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.
Background: Adverse drug reactions (ADRs) are a significant cause of increased morbidity and mortality, prolonged hospitalisation, and financial burden on patients. Regular ADR monitoring helps formulate strategies for the safe and effective use of medicines in healthcare settings. This study was conducted to assess the trends in ADR reporting along with their various aspects. Methods: This record-based observational study was conducted at the ADR Monitoring Centre of our healthcare facility. ADRs reported from April to September 2023 were analysed. The WHO-UMC scale, Modified Hartwig Severity Assessment Scale and Modified Schumock and Thornton Scale were used to assess the causality, severity, and preventability of ADRs, respectively. Descriptive statistics were used for the analyses. Results: A total of 146 adverse drug reactions (ADRs) were reported during the study period. Of these, 68.49% of the ADRs were reported from the Department of Psychiatry. Female patients accounted for 53.42% of reported ADRs. Neurological system involvement was observed in 32.9% of the ADRs. Escitalopram was the most frequently implicated drug. Causality assessment revealed that 63.01% of ADRs were possible. Meanwhile, 83% of the ADRs were mild in severity, and a total of five ADRs were found to be serious in this study, none of which were fatal. Furthermore, 39.73% of the ADRs were classified as probably preventable Discussion: The predominance of neuropsychiatric ADRs observed in this study may reflect both prescribing patterns and improved recognition of CNS-related adverse effects in psychiatric practice. These findings also highlight the importance of strengthening ADR reporting practices across all departments. Conclusion: The ADR reporting pattern observed in this newly established tertiary healthcare facility in eastern India may help increase physicians’ awareness of the importance of timely ADR reporting and support their clinical decision-making process.
Introduction: Dapsone (4,4’- diamino diphenyl sulfone, DDS) is an antimicrobial sulfonamide used for non-dermatological and dermatological disorders. Dapsone has been associated with a wide range of cutaneous adverse effects, with photosensitivity being an unusual side effect. Case Presentation: A case of dapsone-induced photosensitivity was reported in a patient with lepromatous leprosy. A 46-year-old male patient complained of redness and scaling, with itching over his face, nape, the flexural aspect of his neck, and bilateral upper and lower limbs, during the second month of multidrug multibacillary therapy. Examining the face, neck, and upper and lower limbs revealed erythematous scaly plaques with crusting and fissuring. Dapsone-induced photosensitivity was suspected, and the drug was stopped immediately. The patient was started on 0.5 mg/kg of prednisolone, antihistamines, and sunscreen. After improving symptomatically, the patient was discharged from the hospital and started on multidrug multibacillary therapy without dapsone. Conclusion: Although it is uncommon, dapsone-induced photosensitivity should be taken into account when patients exhibit photodermatoses while receiving treatment. Morbidity and unnecessary regimen discontinuation can be avoided with early detection followed by prompt care. This case emphasizes how crucial it is for physicians to be aware of this unusual side effect.
INTRODUCTION:Metabolic disorders have grown more common, with obesity representing a significant chronic illness that leads to various severe health complications. The Obesity Atlas 2022 predicts one billion obese people by 2030. Contributors to obesity encompass heightened oxidative stress, hyperlipidemia, hunger enhancement, fat accumulation, insulin resistance, and diminished caloric expenditure. Numerous synthetic interventions for obesity are accessible today ; nonetheless, they frequently entail detrimental side effects. This research aimed to investigate the formulation of a prospective anti-obesity drug derived from plant origins. METHODS:The anti-obesity effectiveness of a polyherbal formulation, derived from the ethanolic extract of both Hugonia mystax and Blumea lacera in a 1:1 ratio, was assessed in female mice with progesterone-induced obesity. RESULTS:The preliminary phytochemical screening of the formulation specifies the presence of phenolic acids, flavonoids, and tannins. In accordance to OECD recommendations, 200 mg/kg and 400 mg/kg were designated after performing acute oral toxicity assessment as a low dose and high dose. During the study, body weight, BMI, abdomen circumference, glucose levels, lipid profile, SGOT, SGPT, atherogenic index, lipid peroxidation (LPO), and glutathione (GSH) levels were evaluated in all groups. The treatment markedly corrected the abnormal levels of these parameters and dramatically restored GSH levels. DISCUSSION:Metabolic disorders, especially obesity, are increasing globally. Synthetic therapies have negative consequences; therefore, exploration of plant substitutes is encouraged A polyherbal extract of Hugonia mystax and Blumea lacera has shown significant anti-obesity properties in mice. It restored biochemical parameters, likely due to phytochemicals such as polyphenols. Histological examination validated its therapeutic efficacy. CONCLUSION:The formulation's efficacy in addressing obesity is likely attributable to the presence of polyphenols, saponins, and terpenoids. Histopathological examination of hepatic and adipose tissues further corroborated the anti-obesity efficacy of the polyherbal formulation. Future research will focus on isolating and identifying the active chemicals in both plants to better understand their composition.
