FDA Adverse Event Reporting System Research Articles

Long-term safety of lanthanum carbonate in the real word: a 19-year disproportionality analysis from the FDA Adverse Event Reporting System

Background Lanthanum carbonate is widely used to manage serum phosphate and calcium levels in end-stage kidney disease (ESKD) patients, yet comprehensive long-term safety data are lacking. This study leverages the FDA Adverse Event Reporting System (FAERS) to assess the extended safety profile of lanthanum carbonate. Research design and methods We analyzed FAERS data (2004-2022) to study the association between lanthanum carbonate and adverse events (AEs). Using MedDRA v25.0, we identified risk signals through System Organ Classes (SOCs) and Preferred Terms (PTs). Disproportionality analyses quantified lanthanum carbonate-associated AE signals. Results Among 3,284 reports, 2,466 were primary suspected AEs linked to lanthanum carbonate. Males reported AEs more frequently than females. Patients aged over 64 represented the majority. Median onset time for lanthanum carbonate-related AEs was 146 days. Gastrointestinal disorders were prevalent. We identified 16 new signals, including stress, abnormal hepatic function, cholelithiasis, bile duct stone, gastric cancer, and adenocarcinoma gastric. Stress was notable, particularly in male patients over 65 and those with lower weight. Conclusions This study affirms lanthanum carbonate’s long-term safety for reducing elevated blood phosphorus levels. While gastrointestinal disorders were common, attention must focus on emerging AEs, particularly stress, especially in elderly patients.

Analysis of Inclisiran in the US FDA adverse event reporting system (FAERS): a focus on overall patient population and Sex-specific Subgroups.

ABSTRACT Background our study aimed to identify inclisiran-related adverse events(AEs) for primary hypercholesterolemia and arteriosclerotic cardiovascular disease(ASCVD) from the US FDA Adverse Event Reporting System (FAERS) database, analyzing its links to AEs in the overall patient population and sex-specific subgroups to improve medication safety. Methods We analyzed inclisiran-related AEs signals by using statistical methods like Reporting Odds Ratio (ROR), Proportional Reporting Ratios (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma-Poisson Shrinker (MGPS). Results Analyzing 2,400 AE reports with inclisiran as the primary suspected drug in the FAERS database, we identified 70 AE signals over 13 organ systems using the above four methods. Notable findings were strong signals for systemic diseases and various reactions at the site of administration (ROR 1.49, 95% CI 1.41-1.57), and Various musculoskeletal and connective tissue diseases (ROR 4.07, 95% CI 3.83-4.03) in overall and gender-specific populations. Myalgia, a new ADE signal not in the drug insert, was a top signal by intensity and frequency (ROR 14.76, 95% CI 12.84-16.98). Conclusion Our study revealed the strongest AE signals associated with inclisiran in both the overall population and gender subgroups, highlighting potential risks in clinical medication use and guiding balanced clinical decision-making.

Comparison of safety of acetaminophen and ibuprofen in minors: based on the FAERS database

ABSTRACT Objective To investigate adverse events(ADEs) associated with the use of paracetamol and ibuprofen in people under 18 years of age. Background The use of NSAIDs reached a peak as a result of the spread of COVID-19 in previous years. Minors, as a special population, need to pay more attention to the use of corresponding drugs and the occurrence of adverse events (ADEs). Methods The population was divided into four age groups: infant group, preschool group, children group, and adolescent group. ADE report data of the two drugs were extracted from the FDA Adverse Event Reporting System(FAERS) from the first quarter of 2014 to the third quarter of 2022. The reporting odds ratio(ROR) method and the medicine and health products regulatory agency(MHRA) method were used for data mining and analysis. Results The two drugs mainly involved in injuries, poisoning and operational complications in the infant group, preschool group and adolescent group. The use of the two drugs in this population was primarily associated with injury, poisoning and surgical complications. The psychiatric disorders produced by the use of acetaminophen(12.6%) and ibuprofen(9.2%) in the adolescent group were significantly higher than those in the other age groups. The use of acetaminophen in the four age groups involved hepatobiliary disorders was more significantly (10.3%, 8.1%, 9.1%, 11.5%), while the use of ibuprofen was more obviously involved in renal and urinary disorders(5.0%, 6.2%, 9.6%, 7.1%). Conclusions The use of acetaminophen and ibuprofen in children of different age groups has different characteristics. Pediatric clinical pharmacists can provide medication monitoring to minimize ADEs based on these characteristics.

