Expert Opinion on Drug Safety最新文献

Background: Aztreonam was approved by the FDA for treating Gram-negative infections, including metallo-β-lactamase producers. This study extensively evaluated aztreonam-related adverse events (AEs) from the FDA Adverse Event Reporting System (FAERS) database for a better understanding of toxicities.

Methods: The signals of aztreonam-related AEs were quantified using disproportionality analyses, like reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker algorithms.

Results: Among the 18,182,912 records retrieved from the FAERS 11,627 cases were identified where aztreonam was the primary suspect drug. A total of 127 preferred terms with significant disproportionality that simultaneously met the criteria of all algorithms were retained. Unexpected safety signals such as cholestatic liver injury, hypoprothrombinemia, hemoptysis, pulmonary hemorrhage, drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis and so on may also manifest in adults, particularly in elderly patients. The median onset time for AEs related to intravenous aztreonam was 4 days, compared to a year after the initiation of inhaled aztreonam.

Conclusions: Our study identified potential new adverse event signals and offered a thorough understanding of aztreonam's safety profiles. This information is crucial for enhanced clinical monitoring and risk assessment, aiding healthcare professionals in tailoring their approach.

Background: Drug-induced cystitis (DIC) significantly impacts patient quality of life and treatment outcomes. This study investigates the incidence and characteristics of DIC using data from the FDA Adverse Event Reporting System (FAERS).

Methods: We reviewed FAERS reports related to cystitis from Q1 2004 to Q1 2024, compiling a list of potential causative drugs. The top 50 drugs with the highest number of cystitis reports were ranked. Statistical disproportionality analyses, including Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR), were used to detect unusually high reporting frequencies of cystitis associated with specific drugs.

Results: From 17,703,515 FAERS reports spanning 2004-2024, 36399 involved cystitis. The majority of implicated drugs were antineoplastics. Busulfan, BCG, and mitomycin had the highest ROR and PRR values. Additionally, drugs such as defibrotide sodium, milrinone, and dyazide, which do not have cystitis listed on their labels, were identified, highlighting the need for increased clinical vigilance and awareness.

Conclusion: The findings underscore the importance of ongoing pharmacovigilance in identifying and characterizing DIC. Further clinical studies are warranted to validate these associations and to develop strategies for mitigating the risk of DIC, thereby improving patient safety and treatment outcomes.

Background: The use of online and/or compounding pharmacies to access glucagon-like peptide-1 receptor agonists (GLP-1 RAs) increases the risk for prescription error (e.g. accidental overdose) especially in racial, ethnic, and socioeconomic disadvantaged groups.

Methods: We sought to evaluate accidental overdose associated with GLP-1 RAs submitted to the United States FDA Adverse Event Reporting System (FAERS). Case reports of accidental overdose reported to the FAERS were retrieved from Q4 2003 to Q1 2024 using OpenVigil 2.1. Disproportionality of accidental overdose was assessed using reporting odds ratio (ROR). Upper and lower 95% confidence intervals (CI) were calculated at an alpha level of 5%, where disproportionate reporting was considered when the lower 95% CI was greater than 1.0.

Results: We identified 3,348 reports of accidental overdose associated with GLP-1 RAs. The RORs were significant for all agents within the class (ROR range: 2.64-61.12, all p < 0.008), including semaglutide, dulaglutide, exenatide, liraglutide, and tirzepatide compared to niacin.

Conclusions: Inadequate access, availability, and affordability of GLP-1 RAs has contributed to the increased seeking via online and/or compounding pharmacies, and is associated with greater risk for prescription errors that differentially affect racial, ethnic, and socioeconomic vulnerable populations. Pharmacovigilance database analyses cannot establish causation only association.

Background: Belimumab was approved in the US in 2019 for children with Systemic lupus erythematosus (SLE), making it the only medicine that can treat SLE in both adults and children. The authors retrospectively investigated adverse events (AEs) by data-mining a self-reported database.

Research design and methods: PRR, ROR, and BCPNN were used to assess the association between belimumab and AEs. The definition relied on system organ class (SOC) and preferred terms (PT) by the Medical Dictionary for Regulatory Activities (MedDRA).

Results: A total of 15,316,605 AE reports were retrieved from the FAERS database, and 19,832 AE reports were identified after the data cleaning process. Based on the disproportionality analysis at the PT level, depressive (N = 420), ill-defined disorder (N = 304), injection site hemorrhage (N = 297), lupus nephritis (N = 198), live birth (N = 96) and proteinuria (N = 77) had relatively higher frequencies than other AEs, suggesting that these AEs are more likely to occur in the real world for patients taking belimumab.

Conclusions: This study explores valuable potential AEs of belimumab at the SOC and PT levels, respectively. To provide a reference for decision-making on belimumab, including its use in children, and to promote rational clinical dosing.

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.

Background: To evaluate the comparative cardiovascular safety of urate-lowering therapies (ULTs) in patients with gout or hyperuricemia.