Background: Drug-Induced Liver Injury (DILI) is a leading cause of acute hepatic impairment. Underlying liver disease, drug–drug interactions, and multiple hepatotoxic exposures can exacerbate injury. Nutraceuticals may have hepatoprotective potential. Case Presentation: A 37-year-old woman with obesity, hypertension, and PCOS presented with epigastric pain. Two weeks prior, she had taken acetaminophen (1,000–2,000 mg/day), levonorgestrel (three days before admission), and mushrooms one day prior. Laboratory tests revealed elevated AST, ALT, γ-GT, and bilirubin. Imaging showed fatty liver and microlithiasis. DILI was diagnosed, attributed primarily to acetaminophen and methyldopa, in the context of Non-alcoholic fatty liver disease. Offending drugs were discontinued; supportive therapy included ursodeoxycholic acid, dietary modifications, and a nutraceutical formulation (Drolessano®) for 3 months. Liver enzymes peaked on day 11 but gradually improved. By day 64, AST, ALT, and γ-GT normalized, total and indirect bilirubin were normal, and direct bilirubin was slightly elevated (0.55 mg/dL). Conclusion: DILI can result from multiple interacting factors, including polypharmacy and underlying liver disease. Prompt withdrawal of hepatotoxic agents and supportive
Introduction: Bisphosphonates (BPs) are commonly used to treat osteoporosis as well as Bone Marrow Edema (BME). Potential adverse effects include hypocalcemia, flu-like symptoms, musculoskeletal pain, gastrointestinal issues, and, rarely, osteonecrosis of the jaw. This study evaluated the safety of intramuscular formulations of neridronate, clodronate, and their sequential combination in patients with BME. Methods: A retrospective observational study was performed on 128 outpatients referred for BME between May 2020 and June 2025. Primary outcome was reduction in clinical symptoms; secondary outcomes included Adverse Drug Reactions (ADRs) and Drug–Drug Interactions (DDIs). results: In this study we enrolled 128 patients (69 females and 59 males) with a median age of 66 years (IQR: 54.5-75). The median number of sessions needed for recovery differed depending on the drug group: Neridronate took 4 sessions (IQR: 3–4), Clodronate took 12 sessions (IQR: 5–23), and the combination of Clodronate and Neridronate took 14 sessions (IQR: 9–23). No significant interactions were observed between drug type and sex, age, or the presence of other diseases. Results: Median age was 66 years (IQR: 54.5–75), with 69 females and 59 males. Median sessions to recovery were 4 (neridronate), 12 (clodronate), and 14 (combination). Negative binomial regression showed that significantly more sessions were required for clodronate and combination therapy compared with neridronate. No severe ADRs occurred, despite polytherapy and potential DDIs. Male patients showed a non-statistically significant trend to a lower number of sessions and potentially inappropriate prescription. The number of medications was the only factor directly related to DDIs (p < 0.05). Discussion: The lower number of median sessions for clodronate was likely due to a small sample size. The low number of side effects is probably related to intramuscular administration. Factors like age and sex can be relevant in the onset of DDIs in other clinical contexts, but our population displayed a relatively low median age. Conclusion: Bisphosphonates were safe and effective for BME in our cohort, with a low risk of clinically relevant DDIs. However, larger studies are needed to confirm these results.
