Background/Objectives: Pericardial syndromes cause significant morbidity, decreased quality of life, and rarely mortality. Drug-associated pericardial syndromes are underreported. This study characterized reports of pericardial disorders, described demographic and reporting features, and identified disproportionality signals across suspect drugs and therapeutic classes. Methods: This study analyzed FDA Adverse Event Reporting System reports from January 2000 to March 2025, using predefined preferred terms for pericardial syndromes. Duplicate and pediatric reports (<18 years) were excluded, resulting in 12,106 unique reports. A lower 90% confidence limit of the Empirical Bayes Geometric Mean (EB05)>2 and a lower limit of the 95% credibility interval of the Information Component (IC025)>0 were indicators of signals. Results: Raw counts of reports increased from 133 in 2000 to 939 in 2024. The cohort had a balanced sex distribution and a mean age of 55.5 years. Among females, antineoplastic (e.g., rituximab, EB05 = 13.3, IC025 = 3.7) and immunomodulating agents (e.g., adalimumab, EB05 = 3.1, IC025 = 1.6) were most frequently suspected. Among males, antithrombotic agents (e.g., aspirin, EB05 = 7.1, IC025 = 2.8) predominated. A higher age-adjusted reporting odds of death was observed in females versus males (OR=1.14, 95% CI 1.03-1.25; deaths: females n=1,030, males n=925). Discussion: Raw report counts of pericardial syndromes increased over 25 years, supporting heightened vigilance for drug-induced etiologies. Sex-stratified drug rankings were exploratory and do not demonstrate drug-by-sex interactions. The results extend the existing literature by providing a broad descriptive overview of the reporting landscape for pericardial disorders within a national spontaneous reporting system. Conclusions: Immunomodulating, antineoplastic, and antithrombotic agents generated reporting signals involving pericardial disorders, with sex-based differences and reported drug classes and outcomes. These findings do not establish causality and warrant confirmatory studies.
Introduction/ Background: Acute bilateral lower-extremity edema is uncommon and often results from medication side effects, acute heart failure, nephrotic syndrome, or bilateral deep vein thrombosis. Drugs such as dihydropyridine calcium channel blockers, corticosteroids, thiazolidinediones, and nonsteroidal anti-inflammatory agents are known to cause edema. Donepezil, a widely used acetylcholinesterase inhibitor for Alzheimer's disease, has not been previously linked to leg edema. Recognizing rare adverse reactions is essential for patient safety, as edema may indicate serious conditions. Case Presentation: A 75-year-old woman with Alzheimer's disease developed bilateral pitting lower leg edema six months after starting treatment with donepezil. She had no history of cardiac, renal, hepatic, or venous diseases. Laboratory tests, electrocardiography, chest X-ray, and computed tomography venogram were normal, except for mild anemia and a slightly reduced estimated glomerular filtration rate. The edema resolved three weeks after discontinuation and did not recur after the administration of rivastigmine. Conclusion: The temporal association and resolution upon drug cessation suggest a probable association. Possible mechanisms may include cholinergic-induced vasodilation, which increases capillary permeability.
Introduction: Antitubercular Drug-Induced Hepatic Dysfunction (ATDIHD) is a major challenge in treating tuberculosis, especially when using first-line drugs. Research shows that oxidative stress plays a central role in liver injury. Further, it triggers inflammatory and apoptotic pathways in liver cells. As a result, ATDIHD develops through an interplay between these pathways. Flavonoids can protect the liver from the damaging effects of TB medication by exerting antioxidant and anti-inflammatory effects. The study aimed to systematically evaluate preclinical evidence on the hepatoprotective effects of flavonoids and their mechanisms in ATDIHD. Methods: Data were collected from PubMed, Scopus, Google Scholar, and ScienceDirect to screen studies evaluating the protective effects of flavonoids against ATDIHD published up to 18 November 2025. Results: In this review, 38 studies were included. Most were preclinical, with only a few being clinical studies. Silymarin, quercetin, naringenin, and catechin showed protection against hepatic damage. Among these compounds, silymarin has been widely researched and supported by both preclinical and clinical studies. Quercetin has also been found to reduce liver toxicity by activating the Nuclear Factor Erythroid 2-related factor 2 (Nrf2) pathway and blocking Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling. Discussion: This review demonstrates that flavonoids may reduce hepatotoxicity by modulating oxidative stress, inflammatory responses, and apoptotic pathways, indicating their potential role as adjuncts to antitubercular therapy. Most of the available data, however, come from different preclinical models that use varied study designs, doses, and outcome parameters. This makes it difficult to directly apply the findings in clinical practice. Conclusion: Flavonoids show promising hepatoprotective effects in preclinical models of antitubercular drug-induced hepatic dysfunction. Further well-designed clinical studies are needed to confirm their effectiveness and safety as an add-on therapy.
