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Journal of Gastrointestinal and Liver... Sep 2023
PubMed: 37774221
DOI: 10.15403/jgld-4925 -
BMC Infectious Diseases May 2024Amidst limited influenza treatment options, evaluating the safety of Oseltamivir and Baloxavir Marboxil is crucial, particularly given their comparable efficacy. This...
BACKGROUND AND OBJECTIVES
Amidst limited influenza treatment options, evaluating the safety of Oseltamivir and Baloxavir Marboxil is crucial, particularly given their comparable efficacy. This study investigates post-market safety profiles, exploring adverse events (AEs) and their drug associations to provide essential clinical references.
METHODS
A meticulous analysis of FDA Adverse Event Reporting System (FAERS) data spanning the first quarter of 2004 to the fourth quarter of 2022 was conducted. Using data mining techniques like reporting odds ratio (ROR), proportional reporting ratio, Bayesian Confidence Propagation Neural Network, and Multiple Gamma Poisson Shrinkage, AEs related to Oseltamivir and Baloxavir Marboxil were examined. Venn analysis compared and selected specific AEs associated with each drug.
RESULTS
Incorporating 15,104 Oseltamivir cases and 1,594 Baloxavir Marboxil cases, Wain analysis unveiled 21 common AEs across neurological, psychiatric, gastrointestinal, dermatological, respiratory, and infectious domains. Oseltamivir exhibited 221 significantly specific AEs, including appendicolith [ROR (95% CI), 459.53 (340.88 ∼ 619.47)], acne infantile [ROR (95% CI, 368.65 (118.89 ∼ 1143.09)], acute macular neuroretinopathy [ROR (95% CI), 294.92 (97.88 ∼ 888.64)], proctitis [ROR (95% CI), 245.74 (101.47 ∼ 595.31)], and Purpura senile [ROR (95% CI), 154.02 (81.96 ∼ 289.43)]. designated adverse events (DMEs) associated with Oseltamivir included fulminant hepatitis [ROR (95% CI), 12.12 (8.30-17.72), n=27], ventricular fibrillation [ROR (95% CI), 7.68 (6.01-9.83), n=64], toxic epidermal necrolysis [ROR (95% CI), 7.21 (5.74-9.05), n=75]. Baloxavir Marboxil exhibited 34 specific AEs, including Melaena [ROR (95% CI), 21.34 (14.15-32.18), n = 23], cystitis haemorrhagic [ROR (95% CI), 20.22 (7.57-54.00), n = 4], ileus paralytic [ROR (95% CI), 18.57 (5.98-57.71), n = 3], and haemorrhagic diathesis [ROR (95% CI), 16.86 (5.43-52.40)), n = 3]. DMEs associated with Baloxavir Marboxil included rhabdomyolysis [ROR (95% CI), 15.50 (10.53 ∼ 22.80), n = 26].
CONCLUSION
Monitoring fulminant hepatitis during Oseltamivir treatment, especially in patients with liver-related diseases, is crucial. Oseltamivir's potential to induce abnormal behavior, especially in adolescents, necessitates special attention. Baloxavir Marboxil, with lower hepatic toxicity, emerges as a potential alternative for patients with liver diseases. During Baloxavir Marboxil treatment, focused attention on the occurrence of rhabdomyolysis is advised, necessitating timely monitoring of relevant indicators for those with clinical manifestations. The comprehensive data aims to provide valuable insights for clinicians and healthcare practitioners, facilitating an understanding of the safety profiles of these influenza treatments in real-world scenarios.
Topics: Humans; Dibenzothiepins; Triazines; United States; Oseltamivir; Antiviral Agents; United States Food and Drug Administration; Female; Male; Morpholines; Adult; Middle Aged; Pharmacovigilance; Adverse Drug Reaction Reporting Systems; Adolescent; Pyridones; Young Adult; Aged; Influenza, Human; Child; Triazoles; Thiepins; Pyrazines; Pyridines; Child, Preschool; Oxazines
PubMed: 38724914
DOI: 10.1186/s12879-024-09339-4 -
Current Medicinal Chemistry Feb 2024Influenza is an acute respiratory disease caused by influenza viruses. It has the characteristics of fast transmission and strong infectivity, and it does great harm to...
Influenza is an acute respiratory disease caused by influenza viruses. It has the characteristics of fast transmission and strong infectivity, and it does great harm to human health and survival. It is estimated that the seasonal influenza epidemics every year will cause about one billion cases of infections and hundreds of thousands of deaths worldwide, while influenza A virus is the leading cause of infection and death. Currently, the main drugs used in clinics to treat influenza viruses are neuraminidase inhibitors, and these drugs have shown excellent efficacy in treating influenza viruses. However, various mutant strains have developed resistance to these effective drugs in clinics (such as the subtype mutant strains of H274Y in H1N1 or H5N1 and E119V in H3N2 have developed resistance to Oseltamivir). Influenza viruses mutate frequently, and new viral strains are constantly discovered, and the pandemics will break out at any time. Therefore, it is urgent to develop efficient and broad-spectrum drugs to prevent and treat the influenza pandemic caused by the emerging new subtypes. This review focuses on describing the pandemic history, the structure, function and prevention methods of influenza viruses and the progress of the development of anti-influenza drugs, to provide the reference for prevention and treatment of influenza viruses and development of influenza virus inhibitors.
