Oral bowel cleansers and ischemic colitis risk: A real-world disproportionality analysis

Comparing Common Therapies in Polycythemia Vera (PV): A Disproportionality Analysis in the FDA Adverse Event Reporting System (FAERS) Database

Opportunistic Infections in Patients Receiving Daratumumab Regimens for Multiple Myeloma (MM)

Optimizing Adequacy of Bowel Cleansing for Colonoscopy: Recommendations From the US Multi-Society Task Force on Colorectal Cancer

A Real-World Disproportionality Analysis of FDA Adverse Event Reporting System(FAERS) Event for Belatacept.

Nirmatrelvir/Ritonavir, acting as an effective agent against COVID-19, has achieved considerable results in clinical studies in terms of drug efficacy. However, there is little research about its medication safety. Based on the FDA adverse event reporting system (FAERS) database, this study aims to mine the adverse reaction signals of the latest major recommended drug Nirmatrelvir/Ritonavir for the antiviral treatment of COVID-19, so as to provide a basis for safe and rational drug use. The reporting odds ratio (ROR) was used to explore the adverse event report data of all COVID-19 emergency use authorization (EUA) products in the FAERS database with the deadline of third quarter of 2023. In the analysis, 135427 adverse drug event (ADE) reports were found, and 35250 ADEs were reported with Nirmatrelvir/Ritonavir as the primary suspected drug, which was involved in multiple system. There was a high signal intensity of dysgeusia (ROR = 72.98), diarrhea (ROR = 3.03) and headache (ROR = 1.25), which was compatible with the adverse reactions recorded in the manual for Nirmatrelvir/Ritonavir. In addition, it was suggested that Nirmatrelvir/Ritonavir might cause pale-colored stools (ROR = 45.53), chromaturia (ROR = 3.07), yellow skin (ROR = 3.62), tongue coating (ROR = 35.55) and other new adverse reactions (not included in the instructions manual for Nirmatrelvir/Ritonavir). The ADEs of Nirmatrelvir/Ritonavir that are not in the instructions and are highly relevant in the real world are supplemented, prompting clinical attention to the ADEs of the drug, and providing a theoretical basis for the safe and effective application of the drug.

8015 Background: The FDA Adverse Event Reporting System (FAERS) is one of the largest pharmacovigilance databases containing information on adverse events (AEs) received from manufacturers, consumers and healthcare professionals. The purpose of this study is to evaluate the global disparities in multiple myeloma (MM) through data mining of FAERS. Methods: We examined AEs associated with FDA-approved MM drugs from 2003-2022 from FAERS and the Medical Dictionary for Regulatory Activities. Patient data were then stratified based on age, sex (F/M) and 6 geographical regions. We evaluated the reporting odds ratio (ROR) combined with a 95% confidence interval for the elevated incidence of AEs. Results: The data curation provided 381,378 patients with information from North America (NA), Europe (EU), Asia (AS), Africa (AF), Oceania (OC) and Latin America & the Caribbean (LA), merged from 129 countries and 27 phenotypic systems and organs categories when the number of AEs happened more than 0.1% of the total. Cardiotoxicities (n=23160) and vascular toxicities (n=26716) were seen more in NA (M) (ROR=1.16±0.02 and EU (M) (ROR=1.11± 0.03) compared to the rest of the World. Nephrotoxicity (n=17486) was reported more in AF (M) (ROR=2.92±0.41) compared to AS (M) (ROR≥1.17± 0.12), EU (M) (ROR≥1.34± 0.13) and NA (M) (ROR=1.09± 0.03). Peripheral neuropathies (n=14786) were frequent among EU (F) (ROR=1.09±0.07) and OC (M) (ROR=1.08± 0.04). Mortality was higher among AS and EU (ROR≥2.15± 0.93) compared to NA and OC. There were 18,222 secondary neoplasms in FAERS. Skin neoplasms (n=4650) more frequently occurred in OC and EU (ROR≥1.70 ±0.16). Breast neoplasms (n=694) were the highest in EU (F) (ROR=4.01+0.63) and lowest in OC (F) (ROR<1). Gastrointestinal neoplasms (n=1564) were more common among AS, EU and OC (M) with (ROR≥2.23±0.47). Lymphomas (n=542) were predominant in AS(M) (ROR=2.21±0.98) and OC (M) (ROR=3.35±2.23). Leukemias (n=3896) cases were significantly higher in EU (M) (ROR=4.08 ± 0.40) and EU (F) (3.11 ± 0.26). Respiratory tract and mediastinal neoplasms (n=796) were more common in AS, EU and OC(M) where ROR≥1.36±0.33. More phenotypic characterization are tabulated below. Conclusions: FAERS can be used to assess cancer disparity from a global perspective. Our results indicates that certain AEs are influenced by gender and geographical location. These disparities in MM AEs may be the result of factors such as genetics, dosing/regimen, comorbidities, age and sex. These variables must be investigated for improved patient care, strategies for AE reduction, mortality reduction and optimal allocation of healthcare resources. [Table: see text]

