Drug-associated congenital anomalies of the external ear identified in the United States food and drug administration adverse event reporting system database.

Congenital anomalies of the external ear can have a significant impact on a child's development and quality of life. While genetic factors play a crucial role in the etiology of these anomalies, environmental factors such as drug exposure during pregnancy may also contribute to their occurrence. This study aims to investigate the association between drug exposure and congenital anomalies of the external ear using data from an adverse drug reaction report database. Using OpenVigil 2.1, we queried the FAERS database to retrieve adverse event reports from the first quarter of 2004 to the first quarter of 2024. To identify relevant cases, we used Medical Dictionary for Regulatory Activities terms focusing on congenital anomalies of the external ear. Drug generic names were sourced from the DrugBank database. To assess safety signals and rank drugs by their signal strength, we conducted a disproportionality analysis, generating reporting odds ratios (ROR) and proportional reporting ratios (PRR). A total of 20,754,281 AE reports were identified in the FAERS database from Q1 2004 to Q1 2024, of which 1763 were related to congenital anomalies of the external ear. Valproic acid (122 cases) was associated with the most cases, followed by mycophenolate mofetil (105 cases) and lamotrigine (65 cases). According to the disproportionality analysis, the top five drugs with the highest ROR and PRR were primidone (ROR: 397.05, 95% CI 147.21, 1070.9; PRR: 388.71, 95% CI 145.89, 1035.7), valproic acid (ROR: 239.46, 95% CI 123.75, 463.37; PRR: 236.42, 95% CI 123.82, 451.43), tapazole (ROR: 198.35, 95% CI 63.49, 619.67; PRR: 196.25, 95% CI 62.97, 611.67), nevirapine (ROR: 138.24, 95% CI 82.9, 230.51; PRR: 137.23, 95% CI 82.44, 228.44), and sebivo (ROR: 117.1, 95% CI 48.51, 282.67; PRR: 116.37, 95% CI 48.17, 281.12). This study identified several drugs significantly associated with congenital anomalies of the external ear in the FAERS database using disproportionality analysis. The findings can help healthcare professionals better recognize and manage drug-induced congenital anomalies of the external ear, particularly when prescribing high-risk medications. Further research is needed to elucidate the mechanisms underlying these associations and develop strategies for preventing and mitigating drug-induced congenital anomalies of the external ear.

Li X ，Hao J ，Li D ，Zhang R ... -  《Scientific Reports》

Data mining for adverse drug reaction signals of daptomycin based on real-world data: a disproportionality analysis of the US Food and Drug Administration adverse event reporting system.

Previous reports on daptomycin's adverse drug reactions (ADRs) have been insufficient, often because of limited data. Pharmacovigilance risk signal detection is innovative and has been applied to the safety monitoring and reevaluation of drugs post-marketing. The study aimed to promote safe daptomycin prescribing by mining and evaluating the daptomycin ADR signals from the US Food and Drug Administration Adverse Event Reporting System (FAERS). A disproportionality analysis (reporting odds ratio ROR and proportional reporting ratio PRR) was utilized for FAERS data mining from the first quarter of 2004 to the second quarter of 2021 (the most recent quarterly data at the time of the study). Preferred Terms of ADR reports were categorized by System Organ Class (SOC) based on the Medical Dictionary for Regulatory Activities. This study retrieved 12,221 cases within the reporting period. A total of 140 repetitive signals were obtained by ROR and PRR, of which 53 new ADR signals were not recorded in the drug labels/datasheets. The top three ADR reports were "blood creatine phosphokinase elevation" (ROR, 56.66, 95% confidence interval (CI) 51.07-62.87, PRR 51.94), "eosinophilic pneumonia" (ROR 696.71, 95%CI 603.21-804.70, PRR 657.57), and "rhabdomyolysis" (ROR 22.85, 95%CI 19.94-26.18, PRR 21.83). The highest ROR of "antimicrobial susceptibility test resistant" was found at 9808.14. Reports of rare adverse events, such as "necrotizing fasciitis and compartment syndrome," have emerged. The significant SOCs were "Infections and Infestations" and "Investigations." New daptomycin ADR signals were detected. Clinicians should monitor these potential ADRs in patients receiving daptomycin.

Chen JJ ，Huo XC ，Wang SX ，Wang F ，Zhao Q ... -  《-》

Drug-Associated Acute Kidney Injury Identified in the United States Food and Drug Administration Adverse Event Reporting System Database.

