Current drug safety最新文献

Introduction: One of the most important materials needed for root canal therapy is a sealer. The aim of this study was to assess the tissue reaction of a new polycaprolactone-based root canal sealer in a rat model.

Methods: Eighty adult male rats were randomly divided into 5 groups (n=16, for assessment at 3, 7, 15, 30, and 60 days' intervals). The rats were anesthetized with Ketamine and Xylazine. Surgical anesthesia lasted thirty minutes. After shaving their back hair and cleaning the spot with 5% iodine, two grooves with a length of 1 cm were created with a scalpel no. 15 Thus, one of the tested materials was randomly inserted into each of the incisions, and an empty polyethylene angioket tube with a length of 8 mm and an internal diameter of 1.1 mm was inserted into one of the incision sites as a control. After the 3, 7, 15, 30, and 60 day intervals, the rats were anesthetized again. The rats were sacrificed by overdosing on an anesthetic drug injection (barbiturate or ether). The samples were kept in 10% formalin and then sent for slide preparation. After preparing the paraffin blocks, longitudinal sections were prepared along the axis of the tubes with a thickness of 6 μm, passing through the studied material. Four sections were prepared from each block, passing longitudinally through the largest diameter of the tube.

Results: The results showed that there was no significant difference between the case and control groups in the degree of inflammation and the cell count (lymphocytes, macrophages, mast cells, plasma cells, neutrophils, eosinophils) in the study groups during the two-month evaluation period (P-value < 0.05).

Discussion: These results support its potential for clinical application, although further studies are needed to confirm safety and efficacy in human treatments.

Conclusion: The studied new sealer was biocompatible in the animal rat model.

Introduction: With the increasing use of trastuzumab deruxtecan (T-DXd) in the treatment of solid tumors, fatigue has emerged as a clinically significant toxicity. We aimed to quantify the risk and incidence of T-DXd-associated fatigue using randomized evidence and single-arm data, and to corroborate these findings with the evidence from pharmacovigilance databases.

Methods: We searched major databases and oncology meetings up to January 29th, 2025, for randomized controlled trials (RCTs) and single-arm studies in adults receiving T-DXd. Odds ratios, incidences, and 95% confidence intervals (CIs) were synthesized using Peto fixed- or random- effects models, according to the level of heterogeneity. Disproportionality was assessed using reporting odds ratios (RORs) from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER). Additionally, time-to-onset data were analyzed using Weibull modeling.

Results: Five RCTs (2,713 patients) and nine single-arm studies (1,096 patients) met the inclusion criteria. T-DXd increased fatigue risk (OR 1.51; 95% CI 1.28-1.78; I²=12%) as compared to the control. Pooled fatigue incidence in single-arm studies was 49% (95% CI 33%-65%; I²=94.9%). Fatigue was more frequent in breast cancer than in gastrointestinal tumors. Disproportionality signals were consistent (FAERS ROR 2.15, 95% CI 1.97-2.35; JADER ROR 3.33, 95% CI 1.38-8.03). The median onset was 33.5 days, with an early-failure pattern.

Discussion: Fatigue associated with T-DXd is common, appears early, and is clinically significant. Heterogeneity and limitations of spontaneous reports (e.g., under-reporting and confounding) reduce the certainty of findings and underscore the need for standardized assessment and mitigation strategies.

Conclusion: T-DXd is associated with substantially increased fatigue risk and high incidence across solid tumors. Early detection, proactive management, and routine monitoring of patientreported outcomes are recommended to support treatment adherence and quality of life.

Introduction: Testosterone Cypionate (TC) is a widely prescribed anabolic steroid for male hypogonadism and gender-affirming hormone therapy. While therapeutically beneficial, concerns have emerged regarding its potential to increase the risk of serious cardiovascular adverse events, including Pulmonary Embolism (PE), Deep Vein Thrombosis (DVT), and Myocardial Infarction (MI). This study investigates the disproportionality, severity, and stratified risk of TC-related cardiovascular events using real-world pharmacovigilance data.