Repurposing of drugs against bacterial infections: A pharmacovigilance-based data mining approach.

The World Health Organization (WHO) has published a list of priority pathogens that urgently require research to develop new antibiotics. The main aim of the current study is to identify potential marketed drugs that can be repurposed against bacterial infections. A pharmacovigilance-based drug repurposing approach was used to identify potential drugs. OpenVigil 2.1 tool was used to query the FDA Adverse Event Reporting System database. The reporting odds ratio (ROR) < 1, ROR95CI upper bound <1, and no. of cases ≥30 were used for filtering and sorting of drugs. Sunburst plot was used to represent drugs in a hierarchical order using the Anatomical Therapeutic Chemical classification. Molecular docking and dynamics were performed using the Maestro and Desmond modules of Schrodinger 2023 software respectively. A total of 40 drugs with different classes were identified based on the pharmacovigilance approach which has antibacterial potential. The molecular docking results have shown energetically favored binding conformation of lisinopril against 3-deoxy-manno-octulosonate cytidylyltransferase, UDP-2,3-diacylglucosamine hydrolase, and penicillin-binding protein 3 (PBP3) of Pseudomonas aeruginosa; olmesartan, atorvastatin against lipoteichoic acids flippase LtaA and rosiglitazone and varenicline against d-alanine ligase of Staphylococcus aureus; valsartan against peptidoglycan deacetylase (SpPgdA) and atorvastatin against CDP-activated ribitol for teichoic acid precursors of Streptococcus pneumoniae. Further, molecular dynamic results have shown the stability of identified drugs in the active site of bacterial targets except lisinopril with PBP3. Lisinopril, olmesartan, atorvastatin, rosiglitazone, varenicline, and valsartan have been identified as potential drugs for repurposing against bacterial infection.

Pancreatitis with use of new diabetic medications: a real-world data study using the post-marketing FDA adverse event reporting system (FAERS) database

Pancreatitis with use of new diabetic medications: a real-world data study using the post-marketing FDA adverse event reporting system (FAERS) database

A retrospective analysis of drugs associated with the development of cutaneous squamous cell carcinoma reported by patients on the FDA’s adverse events reporting system

Cutaneous squamous cell carcinoma (cSCC) is the second most common type of skin cancer arising from squamous cells of the epidermis. Most cases of cSCC have a good prognosis if detected and treated early; however, certain cases can be aggressive. The primary risk factor for cSCC is prolonged ultraviolet radiation from sun exposure, leading to DNA mutations. Other risk factors have also been observed, including adverse reactions to medications, particularly immunosuppressants. A query of the Food and Drug Administration Adverse Events Reporting System (FAERS) was done, and all reported events of cSCC as adverse events to medication were recorded along with demographic data of patients affected. A total of 4,792 cases of cSCC as an adverse event to medication were reported between 1997 and 2023. Lenalidomide, a chemotherapeutic drug, had the most cases of cSCC as an adverse event. Nine of the top 10 drugs associated with cSCC had immunosuppressive characteristics. While males had higher odds of cSCC associated with corticosteroids and calcineurin inhibitors, females had higher odds of cSCC related to monoclonal antibodies. Geriatric patients accounted for the majority of cSCC cases at 59.7%. Drawing on data from the FAERS database, there’s been a consistent increase in cSCC cases as a side-effect to certain medications, with most having immunosuppressive characteristics. Since there is a lack of up-to-date literature overviewing the most implicated medications for cSCC, we aimed to illustrate this better, as well as patient demographics, to better guide clinicians when prescribing these medications.