ObjectiveLaronidase is the first drug of enzyme replacement therapy approved for the treatment of mucopolysaccharidosis type I (MPS I). However, its adverse events (AEs) have not been investigated in real - world settings. The aim of this study was to investigate AEs associated with laronidase using the Food and Drug Administration Adverse Event Reporting System (FAERS).MethodsData for laronidase were acquired from the FAERS database covering Q1 2004 through Q4 2024. The Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN) and Multi-item Gamma Poisson Shrinker (MGPS) were employed to identify potential safety signals.ResultsA total of 3,677 adverse event reports associated with laronidase were identified in the FAERS from 2004 to 2024. The results revealed that common AEs of laronidase such as pyrexia [n = 465, ROR = 6.23 (5.68–6.83)], pneumonia [n = 223, ROR = 3.22 (2.82–3.68)], cough [n = 167, ROR = 2.78 (2.38–3.23)], influenza [n = 114, ROR = 4.95 (4.12–5.95)], urticaria [n = 106, ROR = 2.99 (2.47–3.62)], disease progression [n = 101, ROR = 3.95 (3.25–4.81)]. Furthermore, we detected probable unexpected AEs like seizures [n = 75, ROR = 3.1 (2.47–3.89)], hydrocephalus [n = 60, ROR = 50.47 (39.1–65.14)], blindness [n = 44, ROR = 5.02 (3.73–6.75)], glaucoma [n = 32, ROR = 7.56 (5.34–10.69)]. Laronidase -induced adverse reactions involved 27 System Organ Class (SOC). No significant difference in AEs was observed between sexes for laronidase. Most AEs (n = 763) emerged more than 360 days following laronidase treatment.ConclusionOur study has identified AEs associated with laronidase that could provide support for clinical monitoring and risk identification of laronidase.

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.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used due to their profound efficacy in glycemic control and weight management. Within real-world contexts, the manifestation of certain psychiatric adverse events (AEs) has been observed, which is potentially linked to the administration of GLP-1 RAs. The objective of this study was to undertake a comprehensive investigation and characterization of the psychiatric AEs associated with GLP-1 RAs. We retrieved reports of AEs associated with treatment with GLP-1 RAs during the period from the first quarter (Q1) of 2004 to Q1 2023 from the FDA Adverse Event Reporting System (FAERS) database. Descriptive analysis was performed to examine the clinical characteristics and time to onset of the psychiatric AEs caused by GLP-1 RAs. Moreover, disproportionality analyses were performed using the reporting odds ratio (ROR) to identify GLP-1 RA-related psychiatric AEs. A total of 8,240 reports of psychiatric AEs were analyzed out of 181,238 AE reports with treatment with GLP-1 RAs. Among these cases, a higher percentage was represented by women compared to men (65.89% vs. 30.96%). The median age of these patients was 56 years, with an interquartile range (IQR) of 48-67 years, based on data available in 286 case reports. This study showed that the median time to onset of the overall GLP-1 RA-related AEs was 31 days (IQR = 7-145.4 days), which varied among GLP-1 RA regimens. Specifically, exenatide had a significantly longer onset time at 45 days (IQR = 11-213 days), with statistically significant differences from the onset times of the other five GLP-1 RAs (p< 0.0001). Moreover, eight categories of psychiatric AEs, namely, nervousness (ROR = 1.97, 95% CI = 1.85-2.11), stress (ROR = 1.28, 95% CI = 1.19-1.38), eating disorder (ROR = 1.57, 95% CI = 1.40-1.77), fear of injection (ROR = 1.96, 95% CI = 1.60-2.40), sleep disorder due to general medical condition-insomnia type (ROR = 2.01, 95% CI = 1.60-2.52), binge eating (ROR = 2.70, 95% CI = 1.75-4.16), fear of eating (ROR 3.35, 95% CI = 1.65-6.78), and self-induced vomiting (ROR = 3.77, 95% CI = 1.77-8.03), were defined as GLP-1 RA-related psychiatric AEs through disproportionality analysis. Our findings demonstrate a significant association between GLP-1 RAs and the development of specific psychiatric AEs. Despite the observational nature of this pharmacovigilance study and the inherent limitations of the FAERS database, our preliminary findings in this work could provide a better basis for understanding the potential psychiatric AEs that may occur with GLP-1 RA treatment, assisting clinicians to focus on these AEs and provide early intervention for optimal risk management.

