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Drug Metabolism Reviews Nov 2023Nebivolol is a beta-1 receptor blocker used to treat hypertension, heart failure, erectile dysfunction, vascular disease, and diabetes mellitus. This review investigated... (Review)
Review
Nebivolol is a beta-1 receptor blocker used to treat hypertension, heart failure, erectile dysfunction, vascular disease, and diabetes mellitus. This review investigated the data regarding pharmacokinetic (PK) parameters, drug-drug interactions, dextrorotatory (D), and levorotatory (L) stereoisomers of nebivolol. The articles related to the PK of nebivolol were retrieved by searching the five databases; Google Scholar, PubMed, Cochrane Library, ScienceDirect, and EBSCO. A total of 20 studies comprising plasma concentration-time profile data following the nebivolol's oral and intravenous (IV) administration were included. The area under the concentration-time curve from zero to infinity (AUC) was 15 times greater in poor metabolizers (PMs) than in extensive metabolizers (EMs). In hypertensive patients, L-nebivolol expressed a higher maximum plasma concentration (C) than D-nebivolol, i.e. 2.5 ng/ml vs 1.2 ng/ml. The AUC of nebivolol was 3-fold greater in chronic kidney disease (CKD). The clearance (CL) was increased in obese than in controls from 51.6 ± 11.6 L/h to 71.6 ± 17.4 L/h when 0.5 mg/ml IV solution was infused. Nebivolol showed higher C, AUC and half-life (t) when co-administered with bupropion, duloxetine, fluvoxamine, paroxetine, lansoprazole, and fluoxetine. This concise review of nebivolol would be advantageous in assessing all PK parameters, which may be crucial for clinicians to avoid drug-drug interactions, prevent adverse drug events and optimize the dosage regimen in diseased patients diagnosed with hypertension and cardiovascular disorders.
Topics: Male; Humans; Nebivolol; Hypertension; Fluvoxamine; Lansoprazole; Drug Interactions
PubMed: 37849071
DOI: 10.1080/03602532.2023.2271195 -
Reviews in Medical Virology Jan 2024This systematic review and meta-analysis of randomised controlled trials (RCTs) aimed to evaluate the efficacy, safety, and tolerability of fluvoxamine for the... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis of randomised controlled trials (RCTs) aimed to evaluate the efficacy, safety, and tolerability of fluvoxamine for the outpatient management of COVID-19. We conducted this review in accordance with the PRISMA 2020 guidelines. Literature searches were conducted in MEDLINE, EMBASE, International Pharmaceutical Abstracts, CINAHL, Web of Science, and CENTRAL up to 14 September 2023. Outcomes included incidence of hospitalisation, healthcare utilization (emergency room visits and/or hospitalisation), mortality, supplemental oxygen and mechanical ventilation requirements, serious adverse events (SAEs) and non-adherence. Fluvoxamine 100 mg twice a day was associated with reductions in the risk of hospitalisation (risk ratio [RR] 0.75, 95% confidence interval [CI] 0.58-0.97; I = 0%) and reductions in the risk of healthcare utilization (RR 0.68, 95% CI 0.53-0.86; I = 0%). While no increased SAEs were observed, fluvoxamine 100 mg twice a day was associated with higher treatment non-adherence compared to placebo (RR 1.61, 95% CI 1.22-2.14; I = 53%). In subgroup analyses, fluvoxamine reduced healthcare utilization in outpatients with BMI ≥30 kg/m , but not in those with lower BMIs. While fluvoxamine offers potential benefits in reducing healthcare utilization, its efficacy may be most pronounced in high-risk patient populations. The observed non-adherence rates highlight the need for better patient education and counselling. Future investigations should reassess trial endpoints to include outcomes relating to post-COVID sequelaes. Registration: This review was prospectively registered on PROSPERO (CRD42023463829).
Topics: Humans; COVID-19; Outpatients; Fluvoxamine; COVID-19 Drug Treatment
PubMed: 38148036
DOI: 10.1002/rmv.2501 -
European Journal of Clinical... May 2024Dabrafenib and trametinib represent targeted therapy options under investigation for treatment of gliomas harboring BRAF V600 mutations. We systematically reviewed the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dabrafenib and trametinib represent targeted therapy options under investigation for treatment of gliomas harboring BRAF V600 mutations. We systematically reviewed the literature and conducted meta-analyses to assess the efficacy and safety of these agents.
