Letter to the FDA Proposing Major Changes in the US Clozapine Package Insert Supported by Clozapine Experts Worldwide. Part II DOI
José de León, Ross J. Baldessarini, Richard Balon

и другие.

Journal of Clinical Psychopharmacology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 8, 2025

Abstract Purpose/Background This is the second part of a 2-part article that proposes improving United States (US) clozapine package insert. Part II focuses on fatal outcomes and 5 boxed warnings, 4 specifically for clozapine: severe neutropenia, seizure, orthostatic hypotension myocarditis, 1 all antipsychotics (elderly with dementia). Methods US reports to World Health Organization's global pharmacovigilance database were analyzed from clozapine's introduction January 15, 2023. Findings/Results The was top reporter worldwide 56,003 9587 associated outcomes. warnings 534 (218 131 seizures, 125 orthostasis, 36 24 cardiomyopathy, 0 mitral valve prolapse). With no pneumonia 674 increased white blood cell count (a sign infection) 596 After considering overlaps, increases in explained 900 fatalities, or 9.4% Food Drug Administration continues focus neutropenia which only 218 2.3% outcomes, whereas 97.7% reported clozapine-treated patients had another cause. Implications/Conclusions To help prevent future deaths patients, insert should during infections. offers detailed solutions regarding current lack warning other Supplementary Material includes letters support 124 non-US experts 44 countries/regions who Parts I II.

Язык: Английский

Risk of drug-induced pericardial effusion: a disproportionality analysis of the FAERS database DOI Creative Commons

Gaocan Ren,

Pingping Huang,

Yanqiu Ding

и другие.

BMC Pharmacology and Toxicology, Год журнала: 2025, Номер 26(1)

Опубликована: Фев. 7, 2025

By using the FAERS database, we aim to identify and assess risk signals of adverse drug events (ADEs) potentially causing pericardial effusion, inform clinical management promote rational use. We obtained reports effusion from database spanning first quarter 2004 second 2024, identified top 50 drugs ranked by report frequency or signal strength. Four algorithms, namely reported odds ratio (ROR), proportional reporting (PRR), Bayesian confidence propagation neural network (BCPNN), multi-item gamma Poisson shrinker (MGPS), were employed for detection these drugs. Furthermore, with positive signals, conducted sensitivity analyses Weibull shape parameter test perform a time onset (TTO) analysis. 20,057 ADEs related involving 19,693 patients The patient population comprised 10,187 males (51.7%) 7,939 females (40.3%). Adults aged 18–65 years largest group (7,798 cases, 39.6%). Regarding outcomes, 9,924 (50.4%) experienced hospitalization, 2,770 cases (14.1%) resulted in death. Ranked ROR strength, 3 hydralazine [ROR (95% CI): 27.11 (22.28–33)], dasatinib 15.62 (14.07–17.33)], mesalazine 8.99 (6.84–11.8)]. TTO analysis 26 signals. median interquartile range (IQR) earliest were: cytarabine 14 (7.5,38), selexipag 14.5 (4.25, 157.75), dabigatran etexilate 29 (9, 229). Most exhibited an early failure type. This study systematically compiled list potential risks effusion. There is significant association between use hydralazine, dasatinib, mesalazine. Moreover, more common groups receiving treatments antineoplastic immunomodulating agents.

Язык: Английский

Процитировано

0

Runchangningshen paste activates NLRP6 inflammasome-mediated autophagy to stimulate colonic mucin-2 secretion and modulates mucosal microbiota in functional constipation DOI
Xuejiao Liu,

Yeliya Yeertai,

Yuebo Jia

и другие.

