Bradycardia Due to Donepezil in Adults: Systematic Analysis of FDA Adverse Event Reporting System

2021 ◽  
pp. 1-11
Author(s):  
Robert Morris ◽  
Hunter Luboff ◽  
Rahul P. Jose ◽  
Kyle Eckhoff ◽  
Kun Bu ◽  
...  
Keyword(s):  
Adverse Event ◽  
Molecular Mechanisms ◽  
Reporting System ◽  
Strong Association ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Systematic Analysis ◽  
Event Reporting ◽  
Drug Classes ◽  
Endothelial Nitric Oxide

Background: Bradycardia is a physiological condition characterized by a decrease in heart rate and is a side effect of many drug classes. Bradycardia has been reported as an adverse event for patients receiving donepezil for Alzheimer’s disease (AD) treatment. Objective: The purpose of the paper is to systematically investigate the association between the occurrence of bradycardia in adults and the usage of donepezil using clinical data derived from the FDA Adverse Event Reporting System (FAERS) database. Methods: The risk of bradycardia in patients who only took donepezil was compared with those of patients who only took over-the-counter medications, multiple arrhythmia drugs, or other medications for AD treatment. In addition, this study sought to determine if this heightened bradycardia risk was influenced by sex, age, and dosage. Results: The results indicated that there was a significant greater likelihood of reporting bradycardia in patients administered donepezil than most of the drugs investigated. There was no significant association between age or the dosage of donepezil and the likelihood of reporting bradycardia. However, males were found to be more likely than females to report bradycardia as an adverse event. Tumor necrosis factor inhibition and stimulation of endothelial nitric oxide synthase were proposed to be the primary mechanism of actions which confer elevated bradycardia risk when using donepezil. Conclusion: These findings identified strong association between the usage of donepezil and bradycardia in adults as well as provide insight into the underlying molecular mechanisms that induce bradycardia by donepezil.

scholarly journals Systematic analysis of safety profile for darunavir and its boosted agents using data mining in the FDA Adverse Event Reporting System database

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaojiang Tian ◽  
Yao Yao ◽  
Guanglin He ◽  
Yuntao Jia ◽  
Kejing Wang ◽  
...  
Keyword(s):  
Data Mining ◽  
Adverse Event ◽  
Reporting System ◽  
Proportional Reporting Ratio ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Reporting Odds Ratio ◽  
Systematic Analysis ◽  
Event Reporting ◽  
Exfoliative Dermatitis

AbstractThis current investigation was aimed to generate signals for adverse events (AEs) of darunavir-containing agents by data mining using the US Food and Drug Administration Adverse Event Reporting System (FAERS). All AE reports for darunavir, darunavir/ritonavir, or darunavir/cobicistat between July 2006 and December 2019 were identified. The reporting Odds Ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN) were used to detect the risk signals. A suspicious signal was generated only if the results of the three algorithms were all positive. A total of 10,756 reports were identified commonly observed in hepatobiliary, endocrine, cardiovascular, musculoskeletal, gastrointestinal, metabolic, and nutrition system. 40 suspicious signals were generated, and therein 20 signals were not included in the label. Severe high signals (i.e. progressive extraocular muscle paralysis, acute pancreatitis, exfoliative dermatitis, acquired lipodystrophy and mitochondrial toxicity) were identified. In pregnant women, umbilical cord abnormality, fetal growth restriction, low birth weight, stillbirth, premature rupture of membranes, premature birth and spontaneous abortion showed positive signals. Darunavir and its boosted agents induced AEs in various organs/tissues, and were shown to be possibly associated with multiple adverse pregnant conditions. This study highlighted some novel and severe AEs of darunavir which need to be monitored prospectively.

scholarly journals The Importance of Reverse Translation for Preclinical Off-Target Mitigation: Quantification and Mitigation of Biases in the FDA Adverse Event Reporting System

2016 ◽  
Author(s):  
Mateusz Maciejewski ◽  
Eugen Lounkine ◽  
Steven Whitebread ◽  
Pierre Farmer ◽  
Bill DuMouchel ◽  
...  
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Molecular Mechanisms ◽  
Reporting System ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Vegf Receptor ◽  
Time Resolved ◽  
Event Reporting ◽  
Chemical Structures