METHODS
PubMed, Embase, and Scopus were searched from inception to September 2023 for studies examining dabrafenib and/or trametinib for gliomas. Outcomes included response rates (ORR, CR, PR), progression rates (PD), 6- and 12-month PFS, adverse events, and dosing modifications. Meta-analyses were conducted using random effect models.
RESULTS
Nine studies met the inclusion criteria. Meta-analysis demonstrated overall response rates (ORR) of 50% (95% confidence interval (CI): 35-65%) for low-grade gliomas (LGG) and 40% (95% CI: 29-51%) for high-grade gliomas (HGG). Pooled ORR was 45% (95% CI: 36-54%) for both glioma grades. The complete response rate was 13% (95% CI: 05-27%) for HGG and 5% (95% CI: 1-10%) for both LGG and HGG. Six-month progression-free survival (PFS) rates reached 87% in LGG and 67% in HGG and a pooled 6-month PFS 78% (95% CI: 58-98%), declining at 12 months to 67% and 44%, respectively, with a pooled 12-month PFS 56% (95% CI: 34-79%). Grade 1-4 adverse events occurred in 100% of LGG and 63% of HGG patients.
CONCLUSIONS
Dabrafenib and trametinib demonstrate promising anti-tumor efficacy in gliomas, particularly low-grade tumors, achieving durable disease stabilization in many patients. However, toxicity significantly limited tolerability. Additional research should further examine efficacy and refine safe administration protocols across glioma subtypes.
Topics: Humans; Imidazoles; Glioma; Oximes; Pyridones; Mutation; Antineoplastic Combined Chemotherapy Protocols; Pyrimidinones
PubMed: 38345637
DOI: 10.1007/s00228-024-03635-3 -
International Journal of Molecular... Jan 2024Craniopharyngiomas present unique challenges in surgical management due to their proximity to critical neurovascular structures. This systematic review investigates... (Review)
Review
Craniopharyngiomas present unique challenges in surgical management due to their proximity to critical neurovascular structures. This systematic review investigates genetic and immunological markers as potential targets for therapy in craniopharyngiomas, assessing their involvement in tumorigenesis, and their influence on prognosis and treatment strategies. The systematic review adhered to PRISMA guidelines, with a thorough literature search conducted on PubMed, Ovid MED-LINE, and Ovid EMBASE. Employing MeSH terms and Boolean operators, the search focused on craniopharyngiomas, targeted or molecular therapy, and clinical outcomes or adverse events. Inclusion criteria encompassed English language studies, clinical trials (randomized or non-randomized), and investigations into adamantinomatous or papillary craniopharyngiomas. Targeted therapies, either standalone or combined with chemotherapy and/or radiotherapy, were examined if they included clinical outcomes or adverse event analysis. Primary outcomes assessed disease response through follow-up MRI scans, categorizing responses as follows: complete response (CR), near-complete response (NCR), partial response, and stable or progressive disease based on lesion regression percentages. Secondary outcomes included treatment type and duration, as well as adverse events. A total of 891 papers were initially identified, of which 26 studies spanning from 2000 to 2023 were finally included in the review. Two tables highlighted adamantinomatous and papillary craniopharyngiomas, encompassing 7 and 19 studies, respectively. For adamantinomatous craniopharyngiomas, Interferon-2α was the predominant targeted therapy (29%), whereas dabrafenib took precedence (70%) for papillary craniopharyngiomas. Treatment durations varied, ranging from 1.7 to 28 months. Positive responses, including CR or NCR, were observed in both types of craniopharyngiomas (29% CR for adamantinomatous; 32% CR for papillary). Adverse events, such as constitutional symptoms and skin changes, were reported, emphasizing the need for vigilant monitoring and personalized management to enhance treatment tolerability. Overall, the data highlighted a diverse landscape of targeted therapies with encouraging responses and manageable adverse events, underscoring the importance of ongoing research and individualized patient care in the exploration of treatment options for craniopharyngiomas. In the realm of targeted therapies for craniopharyngiomas, tocilizumab and dabrafenib emerged as prominent choices for adamantinomatous and papillary cases, respectively. While adverse events were common, their manageable nature underscored the importance of vigilant monitoring and personalized management. Acknowledging limitations, future research should prioritize larger, well-designed clinical trials and standardized treatment protocols to enhance our understanding of the impact of targeted therapies on craniopharyngioma patients.