P.021 Nonclinical studies of abuse potential with dual orexin-receptor antagonists: concordance with real-world use

Background: Traditional insomnia drugs enhance gamma-aminobutyric acid and are associated with abuse/dependence. Dual orexin-receptor antagonists (DORAs) represent an alternate mechanism promoting wakefulness, rather than inhibition. Nonclinical studies indicate DORAs do not demonstrate abuse potential. Nonetheless, based on human abuse potential (HAP) studies and lack of postmarketing data at approval, DORAs are Schedule 4 controlled substances. However, HAP studies may not predict real-world abuse-potential risk. Methods: Adverse events with preferred terms (PTs) of drug-withdrawal-syndrome, drug-abuse, and drug-dependence were evaluated from Eisai’s ongoing global postmarketing safety surveillance system in the US, Canada, and Japan (20/Dec/2019–30/Sep/2023) and the FDA Adverse Event Reporting System (FAERS; 01/Jan/2015–30/Jun/2023). In FAERS, reports of those PTs from DORAs (lemborexant/suvorexant/daridorexant) were compared with zolpidem and with benzodiazepines approved for patients with insomnia (estazolam/temazepam/triazolam). Results: Since lemborexant’s approval, few of the 3 PTs were reported in Eisai’s surveillance system (~0.15 cases per million patient-days of global exposure). Reports in FAERS for PTs of drug-withdrawal-syndrome, drug-abuse, and drug-dependence for DORAs (10,202 reports) were &lt;0.1%/&lt;0.1%/0.1%, respectively. Reports for benzodiazepines (5534 reports) were 0.8%/12.9%/3.7%, respectively, and 1.0%/9.1%/5.3% for zolpidem (18,330 reports), respectively. Conclusions: Abuse potential may be better represented by nonclinical studies and national surveillance systems, suggesting DORAs may not pose meaningful abuse potential and related risks.

Potential adverse events associated with sphingosine-1-phosphate (S1P) receptor modulators in patients with multiple sclerosis: an analysis of the FDA adverse event reporting system (FAERS) database

ObjectiveSphingosine-1-phosphate receptor (S1PR) modulators have recently attracted increasing attention for the treatment of multiple sclerosis (MS). Despite their preference in the clinic, multiple adverse events (AEs) continue to be reported every year. This study aimed to investigate the potential AEs as well as related important medical events (IMEs) signal associated with S1PR modulators, including fingolimod, siponimod and ozanimod in a real-world study using the FDA Adverse Event Reporting System (FAERS) database.MethodsAll data were collected from the FAERS database, spanning from the fourth quarter of 2010(2010Q4) to the second quarter of 2023 (2023Q2). Potential AE and IME signals of S1PR modulators were identified based on a disproportionality analysis using the reporting odds ratio (ROR), proportional reporting ratio (PRR), and the bayesian confidence propagation neural network of information components (IC).ResultsOverall, 276,436 reports of fingolimod, 20,972 reports of siponimod and 10,742 reports of ozanimod were analyzed from the FAERS database. Among reports, females were more prone to develop AEs (73.71% for females vs. 23.21% for males), and more than 50% of patients suffered from AEs were between 18 and 64 years. Subsequently, we investigated the top 20 AEs associated with the signal strength of S1PR modulators at the preferred term (PT) level, and identified 31 (8 vs. 11 vs. 12, respectively) unlabeled risk signals such as thrombosis, uterine disorder and reproductive system and breast disorders. Furthermore, we discovered that the S1PR modulator reported variations in the possible IMEs, and that the IMEs associated with ocular events were reported frequently. It’s interesting to note that infection and malignancy are prominent signals with both fingolimod and siponimod in the top 20 PTs related to mortality reports.ConclusionThe present investigation highlights the possible safety risks associated with S1PR modulators. The majority of AEs are generally consistent with previous studies and are mentioned in the prescribing instructions, however, several unexpected AE signals have also been observed. Ozanimod showed the lowest signal intensity and a better safety profile than the other S1PR modulators. Due to the short marketing time of drugs and the limitations of spontaneous reporting database, further research is required to identify potential AEs related to S1PR modulators.