Material and methods: A retrospective analysis was conducted using the FDA Adverse Event Reporting System (FAERS). Disproportionality was evaluated using Reporting Odds Ratios (ROR) and 95% Confidence Intervals (CI) for PE, DVT, and MI associated with TC. Event severity, temporal trends, polypharmacy levels, and demographic characteristics were also assessed. Stratified analyses and comparison with alternative testosterone formulations (e.g., AndroGel) were included.

Results: The RORs for PE (0.039; 95% CI: 0.036-0.043) and DVT (0.133; 95% CI: 0.122- 0.145) were below 1, indicating no disproportionality. Myocardial infarction had an ROR of 0.83 (95% CI: 0.71-0.97), also below the disproportional threshold. While patients with five or more concomitant medications (polypharmacy) showed numerically higher rates of hospitalization and death, chi-square tests revealed no statistically significant associations between polypharmacy and severity for MI (p = 0.627), PE (p = 0.773), or DVT (p = 0.763). Older age groups and common co-reported cardiovascular medications (e.g., aspirin, lisinopril) were prominent across serious cases. Compared to AndroGel, TC was associated with more frequent and severe MI outcomes.

Discussion: Although no disproportionality signal was detected for PE, DVT, or MI, the severity of outcomes in older individuals and those with multiple medications warrants vigilant prescribing practices. Though polypharmacy was associated with higher raw frequencies of adverse outcomes, statistical testing did not confirm a significant relationship. These findings emphasize the importance of individualized cardiovascular risk assessment in TC users, particularly in older and complex patients receiving testosterone therapy.

Conclusions: Based on the current FAERS data, testosterone cypionate does not appear to increase the risk of major cardiovascular events more than expected. Still, serious outcomes can and do happen, especially in patients with more complex medical histories. These results highlight the importance of evaluating each patient's individual risk and show why post-marketing surveillance remains such an important tool for tracking drug safety in real-world clinical settings.

Introduction: Postoperative nausea and vomiting (PONV) remain among the most frequent and distressing complications following surgery, often hindering patient recovery and comfort. Penehyclidine, an anticholinergic agent, has been explored as a potential treatment for PONV, yet its safety and efficacy are still under investigation. This systematic review and metaanalysis aim to synthesize current evidence on the effectiveness and safety of penehyclidine in preventing and managing PONV.

Methods: A comprehensive search was performed across several major databases, including PubMed, Scopus, Web of Science, and the Cochrane Library, to identify randomized controlled trials evaluating penehyclidine's efficacy in PONV management. Relevant data were extracted from eligible studies, and outcomes of interest were analyzed. A meta-analysis using a randomeffects model was conducted with RevMan software.

Results: Meta-analysis revealed that penehyclidine significantly reduced the incidence of PONV at both 24 hours (RR = 0.61, 95% CI [0.48-0.82]; p = 0.001) and 48 hours postoperatively (RR = 0.69, 95% CI [0.55-0.86]; p = 0.0009). It also significantly lowered the requirement for rescue antiemetics (RR = 0.34, 95% CI [0.19-0.61]; p = 0.0003). Additionally, patients receiving penehyclidine experienced a greater likelihood of complete symptom relief (RR = 1.37, 95% CI [1.10-1.72]; p = 0.005) and a reduced incidence of severe PONV (RR = 0.36, 95% CI [0.22- 0.60]; p < 0.0001). However, there were no significant differences observed in postoperative analgesic use (RR = 0.99, 95% CI [0.71-1.36]; p = 0.93) or length of stay in the post-anesthesia care unit (PACU) (MD = 0.14 minutes, 95% CI [-0.95, 1.23]; p = 0.81). Notably, penehyclidine was associated with an increased risk of dry mouth (RR = 2.68, 95% CI [2.10-3.43]; p < 0.00001), although other adverse effects-including headache, dizziness, fever, and urinary retention- showed no significant differences between groups.