Topics: Humans; Ameloblastoma; Craniopharyngioma; Imidazoles; Oximes; Pituitary Neoplasms
PubMed: 38255797
DOI: 10.3390/ijms25020723 -
Scientific Reports Jun 2024There have been 774,075,242 cases of COVID-19 and 7,012,986 deaths worldwide as of January 2024. In the early stages of the pandemic, there was an urgent need to reduce... (Meta-Analysis)
Meta-Analysis
A systematic review and meta-analysis, investigating dose and time of fluvoxamine treatment efficacy for COVID-19 clinical deterioration, death, and Long-COVID complications.
There have been 774,075,242 cases of COVID-19 and 7,012,986 deaths worldwide as of January 2024. In the early stages of the pandemic, there was an urgent need to reduce the severity of the disease and prevent the need for hospitalization to avoid stress on healthcare systems worldwide. The repurposing of drugs to prevent clinical deterioration of COVID-19 patients was trialed in many studies using many different drugs. Fluvoxamine (an SSRI and sigma-1 receptor agonist) was initially identified to potentially provide beneficial effects in COVID-19-infected patients, preventing clinical deterioration and the need for hospitalization. Fourteen clinical studies have been carried out to date, with seven of those being randomized placebo-controlled studies. This systematic review and meta-analysis covers the literature from the outbreak of SARS-CoV-2 in late 2019 until January 2024. Search terms related to fluvoxamine, such as its trade names and chemical names, along with words related to COVID-19, such as SARS-CoV-2 and coronavirus, were used in literature databases including PubMed, Google Scholar, Scopus, and the ClinicalTrials.gov database from NIH, to identify the trials used in the subsequent analysis. Clinical deterioration and death data were extracted from these studies where available and used in the meta-analysis. A total of 7153 patients were studied across 14 studies (both open-label and double-blind placebo-controlled). 681 out of 3553 (19.17%) in the standard care group and 255 out of 3600 (7.08%) in the fluvoxamine-treated group experienced clinical deterioration. The estimated average log odds ratio was 1.087 (95% CI 0.200 to 1.973), which differed significantly from zero (z = 2.402, p = 0.016). The seven placebo-controlled studies resulted in a log odds ratio of 0.359 (95% CI 0.1111 to 0.5294), which differed significantly from zero (z = 3.103, p = 0.002). The results of this study identified fluvoxamine as effective in preventing clinical deterioration, and subgrouping analysis suggests that earlier treatment with a dose of 200 mg or above provides the best outcomes. We hope the outcomes of this study can help design future studies into respiratory viral infections and potentially improve clinical outcomes.
Topics: Fluvoxamine; Humans; COVID-19 Drug Treatment; COVID-19; SARS-CoV-2; Treatment Outcome; Clinical Deterioration; Selective Serotonin Reuptake Inhibitors
PubMed: 38862591
DOI: 10.1038/s41598-024-64260-9 -
PloS One 2024Recently, several randomized controlled trials (RCTs) of fluvoxamine have been successfully conducted for the treatment of patients with coronavirus disease 2019... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recently, several randomized controlled trials (RCTs) of fluvoxamine have been successfully conducted for the treatment of patients with coronavirus disease 2019 (COVID-19). This systematic review and meta-analysis was to evaluate the efficacy and safety of fluvoxamine in patients with COVID-19.
METHODS
MEDLINE, EMBASE, Cochrane Library and clinicaltrials.gov were searched for RCTs which were performed to evaluate fluvoxamine and placebo up to January 31, 2024. Review Manager 5.3 was used to perform meta-analysis. The risk ratio (RR) and mean difference (MD) was analyzed and calculated with a random effect model.
RESULTS
We pooled 4,711 participants from six RCTs (2,382 in the fluvoxamine group and 2,329 in the placebo group). Compared to the placebo group, the fluvoxamine group had a significantly lower rate of clinical deterioration (RR, 0.73; P = 0.004; 95% CI, 0.59 to 0.90; I2 = 0%) and hospitalization (RR, 0.76; P = 0.04; 95% CI, 0.59 to 0.99; I2 = 0%). In the meantime, compared with the placebo group, fluvoxamine group did not show any higher risk of AEs (P = 0.13 and 0.91, respectively) in safety outcomes analysis. The subgroup analysis showed that fluvoxamine treatment performed more than 200 mg daily appears to be more effective than those performed less than 200 mg daily in reducing clinical deterioration and hospitalization risks, while not exhibiting higher AE and SAE risks than placebo group.
CONCLUSION
Fluvoxamine for patients with COVID-19, especially those who take 200 mg or more daily, is superior to the placebo group in reducing clinical deterioration and hospitalization, and did not show any higher risk of AEs and SAEs in safety concerns, which might be a promising intervention for COVID-19.
