Adverse drug events associated with linezolid administration: a real-world pharmacovigilance study from 2004 to 2023 using the FAERS database.

Introduction: Linezolid is an oxazolidinone antibiotic that is active against drug-resistant Gram-positive bacteria and multidrug-resistant Mycobacterium tuberculosis. Real-world studies on the safety of linezolid in large populations are lacking. This study aimed to determine the adverse events associated with linezolid in real-world settings by analyzing data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Methods: We retrospectively extracted reports on adverse drug events (ADEs) from the FAERS database from the first quarter of 2004 to that of 2023. By using disproportionality analysis including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), along with the multi-item gamma Poisson shrinker (MGPS), we evaluated whether there was a significant association between linezolid and ADE. The time to onset of ADE was further analyzed in the general population and within each age, weight, reporting population, and weight subgroups. Results: A total of 11,176 reports of linezolid as the "primary suspected" drug and 263 significant adverse events of linezolid were identified, including some common adverse events such as thrombocytopenia (n = 1,139, ROR 21.98), anaemia (n = 704, ROR 7.39), and unexpected signals that were not listed on the drug label such as rhabdomyolysis (n = 90, ROR 4.33), and electrocardiogram QT prolonged (n = 73, ROR 4.07). Linezolid-induced adverse reactions involved 27 System Organ Class (SOC). Gender differences existed in ADE signals related to linezolid. The median onset time of all ADEs was 6 days, and most ADEs (n = 3,778) occurred within the first month of linezolid use but some may continue to occur even after a year of treatment (n = 46). Conclusion: This study reports the time to onset of adverse effects in detail at the levels of SOC and specific preferred term (PT). The results of our study provide valuable insights for optimizing the use of linezolid and reducing potential side effects, expected to facilitate the safe use of linezolid in clinical settings.

A real-world pharmacovigilance study of mepolizumab in the FDA adverse event reporting system (FAERS) database.

Mepolizumab is primarily used in the treatment of asthma, eosinophilic granulomatosis with polyangiitis, eosinophilia syndrome, and chronic rhinitis with nasal polyps. The information about its adverse drug reactions is mainly derived from clinical trials, and there is a shortage of real-world studies with extensive sample sizes. In this study, the U.S. FDA's Adverse Event Reporting System (FAERS) database was analyzed to evaluate the side effects of mepolizumab. A total of 18,040 reports of mepolizumab-associated adverse events were identified from the FDA Adverse Event Reporting System database. Multiple disproportionality analysis algorithms were used to determine the significance of these AEs. The study identified 198 instances of mepolizumab-induced AEs, including some important AEs not mentioned in the product labeling. The time to onset of adverse reactions was also analyzed, with a median time of 109 days. Most AEs occurred within the first month of mepolizumab use, but some may still occur after 1 year of treatment. Gender-specific analysis showed different high-risk AEs for females (digestive and neurological side effects) and males (serious adverse effects leading to hospitalization and death). The findings mentioned provide valuable insights on optimizing the use of mepolizumab, enhancing its effectiveness, and minimizing potential side effects. This information will greatly contribute to the practical implementation of the drug in clinical settings.

Synthesis and inhibitory evaluation of cyclohexen-2-yl- and cyclohexyl-substituted phenols and quinones to endothelial cell and cancer cells.

Alkylation of phenols with 1,3-cyclohexadiene (1) has been conducted and a series of cyclohexen-2-yl- and cyclohexyl-substituted phenols and quinones were screened against the proliferation of HUVEC and cancer cells. Phenol type as well as the size and occupied position of the substitute are important for the alkylating reaction and the inhibitory activity and selectivity of a compound. 2,5-di(cyclohexen-2-yl)benzene-1,4-diol (25) bearing two cyclohexen-2-yl groups and 2-tert-butyl-5-(cyclohexen-2-yl)benzene-1,4-diol (30) bearing cyclohexen-2-yl and tert-butyl groups exhibited good selectivity against HUVEC proliferation (IC50s of 2.0 and 1.4 microM, respectively) with relatively low toxicity to ccc-HPF-1.

Synthesis, discovery and preliminary SAR study of benzofuran derivatives as angiogenesis inhibitors.

A series of benzofuran derivatives were synthesized and evaluated against HUVEC proliferation. Among these compounds, compound 32 exhibited good inhibitory activity and remarkable selectivity to HUVEC. Our current data suggested that array order of methyl, acrylate and carboxylate groups in benzofuran scaffold is the basic requirement for inhibitory activity against HUVEC proliferation. These results demonstrated that benzofuran scaffold represents a promising structural core to discover a new class of active and selective angiogenesis inhibitors.