AbstractThe Food and Drug Administration Adverse Event Reporting System (FAERS) is the primary source for post-marketing pharmacovigilance. Though potentially highly useful, the database reflects reporting biases, stimulated reporting, and suffers from lack of standardization and the use of multiple drug synonyms. These biases can suggest adverse drug reactions (ADRs) where none exist, and can obscure others that do exist. To decrease the noise in FAERS, and to reinforce important associations, we mapped over 750,000 drug identifiers in FAERS to the normalized chemical structures of their ingredients. This illuminated associations that would not otherwise be apparent, and also allowed a time-resolved analysis of ADR reporting. It also revealed similarities between drugs and adverse events across therapeutic classes, enabling unbiased classification of adverse events, indications, and drugs with similar clinical profiles. For instance, comparison of two selective cyclooxygenase-2 inhibitors, celecoxib and rofecoxib finds distinctive FAERS profiles after time-resolved analysis. We also investigated key idiosyncrasies, such as confusion between drug indications and drug ADRs, which can tar a drug treating a life-threatening disease, like thalidomide’s use against myeloma, with a deadly ADR that is likely the result of the disease itself, multiplications of the same report, which unjustifiably increases its apparent importance, and the correlation of reported ADRs with public events, regulatory announcements, and with publications. Comparing the pharmacological, pharmacokinetic, and clinical ADR profiles of methylphenidate, aripiprazole and risperidone, and of kinase drugs targeting the VEGF receptor (VEGF-R2), demonstrates how underlying molecular mechanisms can emerge from ADR co-analysis. The precautions and methods we describe may enable investigators to avoid confounding chemistry-based associations and reporting biases in FAERS, and illustrate how comparative analysis of ADRs can reveal underlaying mechanisms.

The Association Between Use of Rivastigmine and Pneumonia: Systematic Analysis of FDA Adverse Event Reporting System

2021 ◽  
pp. 1-11
Author(s):  
Robert Morris ◽  
Gibret Umeukeje ◽  
Kun Bu ◽  
Feng Cheng
Keyword(s):  
Adverse Event ◽  
Medulla Oblongata ◽  
Reporting System ◽  
Inflammatory Responses ◽  
Acetylcholinesterase Inhibitor ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Systematic Analysis ◽  
Event Reporting ◽  
Elevated Frequency

Background: Pneumonia is an inflammatory condition induced by infection of the lungs and is frequently a cause of morbidity and mortality among patients with Alzheimer’s disease (AD). Some studies have shown a correlation between acetylcholinesterase inhibitor use and elevated pneumonia risk. Objective: The purpose of this study was to perform a comparative analysis of the number of reported pneumonia cases in individuals prescribed rivastigmine relative to the association between pneumonia risk for other therapeutics including over-the-counter drugs and other AD therapeutics, as reported to the FDA Adverse Event Reporting System (FAERS) database. Methods: A disproportionality analysis was conducted to investigate the association between using rivastigmine and risk of pneumonia. Age, gender, dosage, route of administration, temporality, and geographic distribution of reported cases were also assessed. Results: Patients prescribed rivastigmine were more likely to report pneumonia as an adverse event than many drugs except galantamine. Males were found to be 46%more likely than females to report pneumonia as an adverse event while likelihood of pneumonia diagnosis increases 3–5-fold in patients older than 65 years of age. Conclusion: The observed elevated frequency of aspiration pneumonia in patients prescribed rivastigmine may be due to an induced cholinergic crisis that is selective for the medulla oblongata, resulting in gastrointestinal distress, impaired swallowing, heightened salivation, and labored breathing. The observed elevated frequency of infectious pneumonia in patients prescribed rivastigmine may also be linked to overstimulation of neurons in the medulla oblongata and downstream suppression of localized inflammatory responses.

scholarly journals Molecular Initiating Events Associated with Drug-Induced Liver Malignant Tumors: An Integrated Study of the FDA Adverse Event Reporting System and Toxicity Predictions

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 944
Author(s):  
Kota Kurosaki ◽  
Yoshihiro Uesawa
Keyword(s):  
Adverse Event ◽  
Reporting System ◽  
Malignant Tumors ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Drug Event ◽  
Drug Induced ◽  
Event Reporting ◽  
Nonalcoholic Fatty Liver ◽  
Drug Classes

