Food And Drug Administration Adverse Event Reporting System Database Research Articles

Post-marketing safety concerns with luspatercept: a disproportionality analysis of the FDA adverse event reporting system.

Luspatercept, approved for treating beta thalassemia, myelodysplastic syndromes (MDS) associated anemia, and MDS with ring sideroblasts or myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis associated anemia, has uncertain long-term safety in large populations. This study analyzed adverse events (AEs) linked to luspatercept using data from the FDA Adverse Event Reporting System (FAERS) with data mining techniques. We collected and analyzed luspatercept-related reports from the FAERS database from the first quarter of 2022 through the first quarter of 2024. Disproportionality analysis was used in data mining to quantify luspatercept-related AE signals. A total of 46 AE signals were detected in 13 SOCs (system organ classes). In addition to the AEs identified during the clinical trial stage, this study also identified some unexpected and important AEs, such as product preparation error, prescribed overdose, product preparation issue, prescribed underdose, and acute hepatitis. Our study provides a comprehensive description of the post-marketing safety of luspatercept and identifies new potential AEs. Healthcare workers must be vigilant in avoiding product preparation errors, an adverse event that highlights the need for enhanced training and the participation of chemists in assessing medication utilization scenarios.

Associations of acute kidney injury with oral anticoagulants: a disproportionality analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) database

ABSTRACT Objective The FDA Adverse Event Reporting System (FAERS) was used to evaluate the associations between oral anticoagulants (OACs) and acute kidney injury (AKI). Methods Disproportionality analysis was applied to data in the FAERS database from January 2004 to December 2023 to detect adverse events (AEs) for various OACs. The adjusted reporting odds ratios (RORs) calculated using multiple logistic regression were used to explore the risk factors for OACs-associated AKI. Results The crude RORs for the associations of AKI with warfarin, rivaroxaban, dabigatran, apixaban, and edoxaban were 1.35, 2.14, 2.98, 1.33, and 3.56, respectively. The risk of OACs-associated AKI was affected by age and sex, being higher in those aged 65 years and males. The adjusted RORs for rivaroxaban, dabigatran, apixaban, and edoxaban were 1.26, 1.67, 0.65, and 2.06, respectively.Nearly 50% of AKI cases occurred within the first 2 months, and each OAC was of the early-failure type. Hospitalization and mortality rates for AKI patients after OACs were 45.53% and 22.98%, respectively. Conclusions The study revealed a strong association between AKI and OACs, emphasizing the need for regular renal function monitoring , especially in elderly male patients. Further in-depth research is needed to confirm these exploratory findings.

Analysis of ADR reports of cetuximab based on the FDA adverse event reporting system database

This study aims to monitor and identify adverse events (AEs) associated with cetuximab, a drug used to treat various late-stage (metastatic) tumors, to improve patient safety and guide drug use. This study retrospectively analyzed the cases reported in the FDA adverse event reporting system (FAERS) related to the application of cetuximab from 2013 Q1 to 2022 Q4. Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the empirical Bayesian geometric mean (EBGM) algorithms, were employed to quantify the signals of cetuximab-associated AEs. A total of 8364225 reports were contained in the FAERS database, of which 5186 reports of cetuximab were identified as ‘primary suspected (PS)’ AEs. The application of cetuximab resulted in AEs in 22 system organ classes (SOCs), which preserved 176 significant disproportionality preferred terms (PTs) through the computation of four algorithms. The main SOCs (Skin and subcutaneous tissue disorders, investigations, metabolism and nutrition disorders, and blood and lymphatic system disorders) accounted for 58.63%. Some AEs were not on the drug label: speech disorder, intervertebral discitis, glomerulonephritis rapidly progressive and disseminated intravascular coagulation. This study identified new signals of adverse drug reactions (ADRs) other than those mentioned in the specification associated with cetuximab, providing valuable insights into the relationship between ADRs and cetuximab use. The findings highlight the importance of continuous surveillance to detect and manage AEs effectively, ultimately improving patient safety during treatment with cetuximab.

