Adverse Events of SARS-CoV-2 Therapy: A Pharmacovigilance Study of the FAERS Database.

Traumatic Brain Injury (TBI) is a significant public health issue, often leading to long-term cognitive, physical, and emotional impairments. Amantadine has emerged as a treatment option due to its potential neuroprotective properties, aiming to enhance recovery. However, its safety profile in TBI patients remains under scrutiny. This study aimed to evaluate the safety of amantadine using the FDA Adverse Event Reporting System (FAERS) database, focusing on identifying novel adverse events to inform clinical decisions. We analyzed adverse event reports of amantadine from FAERS (2004-2024), identifying 2766 reports where it was the primary suspect. Signal detection was conducted using ROR, PRR, BCPNN, and MGPS methods, ranked by ROR values. A gender subgroup analysis with Bonferroni correction ensured statistical significance. Among the 2766 reports, most events were related to nervous (n=2013, ROR=2.9) and psychiatric disorders (n=1631, ROR=3.46). Notable events included hallucinations (n=302, ROR=27.57), falls (n=286, ROR=5.7), and drug inefficacy (n=266, ROR=1.34). Adverse events were more common in patients aged 65+ years (48.5%) and slightly more frequent in females (49.3%). New adverse events identified included falls, drug inefficacy, tremors, and gait disturbances, mostly occurring within the first month of treatment (39.6%). The study revealed significant safety concerns with amantadine, especially regarding nervous and psychiatric reactions. It highlighted the need for careful monitoring in clinical use and further research to understand mechanisms, enhance therapeutic outcomes, and minimize adverse events.

Real-world drug safety study of somatostatin analogs based on the food and drug administration adverse event reporting system database.

Drug-induced osteoporosis/osteopenia (OP/OPN) has emerged as a significant public health concern affecting bone health. However, the risk assessment of OP/OPN induced by various drugs remains incompletely understood, necessitating large-scale real-world data analysis to clarify the associated risks. The present study aims to systematically analyse OP/OPN-related adverse events (AEs). This study utilised the FDA Adverse Event Reporting System (FAERS) database to identify OP/OPN-related adverse event reports from 2004 to 2023. Disproportionality analysis, including the reporting odds ratio and proportional reporting ratio, was applied to evaluate the signal strength of OP/OPN associated with different drug categories. Additionally, the study analysed drug classifications, time-to-onset, and trends over time. Among the 43,685 OP/OPN-related reports, anti-retroviral drugs accounted for the highest proportion of reports (20.73%), with a gradual annual increase in reporting frequency (average annual growth rate of 2.20%). This was followed by immunomodulatory/immunosuppressive agents (12.76%), proton pump inhibitors (6.25%), and hormone-related (2.88%). A significant variation was observed in the time-to-onset of OP/OPN-related adverse event among different drug categories: glucocorticoids-induced osteoporosis occurred earliest (median time-to-onset of 164 days), while anti-retroviral drug-induced osteoporosis had the longest time-to-onset (median of 1,508 days). Regarding reporting frequency, tenofovir and its combinations, esomeprazole, adalimumab, methotrexate, medroxyprogesterone, interferon beta-1A, etanercept, and rituximab were the most frequently reported drugs. In terms of signal strength, tenofovir and its combinations, adefovir, pamidronic acid, and esomeprazole the strongest signals, suggesting that these drugs may represent key risk factors for OP/OPN. This FAERS-based study identified multiple drug classes associated with OP/OPN-related adverse event signals, with anti-viral drugs - particularly tenofovir disoproxil and its combination therapies - exhibiting the strongest signal. Although glucocorticoids had a lower reporting proportion, their short onset time underscores the need for vigilance. These findings provide real-world evidence for drug safety management and highlight the necessity of bone health monitoring in long-term medication users. Future studies should integrate clinical data to validate these findings and explore underlying mechanisms.

ObjectiveThis study aimed to investigate the entire adverse events (AEs) spectrum and to identify some new or rare AEs associated with empagliflozin based on the FAERS database.MethodsA retrospective analysis was conducted on AE reports extracted from the FAERS, spanning from the first quarter of 2004 to that of 2023. Disproportionality analysis methods, including the ROR, PRR, BCPNN, and MGPS, were employed to quantify signals of AEs associated with empagliflozin. Additionally, demographic characteristics and time to onset were further elucidated.ResultsThe results showed a total of 20,734 AE reports related to empagliflozin, identifying 322 significant preferred terms (PTs) covering 27 System Organ Classes (SOCs). Empagliflozin was significantly associated with pre-specified AEs compared to other novel antidiabetic medications. Beyond common AEs, unexpected significant AEs such as pancreatitis, gastroenteritis, cerebral infarction, and cardiac operations were identified. The median onset time for empagliflozin-related AEs was 28 days (interquartile range (IQR) 4–154 days), with the majority of AE cases (n = 2,112, 10.19%) occurring within the first month following initiation of empagliflozin therapy.ConclusionThe clinically observed AEs, along with potential new AE signals associated with empagliflozin were identified based on the FAERS database, which could provide valuable evidence for clinical monitoring, risk identification, and further safety studies of identification.