Introduction: Chronic low-grade inflammation is a recognized risk factor for several chronic diseases, including metabolic, cardiovascular, and neurodegenerative disorders. This study aimed to evaluate the effects of a new fixed nutraceutical combination as an add-on to the standard therapy in patients with basal inflammation. Methods: We conducted an observational, prospective, open-label study in patients attending the Clinical Pharmacology Operative Unit, University Magna Graecia of Catanzaro, Italy. Fifty-six patients (aged 33–86 years) were enrolled and received one tablet daily of the fixed nutraceutical combination for three months. Laboratory assessments were performed at baseline (T0), three months after the end of treatment (T1), and six months after the end of the study (T2) to evaluate blood inflammatory biomarkers and metabolic parameters. Quality of life and mood were assessed using the SF-36, Zung Self-Rating Anxiety Scale, and Zung Self-Rating Depression Scale, while adverse drug reactions (ADRs) were assessed using the Naranjo scale. Results: All patients completed the study. A time-dependent improvement in quality of life was observed (SF-36: T0, 52 ± 11; T2, 86 ± 7), along with significant reductions in anxiety and depression scores (P < 0.05). Inflammatory biomarkers decreased significantly in a time-dependent manner (P < 0.01). Liver function markers, low-density lipoprotein cholesterol, and triglycerides improved, while high-density lipoprotein cholesterol increased (P < 0.05). No ADRs were reported during the study period. Discussion: The observed clinical benefits are likely due to the synergistic anti-inflammatory and antioxidant effects of the nutraceutical components. Silymarin and glutathione may reduce oxidative stress and protect liver function, while tryptophan may improve mood and emotional well-being. Conclusions: In this cohort, nutraceutical supplementation was well tolerated and associated with improvements in liver function, lipid profile, inflammatory markers, and quality of life. These preliminary observations warrant further investigation in randomized controlled trials to confirm efficacy and clarify the underlying mechanism.
Introduction: Metformin-associated lactic acidosis is a rare but life-threatening complication of a widely prescribed therapy for type 2 diabetes. This case report describes a fatal outcome following intentional metformin intoxication in a vulnerable patient with intellectual disability. Case Presentation: The patient was initially asymptomatic but shortly became unresponsive and died. The cause of death was established as metformin intoxication through postmortem toxicological analysis, which revealed a cardiac blood metformin concentration of 53.60 μg/mL. This finding was supported by the presence of metformin tablet debris in the gastric contents and the exclusion of alternative causes, including traumatic injury and co-ingested sulfonylureas. Conclusion: This case underscores the critical need for early detection of metformin toxicity and highlights the essential role of clinical toxicology in guiding postmortem diagnosis.
Pharmacists play a significant role in oncology with respect to the safe handling and administration of anti-cancer drugs. This comprehensive review analyses pharmacists’ roles, emphasising adherence to national and international safety standards and the implementation of institutional programs for protocols, training, and certification. Pharmacists will aid in the formulation and adjustment of chemotherapy medications through Personal Protective Equipment kits and working practices. Among administration methods, intravenous chemotherapy, oral anticancer agents, and special routes, such as intrathecal, can be used. Other notable responsibilities of pharmacists' work are medication safety, occupational exposure risk, and pharmacovigilance. Pharmacists can gain practical insights through case studies and possibly help prevent and control errors by implementing systemic strategies. Pharmacists are also involved in counselling and teaching patients for treatment, managing side effects, and other policies that enhance compliance. This review provides valuable insights into interprofessional collaboration to improve patient safety and achieve optimal outcomes. Emerging technologies and innovations are having a growing impact on medication management, and pharmacists have been recognised as playing a vital role in ensuring safe adoption in oncology practice. Continuous education and professional development enable pharmacists to stay up to date on the latest advancements, providing the best possible care. This review discusses the essential contributions pharmacists make to the oncology department by improving the care, safety, and efficacy of anticancer treatment, demonstrating their commitment to excellence and adaptability in healthcare settings.
Background The diagnosis of drug-induced liver injury (DILI) is difficult due to insufficient awareness of DILI and the lack of specific objective diagnostic tests. The importance of pharmacists' care during hospitalization is underestimated. Our aim is to review the clinical features of fluoroquinolone-induced liver injury and to highlight the importance of pharmacists' intervention in fluoroquinolone-induced liver injury. . Case presentation: An 81-year-old Chinese man was admitted to hospital for the treatment of community-acquired pneumonia. After admission, he developed chronic subdural hematoma as his condition deteriorated, followed by intracranial infection after the cranial trepanation. On day 15, the patient still presented with fever and altered consciousness. Moxifloxacin (IV, 400 mg QD) was administered as the pulmonary infection became worse. Elevated liver enzymes were then observed with alanine aminotransferase (ALT) rising from 27 U/L to 387 U/L after the three-day use of moxifloxacin. With the help of pharmacists' interventions, drug-induced liver injury was identified. Moxifloxacin was discontinued immediately and replaced with meropenem (IV, 1g, Q8h). Within another 7 days, the patient's fever subsided, liver function normalized, and consciousness improved. He was successfully discharged from the hospital 30 days after admission. Written informed consent was obtained from the patient. Ethics approval was waived by the Institutional Review Board of Taikang Tongji (Wuhan) Hospital. Conclusions: Fluoroquinolone-induced liver injury are rare but can be lethal. Pharmacists' interventions enable collaborative decision-making and can help improve the management in fluoroquinolone-induced liver injury.
