Expert Opinion on Drug Safety最新文献

Background: Ranitidine induced tumor adverse events remains a contradictory clinical question, due to the limited evidence of tumor risk associated with ranitidine in the real world. The purpose of this study was to evaluate the association of ranitidine with all types of tumors through the FAERS database and to provide a reference for clinical use.

Research design and methods: Cancer cases associated with ranitidine in the FAERS database from the first quarter of 2004 to the fourth quarter of 2023 were extracted to analyze demographic characteristics, and a disproportion analysis was performed.

Result: A total of 662,998 ranitidine-related cancer cases were screened, and the 50-59 and 60-69 groups accounted for the largest proportion. In PT signal detection, ranitidine was associated with 98 PT, including penal cancer stage II, gastric cancer stage II, et al. In terms of outcome events, adverse events were higher in men (20.65%) than in women (18.47%).

Conclusions: Ranitidine may induce various tumor-related adverse reactions, especially in long-term users and elderly patients. For these patients, tumor screening should be strengthened, and long-term use of ranitidine should be avoided. Since this study cannot prove causality, further evidence is needed for prospective studies with a larger sample size.

Background: Selective serotonin reuptake inhibitors (SSRIs) are the primary choice for antidepressant therapy in cancer patients with depression. Programmed death-1 and programmed cell death-ligand 1 (PD-1/PD-L1) play a critical role in immune checkpoint inhibitors. To date, there have been no studies reporting adverse events (AEs) associated with the real-world use of PD-1/PD-L1 inhibitors-SSRIs combination.

Research design and methods: This study included a comprehensive evaluation of AE cases covered PD-1/PD-L1 inhibitors-SSRIs combination (first quarter of 2004 to second quarter of 2024) using the FDA Adverse Event Reporting System (FAERS) database, and compared with the use of PD-1/PD-L1 inhibitors or SSRIs alone.

Results: By extracting a total of 807 reports of related AEs, the combination therapy was associated with a distinct AE profile characterized by an increased incidence of immune-related and systemic disorders, as well as a higher signal for adverse pregnancy and perinatal outcomes.

Conclusions: This study represents the largest report to date on PD-1/PD-L1 inhibitors-SSRIs -related AEs, providing valuable insights into the potential side effects of SSRIs for cancer patients with depression. Clinicians should exercise caution when prescribing SSRIs alongside PD-1/PD-L1 inhibitors, particularly in vulnerable populations such as pregnant women and those with significant comorbidities.

Introduction: Breast cancer (BC) remains a prevalent and challenging malignancy among women, with significant advancements in treatment strategies over the past decades. Traditional chemotherapy has been progressively supplemented by newer modalities, including Antibody-Drug Conjugates (ADCs), Immunotherapy (IO), and Targeted Therapies (TT). Despite these advancements, there remains a critical need for strategies that maintain efficacy while minimizing toxicity.

Areas covered: This review delves into metronomic chemotherapy (MC), a novel approach involving the frequent administration of low-dose chemotherapy without prolonged breaks. We explore MC's impact across various breast cancer subtypes, such as Estrogen Receptor-Positive (ER+), HER2-Positive, and Triple-Negative Breast Cancer (TNBC). The literature reviewed highlights MC's mechanisms, including its anti-angiogenic, immunomodulatory, and antiproliferative effects, and its potential to improve treatment tolerability and address drug resistance.

Expert opinion: MC represents a promising adjunct to existing therapies, particularly in advanced or resistant cases. Its unique dosing schedule could offer sustained antitumor activity with reduced toxicity, making it a viable option for long-term management. However, further research is warranted to establish optimal dosing regimens, identify predictive biomarkers, and delineate its role within combination treatment strategies. Clarifying these aspects could refine MC's application, potentially reshaping treatment paradigms and enhancing patient outcomes in breast cancer management.