Adverse Events of Oral GLP-1 Receptor Agonist (Semaglutide Tablets): A Real-World Study Based on FAERS from 2019 to 2023.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have attracted much attention because of their significant hypoglycemic and weight-loss effects. Previous preparations can only be subcutaneously injected. Oral administration of GLP-1RAs semaglutide helps to broaden treatment options, but its safety in the real world still needs to be observed. This study is based on FDA adverse event reporting system (FAERS) database to mine adverse drug events (ADE) of oral semaglutide, and provide references for the clinical safe use of this drug. To analyze the signal quality of oral semaglutide, which is a drug used in the FAERS database from the third quarter of 2019 to the third quarter of 2023, we collected ADE data and performed data mining by using disproportionate analysis. Then, we standardized the data and used a variety of signal-quantification techniques, including reported odds ratio (ROR), proportional reporting ratio (PRR), Bayesian belief propagation neural network (BCPNN), and multiple empirical Bayesian gamma Poisson contractions (MGPS), for further analysis. We screened 2398 reports on the use of semaglutide tablets, involving a total of 5653 ADE. These reports were mainly submitted by consumers, and the reporting country was mainly the United States. A total of 23 system organ classes (SOC) and 93 preferred terms (PT) were mined for the signals of semaglutide tablets. The three most common SOC were gastrointestinal disorders, general disorders and administration site conditions, and investigations. At the PT level, metabolism and nutrition disorders exhibit the highest number of signals, with the top three being thyroid cyst, acute cholecystitis, and ketosis. Gastrointestinal disorders rank second, primarily involving eructation, pancreatitis, impaired gastric emptying, and regurgitation. In addition, vith nerve paralysis occurs and the signal intensity is high. Our study provides a deeper and broader understanding of the safety of oral semaglutide. The results of the ROR, PRR, BCPNN, and MGPS algorithms exhibit high consistency, with metabolism and nutrition-related disorders having the highest number of signals. The conclusions align with the technical specifications of the product. Notably, other unexpected effects are reported, including acute cholecystitis, paralysis of the abducens nerve, and positional vertigo.

Neurological disorders following the use of tumor necrosis factor-α inhibitors in inflammatory bowel disease patients: a real-world pharmacovigilance analysis

ABSTRACT Background Tumor necrosis factor-α inhibitors (TNFis) are used for the treatment of inflammatory bowel disease (IBD). The aim of this study was to evaluate the association between neurological adverse events (AEs) and TNFi use. Methods Data of TNFis indicated for IBD were collected from the Food and Drug Administration Adverse Event Reporting System (FAERS) from the marketed date to the second quarter of 2023. The reporting odds ratio (ROR) and a Bayesian confidence propagation neural network were used to identify signals. Results A total of 4,964 neurological AEs were reported in the IBD population. Infliximab had 3 signals, including demyelination [ROR (95% CI): 1.69 (1.33,2.15)], meningitis listeria [ROR (95% CI): 5.05 (3.52,7.25)], and optic neuritis [ROR (95% CI): 1.72 (1.3,2.26)]. The signals for adalimumab were gait disturbance [ROR (95% CI): 1.43 (1.32,1.56)] and muscular weakness [ROR (95% CI): 1.4 (1.27,1.55)]. A peripheral neuropathy signal was found for adalimumab [ROR (95% CI): 1.34 (1.18,1.53)] and certolizumab pegol [ROR (95% CI): 1.49 (1.07,2.08)]. However, there were no signals among neurological AEs for golimumab. Conclusion Neurological signals were detected for TNFi use, indicating that the risk of neurological AEs requires additional attention in clinical use of TNFis.