INTRODUCTION:Explainable Artificial Intelligence (XAI) is rapidly transforming drug safety assessment by making complex AI models interpretable, transparent, and trustworthy for clinicians, healthcare regulators, and patients. This study emphasizes recent advances in the methodologies of XAI, including rule-based, post hoc, and hybrid models, and assesses the effectiveness of these approaches in pharmacovigilance and drug discovery. METHOD:This paper evaluates the state-of-the-art techniques in XAI methods, such as methodbased or rule-based approaches, post-hoc explanation methods, and hybrid methods in general, used in drug safety and pharmaceutical-related research and applications. The role and treatment of explainability in AI in the EU AI Act and EU MDR regulations will also be discussed in this paper. RESULTS:Integration of XAI into clinical prediction systems (CPS) evaluation will increase the level and quality of transparency and error identification, and clinician trust, although with a trade-off between interpretation and accuracy within prediction tasks. There is a shift towards greater focus on transparency and human evaluation mentioned within regulatory frameworks, although there is no standardization with respect to clinical prediction systems (CPS) evaluation and validation of XAI. DISCUSSION:Emerging technologies emphasize the importance of clinician-centric design, personalized and causal inference-based explanations, and the integration of technical aspects and clinician feedback. Large research gaps are present in the standardization of evaluation criteria, ethical integration, and real-world clinically valid XAI systems. CONCLUSION:In clinical applications associated with drug safety, emerging areas of research should be targeted towards collaborations, evaluations, and XAI design adaptable to meeting growing demands for operation, acceptability, and patient safety.
BACKGROUND:Methylcobalamin is a naturally occurring, active form of Vitamin B12. Vitamin B12 is essential for the growth and development of healthy nerves and red blood cell production. Usually, the requirement of vitamin B12 is increased in thyrotoxicosis due to increased utilization and accelerated turnover imposed by increased metabolism. Vitamin B12 is generally well-tolerated and widely used in clinical settings. Parenteral vitamin B12 treatment in hospitalized patients is considered an effective therapy regardless of its etiology. CASE PRESENTATION:Herein, we report the case of a 26-year-old female patient admitted to the Obstetrics and Gynaecology department. She received a slow intravenous methylcobalamin injection on the 4th day of admission for his complaints. Then, she was administered with 2nd dose of intravenous methylcobalamin, after which she developed anaphylactic shock immediately. To address these serious adverse effects, the patient was administered Critical care with cardiopulmonary resuscitation without further delay. The patient had a spontaneous return of circulation within a few minutes of high-quality cardiopulmonary resuscitation. After treatment, the patient recovered and was discharged from the hospital. CONCLUSION:Anaphylactic shock, after slow intravenous methylcobalamin injection, is an uncommon but potentially serious adverse effect. The purpose of this case report is to highlight the importance of this rare but serious life-threatening adverse effect. To our knowledge, this is the first reported case of intravenous methylcobalamin-induced anaphylactic shock. Physicians and healthcare teams should be cautious while administering methylcobalamin to patients, especially via the intravenous route.
BACKGROUND:Omega-3 fatty acids (omega-3 FAs) have been studied for the potential treatment of Atopic Dermatitis (AD). Dietary supplementation with omega-3 FAs may help in reducing AD symptoms, including the severity of lesions, inflammation, dryness, and pruritus. Nevertheless, because of their antiplatelet action, more cautious use of these supplements has been recommended in patients who have an invasive procedure or who are receiving antiplatelet or anticoagulant therapy. CASE PRESENTATION:An 18-year-old male patient with AD self-medicated with 1 gram of overthe-counter omega-3 fatty acid orally once daily for 4 weeks. Over this time, he had ten episodes of epistaxis. Baseline coagulation parameters, such as prothrombin time, activated partial thromboplastin time, and platelet count, were also normal. The patient was not on medications affecting the hemostatic process, nor were there any previous polyps or other structural nasal disorders. CONCLUSIONS:The potential of omega-3 FA supplementation to increase risk of bleeding, even at typical doses used in clinical trials, should be considered as demonstrated in this case.