Conclusion: Penehyclidine demonstrates significant benefits in reducing both the incidence and severity of PONV, along with minimizing the need for additional antiemetic therapy. Its antiemetic effect extends up to 48 hours postoperatively, although this benefit is tempered by a higher likelihood of dry mouth. Importantly, its use does not influence postoperative analgesic consumption or PACU stay duration, supporting its specific utility in PONV management with a manageable safety profile.

Introduction: Sertraline, an SSRI, is widely prescribed for depression and other psychiatric disorders. Although generally well-tolerated, SSRIs can rarely cause bleeding complications due to their effect on platelet aggregation. This case highlights a rare but clinically significant presentation of sertraline-induced ecchymosis in the absence of predisposing factors, contributing to the limited literature on SSRI-associated bleeding events.

Case presentation: A 34-year-old woman presented with large ecchymotic lesions on both arms three weeks after initiating sertraline therapy. She had no history of trauma, bleeding disorders, or concurrent medications. Laboratory evaluations, including coagulation studies and platelet count, were within normal limits. Symptoms resolved after discontinuing sertraline. Causality assessment using the Naranjo adverse drug reaction scale suggested a probable link between sertraline and ecchymosis.

Conclusion: This case underscores the importance of recognizing sertraline as a potential cause of unexplained bruising. Clinicians should maintain a high index of suspicion for rare SSRIinduced bleeding events to ensure timely diagnosis and management.

Introduction: Liposomal amphotericin B is the treatment of choice for visceral leishmaniasis (VL), but its potential adverse effects, including hematologic and neurologic complications, remain a subject of concern. Hemophagocytic lymphohistiocytosis (HLH) is a rare but severe hyperinflammatory syndrome that can occur in VL, and the development of intracerebral hemorrhage (ICH) during treatment adds a critical dimension to patient management. While ICH is an uncommon complication, its possible association with liposomal amphotericin B warrants further exploration.

Case Study: This report discusses a middle-aged man who presented with a 4-month history of recurrent fever. He also reported progressive breathlessness, a sensation of heaviness in the left abdomen, and pedal edema over the past 4 weeks. Additionally, he experienced black discoloration of urine and stool for 2 weeks. Physical examination revealed massive splenomegaly, melena, hematuria, and pancytopenia. Bone marrow aspiration confirmed hemophagocytosis, and the recombinant kinesin antigen-39 (rk39) test for VL was positive. An H-score of 234 indicated a 98-99% probability of HLH. The patient was initiated on treatment with a single dose of liposomal amphotericin B. However, on the fourth day of therapy, he developed a sudden onset of headache followed by altered sensorium. Neuroimaging revealed ICH with surrounding edema and intraventricular extension, causing a significant mass effect. Given the temporal association with treatment initiation, liposomal amphotericin B-induced ICH was considered a potential etiology. He was managed conservatively with three units of single-donor platelets and showed gradual neurological improvement without further invasive intervention. He was eventually discharged in a hemodynamically stable condition.

Conclusion: This case describes the potential risk of ICH as an adverse or trigger effect of liposomal amphotericin B in the setting of VL and HLH. Clinicians should remain vigilant for neurological complications during treatment, emphasizing the importance of close monitoring and individualized therapeutic decisions to optimize patient outcomes.

Introduction: Antimicrobial resistance (AMR) is a pressing global health issue exacerbated by the overuse of antibiotics during the COVID-19 pandemic. Despite WHO guidelines against antibiotics for mild-to-moderate COVID-19 cases without bacterial co-infection, significant misuse has been reported globally. This study aimed to evaluate antibiotic consumption during the COVID-19 pandemic at a hospital in North Macedonia and to analyze adherence to WHO guidelines, with a focus on antimicrobial stewardship, using the ATC and WHO AWaRe classification systems.

Objective: To analyze antibiotic utilization trends from January 2020 to December 2021 and assess adherence to WHO guidelines, focusing on the potential impact on AMR.

Method: This retrospective observational study measured antibiotic consumption in defined daily doses (DDD) per 100 occupied bed-days (DDD/100 OBD) using ATC and WHO AWaRe classifications. Data were obtained only from ICU inpatients treated at the Clinical Hospital in Shtip, North Macedonia. Trends in annual consumption were analyzed, including rate-of-change calculations for individual antibiotics between 2020 and 2021.