On 28 July 2021, Semglee (insulin glargine-yfgn) was approved by the U.S. Food and Drug Administration as the first interchangeable biosimilar to the reference product Lantus (insulin glargine) for treating diabetes mellitus. This study used the FDA Adverse Event Reporting System to identify reporting safety signals of Lantus and Semglee. Adverse event (AE) reports were organized into high-level group terms (HLGTs) using the Medical Dictionary for Regulatory Activities (MedDRA). Disproportionality analysis, including reporting odds ratio (ROR) and empirical Bayesian geometric mean (EBGM), was performed to detect safety signals for serious AE, death, hospitalization, top 6 HLGTs, and specific AEs on products' FDA prescription labels. Both products showed no significant safety signal of serious AE, death, or hospitalization. Lantus exhibited significant safety signals for device issues (ROR = 1.3, 95% confidence interval [CI] = 1.2-1.4; EBGM = 1.3, 90% CI = 1.2-1.3), medication errors and other product use errors and issues (ROR = 2.8, 95% CI = 2.7-2.9; EBGM = 2.1, 90% CI = 2.0-2.1), metabolic, nutritional, and blood gas investigations (ROR = 11.7, 95% CI = 11.2-12.2; EBGM = 9.6, 90% CI = 9.3-9.9), hyperglycaemia (ROR = 2.7, 95% CI = 2.1-3.5; EBGM = 2.3, 90% CI = 1.9-2.8) and hypoglycaemia (ROR = 4.6, 95% CI = 3.6-5.8; EBGM = 3.7, 90% CI = 3.0-4.5). Semglee had significant safety signals for device issues (ROR = 118.7, 95% CI = 103.9-135.7; EBGM = 22.8, 90% CI = 21.7-23.9), medication errors and other product use errors and issues (ROR = 3.4, 95% CI = 3.0-3.8; EBGM = 2.3, 90% CI = 2.1-2.4), metabolic, nutritional, and blood gas investigations (ROR = 3.0, 95% CI = 2.3-3.9; EBGM = 2.5, 90% CI = 2.0-3.1), product quality, supply, distribution, manufacturing, and quality system issues (ROR = 5.4, 95% CI = 4.6-6.3; EBGM = 4.4, 90% CI = 3.9-5.0), physical examination and organ system status topics (ROR = 2.6, 95% CI = 2.0-3.2; EBGM = 2.2, 90% CI = 1.9-2.7), weight gain (ROR = 3.6, 95% CI = 2.6-4.8; EBGM = 2.7, 90% CI = 2.1-3.5), weight loss (ROR = 2.0, 95% CI = 1.4-2.9; EBGM = 1.7, 90% CI = 1.2-2.2), and lipodystrophy (ROR = 146.0, 95% CI = 96.1-221.8; EBGM = 116.0, 90% CI = 81.7-160.8). Findings identified significant post-marketing safety signals of Lantus and Semglee. Longitudinal studies are warranted to verify these signals.

Belzutifan, a first-in-class HIF-2α inhibitor, has been approved for von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC) and previously treated sporadic RCC. While its safety profile has been characterized in LITESPARK clinical trials, real-world pharmacovigilance data remain limited. This study evaluated the characteristics (including frequency, system-specific toxicities, and time-to-onset) of real-world belzutifan-associated adverse events (AEs), aiming to identify emerging safety signals, and assessing potential disease progression-related AEs using data from the FDA Adverse Event Reporting System (FAERS). FAERS reports related to belzutifan were retrieved for the period Q1 2004 to Q4 2024. Duplicate reports and those flagged for deletion were excluded. Disproportionality analysis was conducted using Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and the Medicines and Healthcare Products Regulatory Agency (MHRA) method to identify significant safety signals. Time-to-onset analysis was performed to assess adverse event (AE) occurrence patterns. A total of 248 AE reports were identified, with an increasing trend following FDA approvals in 2021 and 2023. The most frequently reported AEs were anemia (ROR: 19.00, 95% CI 13.51-26.73) and hypoxia (ROR: 59.48, 95% CI 38.09-92.88), consistent with clinical trial data. Significant signals for neurological (brain fog), hepatic (liver injury), metabolic (hypocalcemia), and respiratory (pneumonia) AEs were also observed. Reports of disease progression-related AEs were also prominent. A majority (71.1%) of AEs occurred within the first 6months of treatment initiation, suggesting the need for early monitoring. This study provided the first real-world pharmacovigilance assessment of belzutifan, confirming expected AEs while identifying emerging safety signals. Close monitoring of hematologic, respiratory, hepatic, and neurological toxicities is warranted. Further prospective studies are needed to optimize patient selection and improve AE management.