BACKGROUND:Azelastine is widely used in the treatment of allergic rhinitis, and it is necessary to gain insight into the true extent of adverse events (AEs) associated with it. METHODS:This pharmacovigilance study was based on an analysis of reports from the FDA Adverse Event Reporting System (FAERS) for the period January 1, 2006, to December 31, 2024. AEs of drugs were compared using the Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPN), and Multi-item Gamma Poisson Shrinkage (MGPS). RESULTS:The number of AE occurrences in Respiratory, thoracic, and mediastinal disorders and Product issues was high. There is a significant difference in the proportion of occurrence between men and women. All AEs listed in the drug insert were validated through this analysis. In addition to the improvement of the drug process, the focus should still be on the adverse reactions such as Dysgeusia, Nasal discomfort, and Somnolence. CONCLUSION:This study systematically depicts the safety profile of azelastine by analysing large-scale adverse reaction data and provides empirical evidence for the improvement of clinical dosing guidelines and risk communication strategies. Pharmacovigilance departments should maintain vigilance for rare but serious adverse reactions to azelastine to optimize its risk-benefit profile.
INTRODUCTION:Glucagon-like peptide-1 receptor agonists are widely prescribed for diabetes and obesity. The association between GLP-1 RAs and thrombotic events remains unclear, with conflicting evidence from clinical and experimental studies. This study aims to assess the reporting of thrombotic adverse events with GLP-1 RAs in the FDA Adverse Event Reporting System (FAERS). METHODS:A retrospective pharmacovigilance analysis of FAERS reports was performed. Thrombotic adverse events were identified using Standardized MedDRA Queries. Disproportionality was assessed via Reporting Odds Ratios. Time-to-onset was analyzed, and comparative analyses were conducted with Orlistat and SGLT2i. RESULTS:1,618 unique thrombotic AE reports involving GLP-1 RAs were identified. Arterial events predominated (55.3%), followed by venous (23.2%) and mixed events (21.5%). Compared with all other drugs, GLP-1 RAs were not disproportionately associated with thrombotic AEs (overall ROR = 0.67, 95% CI: 0.64-0.71). Venous events showed the lowest disproportionality (ROR = 0.53, 95% CI: 0.48-0.59). Liraglutide displayed higher RORs than other GLP-1 RAs, while tirzepatide showed the lowest. Compared with Orlistat, GLP-1 RAs had markedly lower odds of venous events (OR 0.27), and, versus SGLT2i, lower odds across all event types. DISCUSSION:In this large FAERS analysis, GLP-1 RAs did not show a disproportionate reporting signal for thrombotic events and, in several comparisons, appeared to have lower thrombotic reporting than alternative agents. While limitations of spontaneous reporting preclude causal inference, these findings provide reassuring real-world safety data. CONCLUSION:GLP-1 RAs were not associated with thrombotic AEs in FAERS and may confer a protective profile. Continued post-marketing surveillance is warranted.
INTRODUCTION:Acute Kidney Injury (AKI) is a rapid decline in renal function. Colistin, a last resort antibiotic for multidrug-resistant infections, is associated with significant nephrotoxicity. Cerium oxide nanoparticles (CeONPs) are potent scavengers of reactive oxygen species (ROS), exhibiting antioxidant and anti-inflammatory properties. This study aimed to investigate the protective effects of CeONPs against colistin-induced renal damage in adult male albino rats. METHODS:Forty-eight adult male albino rats were equally divided into four groups: Group I (Control), Group II (CeONPs), Group III (Colistin), and Group IV (CeONPs + Colistin). At the end of the experiment, blood samples were collected to assess renal function by measuring serum urea and creatinine. Kidney tissue was processed for histological examination and immunohistochemical staining to evaluate the expression of the inflammatory marker for nuclear factor Kappa B (NF-κB). RESULTS:Colistin administration in Group III resulted in significant renal impairment, characterized by elevated serum urea and creatinine, severe histopathological damage (including tubular necrosis), and a marked increase in NF-κB expression. In contrast, rats pre-treated with CeONPs (Group IV) demonstrated significantly improved kidney function tests, a substantial reduction in histopathological lesions, and a notable decrease in NF-κB expression compared to the colistin group. DISCUSSION:Colistin induces AKI through increased membrane permeability, oxidative damage, and acute tubular necrosis. This oxidative stress upregulates inflammatory mediators like NF- κB, exacerbating tissue injury. The renoprotective effect of CeONPs is attributed to their unique ability to switch between Ce³⁷ and Ce³⁷ oxidation states, allowing continuous ROS scavenging. By reducing oxidative stress, CeONPs also suppress the NF-κB-mediated inflammatory pathway. CONCLUSION:CeONPs exhibit notable nephroprotective effects against colistin-induced AKI through their antioxidant and anti-inflammatory characteristics. These findings propose CeONPs as a potential therapeutic adjunct to reduce nephrotoxicity in patients requiring colistin treatment.