Nifedipine, a dihydropyridine calcium channel blocker, is widely used in the management of hypertension and as a tocolytic agent to delay preterm labor, including in pregnant women. However, its safety profile, particularly in pregnant populations, remains insufficiently characterized. This study aimed to evaluate adverse event (AE) signals associated with nifedipine use, with a specific focus on pregnancy-related outcomes. Nifedipine-related AEs reported in U.S. Food and Drug Administration Adverse Event Reporting System database (Q1 2004–Q4 2024) were analyzed. Disproportionality analysis was conducted using 4 established signal detection methods: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network, and Multi-item Gamma Poisson Shrinker. Pregnancy-related reports were identified using Standardized MedDRA Queries, and subgroup analyses were conducted for pregnant women. In the overall population, significant signals at the System Organ Class level were observed for pregnancy-related conditions, vascular disorders, and cardiac disorders. The strongest prominent preferred term signal was gingival hypertrophy (n = 52; ROR = 100.55, PRR = 100.23, information component [IC] = 6.61, empirical Bayesian geometric mean [EBGM] = 97.42). Among pregnant women, prominent signals at the System Organ Class level included vascular disorders, respiratory disorders, and cardiac disorders. The strongest preferred term signal was acute pulmonary edema (n = 27; ROR = 67.23, PRR = 66.70, IC = 5.87, EBGM = 58.29), followed by cardiogenic shock (n = 11; ROR = 41.80, PRR = 41.67, IC = 5.26, EBGM = 38.25), pulmonary edema (n = 51; ROR = 38.57, PRR = 38.00, IC = 5.14, EBGM = 35.15), and hypoxia (n = 28; ROR = 20.62, PRR = 20.46, IC = 4.29, EBGM = 19.62). Several unexpected pregnancy-related AEs were also detected, including eclampsia, fetal distress, placental disorders, and intrauterine growth restriction. This study identified unexpected AE signals associated with nifedipine use during pregnancy. The findings offer valuable insights to guide clinical decision-making and promote safer use of nifedipine in pregnant populations.

BackgroundThe profiles of cardiovascular toxicity associated with angiogenesis inhibitors, including intravenous monoclonal antibodies (mAbs) and oral tyrosine kinase inhibitors (TKIs), targeting vascular endothelial growth factor (VEGF) remain poorly elucidated in real-world settings. This pharmacovigilance analysis aimed to comprehensively investigate the frequency, spectrum, timing, and outcomes of cardiovascular toxicities associated with angiogenesis inhibitors and to explore the differences in such patterns between mAbs and TKIs.MethodsDisproportionality analysis was performed by leveraging reports from the FDA Adverse Event Reporting System (FAERS) database from 2014 to 2021. Cardiovascular adverse events (AEs) were grouped into nine narrow categories using the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs). Reporting odds ratio (ROR) and information components (ICs) were calculated with statistical shrinkage transformation formulas and a lower limit of 95% confidence interval (CI) for ROR (ROR025) > 1 or IC (IC025) > 0, with at least three reports being considered statistically significant.ResultsA total of 757,577 reports of angiogenesis inhibitors and 70,668 (9.3%) reports of cardiovascular AEs were extracted. Significant disproportionality was detected in angiogenesis inhibitors for cardiovascular AEs (IC025/ROR025 = 0.35/1.27). Bevacizumab (31.8%), a mAb, presented the largest number of reports, followed by sunitinib (12.4%), a TKI. Hypertension (SMQ) was detected with the strongest signal value (IC025/ROR025 = 1.73/3.33), followed by embolic and thrombotic events (SMQ) (IC025/ROR025 = 0.32/1.26). Hypertension showed the shortest time to onset with a median (interquartile range) value of 23 (8, 69) days, while embolic and thrombotic events had the longest value of 51 (16, 153) days. Notably, hypertension presented the lowest proportions of death and life-threatening events (10.9%), whereas embolic and thrombotic events posed the highest (29.3%). Furthermore, both mAbs (IC025/ROR025 = 0.47/1.39) and TKIs (IC025/ROR025 = 0.30/1.23) showed increased cardiovascular AEs. Hypertension was detected in both agents (IC025/ROR025 = 1.53/2.90 for mAbs and IC025/ROR025 = 1.83/3.56 for TKIs) with a shorter time to onset of 17 (6, 48) days for TKIs than mAbs of 42 (14, 131) days. By contrast, embolic and thrombotic events were detected for mAbs (IC025/ROR025 = 0.90/1.87) without TKI (IC025/ROR025 = −0.08/0.95).ConclusionAngiogenesis inhibitors were associated with increased cardiovascular toxicity with a discrepancy between intravenous mAbs and oral TKIs, deserving distinct monitoring and appropriate management.