Real-world safety evaluation of brivaracetam: insights from the US FDA Adverse Event Reporting System

ABSTRACT Background Brivaracetam (BRV) is a novel drug for the treatment of epilepsy. This study aimed to detect and characterize adverse events (AEs) associated with BRV from the first quarter of 2016 to the second quarter of 2024 using the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Research design and methods We utilized disproportionality analysis methods, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS), to assess the associations between reported AEs and BRV usage in the FAERS data. Results A total of 1,781 adverse event reports were analyzed, with Brivaracetam as the primary suspected drug. We identified 13 positive system organ classes (SOCs) and 78 positive preferred term signals (PTs), with a particular focus on nervous system disorders, psychiatric disorders, and injury, poisoning, and procedural complications. Exposures related to injury, poisoning, and procedural complications during pregnancy and lactation showed positive signals, including exposure before pregnancy, during breastfeeding, and during pregnancy. These exposures warrant significant attention. Conclusions Based on the FAERS database, we conducted a comprehensive analysis of AEs associated with BRV. This study aims to provide guidance for the clinical application of BRV in epilepsy treatment, thereby improving its safety.

Analysis of immune related adverse events of pembrolizumab using FAERS database

Objective: This study aims to investigate the risk signals associated with pembrolizumab and provide references for its safe and rational clinical use. Methods: Data on adverse events (AEs) related to pembrolizumab, reported from July 2014 to September 2023, were extracted from the US FDA Adverse Event Reporting System (FAERS) database. Data mining was conducted using the Proportional Reporting Ratio (PRR) method. AEs were classified and analyzed according to the System Organ Class (SOC) and Preferred Term (PT) from the Medical Dictionary for Regulatory Activities (version 26.1). Results: A total of 37,511 AE reports related to pembrolizumab were identified, involving 5,259 PTs and 22 SOCs. Using the PRR method, 931 positive signals were detected. The top 10 risk signals for pembrolizumab were all immune-related adverse events (irAEs) and important medical events (IMEs). The five PTs with the highest signal intensity were immune-mediated hypothyroidism, immune-mediated renal disorder, immune-mediated hepatic disorder, immune-mediated gastritis, and immune-mediated hyperthyroidism. The leading SOCs involved in AE reports were general disorders and administration site conditions (8,184; 14.11%), investigations (5,333; 9.19%), gastrointestinal disorders (4,962; 8.55%), respiratory, thoracic, and mediastinal disorders (4,937; 7.57%), and injury, poisoning, and procedural complications (3,611; 6.22%). The median time to onset of AE was 25 days (IQR 6-85 days), with the Weibull distribution test indicating an early failure-type curve. Gender and age analysis revealed that women were more likely to develop hypertension, alopecia, headache, hypothyroidism, and palmar-plantar erythrodysaesthesia syndrome, whereas men were more likely to develop interstitial lung disease, renal impairment, and death. Additionally, neutropenia was more prevalent in patients under 65 years of age, while interstitial lung disease and renal impairment were more common in patients aged 65 and above. Conclusion: Significant age- and gender-related differences were observed in AE signals with pembrolizumab, particularly for irAEs. Clinical attention should be directed towards the potential occurrence of irAEs at the initial stages of drug administration, with appropriate measures implemented as necessary.

Cyclin-dependent kinase 4/6 inhibitor-associated pulmonary toxicity: a disproportionality analysis from 2015 to 2023 based on the FAERS database

