEs). Results This study analyzed 6659 ADE reports associated with rimegepant as the primary suspected (PS) drug. In the disproportionate analysis of system organ classes (SOCs), the significant signal for rimegepant was general disorders and administration site conditions. On the preferred terms level, 35 ADEs were identified following the exclusion. The top 5 ADEs with high signal strengths were medication overuse headache, nasal edema, tension headache, performance status decreased, and motion sickness. The most frequent ADEs were nausea, feeling abnormal, abdominal pain upper, somnolence, and hypersensitivity. In addition, we need to pay attention to the ADEs not mentioned in the instruction and clinically significant: vertigo, hyperacusis, somnolence, Raynaud’s phenomenon, motion sickness, panic attack, and fear. Conclusions This study highlights previously unrecognized safety concerns associated with the use of rimegepant. These novel safety aspects suggest that while these treatments can be effective, additional risks may need further exploration.

Real-world safety profile of zanubrutinib: a disproportionality analysis based on the FAERS database

ObjectiveZanubrutinib is a second-generation Bruton’s tyrosine kinase inhibitor that has been approved for the treatment of several B cell malignancies. The aim of this study was to evaluate adverse events...

Post-marketing safety concerns with rimegepant based on a pharmacovigilance study

PurposeThis study aimed to comprehensively assess the safety of rimegepant administration in real-world clinical settings.MethodsData from the Food and Drug Administration Adverse Event Reporting System (FAERS) spanning the second quarter of 2020 through the first quarter of 2023 were retrospectively analyzed in this pharmacovigilance investigation. This study focuses on employing subgroup analysis to monitor rimegepant drug safety. Descriptive analysis was employed to examine clinical characteristics and concomitant medication of adverse event reports associated with rimegepant, including report season, reporter country, sex, age, weight, dose, and frequency, onset time, et al. Correlation analysis, including techniques such as violin plots, was utilized to explore relationships between clinical characteristics in greater detail. Additionally, four disproportionality analysis methods were applied to assess adverse event signals associated with rimegepant.ResultsA total of 5,416,969 adverse event reports extracted from the FAERS database, 10, 194 adverse events were identified as the “primary suspect” (PS) drug attributed to rimegepant. Rimegepant-associated adverse events involved 27 System Organ Classes (SOCs), and the significant SOC meeting all four detection criteria was “general disorders and administration site conditions” (SOC: 10018065). Additionally, new significant adverse events were discovered, including “vomiting projectile” (PT: 10047708), “eructation” (PT: 10015137), “motion sickness” (PT: 10027990), “feeling drunk” (PT: 10016330), “reaction to food additive” (PT: 10037977), etc. Descriptive analysis indicated that the majority of reporters were consumers (88.1%), with most reports involving female patients. Significant differences were observed between female and male patients across age categories, and the concomitant use of rimegepant with other medications was complex.ConclusionThis study has preliminarily identified potential new adverse events associated with rimegepant, such as those involving the gastrointestinal system, nervous system, and immune system, which warrant further research to determine their exact mechanisms and risk factors. Additionally, significant differences in rimegepant-related adverse events were observed across different age groups and sexes, and the complexity of concomitant medication use should be given special attention in clinical practice.

A real-world pharmacovigilance study using disproportionality analysis of United States Food and Drug Administration Adverse Event Reporting System events for vinca alkaloids: comparing vinorelbine and Vincristine

ABSTRACT Background Vinca alkaloids are widely used in cancer treatment for their ability to target microtubule dynamics. While their efficacy in treating certain cancers is well-established, the full spectrum of their adverse event profiles remains an area of ongoing research. Methods We analyzed AEs related to vinorelbine and vincristine using a retrospective case/non-case approach with data from the FDA Adverse Event Reporting System (FAERS). We applied various algorithms to detect AE signals: the reporting odds ratio (ROR) and proportional reporting ratio (PRR) measured disproportionality and association strength; the Bayesian confidence propagation neural network (BCPNN) calculated the Information Component (IC) for associations against background rates; and the multi-item gamma Poisson shrinker (MGPS) yielded empirical Bayes geometric mean (EBGM) values, accounting for reporting variability. Results Both medications significantly involve the blood and lymphatic systems, with vinorelbine reporting 401 cases in this System Organ Class (SOC), exhibiting a ROR of 17.4, PRR of 12.4, IC of 3.63, and EBGM of 12.38. An intersection analysis of Preferred Terms (PTs) has uncovered previously unreported AEs shared by both drugs, including posterior reversible encephalopathy syndrome and inappropriate antidiuretic hormone secretion. Conclusions This analysis highlights the need for ongoing research of the risks associated with vinorelbine and vincristine.

