Expert Opinion on Drug Safety最新文献

Introduction: Percutaneous nephrolithotomy (PCNL) is a widely used surgical procedure for treating large and complex kidney stones. Although effective, it carries risks of complications such as bleeding, infection, and injury to adjacent structures. Optimization of procedural techniques and perioperative care can help minimize these risks.

Areas covered: This review examines key pre- and post-operative safety considerations for PCNL patients. Topics include pre-operative imaging, patient positioning, puncture techniques, tract dilation, postoperative drainage, and complication management. The literature search involved analyzing recent studies and clinical guidelines to identify best practices. The search was conducted in several databases, including PubMed, Embase, the Cochrane Library and clinical guidelines. Training modalities for improving procedural skills are discussed.

Expert opinion: Improving the safety of PCNL requires a combination of meticulous surgical technique, proper patient selection, and adherence to standardized protocols. Continuous skill development and technological advancements will further improve patient outcomes.

Objective: This study analyzed the signal mining of adverse events caused by finerenone based on the US Food and Drug Administration Adverse Event Reporting System (FAERS) and evaluated the drug's safety to provide a reference for the safe administration of this medication in medical institutions.

Methods: FAERS data from the third quarter of 2021 to the fourth quarter of 2023 were used, and the adverse event codes of the Medical Dictionary for Regulatory Activities were compared. After the data were processed, adverse event reports that featured finerenone as the most suspected drug were extracted.

Results: A total of 905 reported cases of adverse events including finerenone as the first suspected drug were extracted. The ratio of male to female patients was 1.25, and most were aged 65-85 years (30.1%). The adverse events that were reported more frequently with positive signals were decreased glomerular filtration rate, hyperkalemia, increased blood creatinine, and dizziness. The adverse events that were concentrated on in investigations were metabolism and nutrition disorders and diseases of the renal and urinary system.

Conclusions: Our study identified significant novel adverse events (AEs) signals for finerenone that could provide support for clinical monitoring of and risk identification for finerenone.

Background: Dapagliflozin prevents myocardial dysfunction in chronic kidney disease patients regardless of residual kidney function. We hypothesized that this effect is extensible also to patients on dialysis.

Research design and methods: The DARE-ESKD-2 is an ongoing, single-center, open-label randomized clinical trial designed to determine the effects of adding dapagliflozin to standard treatment on myocardial function and structure. Eligible patients were adults on a regular dialysis scheme for more than 3 months. Pregnancy, liver failure, allergy to the investigational drug, and prior use of SGLT2i were exclusion criteria. Participants were randomized in a 1:1 ratio to dapagliflozin or standard treatment groups for 24-weeks. The primary goal is to compare the change in NT-proBNP levels between study arms, and secondary goals include comparing the between-group difference in left ventricle global longitudinal strain, indexed mass, ejection fraction, and E/e` ratio, and on symptoms scale and 6-minute walk test distance. An exploratory analysis will evaluate changes in body composition and bone densitometry.

Results: The trial has finished the enrollment of 80 patients, who are currently being followed-up.

Conclusions: This trial will provide novel data on myocardial effects of SGLT2i in dialysis recipients. Results from this study may provide evidence to support SGLT2i use in ESKD.

Objective: Utilizing the FAERS database, this study aims to analyze the ADE signals of sacituzumab govitecan to provide references for clinical safety.

Methods: By searching the US FAERS database, we applied Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) methods to analyze ADE reports for sacituzumab govitecan from Q2 2020 to Q4 2023, covering 15 quarters.

Results: The total number of reports with sacituzumab govitecan as the first suspicion was 2854. A total of 139 signals involving 26 SOCs were obtained. The most reported were general disorders and administration site conditions (2,307 cases, 25.66%), followed by gastrointestinal disorders (1,125 cases, 12.52%), and investigations (810 cases, 9.01%). Frequent ADEs included sepsis and COVID-19 were not listed in the prescribing information. The signal strength analysis highlighted conditions like cholestasis and epilepsy not mentioned in the prescribing information. Furthermore, an analysis of influencing factors revealed differences in infections and infestations by gender and nationality (p < 0.05), and in gastrointestinal disorders and blood and lymphatic system disorders by gender, treatment duration, and nationality (p < 0.05).