Background Gemtuzumab ozogamicin and inotuzumab ozogamicin play a crucial role in leukemia treatment. This study aims to explore multiple databases to identify adverse event (AE) signals that could enhance the safe use of these drugs. Methods design and methods The FDA Adverse Event Reporting System (FAERS) database ASCII packages, covering 83 quarters from Q1 2004 to Q3 2024, were imported into SAS software (version 9.4) for data cleaning and analysis. Signal detection methods included the ROR, PRR, BCPNN and MGPS. The Japanese Adverse Drug Event Report database (JADER) and WHO Adverse Drug Event Report database (VigiAccess) were used to validate the results. Results In FAERS and VigiAccess, the most frequent positive PT signal for gemtuzumab ozogamicin was ‘febrile neutropenia.’ In FAERS, the most frequent positive PT signal for inotuzumab ozogamicin was ‘death.’ The top five PTs with the highest signal intensity for both drugs across the three databases consistently included ‘fibrin degradation products increased’ and ‘veno-occlusive liver disease.’ Conclusion Mining multiple databases enabled the identification of SOCs and AEs strongly associated with frequent adverse reactions to gemtuzumab ozogamicin and inotuzumab ozogamicin, offering valuable insights for clinical dosing guidance.

Risk of angioedema and thrombolytic therapy among stroke patients: An analysis of data from the FDA Adverse Event Reporting System database

Psychiatric disorders associated with immune checkpoint inhibitors: a pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database

A phenomenon of 'masking' or 'cloaking' in pharmacovigilance data mining has been described, which can potentially cause signals of disproportionate reporting (SDRs) to be missed, particularly in pharmaceutical company databases. Masking has been predicted theoretically, observed anecdotally or studied to a limited extent in both pharmaceutical company and health authority databases, but no previous publication systematically assesses its occurrence in a large health authority database. To explore the nature, extent and possible consequences of masking in the US FDA Adverse Event Reporting System (AERS) database by applying various experimental unmasking protocols to a set of drugs and events representing realistic pharmacovigilance analysis conditions. This study employed AERS data from 2001 through 2005. For a set of 63 Medical Dictionary for Regulatory Activities (MedDRA®) Preferred Terms (PTs), disproportionality analysis was carried out with respect to all drugs included in the AERS database, using a previously described urn-model-based algorithm. We specifically sought masking in which drug removal induced an increase in the statistical representation of a drug-event combination (DEC) that resulted in the emergence of a new SDR. We performed a series of unmasking experiments selecting drugs for removal using rational statistical decision rules based on the requirement of a reporting ratio (RR) >1, top-ranked statistical unexpectedness (SU) and relatedness as reflected in the WHO Anatomical Therapeutic Chemical level 4 (ATC4) grouping. In order to assess the possible extent of residual masking we performed two supplemental purely empirical analyses on a limited subset of data. This entailed testing every drug and drug group to determine which was most influential in uncovering masked SDRs. We assessed the strength of external evidence for a causal association for a small number of masked SDRs involving a subset of 29 drugs for which level of evidence adjudication was available from a previous study. The original disproportionality analysis identified 8719 SDRs for the 63 PTs. The SU-based unmasking protocols generated variable numbers of masked SDRs ranging from 38 to 156, representing a 0.43-1.8% increase over the number of baseline SDRs. A significant number of baseline SDRs were also lost in the course of our experiments. The trend in the number of gained SDRs per report removed was inversely related to the number of lost SDRs per protocol. Both the number and nature of the reports removed influenced the number of gained SDRs observed. The purely empirical protocols unmasked up to ten times as many SDRs. None of the masked SDRs had strong external evidence supporting a causal association. Most involved associations for which there was no external supporting evidence or were in the original product label. For two masked SDRs, there was external evidence of a possible causal association. We documented masking in the FDA AERS database. Attempts at unmasking SDRs using practically implementable protocols produced only small changes in the output of SDRs in our analysis. This is undoubtedly related to the large size and diversity of the database, but the complex interdependencies between drugs and events in authentic spontaneous reporting system (SRS) databases, and the impact of measures of statistical variability that are typically used in real-world disproportionality analysis, may be additional factors that constrain the discovery of masked SDRs and which may also operate in pharmaceutical company databases. Empirical determination of the most influential drugs may uncover significantly more SDRs than protocols based on predetermined statistical selection rules but are impractical except possibly for evaluating specific events. Routine global exercises to elicit masking, especially in large health authority databases are not justified based on results available to date. Exercises to elicit unmasking should be driven by prior knowledge or obvious data imbalances.