Introduction: Duchenne muscular dystrophy (DMD) is a severe X-linked disorder characterized by progressive muscle weakness and eventual death due to cardiomyopathy or respiratory complications. Currently, there is no cure for DMD, with standard treatments primarily focusing on symptom management. Using immunosuppressive measures and optimized vector designs allows for gene therapies to better address the genetic cause of the disease.

Areas covered: This review evaluates the efficacy and safety of emerging DMD gene therapies as of 2024. It also discusses the potential of utrophin upregulation, gene editing, and truncated dystrophin as therapeutic strategies. It highlights safety concerns associated with these therapies, including adverse events and patient deaths. A comprehensive overview of developments covers topics such as CRISPR-Cas9 therapies, micro-dystrophin, and the potential delivery of full-length dystrophin.

Expert opinion: The FDA's recent approval of delandistrogene moxeparvovec (Elevidys) underscores the promise of gene replacement therapies for DMD patients. Understanding the mechanisms behind the adverse effects and excluding patients with specific pathogenic variants may enhance the safety profiles of these therapies. CRISPR/Cas9 therapies, while promising, face significant regulatory and safety challenges that hinder their clinical application. Optimal DMD therapies should target both skeletal and cardiac muscles to be effective.

Background: Autoimmune encephalitis (AE) is a neuroimmune disorder that presents significant diagnostic challenges. The FDA Adverse Event Reporting System (FAERS) database can help explore the relationship between drugs and AE, but comprehensive studies are lacking. This study aims to analyze the association between drugs and AE using the FAERS database, providing insights for clinical practice and pharmacovigilance.

Research design and methods: Adverse event reports in the FAERS database were analyzed, focusing on the incidence of drug-induced AE, as well as characteristics such as gender and age. Multiple statistical methods were employed to assess the association between drugs and adverse reactions.

Results: The study revealed that drug-induced AE predominantly occurred in individuals aged 41 and above, with a higher prevalence among female patients. Nivolumab and pembrolizumab were among the drugs most frequently reported for adverse drug reactions. However, only a minority of drug labels mentioned these adverse reactions.

Conclusion: This study underscores the potential risk of drug-induced AE, advocating for close monitoring in clinical practice. Further epidemiological investigations are warranted to elucidate the exact relationship between drugs and these disorders. While the FAERS database provides crucial leads for such research, additional studies and validation are necessary.

Background: Most antibiotics require dose adjustments in patients with chronic kidney disease (CKD) to avoid accumulation and toxicity. The aim was to characterize the use of systemic antibiotics in a group of patients with CKD and to adjust the dose according to the glomerular filtration rate (GFR).

Research design and methods: Observational study of patients with a diagnosis of CKD who received antibiotics between January-2021 July 2022. The Lexicomp® database was used to determine the dose adjustment according to the GFR.

Results: A total of 473 patients were included, average age of 72.6 years. Patients with CKD were in stage 3 (38.5%), stage 4 (23.5%), or stage 5 (38.1%). Cephalosporins (56.2%), penicillins (43.3%), and glycopeptides (20.3%) were the most widely used antibiotics. A total of 914 antibiotics were used, of which 39.5% did not require dose adjustment, 30.4% had no dose adjustment, and 30.1% had dose adjustment. Treatment with glycopeptides (adjusted Odds Ratio [aOR]:3.86; 95%CI:1.57-9.47), treatment with carbapenems (aOR:4.59; 95%CI:1.75-12.07), stage-4 CKD (aOR:31.61; 95%CI:9.77-102.29), and stage-5 CKD (aOR:21.29; 95%CI:3.66-123.61) increased the probability of receiving antibiotics without dose adjustment according to the GFR.

Conclusions: Almost one-third of the antibiotics used in this group of patients had no dose adjustment, which generates a significant risk of toxicity and the need to identify CKD in a timely manner and the appropriate use of antibiotics.