A real-world pharmacovigilance study of FDA adverse event reporting system events for Capmatinib

Capmatinib is a potent selective mesenchymal-epithelial transition inhibitor approved in 2020 for the treatment of metastatic non-small cell lung cancer. As real-world evidence is very limited, this study evaluated capmatinib-induced adverse events through data mining of the FDA Adverse Event Reporting System database. Four disproportionality analysis methods were employed to quantify the signals of capmatinib-related adverse events. The difference in capmatinib-associated adverse event signals was further investigated with respect to sex, age, weight, dose, onset time, continent, and concomitant drug. A total of 1518 reports and 4278 adverse events induced by capmatinib were identified. New significant adverse event signals emerged, such as dysphagia, dehydration, deafness, vocal cord paralysis, muscle disorder, and oesophageal stenosis. Notably, higher risk of alanine aminotransferase and aspartate aminotransferase increases were observed in females, especially when capmatinib was combined with immune checkpoint inhibitors. Compared with Europeans and Asians, Americans were more likely to experience peripheral swelling, especially in people > 65 years of age. Renal impairment and increased blood creatinine were more likely to occur with single doses above 400 mg and in Asians. This study improves the understanding of safety profile of capmatinib.

Risk of drug-induced delirium in older patients- a pharmacovigilance study of FDA adverse event reporting system database

ABSTRACT Background Drug-induced delirium is one of the numerous known risk factors associated with increased morbidity and mortality in older patients. The objective of this study was to evaluate the risk of drug-related delirium in older patients based on the FDA Adverse Event Reporting System (FAERS). Research design and methods Delirium reports in older patients (age ≥65) from 2004 quarter 1 through 2021 quarter 3 extracted from the FAERS database using Open Vigil 2.1. The reported odds ratio and the proportional r7eported ratio were calculated to detect the adverse reaction signal of delirium. Combined with published evidence, suspected drugs were categorized as known, possible, or new potential delirium-risk-increasing drugs. Results Of the 130,885 reports (including 28,850 delirium events and 1,857 drug) analyzed for this study, 314 positive signal drugs were detected. Positive signal drugs are mainly concentrated on the drug of nervous system [n = 149, ROR 3.60, 95% CI (3.56–3.64)], cardiovascular system [n = 35, ROR 1.45, 95% CI (1.43–1.47)], alimentary tract and metabolism [n = 35, ROR 1.25, 95% CI (1.23–1.26)] and anti-infectives for systemic use [n = 27, ROR 1.70, 95% CI (1.66–1.74)]. Of the positive signal drugs, 26.11% (82/314) were known delirium-risk increasing drugs [ROR 4.12, 95%CI (3.85–4.41)], 44.90% (141/314) were possible [ROR 3.59, 95%CI (3.37–3.83)] and 28.98% (91/314) were new potential [ROR 3.68, 95%CI (3.22–4.21)]. Conclusion Drug-induced delirium risk is prevalent in the older patients according to the FAERS. The risk level of drug-induced delirium should be taken into account to optimize drug therapy in clinical practice.

Differences in ocular adverse events associated with phosphodiesterase-5 inhibitors: a real-world pharmacovigilance study

ABSTRACT Objective Our study aims to characterize the ocular safety profiles of phosphodiesterase type 5 (PDE5) inhibitors and explore the differences among different PDE5 inhibitors. Methods We analyzed reports on ocular adverse events associated with sildenafil, vardenafil and tadalafil submitted to the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the first quarter of 2023. Disproportionality analysis was conducted to evaluate reporting risk profiles. Results Among 61,211 reports qualifying for analysis, 5,127 involved sildenafil, 832 vardenafil, and 3,733 tadalafil. All PDE5 inhibitors showed increased reporting odds ratios (ROR) for ocular adverse events, with vardenafil highest (ROR 4.47) followed by sildenafil and tadalafil. Key ocular adverse events included cyanopsia, optic ischemic neuropathy, visual field defects, unilateral blindness and blindness. Sildenafil showed the highest disproportionality for cyanopsia (ROR 1148.11) while vardenafil and tadalafil showed the highest disproportionality for optic ischemic neuropathy. Time-to-onset analysis also revealed significant differences, with sildenafil having a later median time-to-onset compared to vardenafil and tadalafil. Conclusions This comprehensive pharmacovigilance study reveals distinct patterns of ocular adverse events associated with PDE5 inhibitors. These findings contribute to a better understanding of the safety profiles of PDE5 inhibitors and may guide healthcare professionals in clinical decision-making.