INTRODUCTION:With the rising incidence of Influenza-like Illness (ILI), comprehensive studies on causative drugs remain lacking. This study aimed to detect drugs associated with ILI through disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database. METHODS:Adverse Event (AE) reports were extracted from the FAERS database for the period spanning 2004 Q1 through 2025 Q1. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify ILI cases. Four statistical methods were employed to identify drugs with positive signals: the Reporting Odds Ratio (ROR), the Proportional Reporting Ratio (PRR), the Bayesian Confidence Propagation Neural Network (BCPNN), and the Empirical Bayes Geometric Mean (EBGM). RESULTS:Our analysis identified 77,060 ILI-associated reports. A total of 60 drugs exhibited positive signals. The 5 most frequently reported drugs were interferon β-1a, evolocumab, ofatumumab, interferon β-1b, and zoledronic acid. Under the ATC1 classification, antineoplastic and immunomodulating agents accounted for the majority of reported cases (n=43,436), followed by nervous system agents (n=8,941), cardiovascular system agents (n=6,871), and musculoskeletal system agents (n=5,577). Weibull shape parameter analyses revealed β<1 for most drugs, indicating that drug-induced ILI predominantly manifested early failure types. DISCUSSION:This study confirms known ILI risks (e.g., interferons) and reveals new signals for immunotherapies and lipid-lowering agents, providing evidence for prescribing updates. Timeto- onset analysis shows declining risk over time, highlighting the need for early symptom monitoring. CONCLUSION:This first comprehensive FAERS study identifies key drugs associated with ILI, including interferon β-1a, evolocumab, ofatumumab, interferon β-1b, and zoledronic acid. Clinical monitoring for drug-induced ILI is essential to enhance medication safety.
INTRODUCTION:The mechanistic target of rapamycin (mTOR) pathway regulates cell growth, metabolism, and survival. Its dysregulation contributes to cancer, autoimmune disorders, neurodegeneration, and aging. While mTOR inhibitors such as Sirolimus, Everolimus, and Temsirolimus are therapeutically valuable, they are linked to significant adverse drug reactions (ADRs). OBJECTIVE:To investigate adverse events (AEs) and ADRs associated with mTOR inhibitors using the World Health Organization's VigiAccess database. METHODS:A retrospective descriptive analysis was conducted using ADRs reports from WHOVigiAccess (2000 onward). Data included patient demographics and geographic distribution. Statistical measures such as odds ratios and relative risks were applied to assess risks. RESULTS:Sirolimus showed a 132% increased risk of gastrointestinal (GI) hemorrhage, alongside oral ulceration, highlighting mucosal toxicity. It was also linked to a 67% higher risk of interstitial lung disease and a 63% increased likelihood of ascites. Temsirolimus was associated with a 40% higher risk of pneumonia and a 36% higher risk of sepsis, reflecting immunosuppressive effects. DISCUSSION:The findings underscore the diverse and serious ADRs of mTOR inhibitors, ranging from gastrointestinal and pulmonary complications to heightened infection risk. These outcomes emphasize the need for careful monitoring and risk-benefit evaluation in clinical use. CONCLUSION:mTOR inhibitors, while effective, pose substantial risks of ADRs including hemorrhage, lung disease, ascites, and infections. Clinicians should weigh therapeutic benefits against potential harms and adopt vigilant monitoring strategies to optimize patient safety.