Background: Ezetimibe is known for its lipid-lowering safety and tolerability, but its real-world adverse effects have not been fully evaluated. In this study, adverse events associated with ezetimibe were investigated using the FAERS database for the period 2004 to 2023.

Research design and methods: Adverse events data for ezetimibe, spanning from the first quarter of 2004 to the fourth quarter of 2023, were standardized and analyzed using signal quantification methods like Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (EBGM).

Results: Among 11,550 adverse drug events reports with ezetimibe as the primary suspect drug, 211 preferred terms (PTs) were identified across 24 different system organ classes (SOCs).Notably, in addition to the adverse reactions already specified in the instruction manual, unstable angina (n = 120, ROR 30.53(25.47-36.58), PRR 30.41(25.49-36.28), IC 4.9(4.64), EBGM 29.85(25.66)), crush syndrome(n = 19,ROR 298.83(182.95-488.09), PRR 298.65(182.96-487.49), IC 7.97(7.29),EBGM 251.12(166.57)), and autoscopy (n = 7, ROR 28.81(13.64-60.85), PRR 28.80(13.68-60.65), IC 4.82(3.81), EBGM 28.30(15.14))were new adverse reactions that emerged as strong signals.

Conclusions: Ezetimibe is effective in lowering blood lipids, but there is a risk of adverse reactions such as unstable angina, rhabdomyolysis and autoscopy, which require careful monitoring by physicians.

Background: Ustekinumab is a fully human interleukin-12/23 (p40) inhibitor used to treat immune-mediated diseases. However, the limitations of clinical trials and the expanding target population necessitate an update on the ustekinumab-associated adverse events (AEs). We conducted signal mining for ustekinumab-related AEs using the United States Food and Drug Administration Adverse Event Reporting System (FAERS).

Research design and methods: AE reports were collected from 2009 Q3 to 2024 Q1. Four disproportionality analysis algorithms - reporting odds ratio, medicines and healthcare products regulatory agency, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker - were used to quantify the signals of ustekinumab.

Results: During this period 69,345 AE reports associated with ustekinumab were collected, and ustekinumab was identified as the primary suspect. Overall, 319 signals involving 15 system organ classes were identified, and 111 signals had a medium or strong value for IC₀₂₅. Of them, 67 were classified as important medical events. Squamous cell carcinoma, pertussis, vulval abscess, breast abscess, and fistula exhibited higher signal intensities.

Conclusions: Our study identified the risk signals for ustekinumab using real-world data and provides further evidence to support its rational use. Due to the limitations of FAERS, further studies are warranted to verify these findings.

Objective: The effectiveness and safety of the short-interfering RNA drug inclisiran in lowering patients' lipoprotein cholesterol levels to lower their risk of cardiovascular disease are presently being investigated. Based on the real-world adverse event report record in the FDA Adverse Event Reporting System, this article explores the occurrence and risk of adverse events during inclisiran treatment.

Research design and methods: We retrieved and screened all available data from the Food and Drug Administration website for the period from 2009 to the third quarter of 2023. In addition, we conducted a descriptive analysis of adverse event reports and calculated relevant pharmacovigilance measures, including reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and empirical Bayesian geometric mean.

Results: 4054 adverse reaction reports were filtered from 1151 patient reports of inclisiran. The top three incidence rates of adverse reaction signals for System Organ Class in adverse event reports are GENERAL DISORDERS AND ADMINITRATION SITE CONDITIONS (24.9% reported), MUSCOSKELETAL AND CONNECTIVE TISSUE DISORDERS (18.5% reported), and GASTROINTESTINAL DISORDERS (8.7% reported). The top five preferred terms screened for frequency of occurrence with the strongest risk signals for each of the top three system organ categories are INJECTION SITE PAIN，MYALGIA and DIARRHOEA.

Conclusions: Inclisiran has good long-term treatment outcomes and safety and can be used for a long time. However, attention should be paid to adverse events with high-risk signals, especially Injection Site Reactions.