Adverse event signal mining and serious adverse event influencing factor analysis of fulvestrant based on FAERS database

Fulvestrant, as the first selective estrogen receptor degrader, is widely used in the endocrine treatment of breast cancer. However, in the real world, there is a lack of relevant reports on adverse reaction data mining for fulvestrant. To perform data mining on adverse events (AEs) associated with fulvestrant and explore the risk factors contributing to severe AEs, providing a reference for the rational use of fulvestrant in clinical practice. Retrieved adverse event report information associated with fulvestrant from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, covering the period from market introduction to September 30, 2023. Suspicious AEs were screened using the reporting odds ratio (ROR) and proportional reporting ratio methods based on disproportionality analysis. Univariate and multivariate logistic regression analyses were conducted on severe AEs to explore the risk factors associated with fulvestrant-induced severe AEs. A total of 6947 reports related to AEs associated with fulvestrant were obtained, including 5924 reports of severe AEs and 1023 reports of non-severe AEs. Using the disproportionality analysis method, a total of 210 valid AEs were identified for fulvestrant, with 45 AEs (21.43%) not listed in the product labeling, involving 11 systems and organs. The AEs associated with fulvestrant were sorted by frequency of occurrence, with neutropenia (325 cases) having the highest number of reports. By signal strength, injection site pruritus showed the strongest signal (ROR = 658.43). The results of the logistic regression analysis showed that concurrent use of medications with extremely high protein binding (≥ 98%) is an independent risk factor for severe AEs associated with fulvestrant. Age served as a protective factor for fulvestrant-related AEs. The co-administration of fulvestrant with CYP3A4 enzyme inhibitors did not show statistically significant correlation with the occurrence of severe AEs. Co-administration of drugs with extremely high protein binding (≥ 98%) may increase the risk of severe adverse reactions of fulvestrant. Meanwhile, age (60–74 years) may reduce the risk of severe AEs of fulvestrant. However, further clinical research is still needed to explore and verify whether there is interaction between fulvestrant and drugs with high protein binding through more clinical studies.

Adverse cardiovascular events in rheumatoid arthritis patients treated with JAK inhibitors: An analysis of postmarketing spontaneous safety reports

ObjectivesThe ORAL Surveillance trial, a postmarketing safety clinical trial, found an increased risk of adverse cardiovascular events and venous thromboembolism (VTE) in patients treated with Janus Kinase (JAK) inhibitors compared to tumor necrosis factor (TNF) inhibitors. However, additional studies yielded mixed results and data on other JAK inhibitors are limited. MethodsA retrospective, pharmacovigilance study using the FDA adverse event reporting system (FAERS) to assess reporting of adverse cardiovascular events following treatment with JAK inhibitors in rheumatoid arthritis (RA) patients between January 2015 and June 2023. To identify disproportionately increased reporting, an adjusted reporting odds ratio (adj.ROR) was calculated with a multivariable logistic regression model. ResultsWe identified safety reports of 75,407 RA patients treated with JAK inhibitors (tofacitinib, n = 52,181; upadacitinib, n = 21,006; baricitinib, n = 2,220) and 303,278 patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs; TNF inhibitors, rituximab, and tocilizumab). The mean age was 61.2(±12) and 59.0(±13), respectively; 82 % and 81 % were women. Compared to bDMARDs, JAK inhibitors were associated with an increased reporting of VTE [n = 1,393, adj.ROR=2.11 (1.97−2.25)], stroke [n = 973, adj.ROR=1.25 (1.16−1.34)], ischemic heart disease [IHD, n = 999, adj.ROR=1.23 (1.13−1.33)], peripheral edema [n = 2699, adj.ROR=1.22 (1.17−1.28)], and tachyarrhythmias [n = 370, adj.ROR=1.15 (1.00–1.33)]. Most of the events occurred in the first year after treatment initiation. When different JAK inhibitors were compared, VTE, stroke, and IHD were more frequently reported with upadacitinib and baricitinib than tofacitinib. When stratified by age category, all safety signals were statistically significant in patients aged≤65 years. ConclusionIn this global postmarketing study, JAK inhibitors are associated with increased reporting of VTE, stroke, IHD, and tachyarrhythmias. These adverse events were reported following all JAK inhibitors that were studied, suggesting a class effect.