Objective: Carpal tunnel syndrome (CTS) is a prevalent compression neuropathy with multiple well-documented mechanical and systemic risk factors. However, the role of pharmacological agents in the development of CTS remains underexplored. This study aims to identify drugs disproportionately associated with CTS reports using data from the Food and Drug Administration Adverse Event Reporting System (FAERS).Methods: A retrospective pharmacovigilance analysis was conducted using OpenVigil 2.1 to evaluate adverse event (AE) reports of CTS from the FAERS database from October 2003 to September 2024. Only drugs identified as the primary suspect in at least 10 AE reports were included. Disproportionality analysis, including reporting odds ratios (RORs), was used to assess associations between CTS and specific drugs. Positive signals were validated using Bayesian confidence propagation neural network algorithms, with drugs having ROR ≥10 and significant Bayesian confidence intervals (IC025 > 0) considered strongly associated with CTS.Results: Of 12,929,504 AEs reported during the study period, 6,837 (0.05%) involved CTS. Female patients comprised 69.5% of CTS cases, with a mean age of 57.0±14.9 years. Ten drugs were found to have significant overreporting of CTS, including idursulfase (ROR=51.2, 95% CI=39.0-67.2), galsulfase (ROR=26.8, 95% CI=17.2-41.7), laronidase (ROR=20.9, 95% CI=14.4-30.3), tesamorelin (ROR=20.7, 95% CI=13.7-31.3), anastrozole (ROR=20.6, 95% CI=17.0-24.9), alendronic acid (ROR=17.1, 95% CI=14.5-20.1), gamma-hydroxybutyric acid (GHB) (ROR=16.3, 95% CI=9.6-27.6), rofecoxib (ROR=16.1, 95% CI=14.3-18.2), alendronate (ROR=12.9, 95% CI=11.0-15.2), and tafamidis (ROR=12.0, 95% CI=9.2-15.7).Conclusions: Several drugs were disproportionately associated with CTS in the FAERS database, including enzyme replacement therapies (ERTs), aromatase inhibitors, bisphosphonates, growth hormone (GH)-releasing factor analogs, GHB, rofecoxib, and tafamidis. These findings highlight the critical need for increased vigilance and monitoring of new-onset or worsening CTS in high-risk populations prescribed the aforementioned medications. Clinicians should carefully scrutinize pharmacological history when evaluating patients in this context.

BackgroundNumerous digestive system adverse events (dsAEs) have been observed during the use of anti-obesity medications (AOMs), leading to concerns about the safety of these medications. However, most current studies are limited to the association of one class of drugs with specific digestive disorders, and there is no cascading analysis of AOMs in the digestive system. This study aims to use data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) for a stratified analysis of the reported associations between AOMs and dsAEs.MethodsWe analyzed adverse event reports submitted to FAERS between January 2015 and December 2023 related to obesity treatment. It is important to note that FAERS data cannot establish causality or incidence rates. Pharmacovigilance (PV) signals were detected by disproportionate analyses through proportionate reporting ratio (PRR), reporting odds ratios (ROR), and information components (IC) to detect dsAEs associated with AOMs. Reporting rates, severity, and response outcomes of digestive adverse events were compared across AOMs by multivariate logistic regression analysis.ResultsAmong 34,396 adverse events (AEs) related to obesity treatment, 8844 dsAEs were analyzed. Comparing with semaglutide and liraglutide, tirzepatide exhibited fewer reported dsAEs while semaglutide and liraglutide showed a high correlation with non-lethal pancreatitis reports. Bupropion-naltrexone (31.65%) reported the highest number of dsAEs, and a PV signal was detected in mouth and lips AEs (ROR = 2.97, 95% CI: 2.42–3.6). Orlistat (ROR = 3.30, 95% CI: 3.08–3.55) exhibited the highest association with gastrointestinal AEs compared to other AOMs. PV signal for hepatobiliary AEs (ROR = 6.13, 95% CI: 3.45–10.88) with phentermine-topiramate still needs further clarification.ConclusionsTirzepatide may be considered for patients with a history of digestive system disease or an elevated risk of pancreatitis based on the pattern of reported dsAEs. Caution is needed for the orofacial AEs when using bupropion-naltrexone. Orlistat has a higher reporting rate of gastrointestinal AEs, but these events are typically less severe. Phentermine-topiramate’s association with liver impairment requires further clinical investigation. This article provides insights into the reported associations between AOMs and dsAEs, which may aid clinicians in making more informed decisions about individualizing medication and managing potential adverse events.