Liver malignant tumors (LMTs) represent a serious adverse drug event associated with drug-induced liver injury. Increases in endocrine-disrupting chemicals (EDCs) have attracted attention in recent years, due to their liver function-inhibiting abilities. Exposure to EDCs can induce nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, which are major etiologies of LMTs, through interaction with nuclear receptors (NR) and stress response pathways (SRs). Therefore, exposure to potential EDC drugs could be associated with drug-induced LMTs. However, the drug classes associated with LMTs and the molecular initiating events (MIEs) that are specific to these drugs are not well understood. In this study, using the Food and Drug Administration Adverse Event Reporting System, we detected LMT-inducing drug signals based on adjusted odds ratios. Furthermore, based on the hypothesis that drug-induced LMTs are triggered by NR and SR modulation of potential EDCs, we used the quantitative structure–activity relationship platform for toxicity prediction to identify potential MIEs that are specific to LMT-inducing drug classes. Events related to cell proliferation and apoptosis, DNA damage, and lipid accumulation were identified as potential MIEs, and their relevance to LMTs was supported by the literature. The findings of this study may contribute to drug development and research, as well as regulatory decision making.

scholarly journals Cardiovascular Safety Profile of Romosozumab: A Pharmacovigilance Analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS)

2021 ◽  
Vol 10 (8) ◽  
pp. 1660
Author(s):  
Annika Vestergaard Kvist ◽  
Junaid Faruque ◽  
Enriqueta Vallejo-Yagüe ◽  
Stefan Weiler ◽  
Elizabeth M. Winter ◽  
...  
Keyword(s):  
Adverse Event ◽  
Drug Administration ◽  
Cardiovascular Events ◽  
Reporting System ◽  
Food And Drug Administration ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Cardiovascular Safety ◽  
Event Reporting ◽  
The Us

Background: Cardiovascular safety concerns for major cardiovascular events (MACE) were raised during the clinical trials of romosozumab. We aimed to evaluate the cardiovascular safety profile of romosozumab in a large pharmacovigilance database. Methods: All cases reported between January 2019 and December 2020 where romosozumab was reported were extracted from the Food and Drug Administration Adverse Event Reporting System (FAERS). The outcome of interest was MACE (myocardial infarction (MI), stroke, or cardiovascular death). A disproportionality analysis was conducted by estimating the reporting odds ratios (RORs) and 95% confidence intervals. Disproportionality analyses were stratified by sex and reporting region (US, Japan, other). Results: Of the 1995 eligible cases with romosozumab, the majority (N = 1188; 59.5%) originated from Japan. Overall, 206 suspected MACE reports were identified, of which the majority (n = 164; 13.8%) were from Japan, and 41 (5.2%) were from the United States (US). Among Japanese reports, patients were older and more frequently male than reports from the US. Similarly, cases with a reported MACE were older and had higher reports of cardioprotective drugs than those without cardiovascular events. Elevated reports for MACE (ROR 4.07, 95% CI: 2.39–6.93) was identified overall, which was primarily driven by the significant disproportionality measures in the Japanese reports. Conclusions: The current pharmacovigilance study identified a potential signal for elevated MACE, particularly in Japan. The results support the current safety warnings from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to avoid use in high-risk patients.

scholarly journals Estimated Incidence of Sugammadex-Induced Anaphylaxis Using the Korea Adverse Event Reporting System Database

2021 ◽  
Vol 10 (15) ◽  
pp. 3202
Author(s):  
Jae-Woo Ju ◽  
Nayoung Kim ◽  
Seong Mi Yang ◽  
Won Ho Kim ◽  
Ho-Jin Lee
Keyword(s):  
Risk Management ◽  
Adverse Event ◽  
General Anesthesia ◽  
Drug Safety ◽  
Reporting System ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Sales Volume ◽  
Event Reporting ◽  
Pharmacovigilance Database

We aimed to investigate the incidence of sugammadex-induced anaphylaxis in a large Korean population. We retrospectively investigated the incidence of sugammadex-induced anaphylaxis between 2013 and 2019 from the database of the Korea Institute of Drug Safety-Risk Management-Korea Adverse Event Reporting System (KIDS-KAERS). We estimated the incidence of sugammadex-induced anaphylaxis from the KIDS-KAERS database, assuming that the reporting efficiency was 10%, 50%, and 100%, respectively. We also investigated its annual sales volume in Korea and assumed that the exposure to sugammadex was 95% of the estimated sales volume. During the study period, 1,401,630 sugammadex vials were sold, and 19 cases of sugammadex-induced anaphylaxis were identified in the KIDS-KAERS database. The estimated incidence of sugammadex-induced anaphylaxis was 0.0143%, 0.00279%, and 0.0014%, assuming a reporting efficiency of 10%, 50%, and 100%, respectively. All patients, except for one with a missing record, fully recovered after anaphylaxis. The incidence of sugammadex-induced anaphylaxis identified in the national pharmacovigilance database was lower than previously reported rates in other countries. Therefore, its use in general anesthesia should not be hindered by concerns about the resulting risk of anaphylaxis in Korea.

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