ABSTRACT Objectives This study aimed to describe the pulmonary toxicity of cyclin-dependent kinase 4/6 inhibitors (CDK 4/6 inhibitors) (palbociclib, ribociclib, and abemaciclib) in patients being treated for breast cancer using the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Research design and Methods Disproportionality analysis was performed to assess pulmonary toxicity associated with CDK 4/6 inhibitors. Clinical characteristics, onset time, sensitivity analysis, subgroup analyses, drug combinations, comorbidities, and co-reported events were performed. Results Out of 83,505 CDK 4/6 inhibitor-related adverse events (AEs) documented in the FAERS database during the study period, 437 cases of pneumonitis, 555 cases of pulmonary edema, and 181 cases of pulmonary thrombosis related to CDK 4/6 inhibitors were analyzed. Pneumonitis and pulmonary thrombosis had the strongest signal strength in abemaciclib, pulmonary edema had the strongest signal strength in ribociclib. The median latency for pneumonitis, pulmonary edema, and pulmonary thrombosis was 66-173.5 days 27-131 days, and 68-279 days), respectively. Pulmonary toxicity is statistically significant disproportionality in females as well as in patients over 60 years old. Conclusion Abemaciclib was most strongly associated with pneumonitis and pulmonary thrombosis. Ribociclib was most strongly associated with pulmonary edema. The correlation with pulmonary toxicity was, in descending order, abemaciclib, ribociclib, and palbociclib.

Vancomycin Drug Reaction with Eosinophilia and Systemic Symptoms: Meta-Analysis and Pharmacovigilance Study

Background: Drug reaction with eosinophilia and systemic symptoms is a severe cutaneous reaction with a high mortality rate. It is challenging to diagnose due to its similar presentation to infectious disease syndromes, variation with the culprit drug, and lack of awareness. Methods: We searched PubMed, and Embase, for RegiSCAR-scored observational studies, the FDA Adverse Events Reporting System (FAERS) for adverse event reports, and the Allele Frequency Net Database (AFND) for HLA allele frequency. In our meta-analysis, we employed a random effects model to subgroup patients by ethnicity to determine the proportion of DRESS cases compared with various associated medications. Additionally, we identified a correlation between the proportion of cases and the presence of the HLA*A-32:01allele, which is suspected to predispose individuals to DRESS. Results: Twenty-one studies on 1949 DRESS cases in vancomycin and 2558 antimicrobial DRESS reports in the FAERS database were analyzed. Meta-analysis showed a 27% incidence of vancomycin-DRESS, with Caucasians having the highest proportion at 36%. The median latency for symptom onset was 21 days, with no female predisposition. The proportional incidence of vancomycin-DRESS did not correlate with the HLA-A*32:01 allele. The adjusted ROR for vancomycin was 2.40 compared to other antimicrobials, and the risk increased by 77% with concurrent antimicrobials. Piperacillin/tazobactam had a similar DRESS reporting risk at 0.95 (95%CI: 0.88–1.02). Conclusion: Vancomycin significantly contributes to the incidence of DRESS and is more closely related to ethnicity than to allele frequency, indicating that the HLA-A*32:01 allele may not be directly involved. Furthermore, the use of other antimicrobials can influence the reaction, underscoring the need to minimize antimicrobial use for better coverage.

A real-world pharmacovigilance analysis for Demethylation drug: findings from the FDA adverse event reporting database.

