Approaches to Assessing the Safety of Medicines during the COVID-19 Pandemic Using the Example of Azithromycin

Most of the medicines used to treat the novel coronavirus infection (COVID-19) are either approved under an accelerated procedure or not approved for the indication. Consequently, their safety requires special attention. The aim of the study was to review methodological approaches to collecting data on the safety of medicines, using COVID-19 treatment regimens involving azithromycin as a case study. Material(s) and Method(s): PubMed (MEDLINE), Scopus, eLIBRARY, and Cyberleninka databases were searched for publications on azithromycin as part of combination therapy for COVID-19 in 2020-2021. Search queries included names of the medicinal product or its pharmacotherapeutic group and words describing adverse drug reactions (ADRs) during treatment. Result(s): the analysis included 7 publications presenting the results of studies covering the use of azithromycin as part of COVID-19 combination therapy in more than 4000 patients. Most commonly, the patients receiving COVID-19 therapy including azithromycin developed cardiovascular ADRs (up to 30% of azithromycin prescription cases). In 3 of the analysed publications, safety information was collected through spontaneous reporting and active identification based on the findings of laboratory and instrumental investigations performed during the clinical studies;in other 3, only spontaneous reports were used;and in the last one, ADR database information was studied. Conclusion(s): currently, information on ADRs associated with the use of medicines is mainly gathered via spontaneous reporting. Direct sourcing of information on personal experiences with a certain product from patients, among other means through social media analysis, opens a promising direction towards the improvement of existing approaches to collecting safety data. Copyright © 2022 Obstetrics, Gynecology and Reproduction. All rights reserved.

A systematic review and meta-analysis of the safety of anti-interleukin therapy in COVID-19

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. © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

A systematic review of real-world clinical practice data in COVID-19: non-interventional studies

Introduction. As defined by the Food and Drug Administration, real-world data (RWD) is data related to a patient's health and/or health care delivery, usually collected from various sources as part of real-world clinical practice research. Objective: to describe the feasible and the most sought-after designs of non-interventional real-world clinical practice trials that provide evidence for the efficacy and safety of drug administration in the therapy of novel coronavirus infection. Material and methods. A search strategy for the terms “COVID-19 AND real-life”, “COVID-19 AND real-data”, “COVID-19 AND real-world” was developed to extract articles published between December 1, 2020 and March 12, 2021 from the databases: PubMed/MEDLINE, the Cochrane Database of Systematic Reviews, and the ClinicalTrials.gov database. Results. The search yielded 137 non-repetitive articles, 32 of them were included in the review. All randomized clinical trials (pragmatic and simplified large ones), studies of the effectiveness of laboratory diagnostic methods, medical triage, social distancing and other sanitary and epidemiological measures to cope with the epidemic were excluded. Conclusion. High-quality, non-randomized RWD studies can enhance the external validity of registration randomized clinical trials by complementing them with a broader range of indicators, which is essential in supporting medical and public health decision-making in the COVID-19 pandemic.

Safety profile assessment of drug products used for the pathogenetic treatment of COVID-19

Objective. To review and summarize literature data in studies of safety of the drug products used for the pathogenetic treatment of COVID-19. Materials and methods. As the first stage of monitoring the drug’s safety, which are used in the treatment of COVID-19 in Russia, a systematic review of studies of the drug’s safety profiles was carried out: Mefloquine, hydroxychloroquine, azithromycin, lopinavir/ritonavir, favipiravir, tocilizumab, olokizumab, baricitinib in the international databases Medline, PubMed, ClinicalTrials.gov and Cochrane Library for the period 2019–2021. Results. The review included 51 articles that met the selection criteria. Based on the results of the review, it can be concluded that the safety profile (frequency, severity and severity) of most drugs repurposed for COVID-19 corresponds to those for the registered indications. At the same time, according to world experience, there is an increase in the number of reports of adverse drug reactions of hydroxychloroquine and azithromycin, which is provoked by the active use of these drugs for combination therapy. Conclusions. According to the literature, a high incidence of adverse events was noted in hydroxychloroquine, chloroquine and azithromycin. Subsequent analysis and comparison of the safety profiles of hydroxychloroquine, chloroquine and azithromycin with data from the national automated information system (AIS) database of Roszdravnadzor is a necessary component of effective and safe pharmacotherapy for COVID-19. © 2021, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

COVID-19 and clinical pharmacology

The article provides an overview of the role of clinical pharmacology in the management of the COVID-19 pandemic, including various strategies and horizons for studying the infection and analysis of the individual groups of drugs from the mechanism of action on the coronavirus to the effects they cause, the current clinical trials in COVID-19, the main trends, problems and challenges facing clinical pharmacology. The experience of using various drugs in real clinical practice and the role of clinical recommendations are discussed. The main directions of the work of a clinical pharmacologist and discipline in general for coronavirus infection are given. В статье рассматривается роль клиническойфармакологии в управлении пандемией COVID-19, в частности разработке лекарственныхсредств, оказывающих действие на коронавирусную инфекцию. Предлагаются различныестратегии и горизонты изучения данной инфекции и анализируются отдельные группылекарств. Подробно обсуждаются текущие клинические исследования при COVID-19, основные тренды, проблемы и задачи, стоящие передклинической фармакологией, роль клинических рекомендаций. Приведены результатыприменения различных лекарственных средствв реальной клинической практике и рассматриваются основные направления работы врачаклинического фармаколога и дисциплины вцелом при коронавирусной инфекции.

AN EARLY ASSESSMENT OF THE EFFICACY OF MEDICINES IN THE TREATMENT OF PATIENTS WITH COVID-19

Coronavirus infection 2019 is considered a modern challenge to the world community. In the absence of vaccines and antivirals, effective and safe medicines are an urgent request from the healthcare system. We have evaluated the medical technologies for COVID-19 which are being examined. The search was conducted on the ClinicalTrials.gov at the beginning of April 2020. As a result it was shown that the growth of new clinical trials in the world devoted to COVID-19 is growing by 65% per week. More often, interventional clinical trials of the II and III phases are carried out. Most studies are planned or conducted in Western Europe (n = 92), China (n = 79), and the United States (n = 51). Surrogate points are usually evaluated, such as: clinical recovery, symptom-based disease relief (fever, cough, diarrhea, myalgia, shortness of breath), lack of progression of shortness of breath, rate of artificial ventilation, rate of admission to the intensive care unit, etc. It is antimalarial drugs that are mainly studied. Currently, it is not possible to discuss the efficacy and safety of a drug in the treatment of COVID-19, as most studies have just begun. The therapeutic regimens proposed now in clinical recommendations have no evidence base, and the studies indicated in them are at best considered hypothesizing.