Research design and methods: Randomized controlled trials (RCTs) for ULTs with reported cardiovascular outcomes were included. Pairwise and network random-effect meta-analyses were performed to obtain the odds ratios (ORs) with 95% confidence intervals (CIs). The surface under the cumulative ranking curve (SUCRA) was employed to assess and rank the cardiovascular safety of ULTs.

Results: A total of 3,663 literature were retrieved, of which 26 RCTs involving 25,329 patients were finally included. Pairwise and network meta-analyses showed that allopurinol demonstrated a significant reduction in arrhythmia compared with febuxostat (for pairwise meta-analysis, OR = 0.69, 95%CI 0.49 to 0.97; for network meta-analysis, OR = 0.71, 95%CI 0.51 to 0.99). Nevertheless, there was no statistically significant difference observed in other outcomes between different ULTs or between ULTs and placebo (p > 0.05). According to the SUCRA, febuxostat and pegloticase, had the highest probability of mitigating the occurrence of major adverse cardiovascular events (MACEs) and all-cause mortality respectively.

Conclusions: Overall, ULTs showed relatively good cardiovascular safety in patients with gout or hyperuricemia. However, febuxostat has a higher risk of arrhythmia compared with allopurinol. Further studies are needed to confirm our findings.

Objective: This study was designed to conduct data mining through the Food and Drug Administration Adverse Event Reporting System (FAERS) to assess adverse events (AEs) associated with cabozantinib in the treatment of renal cell carcinoma.

Methods: Reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms were used to detect drug-related AEs signals from reporting data in FAERS database from 2016 to 2024.

Results: A total of 32,129 AE reports identifying cabozantinib as a 'primary suspect' were retrieved from the FAERS database. Among them, there were 21,549 reports of renal cell carcinoma as an indication. AEs induced by cabozantinib were observed in 23 system organ classes (SOCs). 215 AE signals were detected in 16 SOCs after four algorithms were simultaneously met. Among them, signals related to gastrointestinal disorders, general disorders and administration site conditions, and skin and subcutaneous tissue disorders were the most common. Of note, the median time to onset of AEs was 38 days (interquartile range (IQR) 14-116 days).

Conclusion: This study provides new insights into the monitoring, surveillance, and management of cabozantinib-related adverse drug reactions and provides a comprehensive long-term post-marketing safety assessment of cabozantinib.

Background: Aromatase inhibitors (AIs) are commonly used to treat postmenopausal hormone receptor positive breast cancer, but there is currently a lack of comprehensive safety reports on AIs in large-scale cohorts.

Research design and methods: We conducted a retrospective pharmacovigilance survey based on the FDA Adverse Event Reporting System, retrieving relevant reports from the 2004 to the 2023, aiming to conduct a comprehensive comparative analysis of adverse reactions associated with AIs. In addition, we elucidated the potential toxicological mechanisms of AIs related adverse events through functional enrichment analysis.

Results: A total of 7,933 adverse event reports related to AIs were collected, and there were 642 positive signals at the preferred term level. The top three signal intensities for anastrozole are: antiphospholipid syndrome, plantar fasciitis and autoimmune pancreatitis. The top three signal intensities for letrozole are: androgenetic alopecia and myosclerosis, pneumonic herpes virus. The top three signal intensities for exemestane are: infection reactivation, thyroxine free decreased and dilatation atrial. In terms of onset time, letrozole has the earliest onset time overall, followed by exemestane, and finally anastrozole.

Conclusions: Our research corroborates the typical adverse events linked to AIs while highlighting potential safety concerns in their real-world clinical application.

Background: Levetiracetam, a widely prescribed antiseizure medication, is recognized for its broad-spectrum efficacy, good tolerability, and minimal drug interactions. This study examines the association between levetiracetam and rhabdomyolysis, utilizing real-world data from the FDA Adverse Event Reporting System (FAERS) database to further elucidate its safety profile.

Methods: This study extracted adverse events related to levetiracetam from the FAERS database (Q1 2013 to Q1 2024). Four types of disproportionality analysis identified rhabdomyolysis as a significant adverse event. Logistic regression assessed risk factors, including gender, age, and severity. A Gaussian Mixture Model analyzed the time-to-onset distribution of rhabdomyolysis, while the impact of concomitant medications on its risk was evaluated using Reporting Odds Ratio (ROR).

Results: Levetiracetam significantly increased rhabdomyolysis risk (ROR = 13.5). Males showed a higher incidence (OR = 2.60). Most adverse events occurred within the first 30 days, with a bimodal onset distribution. Co-administration of antibiotics, antipsychotics, and PPIs elevated the risk while other antiseizure medications did not.

Conclusion: This study found a significant association between levetiracetam and the risk of rhabdomyolysis, highlighting the need for increased clinical vigilance in this patient population. Future research should focus on elucidating the underlying mechanisms and optimizing clinical guidelines.