BackgroundAlthough arrhythmias have been reported in patients treated with immune checkpoint inhibitors (ICIs), the association between arrhythmias and ICIs has not been thoroughly evaluated in real‐world studies. We aimed to describe the major features of ICI‐related arrhythmic events and identify the factors that contributed to death.MethodsA disproportionality analysis was performed using data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database from January 2011 to December 2021. Reporting odds ratios (RORs), proportional reporting ratio and information component were used to assess whether adverse arrhythmic events were associated with ICIs. The clinical characteristics of patients with ICI‐associated arrhythmias were compared with fatal and non‐fatal arrhythmias. The time to onset (TTO), fatality rates of arrhythmic events were also investigated.ResultsWe identified a total of 1945 cases of ICI‐related arrhythmic events. Men (64.78%) were identified significantly more frequently than women (28.84%). The median age was 68 years ([interquartile range, IQR] 60–75 years). Anti‐programmed cell death‐1 (PD‐1) and anti‐programmed cell death ligand‐1 (PD‐L1) were associated with adverse arrhythmic events, corresponding to ROR 1.11 (95% confidence interval [CI] 1.05–1.17) and ROR 1.34 (95% CI 1.20–1.49), respectively. However, anti‐cytotoxic T‐lymphocyte associated protein 4 or combination immunotherapy did not appear to be associated with arrhythmic events. Atrial fibrillation (N = 576, 0.62%), cardiac arrest (N = 284, 0.31%), tachycardia (N = 175, 0.19%) were the most common adverse arrhythmic events. Sudden death and complete atrioventricular block are adverse events that are significantly associated with ICI‐related arrhythmic events and have strong signal intensity. The TTO of cases that resulted in death (30 days [IQR] 11–73.75) was significantly earlier than that of cases that did not result in death (33 days [IQR 10.5–88.5], p = 0.003). ICI‐related arrhythmic events were severe with death occurring in 507 (26.07%) of 1945 arrhythmias cases.ConclusionsTreatment with PD‐1/PD‐L1 may cause arrhythmic events, which are severe and tend to occur early on during treatment. It is important to identify ICI‐related arrhythmias as early as possible, and to manage them appropriately.

Ocrelizumab, a humanized anti-CD20 monoclonal antibody approved for multiple sclerosis in 2017, modulates B-cell activity to reduce disease progression. While clinical trials demonstrate its efficacy, real-world safety data remain critical to identify rare or long-term adverse events (AEs) not captured in controlled studies. This study analyzed post-marketing AEs of ocrelizumab using data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) to assess safety under real-world conditions. A retrospective pharmacovigilance analysis was conducted on FAERS data from Q1 2017 to Q4 2023. Disproportionality analyses including reporting odds ratio, proportional reporting ratio, Bayesian Confidence Propagation Neural Network, and Multi-item Gamma Poisson Shrinker were used to detect safety signals. Subgroup, sensitivity, and time-to-onset analyses further characterized AE profiles. Among 50,967 reports, the analysis confirmed several AEs consistent with the ocrelizumab prescribing information, including urinary tract infection, depression, cough, herpes zoster, and breast cancer. Furthermore, potential new safety signals not previously documented in the drug’s label were identified, such as alopecia, insomnia, weight increased, and sepsis. This study confirms known AEs and identifies unexpected AEs, emphasizing the need for targeted monitoring, particularly during early therapy. Real-world FAERS data complement trial findings, aiding clinicians in optimizing multiple sclerosis treatment strategies.