Acute kidney injury (AKI) is a common condition associated with both short-term and long-term consequences including dialysis, chronic kidney disease, and mortality. Although the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database is a powerful tool to examine drug-associated events, to our knowledge, no study has analyzed this database to identify the most common drugs reported with AKI. The objective of this study was to analyze AKI reports and associated medications in the FAERS database. Retrospective pharmacovigilance disproportionality analysis. Food and Drug Administration Adverse Event Reporting System database. We queried the FAERS database for reports of AKI from 2004 quarter 1 through 2015 quarter 3. Extracted drugs were assessed using published references and categorized as known, possible, or new potential nephrotoxins. The reporting odds ratio (ROR), a measure of reporting disproportionality, was calculated for the 20 most frequently reported drugs in each category. We retrieved 7,241,385 adverse event reports, of which 193,996 (2.7%) included a report of AKI. Of the AKI reports, 16.5% were known nephrotoxins, 18.6% were possible nephrotoxins, and 64.8% were new potential nephrotoxins. Among the most commonly reported drugs, those with the highest AKI ROR were aprotinin (7614 reports; ROR 115.70, 95% confidence interval [CI] 110.63-121.01), sodium phosphate (1687 reports; ROR 55.81, 95% CI 51.78-60.17), furosemide (1743 reports; ROR 12.61, 95% CI 11.94-13.32), vancomycin (1270 reports, ROR 12.19, 95% CI 11.45-12.99), and metformin (4701 reports; ROR 10.65, 95% CI 10.31-11.00). The combined RORs for the 20 most frequently reported drugs with each nephrotoxin classification were 3.71 (95% CI 3.66-3.76) for known nephrotoxins, 2.09 (95% CI 2.06-2.12) for possible nephrotoxins, and 1.55 (95% CI 1.53-1.57) for new potential nephrotoxins. Acute kidney injury was a common reason for adverse event reporting in the FAERS. Most AKI reports were generated for medications not recognized as nephrotoxic according to our classification system. This report provides data on medications needing further research to determine the risk of AKI with these new potential nephrotoxins.

Welch HK ，Kellum JA ，Kane-Gill SL 《-》

Drug-induced torsades de pointes: Disproportionality analysis of the United States Food and Drug Administration adverse event reporting system.

This study aimed to identify the most common and top drugs associated with the risk of torsades de pointes (TdP) based on the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. We used OpenVigil 2.1 to query FAERS database and data from the first quarter of 2004 to the third quarter of 2021 were retrieved. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify TdP cases. We listed the most common drugs associated with the reported TdP cases. Then, the reporting odds ratio (ROR) and the proportional reporting ratio (PRR) for the reporting association between different drugs and TdP risk were calculated. Meanwhile, comparisons were conducted with the QT drug lists of CredibleMeds® in an attempt to identify drugs with a potential risk of TdP that were not on the list. A total of 9,217,181 adverse event reports were identified, of which 3,807 (0.04%) were related to TdP. TdP was more likely to occur in the elderly and females. Amiodarone (464 cases) was associated with most cases of TdP. According to the disproportionality analysis, the top five drugs with the highest ROR and PRR were tolazoline (ROR 1615.11, 95% confidence interval [CI] 455.59-5725.75, PRR 969.46, χ2 2960.10), levomethadyl (ROR 1211.01, 95% CI 302.75-4844.04, PRR 807.67, χ2 1677.03), ibutilide (ROR 1118.74, 95% CI 425.00-2944.91, PRR 765.77, χ2 3845.27), halofantrine (ROR 660.55, 95% CI 184.21-2368.69, PRR 519.22, χ2 1076.31), and isoproterenol (ROR 352.20, 95% CI 227.19-546.00, PRR 307.82, χ2 6692.53). Approximately half of the top 50 drugs (22 for ROR, 30 for PRR) were not outlined on the QT drug lists of CredibleMeds®. Approximately half of the top risk drugs (22 for ROR, 30 for PRR) were not outlined in the QT drug lists of CredibleMeds®. Notably, potential risks are of great importance and should be closely monitored in clinical practice. Also, further research is needed to investigate the association between these drugs and TdP.

Wu Z ，Zhou P ，He N ，Zhai S ... -  《Frontiers in Cardiovascular Medicine》

Drug-induced hypoglycemia: a disproportionality analysis of the FAERS database.

Li J ，Wang Y ，Yang X ，Zhu H ，Jiang Z ... -  《-》