ObjectiveTo comprehensively analyze the safety profile of Methotrexate in clinical use, clarify the incidence of adverse reactions and associated influencing factors, and provide evidence for safe medication practices in clinical settings.MethodsThis study retrieved data from the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the fourth quarter of 2024. Data filtering was conducted on the main suspect drug. Data extraction and cleaning were performed using R software, and various statistical methods, including ROR (Reporting Odds Ratio), PRR (Proportional Reporting Ratio), BCPNN (Bayesian Confidence Propagation Neural Network), and MGPS (Multi-Item Gamma Poisson Shrinker), were employed to detect adverse drug reaction signals. Subgroup analyses based on gender, age, and reporter categories were performed to explore differences.ResultsA total of 130,818 methotrexate (MTX)-related adverse event (AE) reports were included. Females accounted for 64.2% of reporters, with adults aged 18–64.9 years reporting the most. AEs primarily affected the immune, musculoskeletal, and hematologic systems. “General Disorders and Administration Site Conditions” was the most frequently reported system organ class [n=106,183, ROR (95% CI)=1.21 (1.21–1.22)], while “Immune System Disorders” showed the strongest signal [n=13,313, ROR (95% CI)=2.35 (2.31–2.39)]. Adverse reactions varied by gender and age: females were more likely to report Drug Hypersensitivity [n=6,192, ROR (95% CI)=4.69 (4.57–4.82)], while males reported Nausea more often [n=1,624, ROR (95% CI)=1.17 (1.12–1.23)]. Elderly patients (≥65 years) had an increased risk of drug hypersensitivity [n=2,894, ROR (95% CI)=7.91 (7.61–8.22)]. Reporting priorities differed: consumers frequently reported “Drug Ineffective” [n=5,729, ROR (95% CI)=2.24 (2.18–2.3)] and “Pain” [n=1,746, ROR (95% CI)=1.69 (1.61–1.77)], while healthcare professionals focused on DRUG INEFFECTIVE [n=9,982, ROR (95% CI)=4.16 (4.08–4.25)]. Additionally, the time to onset of MTX-induced AEs varied significantly across subgroups.ConclusionThis study reveals the safety characteristics of MTX in clinical use, confirms known adverse reactions, and identifies new potential adverse effects. It suggests that clinicians should enhance monitoring based on patient factors such as gender and age, particularly for immune system-related adverse reactions in elderly patients. Moreover, the spectrum of MTX’s side effects may be broader than previously recognized, warranting further research to ensure patient safety in drug use.

The present study aimed to evaluate the non-inferiority of low-volume oral sulfate solution (OSS) to 4-L polyethylene glycol (PEG) solutions administered in a split-dose regimen as bowel preparation for colonoscopy. The safety and tolerability were also compared between the two regimens. In this prospective, randomized, single-blind, active-control, parallel group, and non-inferiority trial, consecutive outpatients and health checkup recipients aged 19-65 years undergoing elective colonoscopy were enrolled to receive OSS or 4-L PEG in a split-dose regimen. The quality of bowel preparation was evaluated using the Boston Bowel Preparation Scale. The occurrence of any adverse events, acceptance, compliance, and satisfaction during bowel preparation were evaluated by participant interviews. Overall, 210 participants were randomized, and 199 were administered by the study agents. Adequate bowel preparation was achieved in 98.0% (97/99) of the OSS group, which was non-inferior to the PEG group (96%; 96/100) with a difference of +2.8% (95% confidence interval; -2.8, +6.8). There were no differences in the incidence of adverse events except for abdominal pain, which was more frequent in the OSS (7.1%, 7/99) than in the PEG (1.0%, 1/100; P = 0.035) group. Acceptance, compliance, and satisfaction were significantly higher in the OSS than in the PEG group (all P < 0.05). Split-dose OSS was non-inferior to split-dose 4-L PEG with regard to bowel preparation efficacy before colonoscopy in adult outpatients or screening colonoscopy recipients aged ≤65 years with acceptable safety and superior tolerability.