The real-world safety profiles of the demethylating agents Azacitidine and Decitabine remain inadequately characterized despite their widespread clinical use. Both drugs are extensively employed for the treatment of hematologic malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). This study aims to evaluate their adverse event (AE) profiles by leveraging data from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. All adverse drug event (ADE) data related to Azacitidine and Decitabine were collected from the FAERS database from its inception through the second quarter of 2024 (Q2). After standardizing the data, four disproportionality methods were applied to evaluate the association between Azacitidine, Decitabine, and ADEs. The Weibull shape parameter (WSP) was used to analyze the time-to-onset curves. Among the 15,538 ADEs where Azacitidine was the primary suspect drug, a total of 439 preferred terms (PTs) and two system organ classes (SOCs) showed significant disproportionality across all four algorithms. These SOCs included INFECTIONS AND INFESTATIONS (n=7328, ROR 3.78) and BLOOD AND LYMPHATIC SYSTEM DISORDERS (n=5613, ROR 8.92). Compared with the Azacitidine label, 52 previously unreported ADEs were identified at the PT level. Among the 3,064 ADEs where Decitabine was the primary suspect drug, a total of 200 PTs and two SOCs exhibited significant disproportionality across all four algorithms. These SOCs included BLOOD AND LYMPHATIC SYSTEM DISORDERS (n=1284, ROR 6.53) and SURGICAL AND MEDICAL PROCEDURES (n=571, ROR 3.41). Compared with the Decitabine label, 29 previously unreported ADEs were identified at the PT level. Furthermore, the Bayesian Confidence Propagation Neural Network (BCPNN) algorithm revealed that the highest IC025 values for both Azacitidine and Decitabine were concentrated in SOCs related to benign, malignant, and unspecified tumors. In summary, using the FAERS database, we compared the real-world safety profiles of two demethylating agents, Azacitidine and Decitabine. The results indicate that adverse drug reactions (ADRs) related to these two agents are concentrated in the hematologic, respiratory, circulatory, and digestive systems, as well as in neoplasms of unspecified nature, warranting close clinical attention.

Data mining and safety analysis of voriconazole in patients with a hematological malignant tumor based on the FAERS database: differences between children and adults

ObjectiveVoriconazole is a broad-spectrum antifungal agent. It is used widely for the prevention and treatment of invasive fungal infections in patients with a hematological malignancy, but studies on its safety in this population are scarce. We assessed the adverse drug events (ADEs) of voriconazole in this population based on the US Food and Drug Administration Adverse Event Reporting System (FAERS) database to improve understanding of the safety of voriconazole.Research design and methodsADE reports for patients with a hematological malignant tumor using voriconazole between the first quarter of 2004 to the first quarter of 2024 were retrieved. Then, they were classified using the preferred terminology (PT) and system organ category (SOC) in the Medical Dictionary for Regulatory Activities. Data mining was done using reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS).ResultsA total of 605 ADEs were included: 116 (19.17%) in children and 489 (80.83%) in adults. The types of SOC involved in children and adults were 22 and 24, respectively. The only positive SOC signal that satisfied all four algorithms simultaneously in children was “psychiatric disorders”, whereas in adults they were “endocrine disorders” and “hepatobiliary disorders”. At the PT level, the types involved in children and adults were 28 and 74, respectively. The highest ROR signal intensities were found for “hallucinations, mixed” in children and “toxic optic neuropathy” in adults. The median time of onset of the ADE in children and adults was 11 and 8.5 days, respectively.ConclusionWe used four algorithms (ROR, PRR, BCPNN, MGPS) to mine the signals of voriconazole in patients with a hematological malignant tumor, and compared the differences between children and adults. This study is important for targeting the monitoring, and could help to improve the safety of voriconazole.

Post-Marketing Safety of Temozolomide: A Pharmacovigilance Study Based on the Food and Drug Administration Adverse Event Reporting System

Introduction: Temozolomide (TMZ) is a widely used chemotherapy agent for the treatment of malignant gliomas and other brain tumors. Despite its established therapeutic benefits, there is an ongoing need to understand better its safety profile, particularly in real-world clinical settings. This study aimed to identify critical adverse drug reactions (ADRs) associated with TMZ by utilizing the FDA Adverse Event Reporting System (FAERS) database, thereby providing valuable safety insights for clinical practice. Methods: We utilized the reported odds ratio, proportional reporting ratio, Bayesian Confidence Propagation Neural Network, and Empirical Bayes Geometric Mean as primary algorithms for disproportionality analysis. Adverse events (AEs) were classified as ADRs only upon meeting the criteria set by all four algorithms. To ensure the accuracy of our results, we meticulously excluded any AEs deemed unrelated to TMZ. Results: From October 2003 to September 2023, a total of 10,502,538 case reports and 9,073 cases explicitly attributed to TMZ were retrieved from the FAERS database. After applying our filters, 116 ADRs, each with a corresponding Preferred Term (PT), were identified across 18 System Organ Classes (SOCs). The identified ADRs associated with TMZ primarily involved bone marrow suppression, hepatotoxicity, and various infections, notably Pneumocystis jirovecii pneumonia. Furthermore, our analysis identified valuable ADRs not listed in the drug label, including congenital, familial, and genetic disorders at the SOC level, as well as unexpected ADRs at the PT level, such as seizures, pulmonary embolism, and sepsis. Conclusion: This real-world pharmacovigilance study has identified significant and previously unreported ADRs associated with TMZ. Further research for validation and resolution is urgently needed to guide the clinical application of TMZ, ensuring the safety and efficacy of its use in treating brain tumors.

