Journal of clinical pharmacy and therapeutics
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Direct oral anticoagulants (DOACs) were developed to avoid the limitations of vitamin K antagonists (VKAs). DOACs are associated with a greater incidence of gastrointestinal bleeding and a smaller number of intracranial haemorrhages than VKAs. Therefore, it is important to deepen our knowledge of their safety profiles. The aim of this study was thus to analyse adverse drug reaction (ADR) reports on DOACs and VKAs using the Sicilian Spontaneous Reporting System (SRS) database. ⋯ The ADRs most commonly associated with DOACs, especially dabigatran, were gastrointestinal disorders, particularly gastrointestinal bleeding. Our study also highlights the potential role of drug-drug interactions in the ADRs. The cases of gastrointestinal bleeding highlight the need for careful prescribing of DOACs and use of potentially interacting concomitant drugs.
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Review Meta Analysis
Hepatotoxicity with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer patients: A network meta-analysis.
The efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients diagnosed with non-small-cell lung cancer (NSCLC) has been confirmed by a large number of studies. However, hepatotoxicity caused by EGFR-TKIs has not been widely investigated. This review compares the hepatotoxicity of different EGFR-TKIs through a network meta-analysis. ⋯ Current evidence indicates that the association between afatinib or dacomitinib and risk of liver enzyme elevation remains uncertain in patients diagnosed with NSCLC. Some evidence suggests that gefitinib and erlotinib may be associated with a significantly increased risk for hepatotoxicity in patients with NSCLC. However, given that the elevation of liver enzymes was not definitely associated with EGFR-TKIs and publication bias, further studies are required to confirm these results.
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Glycerol is thought to be superior to mannitol in the treatment of cerebral oedema and elevated intracranial pressure (ICP), particularly with safety concerns. However, the current evidence remains insufficient. Therefore, we aimed to compare the efficacy and safety of glycerol versus mannitol in this meta-analysis. ⋯ Regarding the balance between efficacy and safety, glycerol could be an effective and more tolerable alternative therapy for cerebral oedema and elevated ICP than mannitol, especially for high-risk populations of renal failure.
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The coronavirus disease 2019 (COVID-19) associated cytokine activation can lead to a rapid progression into respiratory failure, shock and multiorgan failure. Interleukin-6 (IL-6) is a pro-inflammatory cytokine that likely contributes to the pathogenesis of cytokine release syndrome. It is hypothesized that modulating IL-6 levels or its effects with tocilizumab, a recombinant humanized anti-IL-6 receptor monoclonal antibody, may alter the course of disease. ⋯ Tocilizumab and other IL-6 receptor monoclonal antibodies may evolve as a viable option in treating patients with moderate and severe COVID-19.
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Review
Chloroquine and hydroxychloroquine for COVID-19: Perspectives on their failure in repurposing.
Non-clinical studies suggest that chloroquine (CQ) and hydroxychloroquine (HCQ) have antiviral activities. Early clinical reports of successful HCQ-associated reduction in viral load from small studies in COVID-19 patients spurred a large number of national and international clinical trials to test their therapeutic potential. The objective of this review is to summarize the current evidence on the safety and efficacy of these two agents and to provide a perspective on why their repurposing has hitherto failed. ⋯ The strategy to repurpose CQ/HCQ to combat COVID-19 infection is overshadowed by concerns about their QT liability, resulting in choice of potentially subtherapeutic doses. Although the risk of QT-related proarrhythmia is real, it is low and manageable by careful monitoring. Recent discontinuation of HCQ from at least four large studies effectively marks the end of efforts at repurposing of CQ or HCQ for COVID-19 infection. This episode leaves behind important questions on dose selection and risk/benefit balance in repurposing drugs generally.