Conclusions: Common ADEs generally correspond with the prescribing information. Clinicians should be vigilant regarding unlisted ADEs about sacituzumab govitecan, and close monitoring of laboratory indicators ensure patient medication safety.

Introduction: Insulin remains the mainstay of diabetes management. Once weekly insulins (OWI) being investigated as viable options for both type 1 and type 2 diabetes. Less frequent dosing and better pharmacokinetic profile with these products hold the promise for improved patient adherence and enhanced efficacy in everyday practice.

Areas covered: We conducted a biomedical literature review of the PubMed database from 2009 to 2025. This narrative review summarizes the characteristics, advantages, and drawbacks of the two OWI products on the market and in development, namely insulin icodec and insulin efsitora. We review the published data with an emphasis on the safety of these when compared with daily long-acting insulin in insulin-treated and insulin-naïve patients with diabetes.

Expert opinion: The available data for OWI thus far points to similar adherence, acceptability, and efficacy when compared to once-daily insulin. OWI use was associated with comparable lowering of glycosylated hemoglobin and achievement of glycemic targets, potentially widening the treatment options for individuals with diabetes. However, increased risks of hypoglycemia and weight gain were seen in some studies. The clinical concerns regarding hypoglycemia led the U.S. regulatory agency to vote against recommending approval of icodec for use in patients with type 1 diabetes.

Background and aims: Ciprofol (HSK3486), a novel intravenous anesthetic with a chemical structure similar to propofol, is not inferior to propofol in terms of its effectiveness. We compared the effects of ciprofol and propofol on dreams and emotional states in patients following painless gastroscopy.

Research design and methods: This was a single-center, randomized controlled trial. The primary outcome was the proportion of positive dreams during sedation.

Results: A total of 110 outpatients were included, with 55 in each group. The proportion of positive dreams among dreamers was significantly greater in the propofol group than in the ciprofol group (60.9% vs 20.0%; p = 0.020). Additionally, the propofol group exhibited significantly higher positive emotion scores compared to the ciprofol group (19 [15,25] vs 17 [12,21]; p = 0.021). No significant differences were observed in vital signs, BIS values, or satisfaction with the procedure between the two groups. As for the adverse drug reactions, the incidence of injection pain of propofol was significantly higher than that of ciprofol (12.7% vs 0%; p = 0.013).

Conclusions: Compared to propofol, ciprofol demonstrated a weaker capacity to induce positive dreams and emotions during painless gastroscopy. However, this does not impact patient satisfaction with the procedure.

Clinical trial registration: www.chictr.org.cn; identifier: ChiCTR2400082655.

Background: There is conflicting real-world evidence regarding the risk of breast and bladder cancer associated with sodium glucose cotransporter 2 (SGLT2) inhibitors. We conducted a pharmacovigilance study on SGLT2 inhibitors and breast and bladder cancer using the US FDA Adverse Event Reporting System (FAERS) and a Mendelian randomization (MR) study.

Research design and methods: We used AERSMine to mine adverse events from FAERS. We provided proportional reporting ratio (PRR) with 95% confidence interval (CI), and the lower limit of the 95% credible interval of the information component (IC₀₂₅). A two-sample MR approach was used to investigate the causal relationship between SGLT2 inhibition and breast and bladder cancer.

Results: We did not find a disproportionate association between SGLT2 inhibitors (PRR = 1.26; 95%CI 1.05-1.51; p = 0.014; IC₀₂₅ = 0.01) and their molecules with breast cancer. SGLT2 inhibitors were associated with a disproportionately higher reporting frequency of bladder cancer events compared to metformin, dipeptidyl peptidase 4 inhibitors, or glucagon-like peptide-1 receptor agonists. MR analysis results showed that SGLT2 inhibition was associated with a higher risk of bladder cancer (odds ratio 1.01; 95%CI 1.00-1.01; p = 0.004).

Conclusion: Our results suggest that the use of SGLT2 inhibitors is associated with a higher reporting frequency/risk of bladder cancer, rather than breast cancer.