A Real-World Data Analysis of Alglucosidase Alfa in the FDA Adverse Event Reporting System (FAERS) Database.

Alglucosidase alfa for injection is used as an enzyme replacement therapy for the treatment of Pompe disease. The safety profile of alglucosidase alfa-associated adverse events requires a comprehensive evaluation. In this study, we aimed to identify drug safety alert signals and investigate the real-world safety of alglucosidase alfa to guide clinical decision making and optimize the risk-benefit balance. The adverse event reports from the first quarter of 2006 to the fourth quarter of 2023 were selected by exploring the Food and Drug Administration Adverse Event Reporting System (FAERS) database. The new and unexpected potential adverse event signals were detected using a disproportionality analysis, including the reporting odds ratio, the proportional reporting ratio, the Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Then, the Medical Dictionary for Regulatory Activities was used to systematically classify the results. After analyzing 16,945,027 adverse event reports, a total of 4326 cases of adverse events related to alglucosidase alfa were identified, spanning 27 system organ classes. A total of 359 preferred terms of adverse events for glucosidase alpha were detected. Pyrexia ranked first, followed by pneumonia, dyspnea, respiratory failure, and disease progression according to occurrence frequency. The top three system organ classes were general disorders and administration-site conditions (n = 2466), respiratory, thoracic, and mediastinal disorders (n = 1749), and infections and infestations (n = 1551). In addition to adverse effects mentioned in the product label, our study also discovered rare but high signal intensity adverse events such as chronic recurrent multifocal osteomyelitis. There are many adverse events associated with the clinical use of alglucosidase alfa, which should be closely monitored in the FAERS database. As the most effective enzyme replacement therapy for Pompe disease, it is crucial to closely monitor these adverse events. Ensuring patient safety while balancing drug effectiveness is particularly important.

Real-world safety of maribavir: a retrospective study based on signal detection in the FDA adverse event reporting system.

Maribavir is a novel antiviral agent targeting cytomegalovirus through inhibition of the UL97 protein kinase, exhibiting a distinct mechanism of action. However, limited data are available on its safety profile post-marketing. This study aimed to evaluate the adverse events (AEs) associated with maribavir using the Food and Drug Administration's Adverse Event Reporting System (FAERS), providing insights to inform clinical practice. We conducted a retrospective analysis of maribavir-related adverse event reports from the FAERS database, spanning the fourth quarter of 2021 to the second quarter of 2024. Signal detection was performed using four statistical methods: the proportional reporting ratio, reporting odds ratio, Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker. A total of 1372 reports associated with maribavir were identified. Seven significant signals emerged at the system organ class level. At the preferred term level, 76 adverse events (AEs) demonstrated positive signals, including novel events such as pleural effusion, hypersomnia, and anosmia, alongside signals related to ear disorders. The majority of AEs were reported within the first month of maribavir use. This study identified several new adverse event signals for maribavir, offering healthcare professionals a deeper understanding of its safety profile, which may guide safer clinical usage.