PubMed: 38362681
DOI: 10.2174/0109298673268314231204061224 -
Journal of Ethnopharmacology Feb 2024Jingfang Granules (JFG) originate from the traditional herbal formula Jingfang Baidu powder. It has the effects of inducing sweating and dispelling wind. It is a classic...
ETHNOPHARMACOLOGICAL RELEVANCE
Jingfang Granules (JFG) originate from the traditional herbal formula Jingfang Baidu powder. It has the effects of inducing sweating and dispelling wind. It is a classic medication used for treating external pathogenic factors and viral diseases. However, the therapeutic mechanism of JFG for viral myocarditis needs further clarification.
AIM OF THE STUDY
This study aimed to explore the therapeutic efficacy of JFG on coxsackievirus B3-induced viral myocarditis (VMC), along with the elucidation of its underlying mechanisms.
MATERIALS AND METHODS
C57 BL/6JNifdc mice were divided randomly into several groups: control, model, Jingfang Granule groups (0.23, 0.46, and 0.69 g/20g, respectively), and a positive group (oseltamivir, 19.33 mg/kg). Following the establishment of the VMC model, the mice underwent an 8 -week treatment regimen. Pathological alterations in cardiac tissues and inflammatory protein expression were monitored. Differential gene analysis was conducted utilizing transcriptomic techniques. The differential gene mucolipin 1 (Mcoln1) was knocked down by transfection with siRNA in H9C2 cell, and investigative techniques such as immunoblotting, qRT-PCR, immunofluorescence, JC-1 staining, reactive oxygen species (ROS) detection, and mitochondrial stress testing were employed to examine its mechanism of action.
RESULTS
JFG significantly mitigates the pathological damage observed in the cardiac tissues of CVB3-induced VMC mice and attenuates the expression of inflammatory genes. Subsequently, differentially expressed genes are identified through transcriptomic analysis and validated via PCR. Among these, the upregulation of Mcoln1 promotes autophagy, facilitating the clearance of damaged mitochondria and excessive ROS. This has been substantiated through in vitro experiments. Excessive ROS precipitates a reduction in mitochondrial membrane potential, instigating cell apoptosis. In accordance with TUNEL staining results, JFG acts to inhibit cell apoptosis. To ascertain whether Mcoln1 is a crucial target for JFG in treating VMC, Mcoln1 was suppressed in H9C2 cells. The suppression of Mcoln1 hinders the elevation in autophagy levels post-JFG treatment, obstructs the enhancement of mitochondrial function, and impedes the clearance of ROS. Furthermore, the inhibitory effect of JFG on cell apoptosis is attenuated.
CONCLUSION
The research findings indicate that JFG has a protective effect on CVB3-induced H9C2 cell injury. JFG may exert its effects in VMC treatment by enhancing autophagy to suppress cell apoptosis through the mitochondrial pathway, thereby counteracting cell damage.
Topics: Mice; Animals; Myocarditis; Reactive Oxygen Species; Coxsackievirus Infections; Myocardium; Heart; Enterovirus B, Human; Mice, Inbred BALB C
PubMed: 37951374
DOI: 10.1016/j.jep.2023.117396 -
Drug and Therapeutics Bulletin Mar 2024Hanula R, Bortolussi-Courval É, Mendel A, et al. Evaluation of oseltamivir used to prevent hospitalization in outpatients with influenza: a systematic review and... (Meta-Analysis)
Meta-Analysis
Hanula R, Bortolussi-Courval É, Mendel A, et al. Evaluation of oseltamivir used to prevent hospitalization in outpatients with influenza: a systematic review and meta-analysis. JAMA Internal Medicine 2024;184:18-27.
Topics: Humans; Oseltamivir; Influenza, Human; Antiviral Agents; Treatment Outcome; Hospitalization
PubMed: 38527768
DOI: 10.1136/dtb.2024.000016 -
MBio Aug 2023Obesity has been epidemiologically and empirically linked with more severe diseases upon influenza infection. To ameliorate severe disease, treatment with antivirals,...