Post-marketing safety of tralokinumab: a real-world pharmacovigilance study based on the FDA adverse event reporting system

ABSTRACT Background Tralokinumab is a fully human IgG4 monoclonal antibody targeting IL-13, used for treating atopic dermatitis. This study analyzed tralokinumab-related adverse drug events by mining the Food and Drug Administration Adverse Event Reporting System (FAERS) database to provide a safety reference for clinical application. Methods Adverse drug event reports from Q1 2022 to Q2 2024 were extracted from the FAERS database. After standardizing the data, various signal detection methods were used for analysis, including ROR, PRR, BCPNN, and MGPS. Results A total of 1,820 reports of adverse events (AEs) with tralokinumab as the primary suspected drug were identified. 70 preferred terms (PTs) met the criteria across four signal detection methods, involving 11 system organ classes (SOCs). These included known adverse reactions like conjunctivitis and injection site reactions, and signals not previously reported in clinical trials, such as eye pruritus, dry eye, eye swelling, pneumonia pneumococcal, and cutaneous T-cell lymphoma. Most AEs occurred within one month of initiating tralokinumab treatment. Conclusions Based on the FAERS database, this study comprehensively and systematically analyzed AE signals in tralokinumab treatment. The results enhance the understanding of tralokinumab’s safety and serve as valuable references for reducing the risk of adverse reactions during clinical use.

Adverse Event Assessment of Upadacitinib: A Pharmacovigilance Study Based on the FAERS Database.

Upadacitinib, a Janus kinase (JAK) inhibitor, has been approved by the FDA to treat various autoimmune conditions. This study assessed its adverse events by analyzing reports from the FDA Adverse Event Reporting System (FAERS). FAERS data from Q3 2019 to Q4 2023 were extracted, and disproportionality analyses were conducted using four statistical measures, reporting odds ratio, proportionate reporting ratio, Bayesian confidence propagation neural network, and empirical Bayesian geometric mean. A total of 6 879 398 adverse event reports were collected, with 37 700 reports identifying upadacitinib as the "primary suspected." These reports involved 24 system organ classes and 246 preferred terms that met the criteria across all four algorithms. The distribution of adverse events was assessed separately for female and male patients. Further analysis of the top 25 preferred terms revealed that, although the system organ classes were similar between sexes, the specific adverse events differed. The adverse events were analyzed by gender, showing musculoskeletal and skin disorders were prevalent and severe in male patients, while musculoskeletal issues, infections, and abnormal laboratory tests were common in female patients. Unexpected events like trigger finger, biliary sepsis, and serious events such as oral neoplasm were also identified. This study provides real-world evidence for the safety evaluation of upadacitinib and underscores the need to monitor sex-specific adverse events. Future prospective studies are necessary to confirm these pharmacovigilance findings.

A Real-World Study on Adverse Reactions of Belimumab Based on the FDA Adverse Event Reporting System Database.

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.

Safety assessment of Tafamidis: a real-world pharmacovigilance study of FDA adverse event reporting system (FAERS) events

ObjectiveTafamidis-associated adverse events (AEs) were investigated retrospectively by data mining the US Food and Drug Administration Adverse Event Reporting System (FAERS) to inform clinical safety.MethodsData were gathered from the FAERS database, which spans the second quarter of 2019 to the fourth quarter of 2023. A total number of 8532 reports of Tafamidis-related adverse events were detected after evaluating 8,432,351 data. Disproportionality analyses were used to quantify the signal and assess the significance of Tafamidis-associated AEs using four algorithms, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the multi-item gamma Poisson shrinker (MGPS) and the Bayesian confidence propagation neural network (BCPNN).ResultsAmong the 8532 reports of AEs with Tafamidis as the primary suspected drug, Tafamidis-induced AEs were identified as occurring in 27 system organ classes (SOC). A total of 207 Tafamidis-induced AEs were detected which simultaneously complied with the four algorithms. Our analysis also identified new adverse reactions including Hypoacusis, Deafness, and Essential hypertension. The median onset of adverse reactions associated with Tafamidis was 180 days (interquartile range [IQR] 51–419 days).ConclusionTafamidis is a drug that has shown favorable safety and tolerability results in clinical trials. However, a number of adverse reactions associated with Tafamidis have been identified through analysis of the FAERS database. In clinical applications, it is recommended to closely monitor patients’ hearing while using Tafamidis. In addition, it is hoped that further experimental and clinical studies will be conducted in the future to understand the mechanism of occurrence between Tafamidis and adverse reactions such as primary hypertension, hyperlipidemia, and height reduction.