A retrospective analysis of medications associated with pityriasis rosea reported in the FDA adverse events reporting system

Pityriasis rosea (PR) is an acute exanthematous disease with an uncertain physiopathology, increasingly recognized as potentially drug induced. This study aims to investigate medication triggers associated with PR by analyzing cases reported in the FDA Adverse Event Reporting System (FAERS) database. A retrospective review of 343 PR cases reported in the FAERS database from January 1, 1998, to March 31, 2024, was conducted. Reporting odds ratios (ROR) were calculated to assess associations between PR and specific drug classes, including tumor necrosis factor (TNF) inhibitors and angiotensin-converting enzyme (ACE) inhibitors. Logistic regression analysis evaluated the influence of factors such as sex, age group, and seriousness of outcomes on the occurrence of PR. Females represented 56.3% of cases and the 18–64 age group comprised 55.4% of cases. TNF inhibitors were significantly associated with PR (ROR = 4.1881 [3.1970–5.4865], P < 0.0001), particularly infliximab (ROR = 6.5284 [3.9523–10.7837], P < 0.0001), etanercept (ROR = 3.4921 [2.2873–5.3315], P < 0.0001), and adalimumab (ROR = 3.086 [2.0213–4.7115], P < 0.0001). ACE inhibitors were also associated with PR (ROR = 9.9808 [6.0423–16.4864], P < 0.0001), with higher odds in older patients (OR 14.08 [4.2–47.2], P < 0.0001) and those reporting serious outcomes (OR 9.53 [1.24–72.99], P = 0.03). Based on the FAERS, there has been a consistent rise in PR cases, with TNF inhibitors and ACE inhibitors being associated medication classes tied to PR. Given the limited literature on drug-related triggers and patient demographics, we aimed to highlight the characteristics of PR cases that could enhance awareness and inform better clinical outcomes for affected patients.

Postmarketing safety evaluation of belimumab: a pharmacovigilance analysis

ObjectiveThe present study aimed to provide a comprehensive evaluation of the postmarketing safety of belimumab based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database.MethodsAdverse event (AE)...

The safety of cyclosporine and tacrolimus in pediatric nephrotic syndrome patients: a disproportionate analysis based on the FAERS database.

This study aimed to systematically evaluate the safety of cyclosporine (CsA) and tacrolimus (TAC) in pediatric nephrotic syndrome (NS) patients using real-world data from the FDA Adverse Event Reporting System (FAERS). We analyzed adverse event (AE) reports from the FAERS database between Q4 2003 and Q2 2024, focusing on AEs associated with CsA and TAC in NS patients aged 18 years and younger. We employed three signal detection methods-Proportional Reporting Ratio (PRR), Relative Reporting Ratio (RRR), and Reporting Odds Ratio (ROR)-to assess the risk of drug-related AEs. Sensitivity analyses were conducted to explore the influence of gender on AE occurrence. A total of 207 CsA-related and 145 TAC-related AE reports were included. CsA was significantly associated with nephropathy toxic (ROR = 8.26, 95% CI: 4.21-16.20), urine output decreased (ROR = 29.93, 95% CI: 3.66-244.61), and posterior reversible encephalopathy syndrome (ROR = 6.70, 95% CI: 3.17-14.14). TAC was associated with an increased risk of dystonia (ROR = 67.93, 95% CI: 8.63-534.86), kidney fibrosis (ROR = 22.65, 95% CI: 8.16-62.87), and diabetic ketoacidosis (ROR = 46.51, 95% CI: 5.68-380.97). Sensitivity analysis indicated that gender influenced the occurrence of AEs, with CsA showing higher nephrotoxicity in male patients, while TAC was more strongly associated with metabolic disorders and neurological AEs in female patients. In pediatric NS patients, CsA primarily induces nephrotoxicity and neurological complications, whereas TAC is more likely to cause kidney fibrosis and metabolic disorders. Enhanced monitoring of these AEs and individualized drug adjustments based on patient characteristics are recommended to optimize treatment outcomes and reduce AE incidence.

Comprehensive analysis of adverse events associated with onasemnogene abeparvovec (Zolgensma) in spinal muscular atrophy patients: insights from FAERS database.