Obesity has been epidemiologically and empirically linked with more severe diseases upon influenza infection. To ameliorate severe disease, treatment with antivirals, such as the neuraminidase inhibitor oseltamivir, is suggested to begin within days of infection especially in high-risk hosts. However, this treatment can be poorly effective and may generate resistance variants within the treated host. Here, we hypothesized that obesity would reduce oseltamivir treatment effectiveness in the genetically obese mouse model. We demonstrated that oseltamivir treatment does not improve viral clearance in obese mice. While no traditional variants associated with oseltamivir resistance emerged, we did note that drug treatment failed to quench the viral population and did lead to phenotypic drug resistance . Together, these studies suggest that the unique pathogenesis and immune responses in obese mice could have implications for pharmaceutical interventions and the within-host dynamics of the influenza virus population. IMPORTANCE Influenza virus infections, while typically resolving within days to weeks, can turn critical, especially in high-risk populations. Prompt antiviral administration is crucial to mitigating these severe sequalae, yet concerns remain if antiviral treatment is effective in hosts with obesity. Here, we show that oseltamivir does not improve viral clearance in genetically obese or type I interferon receptor-deficient mice. This suggests a blunted immune response may impair oseltamivir efficacy and render a host more susceptible to severe disease. This study furthers our understanding of oseltamivir treatment dynamics both systemically and in the lungs of obese mice, as well as the consequences of oseltamivir treatment for the within-host emergence of drug-resistant variants.
Topics: Mice; Animals; Humans; Oseltamivir; Mice, Obese; Influenza, Human; Influenza A Virus, H1N1 Subtype; Antiviral Agents; Neuraminidase; Drug Resistance, Viral
PubMed: 37341495
DOI: 10.1128/mbio.00887-23 -
Current Pediatric Reviews Aug 2023From time to time, physicians face challenging diagnostic and therapeutic issues concerning the acute management of children with viral encephalitis.
BACKGROUND
From time to time, physicians face challenging diagnostic and therapeutic issues concerning the acute management of children with viral encephalitis.
OBJECTIVE
The aim of this article is to provide an updated narrative review on the similarities and differences between SARS-CoV-2 and influenza encephalitis.
METHODS
A PubMed search was performed with the function "Clinical Queries" using the key terms "SARS-CoV-2" OR "Influenza" AND "Encephalitis". The search strategy included meta-analyses, clinical trials, randomized controlled trials, reviews and observational studies. The search was restricted to the English literature and pediatric population. This article compares similarities and contrasts between SARS-CoV-2 and influenza-associated encephalitis.
RESULTS
Encephalitis is an uncommon manifestation of both influenza and SARS-CoV-2. Both vi-ruses are associated with fever and respiratory symptoms. However, SARS-CoV-2 patients may on-ly have mild symptoms or be asymptomatic as silent carriers, rendering the disease spread difficult to control. Influenza patients usually have more severe symptomatology and are often bed bound for several days limiting its spread. Influenza is associated with seasonal and annual outbreaks, whereas SARS-CoV-2 has become endemic. Complications of encephalitis are rare in both viral infections but, when present, may carry serious morbidity and mortality. Many long-term sequelae of COVID-19 infections (long COVID-19) have been described but not with influenza infections. Mortality as-sociated with encephalitis appears higher with influenza than with SARS-CoV-2. Prophylaxis by immunization is available for both influenza and SARS-CoV-2. Specific efficacious antivirals are also available with oseltamivir for influenza and nirmatrelvir/ritonavir for SARS-CoV-2. Steroids are indicated with more severe SARS-CoV-2 but their role is not distinct in influenza disease.
CONCLUSION
Encephalitis is a rare complication of influenza and SARS-CoV-2 infections. Both car-ry significant morbidity and mortality. Efficacious vaccines for prophylaxis and antivirals for treat-ment are available for both viruses.
PubMed: 37605390
DOI: 10.2174/1573396320666230821110450 -
Medicina (Kaunas, Lithuania) Aug 2023: Baloxavir marboxil is a novel cap-dependent endonuclease inhibitor prescribed for influenza treatment. Unlike neuraminidase inhibitors like oseltamivir, which impair...
: Baloxavir marboxil is a novel cap-dependent endonuclease inhibitor prescribed for influenza treatment. Unlike neuraminidase inhibitors like oseltamivir, which impair viral release from infected host cells, baloxavir blocks influenza virus proliferation by inhibiting viral mRNA transcription. This study aimed to compare the effectiveness of baloxavir and oseltamivir for the treatment of early childhood influenza. : Of 1410 patients diagnosed with influenza between 2015 and 2018 at a Japanese primary care outpatient clinic, 1111 pediatric patients aged 0-6 years who were treated with baloxavir ( = 555) or oseltamivir ( = 556) were enrolled retrospectively. The following clinical factors were compared between patients treated with baloxavir and oseltamivir: age, sex, time from fever onset to drug administration (<24 h or 24-48 h), time from drug administration to fever reduction, influenza type (A or B), and influenza vaccination before disease onset. The duration of the fever, which was used as an index of clinical effectiveness, was compared using the log-rank test. Clinical factors associated with fever duration were determined using multivariate logistic regression analysis. : Median age (3.0 vs. 2.5 years), influenza type A (99% vs. 47%), median duration from drug administration to fever resolution (1 day vs. 2 days), and influenza vaccination (done, 41% vs. not done, 65%) were significantly different between the baloxavir and oseltamivir groups ( < 0.001). The number of patients with a fever duration of one day was 553 (99.6%) in the baloxavir group and 6 (1.1%) in the oseltamivir group ( < 0.001). Baloxavir use was only significantly associated with fever duration in the multivariate analysis (odds ratio 50,201, < 0.001). Apparent adverse effects were not observed in the baloxavir-treated group. : Baloxavir treatment resulted in a shorter fever duration than oseltamivir treatment in early childhood influenza.