Result: Total antibiotic consumption decreased from 2902.6 DDD/100 OBD in 2020 to 2286.5 DDD/100 OBD in 2021. A third-generation cephalosporin, ceftriaxone, was the most consumed antibiotic, accounting for 57.62% of total consumption in 2020 and 48.55% in 2021. Tetracycline use slightly increased from 13.88% in 2020 to 15.83% in 2021. Fluoroquinolone use decreased significantly from 15.22% in 2020 to 6.5% in 2021. Carbapenem consumption rose sharply from 1.7% in 2020 to 14.37% in 2021, while azithromycin use declined threefold. Antibiotics in the Access group accounted for less than 20% of total usage, while those in the Watch group predominated.

Discussion: The study highlights a continued reliance on broad-spectrum antibiotics during the pandemic, diverging from WHO recommendations emphasizing Access to antibiotics. These trends suggest inadequate implementation of antimicrobial stewardship practices and raise concerns about their long-term impact on AMR. Limitations include the retrospective, single-center design, which may limit the generalizability of the findings.

Conclusion: The findings underscore the high dependency on Watch category antibiotics and a limited focus on Access antibiotics, contrary to WHO recommendations. This highlights the urgent need for robust antimicrobial stewardship programs to control inappropriate antibiotic use and combat AMR.

Introduction: Clopidogrel is a widely used agent in the management of cardiovascular disease. However, there have been reports of liver injury associated with its use, some of which have resulted in death. The atypical presentation of this liver injury has often led to delayed diagnosis and inappropriate treatment. We conducted a systematic review of reported cases to summarize the clinical characteristics, diagnostic approaches, and recovery durations associated with clopidogrel-induced liver injury.

Method: Electronic databases, including MEDLINE, OVID, and EMBASE, were used to identify eligible studies from inception to December 2024. Eligible cases were required to have a clear diagnosis of clopidogrel-induced liver injury. Descriptive analysis and Kaplan-Meier analysis were used to explore the clinical features and survival durations.

Results: Our systematic review included 29 eligible studies, comprising 29 cases of hepatic abscess with a mean age of 67 years (58% male). Patients presented with abdominal pain in only 24% of cases, fever in 17%, but jaundice in 55%. The median recovery time was 25 days after the final diagnosis. A hepatocellular pattern was reported in 37% of cases. Diagnostic criteria were proposed and summarized based on these findings.

Conclusion: Clinicians should be aware of clopidogrel-induced liver injury, as patients can present with a wide range of symptoms. Implementing our proposed diagnostic criteria is recommended to facilitate prompt diagnosis and treatment of clopidogrel-induced liver injury.

The drug approval and review process plays a crucial role in the pharmaceutical industry, aiming to ensure that newly marketed drugs are safe, effective, and of high quality. Regulatory authorities overseeing this process, tailored to geographically distinct needs, include the U.S. FDA, EMA, Japan's Pharmaceuticals and Medical Devices Agency (PMDA), China's National Medical Products Administration (NMPA), and India's Central Drugs Standard Control Organization (CDSCO). This analysis offers insight into the various drug approval processes employed by these authorities and examines the International Council for Harmonisation's ongoing efforts to establish a global consensus on drug regulation standards. It also compares regulatory pathways and highlights current harmonization initiatives. The focus is on analyzing operational aspects of drug regulation and identifying challenges arising from these regulations. The ultimate goal is to present a clear understanding of the intricacies and dynamics of the global drug approval process. Regulating the drug approval process is essential to ensure that new drugs are safe for public consumption, as the introduction of a new drug often faces numerous hurdles beyond safety and efficacy. The challenges highlighted include variations in regulations between authorities, the complexity of modern therapeutics, and the balance between safety and speed. This paper provides an overview of innovations in drug development, their impact on regulatory pathways, ongoing harmonization efforts, and potential obstacles that may arise during the regulatory process.