Onasemnogene Abeparvovec (Zolgensma) is a gene therapy for the treatment of Spinal Muscular Atrophy (SMA) with improved motor neuron function and the potential for a singular treatment. Information on its adverse drug reactions is mainly from clinical trials and real-world studies with extensive sample sizes are lacking. In this study, we analyzed the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) database to assess the drug safety profile of Zolgensma. A total of 1951 adverse event reports associated with onasemnogene abeparvovec (Zolgensma), containing 778 import important medical event (IME) signals, were identified from the FAERS database, and multiple disproportionate analysis algorithms were used to determine the significance of these adverse events. This study identified 281 onasemnogene abeparvovec-related adverse events (AEs), including some significant adverse events not mentioned in the product labelling. Elevated liver enzymes, fever, vomiting, and thrombocytopenia were the most common adverse reactions. Most adverse events manifested within the initial month of onasemnogene abeparvovec use, especially the first 8days, but some may still occur after 1year of treatment. Sex-specific scrutiny revealed differing risk levels for adverse events among women and men. Thrombocytopenia and thrombotic microangiopathy are more common in patients weighing ≥8.5kg, and changes in renal function need to be closely monitored if thrombotic microangiopathy occurs. The above findings provide valuable insights into optimizing the utilization of onasemnogene abeparvovec, improving its effectiveness, and minimizing potential side effects, thereby greatly facilitating its practical application in clinical settings.

Drug-induced dementia: a real-world pharmacovigilance study using the FDA Adverse Event Reporting System database.

Dementia is a serious adverse event (AE) that requires attention in clinical practice. However, information on drug-induced dementia is limited. The U.S. FDA Adverse Event Reporting System (FAERS) serves as an important resource for identifying real-world adverse drug reactions and safety signals. This study aimed to use FAERS data to identify drugs associated with increased dementia risk. A secondary analysis of the FAERS database was conducted using disproportionality analysis methods. We reviewed dementia-related reports in the FAERS database from the first quarter of 2004 to the fourth quarter of 2023, used the Medical Dictionary for Regulatory Activity to identify dementia cases and summarized the corresponding list of potential medications, counted the dementia-causing medication classes with the highest frequency of reports, and disaggregated all medications. The study identified 31,881 dementia-related AEs in the FAERS database, with an increasing trend over time, particularly among females and individuals over 65. Apixaban had the most reports (1631). Disproportionality analyses revealed that rivastigmine, nicergoline, aducanumab, amlodipine/atorvastatin, and dihydroergometrine had the highest risk, based on reporting odds ratio, proportional reporting ratio, and information component. Only valproate and tramadol among the top 50 drugs included a potential dementia risk in their package inserts. This study identified a list of medications associated with dementia risk, many of which lack dementia warnings on their labels. Increased monitoring is necessary for high-risk individuals, and further research is required to clarify these associations and improve patient safety.

Pharmacologically induced autoimmune encephalitis—disproportionality analysis utilizing FAERS database

ABSTRACT Background Autoimmune encephalitis (AE) is a neuroimmune disorder that presents significant diagnostic challenges. The FDA Adverse Event Reporting System (FAERS) database can help explore the relationship between drugs and AE, but comprehensive studies are lacking. This study aims to analyze the association between drugs and AE using the FAERS database, providing insights for clinical practice and pharmacovigilance. Research Design and Methods Adverse event reports in the FAERS database were analyzed, focusing on the incidence of drug-induced AE, as well as characteristics such as gender and age. Multiple statistical methods were employed to assess the association between drugs and adverse reactions. Results The study revealed that drug-induced AE predominantly occurred in individuals aged 41 and above, with a higher prevalence among female patients. Nivolumab and pembrolizumab were among the drugs most frequently reported for adverse drug reactions. However, only a minority of drug labels mentioned these adverse reactions. Conclusion This study underscores the potential risk of drug-induced AE, advocating for close monitoring in clinical practice. Further epidemiological investigations are warranted to elucidate the exact relationship between drugs and these disorders. While the FAERS database provides crucial leads for such research, additional studies and validation are necessary.