World Journal of Gastroenterology, Год журнала: 2025, Номер 31(9)

Опубликована: Фев. 18, 2025

Runchangningshen paste (RCNSP) is a made of four medicinal and edible homologous Chinese medicine mixed with honey. It known for its ability to nourish yin blood as well loosen the bowel relieve constipation. The pathophysiology functional constipation (FC) associated reduction in mucin-2 (MUC2) secretion microbial dysbiosis. To investigate underlying mechanism RCNSP against FC through MUC2 gut mucosal microbiota. Ultra-performance liquid chromatography tandem mass spectrometry characterized composition elucidate material basis action. model was induced via loperamide gavage (16 mg/kg) twice daily 7 days. Applying defecation function gastrointestinal motility assess severity. Hematoxylin eosin Alcian blue-periodic acid-schiff staining analyzed colonic morphology. Transmission electron microscope used observe ultrastructure goblet cells (GCs). Immunofluorescence colocalization, quantitative PCR, western blot assessed impact on gene protein expression within NLRP6/autophagy pathway. 16S rDNA employed sequence contained 12 components potential laxative effects. enhanced function, accelerated motility, maintained integrity. treatment significantly increased GC abundance production while preserving ultrastructure. At molecular level, colocalized key regulatory proteins modulated mRNA expressions Through sequencing analysis, altered microbiota composition. Specifically, it beneficial bacterial strains reducing harmful ones. Simultaneously, reduced butyrate-producing bacteria like Proteobacteria, Enterobacteriaceae, Blautia, Eubacterium decreased hydrogen sulfide-producing species, such Prevotellaceae. also bile acid-inhibiting g_Eubacter_coprostanoligenes_group Erysipelotrichaceae increasing acid-producing Colidextribacter. Our findings suggested that ameliorated dual mechanism: stimulated by activating NLRP6 inflammasome-mediated autophagy

Язык: Английский

Процитировано

0

Risk assessment of the top 50 drugs associated with drug-induced orthostatic hypotension: a disproportionality analysis of the FAERS and JADER databases DOI Creative Commons

Gaocan Ren,

Xiansu Chi,

Pingping Huang

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 26, 2025

To use the FDA Adverse Event Reporting System (FAERS) database to identify drugs associated with orthostatic hypotension. event reports of hypotension from Q1 2004 Q3 2024 were obtained FAERS and JADER databases. We employed algorithms such as reporting odds ratio (ROR), proportional (PRR), Bayesian confidence propagation neural network (BCPNN), multi-item gamma Poisson shrinker (MGPS) for signal detection. was used validate findings analysis. identified 15,737 adverse events hypotension, involving 15,480 patients The patient demographic included 6,745 males (43.5%) 7,248 females (46.8%), largest group comprising adults over 65 years (7,654 cases, 49.4%). three highest ROR risk signals terazosin [ROR (95% CI): 153.96 (124.57-190.28)], rasagiline 37.46 (29.99–46.78)], doxazosin 37.06 (31.32–43.86)]. Apomorphine, abalopatine levodopa shortest onset time Most detection results verified in database. Drugs hypertension still focused on cardiovascular nervous system drugs. This study 33 that may be potentially linked Medical workers should remain vigilant regarding these causing

Язык: Английский

Процитировано

0

Letter to the FDA Proposing Major Changes in the US Clozapine Package Insert Supported by Clozapine Experts Worldwide. Part II DOI
José de León, Ross J. Baldessarini, Richard Balon

и другие.

Journal of Clinical Psychopharmacology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 8, 2025

Abstract Purpose/Background This is the second part of a 2-part article that proposes improving United States (US) clozapine package insert. Part II focuses on fatal outcomes and 5 boxed warnings, 4 specifically for clozapine: severe neutropenia, seizure, orthostatic hypotension myocarditis, 1 all antipsychotics (elderly with dementia). Methods US reports to World Health Organization's global pharmacovigilance database were analyzed from clozapine's introduction January 15, 2023. Findings/Results The was top reporter worldwide 56,003 9587 associated outcomes. warnings 534 (218 131 seizures, 125 orthostasis, 36 24 cardiomyopathy, 0 mitral valve prolapse). With no pneumonia 674 increased white blood cell count (a sign infection) 596 After considering overlaps, increases in explained 900 fatalities, or 9.4% Food Drug Administration continues focus neutropenia which only 218 2.3% outcomes, whereas 97.7% reported clozapine-treated patients had another cause. Implications/Conclusions To help prevent future deaths patients, insert should during infections. offers detailed solutions regarding current lack warning other Supplementary Material includes letters support 124 non-US experts 44 countries/regions who Parts I II.

Язык: Английский

Процитировано

0