Data mining and safety analysis of avatrombopag: a retrospective pharmacovigilance study based on the US food and drug administration’s adverse event reporting system

With its increasing use in the treatment of thrombocytopenia, avatrombopag’s associated adverse events (AEs) pose a major challenge to its clinical application. This study aims to comprehensively study AEs associated with avatrombopag by using real-world evidence. We curated AE reports for avatrombopag from the first quarter of 2018 to the fourth quarter of 2023 in the US Food and Drug Administration’s Adverse Event Reporting System (FAERS) database. AEs were coded using the Medical Dictionary for Regulatory Activities of Preferred Terms and System Organ Classes. The reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item Gamma-Poisson Shrinker were used to investigate the relationship between avatrombopag and AE reports. Among 9,060,312 reported cases in the FAERS database, 1211 reports listed avatrombopag as “primary suspected” drug. Disproportionality analysis identified 44 preferred terms across 17 organ systems met the criteria for at least one of the four algorithms. The most commonly reported AEs were platelet count decreased (20.2%), headache (16.7%), platelet count increased (11.9%), platelet count abnormal (6.3%), contusion (2.7%), pulmonary embolism (2.3%), and deep vein thrombosis (2.1%). Unexpected AEs such as seasonal allergy, rhinorrhea, antiphospholipid syndrome, ear discomfort, and photopsia were also observed. Excluding the other serious outcomes, hospitalization (34.6%) was the most frequently reported serious outcome, followed by death (15.4%). Most reported AEs occurred within the first 2 days of initiating avatrombopag therapy, and the median onset time was 60 days. We identified new and unexpected AEs with clinical use of avatrombopag, and our results may provide valuable information for clinical monitoring and identifying risks associated with avatrombopag.

Exploring the Link Between Exogenous Thyroid Hormones and Dementia Symptoms: A Real-World Disproportionality Analysis of FDA Adverse Event Reporting System.

A growing body of evidence indicates a strong association between exogenous thyroid hormone (ETH) and brain health. Establishing the potential relationship between ETH therapy and dementia symptoms is crucial for patients with thyroid disorders. In this study, we investigate the potential association between ETH therapy and dementia symptoms by exploring the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Disproportionality analysis (DPA) was conducted using postmarketing data from the FAERS repository (Q1 2004 to Q4 2023). Cases of dementia symptoms associated with ETH therapy were identified and analyzed through DPA using reporting odds ratios and information component methods. Dose and time-to-onset analyses were performed to assess the association between ETH therapy and dementia symptoms. A total of 9889 cases of ETH-associated symptoms were identified in the FAERS database. Dementia accounted for a consistent proportion of adverse drug reactions each year (3.4%-6.3%). The DPA indicated an association between ETH therapy and dementia symptoms, which remained significant even across sex, age, and indications. The median time-to-onset of dementia symptoms was 7.5 days, and the median treatment time was 40.5 days. No significant dose-response relationship was observed. This study provides evidence for a link between ETH therapy and dementia. Clinicians are therefore advised to exercise vigilance, conduct comprehensive monitoring, and consider individualized dosing to mitigate potential reactions to ETH drug administration.