Topics: Child, Preschool; Humans; Child; Oseltamivir; Influenza, Human; Retrospective Studies; Dibenzothiepins; Fever
PubMed: 37763660
DOI: 10.3390/medicina59091543 -
Journal of Medical Virology Jul 2023Influenza viruses pose a significant threat to human health worldwide due to seasonal epidemics and occasional global pandemics. These viruses can cause severe upper...
Influenza viruses pose a significant threat to human health worldwide due to seasonal epidemics and occasional global pandemics. These viruses can cause severe upper respiratory tract infections that contribute to high morbidity and mortality rates. The emergence of drug-resistant influenza viruses has created the need for the development of novel broad-spectrum antivirals. Here, we present a novel anti-influenza agent with new targets and mechanisms of action to address this problem. Our findings led to the discovery of a novel influenza virus inhibitor, a ligustrazine derivative known as A9. We have found that it exhibits broad-spectrum antiviral properties against influenza A and B viruses (IAV and IBV, respectively), including oseltamivir-resistant strain. Through multiple bioassays such as time-of-addition assay, indirect immunofluorescence assay, and nuclear-cytoplasmic fractionation assay, we demonstrated that A9 inhibits the nuclear export of the viral ribonucleoprotein (vRNP). Furthermore, escape mutant analyses and affinity studies determined by surface plasmon resonance indicated that A9 specifically targets the nucleoprotein. In addition, four chalcone derivatives developed from A9 (B14, B29, B31, and B32), were found to effectively inhibit the replication of influenza virus through the same mechanism of action. In this manuscript we highlight A9 and its four derivatives as potential leads for the treatment of IAV and IBV infections, and their unique and novel mechanism of action probable benefit the field of anti-influenza drug discovery.
Topics: Humans; Nucleoproteins; Chalcones; Active Transport, Cell Nucleus; Influenza, Human; Antiviral Agents; Chalcone; Orthomyxoviridae
PubMed: 37489704
DOI: 10.1002/jmv.28968 -
Pediatrics Dec 2023Influenza antivirals improve outcomes in children with duration of symptoms <2 days and those at high risk for influenza complications. Real-world prescribing of...
BACKGROUND
Influenza antivirals improve outcomes in children with duration of symptoms <2 days and those at high risk for influenza complications. Real-world prescribing of influenza antivirals in the pediatric population is unknown.
METHODS
We performed a cross-sectional study of outpatient and emergency department prescription claims in individuals <18 years of age included in the IBM Marketscan Commercial Claims and Encounters Database between July 1, 2010 and June 30, 2019. Influenza antiviral use was defined as any dispensing of oseltamivir, baloxavir, or zanamivir. The primary outcome was the rate of antiviral dispensing per 1000 enrolled children. Secondary outcomes included antiviral dispensing per 1000 influenza diagnoses and inflation-adjusted costs of antiviral agents. Outcomes were calculated and stratified by age, acute versus prophylactic treatment, influenza season, and geographic region.
RESULTS
The analysis included 1 416 764 unique antiviral dispensings between 2010 and 2019. Oseltamivir was the most frequently prescribed antiviral (99.8%). Dispensing rates ranged from 4.4 to 48.6 per 1000 enrolled children. Treatment rates were highest among older children (12-17 years of age), during the 2017 to 2018 influenza season, and in the East South Central region. Guideline-concordant antiviral use among young children (<2 years of age) at a high risk of influenza complications was low (<40%). The inflation-adjusted cost for prescriptions was $208 458 979, and the median cost ranged from $111 to $151.
CONCLUSIONS
There is wide variability and underuse associated with influenza antiviral use in children. These findings reveal opportunities for improvement in the prevention and treatment of influenza in children.
Topics: Child; Humans; Adolescent; United States; Child, Preschool; Influenza, Human; Oseltamivir; Antiviral Agents; Outpatients; Cross-Sectional Studies
PubMed: 37953658
DOI: 10.1542/peds.2023-061960