Topics: Fluvoxamine; Humans; COVID-19 Drug Treatment; Randomized Controlled Trials as Topic; SARS-CoV-2; COVID-19; Treatment Outcome; Hospitalization
PubMed: 38753761
DOI: 10.1371/journal.pone.0300512 -
The Annals of Pharmacotherapy Dec 2023Fluvoxamine may be beneficial for the management of coronavirus disease 2019 (Covid-19) because of its effect on the sigma-1 receptor. Available evidence from randomized... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Fluvoxamine may be beneficial for the management of coronavirus disease 2019 (Covid-19) because of its effect on the sigma-1 receptor. Available evidence from randomized clinical trials (RCTs) has shown conflicting results.
OBJECTIVE
This study sought to analyze the efficacy and safety of fluvoxamine as an outpatient treatment for Covid-19.
METHODS
Using specific keywords, we comprehensively go through the potential articles on PubMed, Scopus, Europe PMC, and ClinicalTrials.gov sources until February 1, 2023. We collected all published clinical trials on fluvoxamine and Covid-19. We were using Review Manager 5.4 to conduct statistical analysis.
RESULTS
We include a total of 6 trials. Our pooled analysis revealed that fluvoxamine did not offer any significant benefit when compared with placebo in reducing the risk of clinical deterioration (risk ratio [RR] = 0.83; 95% CI: 0.65-1.06, = 0.14, = 29%), and hospitalization (RR = 0.80; 95% CI: 0.62-1.04, = 0.09, = 0%) of Covid-19 outpatients. The serious adverse events did not differ significantly between the 2 groups.
CONCLUSIONS AND RELEVANCE
This study indicates that although safe, fluvoxamine was not effective for outpatient treatment of Covid-19. Until more evidence can be obtained from larger RCTs, our study did not encourage the use of fluvoxamine as routine management for patients with Covid-19.
Topics: Humans; COVID-19; Fluvoxamine; Outpatients; COVID-19 Drug Treatment; Europe
PubMed: 37002592
DOI: 10.1177/10600280231162243 -
Frontiers in Endocrinology 2024Tyrosine kinase inhibitors (TKIs) contribute to the treatment of patients with anaplastic thyroid cancer (ATC). Although prospective clinical studies of TKIs exhibit...
BACKGROUND
Tyrosine kinase inhibitors (TKIs) contribute to the treatment of patients with anaplastic thyroid cancer (ATC). Although prospective clinical studies of TKIs exhibit limited efficacy, whether ATC patients benefit from TKI treatment in real-world clinical practice may enlighten future explorations. Therefore, we conducted this effective analysis based on real-world retrospective studies to illustrate the efficacy of TKI treatment in ATC patients.
METHODS
We systematically searched the online databases on September 03, 2023. Survival curves were collected and reconstructed to summarize the pooled curves. Responses were analyzed by using the "meta" package. The primary endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR).
RESULTS
12 studies involving 227 patients were enrolled in the study. Therapeutic strategies included: anlotinib, lenvatinib, dabrafenib plus trametinib, vemurafenib, pembrolizumab plus dabrafenib and trametinib, pembrolizumab plus lenvatinib, pembrolizumab plus trametinib, and sorafenib. The pooled median OS and PFS were 6.37 months (95% CI 4.19-10.33) and 5.50 months (95% CI 2.17-12.03). The integrated ORR and DCR were 32% (95% CI 23%-41%) and 40% (95% CI 12%-74%).
CONCLUSION
In real-world clinical practice, ATC patients could benefit from TKI therapy. In future studies, more basic experiments and clinical explorations are needed to enhance the effects of TKIs in the treatment of patients with ATC.
Topics: Humans; Thyroid Carcinoma, Anaplastic; Retrospective Studies; Tyrosine Kinase Inhibitors; Prospective Studies; Thyroid Neoplasms; Imidazoles; Oximes; Phenylurea Compounds; Quinolines
PubMed: 38469143
DOI: 10.3389/fendo.2024.1345203 -
Journal of the American Academy of... Feb 2024
Topics: Humans; Proto-Oncogene Proteins B-raf; Melanoma; Protein Kinase Inhibitors; Panniculitis; Antineoplastic Combined Chemotherapy Protocols; Mutation; Skin Neoplasms; Pyridones; Oximes
PubMed: 37943239
DOI: 10.1016/j.jaad.2023.10.008