Exploring adverse events of Vilazodone: evidence from the FAERS database

ObjectiveThis study aims to conduct an exhaustive evaluation of Vilazodone's safety in clinical application and to unearth the potential adverse event (AE) risks associated with its utilization based on FDA Adverse Event Reporting System (FAERS) database.MethodsThis research employed data spanning from the first quarter of 2011 to the third quarter of 2023 from the FAERS database. Various signal detection methodologies, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), were utilized to ascertain the correlation between Vilazodone and specific AEs.ResultsThe study compiled a total of 17,439,268 reports of drug AEs, out of which 5,375 were related to Vilazodone. Through signal mining, 125 Preferred Terms (PTs) encompassing 27 System Organ Classes (SOCs) were identified. The findings indicated a higher prevalence among females and patients within the 45 to 65 age bracket. The principal categories of AEs included Psychiatric disorders, Nervous system disorders, and Gastrointestinal disorders, with prevalent incidents of Diarrhoea, Nausea, and Insomnia. Moreover, the study identified robust signals of novel potential AEs, notably in areas such as sleep disturbances (Sleep paralysis, Hypnagogic hallucination, Rapid eye movements sleep abnormal, Sleep terror, Terminal insomnia, Tachyphrenia), sexual dysfunctions (Female orgasmic disorder, Orgasm abnormal, Disturbance in sexual arousal, Spontaneous penile erection, Anorgasmia, Sexual dysfunction, Ejaculation delayed), and other symptoms and injuries (Electric shock sensation, Violence-related symptom, Gun shot wound).ConclusionAlthough Vilazodone presents a positive prospect in the management of MDD, the discovery of AEs linked to its use, particularly the newly identified potential risks such as sleep and sexual dysfunctions, necessitates heightened vigilance among clinicians.

Abrocitinib-associated adverse events: a real-world pharmacovigilance study using the FAERS database

ABSTRACT Background Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Janus kinase (JAK) modulates cytokines involved in AD pathophysiology, and JAK inhibitors have emerged as effective pharmacotherapeutic remedies for AD. Abrocitinib, an oral selective inhibitor of JAK1, is indicated for the management of moderate-to-severe AD. The current study evaluated the adverse events (AEs) associated with abrocitinib in a real-world setting. Methods To quantify the signals of abrocitinib-associated AEs, we used the US Food and Drug Administration Adverse Event Reporting System (FAERS) for this pharmacovigilance study with two established pharmacovigilance methods. Results A total of 1071 AEs of abrocitinib were investigated as the primary suspected from the FAERS to detect and characterize relevant safety signals. The analysis revealed 85 signals for abrocitinib. The most common AE for abrocitinib was drug ineffective. The signal strength of eczema herpeticum was 515.87 (277.80–957.98) and 510.59 (5148.65) and exhibited the highest strength for abrocitinib. Rare AEs such as aggravated condition, pruritus, and hypersensitivity were not listed on the label, and attention to these AEs is required. Conclusion The analysis of the AE signals may provide support for clinical monitoring and risk identification of abrocitinib.

A real-world pharmacovigilance study of drug-induced QT interval prolongation: analysis of spontaneous reports submitted to FAERS.

To identify the most commonly reported drugs associated with QT interval prolongation in the FDA Adverse Event Reporting System (FAERS) and evaluate their risk for QT interval prolongation. We employed the preferred term (PT) "electrocardiogram QT prolonged" from the Medical Dictionary for Regulatory Activities (MedDRA) 26.0 to identify adverse drug events (ADEs) of QT interval prolongation in the FAERS database from the period 2004-2022. Reporting odds ratio (ROR) was performed to quantify the signals of ADEs. We listed the top 40 drugs that caused QT interval prolongation. Among them, the 3 drugs with the highest number of cases were quetiapine (1,151 cases, ROR = 7.62), olanzapine (754 cases, ROR = 7.92), and citalopram (720 cases, ROR = 13.63). The two most frequently reported first-level Anatomical Therapeutic Chemical (ATC) groups were the drugs for the nervous system (n = 19, 47.50%) and antiinfectives for systemic use (n = 7, 17.50%). Patients with missing gender (n = 3,482, 23.68%) aside, there were more females (7,536, 51.24%) than males (5,158, 35.07%) were involved. 3,720 patients (25.29%) suffered serious clinical outcomes resulting in deaths or life-threatening conditions. Overall, most drugs that caused QT interval prolongation had early failure types according to the assessment of the Weibull's shape parameter (WSP) analysis. Our study offered a list of drugs that frequently caused QT interval prolongation based on the FAERS system, along with a description of some risk profiles for QT interval prolongation brought on by these drugs. When prescribing these drugs in clinical practice, we should closely monitor the occurrence of ADE for QT interval prolongation.