Introduction: Advanced chronic kidney disease (CKD), defined as an estimated glomerular filtration rate < 30 ml/min/1.73 m², significantly amplifies the challenges of managing atrial fibrillation (AF), highly prevalent in this population. People with advanced CKD besides increased cardiovascular risk are also at increased risk of both thromboembolic events and bleeding complications. Evidence regarding optimal anticoagulants use in this specific population remains limited, as most pivotal trials exclude people with advanced CKD, also those on maintenance dialysis.

Areas covered: This review examines the safety and efficacy of anticoagulation strategies, namely vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) in people with AF and advanced CKD. It highlights the shortcomings of existing thromboembolism risk stratification tools and explores the off-target effects of anticoagulants. The literature search utilized PubMed, Embase, and Web of Science.

Expert opinion: Some emerging data suggest that DOACs, particularly rivaroxaban and apixaban, may offer improved safety profiles compared to VKA in advanced CKD, with comparable efficacy. Observational studies indicate a potential advantage of DOACs in preventing stroke or systemic embolism (SSE) over VKA. Large clinical trials including a non-anticoagulation arm and validation of risk stratification tools specific to advanced CKD are urgently needed.

Background: This study conducts a comprehensive comparative analysis of adverse event (AE) signals between sacubitril/valsartan and valsartan, two pivotal cardiovascular drugs for heart failure and hypertension, utilizing the FAERS database to identify differential safety risks and optimize clinical monitoring.

Research design and methods: Data from the FAERS database (2004Q1-2024Q2) were analyzed using disproportionality analysis and Bayesian methods to detect and evaluate AE signals associated with sacubitril/valsartan and valsartan, enabling a comparative assessment.

Results: A total of 102,678 adverse event reports (AERs) were linked to sacubitril/valsartan, compared to 24,318 AERs for valsartan. Sacubitril/valsartan demonstrated the strongest association with cardiac disorders (ROR 4.13), while valsartan exhibited the highest association with vascular disorders (ROR 2.67). Common AE signals aligned with the respective drug labels. Unexpected AEs for sacubitril/valsartan included myocardial infarction (n = 2,909, ROR 6.45), arrhythmia (n = 1,691, ROR 4.07), decreased activity (n = 544, ROR 11.13), and fluid imbalance (n = 44, ROR 11.98). Unique AEs for valsartan included fear of disease (n = 137, ROR 47.57), thrombotic stroke (n = 31, ROR 25.60), merycism (n = 30, ROR 79.41), and eosinophilic colitis (n = 11, ROR 20.62).

Conclusions: Sacubitril/valsartan and valsartan exhibit distinct AE risk profiles in cardiovascular disease treatment, underscoring the need for large-scale clinical trials and mechanistic studies on sacubitril to validate these findings.

Introduction: Placental abruption is a significant cause of fetomaternal mortality/morbidity. Management requires a difficult balance between opposing advantages/disadvantages for the fetus and mother. Remote from term, prompt delivery is best for the mother, but delayed delivery better for the fetus.

Areas covered: Prevalence of fetomaternal morbidity/mortality; range of clinical situations: certainty of diagnosis, gestational age, labor status, fetal condition/viability, presence of maternal shock/consumption coagulopathy, feasibility of prompt delivery. Pathophysiology: maternal hypovolaemia; abruption size; impairment of placental oxygenation; intrauterine tone and pressure; safety, efficacy, and application of tocolytic therapy to abruption; potential role of atosiban with emphasis on safety.

Expert opinion: The fetomaternal morbidity/mortality of placental abruption deserves consideration of further interventions that may improve fetomaternal outcome. More information is now available about signs/symptoms that do not require invasive diagnostic procedures. The contribution of maternal uterine hypertonus/tachysystole and increased uterine tone/pressure that affects fetal hypoxia/acidosis and consumption coagulopathy, strengthens the case for the use of a tocolytic to relax the uterus and improve fetal oxygenation. Due to its safety and efficacy profile, we make the case for atosiban as an agent to reduce uterine contractile frequency, tone, and pressure to improve fetal oxygenation and improve fetomaternal outcome.