Background The comprehensive quantitative and comparative risk data of drug-induced erectile dysfunction (ED) are still lacking, and this study aims to supplement this information. Research design and methods We reviewed all the ED reports in the FDA Adverse Event Reporting System (FAERS) database from 2004 to 2023 and summarized a potential ED culprit-drug list and its corresponding reporting frequency. The reporting odds ratio (ROR) method was used to conduct disproportionality analysis. Results A total of 20,098 ED reports were retrieved from the FAERS database, which recorded 734 different ED culprit-drugs, involving 74 drug classes. Finasteride was the drug with the highest reporting frequency, and urologicals was the drug class with the highest reporting frequency. In disproportionality analysis, 209 drugs with positive signals showed a close relationship with ED occurrence, among which finasteride was the drug with the highest signal strength. Among 209 drugs with positive signals, 27 were compound preparations, and the risk level of compound preparations was usually higher than their single active ingredient. Conclusions Our study integrated quantitative and comparative ED risk data of 734 drugs by using the FAERS database, which can provide reference information for regulators, medical personnel, and others involved in drug management and use.

Trastuzumab emtansine (T-DM1) is widely utilized as a second-line and subsequent treatment for metastatic HER2+ breast cancer and has shown promise in early breast cancer treatment, particularly in adjuvant settings for residual disease after neoadjuvant chemotherapy. However, concerns have arisen regarding long-term hepatic adverse drug reactions (ADRs) not identified in clinical trials. We investigated potential safety signals of T-DM1 in hepatobiliary disorders and the time-to-onset of ADRs using the FDA Adverse Event Reporting System (FAERS) database. Suspected ADRs were extracted and divided into two groups: T-DM1 (N = 3387) and other drugs (N = 11,833,701). Potential signal for T-DM1 in hepatobiliary disorder were identified (reporting odds ratio [ROR] = 5.66, 95% confidence interval [CI] = 5.11–6.27; information component [IC] = 2.35, 95% Credibility Interval [Crl] = 2.18–2.51). A breast cancer indicated subgroup analysis (2519 T-DM1; 172,329 other drugs) also identified a potential safety signal (ROR = 3.28, 95% CI = 2.92–3.68; IC = 1.53, 95%CrI = 1.35–1.71). The median time-to-onset for T-DM1-associated hepatobiliary disorders was 41 days. For prolonged and chronic hepatobiliary disorders, median times were 322.5 and 301.5 days, respectively. These findings highlight the need for further research to inform clinical decisions on optimal T-DM1 treatment duration, balancing benefits with potential adverse reactions.

The purpose of this study is to explore and analyze the FDA Adverse Event Reporting System (FAERS) database to identify drug adverse reaction signals associated with angioedema. The findings aim to provide valuable insights for clinical drug safety considerations. The Open Vigil 2.1 data platform was utilized to collect adverse event reports related to angioedema from the first quarter of 2004 to the fourth quarter of 2023. The reporting odds ratio (ROR) and proportional reporting ratio (PRR) were employed as disproportionality measures to detect adverse reaction signals Sof drugs associated with angioedema. A total of 38,921 reports were retrieved, with the majority being reported by healthcare professionals. The analysis included predominantly adult patients (≥18years of age), with slightly higher representation of females compared to males. Among the top 30 drugs associated with the occurrence of angioedema, 24 drugs showed positive signals in the risk analysis. Based on the individual drug reporting odds ratio (95% confidence interval) as a measure of risk signal strength, the top five drugs are as follows: lisinopril [ROR (95% CI): 46.43 (42.59-50.62)], enalapril [ROR (95% CI): 43.51 (39.88-47.46)], perindopril [ROR (95% CI): 31.17 (27.5-35.32)], alteplase [ROR (95% CI): 29.3 (26.95-31.85)], ramipril [ROR (95% CI): 20.93 (19.66-22.28)]. After categorizing the drugs, the strongest positive signal was observed in the antithrombotic agents [ROR (95% CI): 22.53 (21.16-23.99)], following that, cardiovascular drugs [ROR (95% CI): 9.17 (8.87-9.48)], antibiotics [ROR (95% CI): 6.42 (5.91-6.96)], immunosuppressors [ROR (95% CI): 5.95 (5.55-6.39)], anti-inflammatory analgesics [ROR (95% CI): 4.65 (4.45-4.86)], antiallergic drugs [ROR (95% CI): 4.47 (3.99-5)], antiasthmatics [ROR (95% CI): 2.49 (2.14-2.89)], blood sugar control drugs [ROR (95% CI): 1.65 (1.38-1.97)], and digestive system drugs [ROR (95% CI): 1.59 (1.45-1.74)] exhibited progressively decreasing ROR values. Many medications are associated with a high risk of angioedema. These medications play a crucial and potentially preventable role in controlling the occurrence of angioedema. It is essential to consider the risk level of drug-induced angioedema in clinical practice to optimize medication therapy.