ABSTRACT
The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.Copyright © 2023 Safety and Risk of Pharmacotherapy. All rights reserved.
ABSTRACT
Introduction: The course of SARS-CoV-2 disease has a clinical spectrum ranging from mild upper respiratory tract infection to fulminant pneumonia. The use of corticosteroids is recommended in the treatment of severe COVID-19 pneumonia. The present study aimed to compare the efficacy of high-dose methylprednisolone and dexamethasone treatment in patients hospitalized with severe COVID-19 pneumonia. Material(s) and Method(s): The participants were divided into Group M, receiving >=250 mg intravenous methylprednisolone therapy, and Group D receiving 6 mg intravenous dexamethasone therapy. The efficacy of treatments, length of hospital stays, ventilator requirements, anti-cytokine treatment requirements, and mortality rates were evaluated in both groups. Result(s): Two hundred eighty-eight (69.1%) patients received dexamethasone and 129 (30.9%) received methylprednisolone. While overall mortality in the study was 11%, this rate was 10.4% in Group D and 12.4% in Group M (p> 0.05). The rate of patients requiring intensive care was 15.8% in total, with a rate of 14.6% in Group D and 18.6% in Group M (p> 0.05). However, the total length of hospital stay was nine (7-39) days in Group M and 13 (7-29) days in Group D (p= 0.009). Anticytokines were required in 14.4% of the patients during treatment [40 in Group D, 20 in Group M (p> 0.05)]. Conclusion(s): In this study, it was determined that early methylprednisolone treatment shortened the hospital stay. In addition, there was no statistically significant difference between Group M and Group D in terms of mechanical ventilation requirement, which showed an additional positive effect. However, mortality rates in patients receiving dexamethasone were found to be lower than in those receiving methylprednisolone, yet this difference did not reach statistical significance.Copyright © 2023 Bilimsel Tip Yayinevi. All rights reserved.
ABSTRACT
Objective. To evaluate safety of anti-interleukin drugs used as a pathogenetic therapy of COVID-19 as assessed by risks of infectious complications. Materials and methods. A systematic review of publications related to safety assessment of anti-interleukin drugs recommended as pathogenetic therapy in COVID-19 patients in terms of incidence of serious adverse events and adverse events of "Infections and Invasions" class and a meta-analysis of the data were performed. Results. The meta-analysis included 16 randomized and 3 non-randomized studies. The hazard ratio of serious adverse events between the comparison groups was 0.93 [95% CI 0.85;1.01] (p = 0.1), the hazard ratio of adverse event of "Infections and Invasions" class was 0.9 [95% CI 0.8;1.02] (p = 0.09), showing no differences in the incidence of those events. Conclusions. This meta-analysis did not demonstrate statistically significant differences in the relative risks of serious adverse events and adverse events of "Infections and Invasions" class for the use of anti-interleukin drugs in COVID-19 patients.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.
ABSTRACT
The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.Copyright © 2023 Safety and Risk of Pharmacotherapy. All rights reserved.
ABSTRACT
Objectives: Cytomegalovirus (CMV) reactivation is a significant cause of morbidity and mortality in critically ill patients. Existing or newly developed immunosuppression appears to be the main factor for reactivation. COVID-19 patients with acute respiratory distress syndrome can be affected by a variety of conditions that cause immunosuppression. Clarifying CMV reactivation and notably its predictive features became important during the epidemic. Method(s): This is a retrospective, observational, and cohort study. All COVID-19 patients admitted to the ICU between March 11, 2020 and March 11, 2021 were analyzed. All of the information was gathered from the hospital's electronic records. CMV reactivation was defined as CMV DNA >=1000 copies/ml in tracheal samples. The patient population was analyzed in two groups, namely, patients with CMV reactivation and patients without reactivation. Result(s): During the study period, 99 of all COVID-19 ARDS patients fulfilled the inclusion criteria, and CMV reactivation was detected in 55 (55.6%) of them. Age, BMI, APACHE-II score, hypertension, chronic respiratory disease, the usage of interleukin blockers, the duration of steroid usage, procalcitonin (PCT), and CD-8 T-cell levels differed significantly from the patients without CMV reactivation. Furthermore, the reactivation group had longer ICU stays, longer durations of mechanical ventilation, and higher mortality. Conclusion(s): CMV can be reactivated in critically ill COVID-19 ARDS patients, which appears to correlate with worse outcomes. Obesity, the usage of IL-blockers and steroids >12 days, high PCT, and low CD-8 T-cell levels appear to be risk factors. Critically ill COVID-19 patients should be closely monitored with regard to immunosuppression and CMV status.Copyright © 2022 by The Cardiovascular Thoracic Anaesthesia and Intensive Care.
ABSTRACT
The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.
ABSTRACT
Screening advanced compounds enables discovery of direct repurposing candidates, novel drug-like leads for optimization, and informative pharmacological probes. In this chapter, we describe different types of screening collections used in drug repurposing, discuss issues and considerations in preparing and executing a repurposing screen, and present examples of in vitro and in vivo repurposing assays. We further describe various data sources reporting information on de-risked compounds of different types and illustrate how data mining and chemoinformatic and chemogenomic searches can be used to access large numbers of advanced compounds and assemble collections most suitable for screening in a given disease model. We argue that a view of repurposing screening as a large-scale bet on finding candidates for clinical testing is narrow and incomplete. Rather, when thoughtfully executed, screening of re-risked compounds is informed by target pathobiology and offers a means to efficiently convert advances in the development of sophisticated non-clinical models and new insights in disease mechanisms into novel drug-like leads and candidates for development.