The systematic monitoring of post-marketing drug safety is paramount to ensuring patient welfare and population-level health, requiring the timely detection and prevention of adverse drug events. Traditional pharmacovigilance schemes, which largely rely on spontaneous reporting, have weaknesses, including underreporting, delays in the detection of signals, and a lack of cohesion in data sources. As heterogeneous health data grows exponentially, conventional methods are becoming less effective at providing complete, real-time ADR monitoring. This study examined the potential of improved computational methods, particularly artificial intelligence (AI) and deep learning, to enhance pharmacovigilance practices. Neural network architectures, including Bidirectional Encoder Representations with Transformers (BERT), Long Short-term Memory (LSTM), and Convolutional Neural Networks (CNNs), are capable of detecting meaningful patterns in unstructured and complex data. Natural language processing methods have been identified as capable of interpreting free-text clinical narratives, PROs, and biomedical literature relevant to drug safety monitoring. A wide range of data environments has been studied, including electronic health records, global safety-reporting schemes, the scientific literature, and patient communities on the Internet. The commonly used performance evaluation metrics were also reviewed in this study to assess the model's strength and reliability. The feasibility of such technologies in practice can be seen in the field of operation of these robots, such as automated ADR detection using the FDA Adverse Event Reporting System (FAERS) and early signal detection via social media mining. These results indicate the potential for substantial improvements in current pharmacovigilance systems through the use of AI-based models that can identify latent relationships and deliver safety alerts in near-real time. Nevertheless, there are still problematic areas, including data heterogeneity, lack of standardization, algorithmic bias, low interpretability, and ethical and regulatory issues. This work highlights the need to ensure the integration of AI in pharmacovigilance by collaborating with other disciplines and revising regulatory guidelines. Overall, this research offers practical recommendations for the development of data-driven surveillance of drug safety in recent healthcare systems.
Background: Proton Pump Inhibitors (PPIs) are widely prescribed for acid-related disorders and are generally considered safe for short-term therapy. However, growing evidence has raised concerns regarding Serious Adverse Events (SAEs) associated with long-term PPI use. This systematic review synthesizes current evidence on the spectrum of SAEs linked to prolonged PPI exposure. Methods: A comprehensive literature search was conducted in MEDLINE, Scopus, and the Cochrane Library from database inception to August 2025. Eligible studies included randomized controlled trials, cohort studies, case–control studies, and meta-analyses reporting effect estimates (HR, RR, or OR) with 95% confidence intervals. Due to substantial heterogeneity in study design, populations, exposure definitions, and outcome measures, findings were synthesized narratively in accordance with PRISMA guidelines. Risk of bias was assessed using validated tools appropriate for each study design. Results: A total of 99 studies met the inclusion criteria. Chronic PPI use was associated with increased risks of several renal outcomes, including acute kidney injury, chronic kidney disease, endstage renal disease, and nephrolithiasis. Elevated risks were also reported for infectious complications, particularly Clostridioides difficile infection, campylobacteriosis, and spontaneous bacterial peritonitis. Gastrointestinal and hepatobiliary outcomes included microscopic colitis, inflammatory bowel disease, cholelithiasis, fundic gland polyps, and gastrointestinal malignancies. Neurological associations were observed for dementia and Parkinson's disease. Cardiovascular outcomes linked to longterm PPI use included stroke, myocardial infarction, heart failure, atrial fibrillation, venous thromboembolism, and hypertension. Additional associations were reported for type 2 diabetes mellitus, bone fractures, rheumatoid arthritis, respiratory infections, and increased all-cause mortality. Most evidence was observational and subject to residual confounding. Discussion: The findings of this systematic review demonstrate that chronic PPI use is associated with a broad and concerning spectrum of serious adverse events across multiple organ systems. The evidence is predominantly derived from observational studies, which are subject to residual confounding, protopathic bias, and reverse causality. The dose-response relationships observed in several studies strengthen the biological plausibility of these associations, particularly for renal outcomes, C. difficile infection, and bone fractures. The clinical implications are substantial given the widespread and often inappropriate long-term use of PPIs. This review highlights the urgent need for more judicious prescribing practices, periodic reassessment of treatment indications, and further high-quality research, including large prospective cohorts and ethically feasible randomized trials, to establish causal relationships and identify populations at greatest risk. Conclusion: Long-term PPI use is associated with a broad range of potential serious adverse events across multiple organ systems. Although causality cannot be definitively established, the consistency of findings and biological plausibility support cautious prescribing, periodic reassessment of longterm therapy, and consideration of alternative treatment strategies when appropriate.