Risk of congenital anomalies associated with psychotropic medications: a review of neonatal reports in the FDA adverse event reporting System (FAERS).

This study investigates the potential association between commonly prescribed psychotropic medications, such as Atypical Antipsychotics (AAs), Selective Serotonin Reuptake Inhibitors (SSRIs), and Serotonin Norepinephrine Reuptake Inhibitors (SNRIs), and congenital anomalies in newborns. The analysis uses data from the Food and Drug Administration Adverse Event Reporting System (FAERS). Spontaneously reported cases of congenital anomalies in newborns (under 28 days old) were extracted from the FAERS database, covering January 2004 to June 2023. Four signal detection methods-Reporting Odds Ratio (ROR), Medicines and Healthcare products Regulatory Agency (MHRA), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS)-were employed to identify signals associated with neonatal deformities caused by specific drugs, ensuring signal stability and reliability. The FAERS database contains 21,605 reports involving neonates, with 6,208 cases reporting congenital anomalies. Of these, 6,164 cases (99.29%) attributed the adverse events to drugs. The top ten psychotropic drugs associated with neonatal congenital anomalies were venlafaxine, quetiapine, olanzapine, sertraline, citalopram, mirtazapine, duloxetine, paroxetine, aripiprazole, and fluoxetine. Different drug classes showed varying risks of congenital anomalies, with higher signal frequencies observed for cardiac, nervous system, respiratory-thoracic-mediastinal, and musculoskeletal-connective tissue disorders. Our study suggests that commonly used psychotropic drugs may increase the risk of congenital abnormalities in newborns, necessitating caution for pregnant women. Compared to other psychotropic drugs, the teratogenic effects of aripiprazole and fluoxetine are relatively minor. Overcoming the Limitations of Clinical Trials in Special Populations: Due to ethical considerations involving pregnant women and newborns, conducting clinical trials is often challenging. Real-world studies are currently one of the most important sources of evidence for evaluating the safety of medication use during pregnancy. Addressing Challenges in International Signal Detection: There is no established gold standard for signal detection, and different countries use varying methods. To minimize the impact of false-positive signals on the results, this study employs a combination of four different methods for signal mining. Advancing Beyond Small Retrospective Cohort Studies and Case Reports: Most current research on the safety of medication use during pregnancy relies on small retrospective cohort studies or case reports. Studies based on large pharmacovigilance databases overcome these limitations. This approach not only captures information on all drugs that may lead to congenital anomalies in newborns but also monitors rare yet significant safety information, providing more comprehensive data support for assessing the safety of medication use during pregnancy.

Fulminant type 1 diabetes mellitus: a neglected but high-risk adverse event associated with immune checkpoint inhibitors.

Immune checkpoint inhibitor (ICI) therapy has revolutionized cancer treatment but is associated with fulminant type 1 diabetes mellitus (FT1DM). Our study aims to investigate the association between ICI therapy and FT1DM using the FDA Adverse Event Reporting System (FAERS) database. We conducted a retrospective analysis from the first quarter of 2004 to the first quarter of 2023. The disproportionality analysis incorporating the reporting odds ratio (ROR) and information component (IC) was performed to assess the magnitude of the adverse event signal between ICIs and FT1DM. A total of 520 cases of FT1DM were identified in association with ICI therapy, representing 75.9% of all FT1DM cases reported in the FAERS database. Descriptive analyses revealed a predominance in males (60.2%) and the elderly (70.6%). The median time to onset was 69 days and 337 patients (64.81%) were hospitalized while 35 (6.73%) cases resulted in death. Disproportionality analysis showed a strong signal for FT1DM with ICI treatment (ROR 438.84) versus other drugs. These findings provide compelling evidence linking ICI therapy to the development of FT1DM, underscoring the need for clinical vigilance and early intervention strategies to optimize patient outcomes while leveraging the remarkable therapeutic potential of cancer immunotherapy.