Adverse reactions of immune checkpoint inhibitors combined with Proton pump inhibitors: a pharmacovigilance analysis of drug-drug interactions

BackgroundCombining immune checkpoint and proton pump inhibitors is widely used in cancer treatment. However, the drug-drug interactions of these substances are currently unknown. This study aimed to explore drug-drug interactions associated with concomitant immune checkpoint and proton pump inhibitors.MethodsData were obtained from the US Food and Drug Administration Adverse Event Reporting System from 2014 to 2023. Disproportionality analysis was used for data mining by calculating the reporting odds ratios (RORs) with 95% confidence intervals (95%Cls). The adjusted RORs (RORadj) were then analysed using logistic regression analysis, considering age, sex, and reporting year. Drug-drug interactions occur when a combination treatment enhances the frequency of an event. Further confirmation of the robustness of the findings was achieved using additive and multiplicative models, which are the two statistical methodologies for signal detection of DDIs using spontaneous reporting system.ResultsThe total number of reports on immune checkpoint combined with proton pump inhibitors was 4,276. Median patient age was 66 years (interquartile range [IQR]: 60–74 years). Significant interaction signals were observed for congenital, familial and genetic disorders (RORadj = 2.66, 95%CI, 1.38–5.14, additive models = 0.7322, multiplicative models = 3.5142), hepatobiliary disorders (RORcrude = 6.64, 95%CI, 5.82–7.58, RORadj = 7.10, 95%CI, 6.16–8.18, additive models = 2.0525, multiplicative models = 1.1622), metabolism and nutrition disorders (RORcrude = 3.27, 95%CI, 2.90–3.69, RORadj = 2.66, 95%CI, 2.30–3.08, additive models = 0.6194), and skin and subcutaneous tissue disorders (RORcrude = 1.41, 95%CI, 1.26–1.58, RORadj = 1.53, 95%CI, 1.34–1.75, additive models = 0.6927, multiplicative models = 5.3599). Subset data analysis showed that programmed death-1 combined with proton pump inhibitors was associated with congenital, familial, and genetic disorders; hepatobiliary disorders; and skin and subcutaneous tissue disorders. Programmed death ligand-1 combined with proton pump inhibitors was associated with adverse reactions of metabolism and nutrition disorders. Cytotoxic T-lymphocyte antigen-4 combined with proton pump inhibitors was associated with congenital, familial, and genetic disorders, and skin and subcutaneous tissue disorders.ConclusionsBased on real-world data, four Standardized MedDRA Query System Organ Class toxicities were identified as drug-drug interactions associated with combining immune checkpoint and proton pump inhibitors. Clinicians should be cautious when administering these drugs concomitantly. Preclinical trials and robust clinical studies are required to explore the mechanisms and relationships underlying interactions, thus improving understanding of drug-drug interactions associated with this combination therapy.

Mining and evaluation of adverse event signals for capmatinib based on the FAERS database.

To conduct a comprehensive data analysis based on the FDA's Adverse Event Reporting System (FAERS) to mine possible adverse event (AE) signals of Capmatinib, providing valuable references for its clinical application. Capmatinib was the primary suspected drug in the search of FAERS database from the second quarter of 2020 to the fourth quarter of 2023. Data processing, screening, and classification were performed using methods such as the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). A total of 1,991 AE reports directly related to Capmatinib were screened, identifying 269 Preferred Terms (PTs) involving 26 System Organ Classes (SOCs). Besides the AEs recorded in the drug label (such as edema, nausea, fatigue, and dyspnea), the study unearthed other high-risk AEs not listed in the label, including Renal and urinary disorders, Vocal cord paralysis, and Ear and labyrinth disorders. Among these, renal and urinary disorders, and ear and labyrinth disorders had a higher frequency and intensity of signals, suggesting that their mechanisms of occurrence could be a future research direction. This study uncovered new potential AEs of Capmatinib based on the FAERS database, providing reference for its safe clinical use. Special attention should be given to the occurrence of ear and labyrinth disorders and renal and urinary disorders, primarily presenting as pseudo-acute kidney injury, during treatment.

A real-world disproportionality analysis of baloxavir marboxil: post-marketing pharmacovigilance data

ABSTRACT Objective Baloxavir marboxil (hereafter referred to as baloxavir) is the only cap-dependent endonuclease inhiabitor approved for the treatment and prevention of influenza. However, as a new drug marketed in 2018, the long-term safety of baloxavir in large sample population was unclear. This study aims to evaluate baloxavir-associated adverse events (AEs) through data mining of the international pharmacovigilance database of US FDA Adverse Event Reporting System (FAERS). Methods Disproportionality analysis was conducted to assess the association between baloxavir and its AEs. Data were collected from FAERS from March 2018 to June 2023. After standardizing the data, signal quantification techniques including ROR, PRR, BCPNN and MGPS were used for analysis. Results A total of 49 significant baloxavir-related preferred terms (PTs) in 20 system organ classes (SOCs) were identified in our data analysis. Compared to baloxavir’s FDA label, some new PTs emerged, with the top 10 being pneumonia, loss of consciousness, rhabdomyolysis, seizure, altered state of consciousness, hepatic function abnormal, delirium, depressed level of consciousness, encephalopathy and cardio-respiratory arrest. Conclusion In clinical application of baloxavir, attention should be paid to the new AE signals in addition to the those recorded in the labels, so as to ensure the safety of the patients.