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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">safetyrisk</journal-id><journal-title-group><journal-title xml:lang="ru">Безопасность и риск фармакотерапии</journal-title><trans-title-group xml:lang="en"><trans-title>Safety and Risk of Pharmacotherapy</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2312-7821</issn><issn pub-type="epub">2619-1164</issn><publisher><publisher-name>Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.30895/2312-7821-2022-10-4-326-344</article-id><article-id custom-type="elpub" pub-id-type="custom">safetyrisk-340</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ГЛАВНАЯ ТЕМА: ПРЕПАРАТЫ ДЛЯ ПРОФИЛАКТИКИ И ЛЕЧЕНИЯ COVID-19: ЭФФЕКТИВНОСТЬ И БЕЗОПАСНОСТЬ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>MAIN TOPIC: MEDICINAL PRODUCTS FOR COVID-19 TREATMENT AND PREVENTION: EFFICACY AND SAFETY</subject></subj-group></article-categories><title-group><article-title>Безопасность фармакотерапии у пациентов с COVID-19: обзор литературы</article-title><trans-title-group xml:lang="en"><trans-title>Safety of Pharmacotherapy in COVID-19 Patients: A Literature Review</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7903-2977</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Крюков</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Kryukov</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Крюков Александр Валерьевич, кандидат медицинских наук.</p><p>Баррикадная ул., 2/1, стр. 1, Москва, 125993;</p><p>Ул. Вешняковская, д. 23, Москва, 111539</p></bio><bio xml:lang="en"><p>Alexander V. Kryukov, Cand. Sci. (Med.).</p><p>2/1/1 Barrikadnaya St., Moscow 125993;</p><p>23 Veshnyakovskaya St., Moscow 111539</p></bio><email xlink:type="simple">alex.kryukov90@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4192-654X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Жирякова</surname><given-names>А. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Zhiryakova</surname><given-names>A. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Жирякова Анна Сергеевна.</p><p>Баррикадная ул., 2/1, стр. 1, Москва, 125993</p></bio><bio xml:lang="en"><p>Anna S. Zhiryakova.</p><p>2/1/1 Barrikadnaya St., Moscow 125993</p></bio><email xlink:type="simple">mya1017@yandex.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2289-1900</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шевчук</surname><given-names>Ю. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Shevchuk</surname><given-names>Yu. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Шевчук Юлия Викторовна.</p><p>Баррикадная ул., 2/1, стр. 1, Москва, 125993</p></bio><bio xml:lang="en"><p>Yuliya V. Shevchuk.</p><p>2/1/1 Barrikadnaya St., Moscow 125993</p></bio><email xlink:type="simple">ju-viktorovna@yandex.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6636-3950</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Матвеев</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Matveev</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Матвеев Александр Васильевич, кандидат медицинских наук, доцент.</p><p>Баррикадная ул., 2/1, стр. 1, Москва, 125993</p></bio><bio xml:lang="en"><p>Alexander V. Matveev, Cand. Sci. (Med.), Associate Professor.</p><p>2/1/1 Barrikadnaya St., Moscow 125993</p></bio><email xlink:type="simple">avmcsmu@gmail.com</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3568-5065</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Вечорко</surname><given-names>В. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Vechorko</surname><given-names>V. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Вечорко Валерий Иванович, доктор медицинских наук.</p><p>Баррикадная ул., 2/1, стр. 1, Москва, 125993;</p><p>Ул. Вешняковская, д. 23, Москва, 111539</p></bio><bio xml:lang="en"><p>Valeriy I. Vechorko - Dr. Sci. (Med.).</p><p>2/1/1 Barrikadnaya St., Moscow 125993;</p><p>23 Veshnyakovskaya St., Moscow 111539</p></bio><email xlink:type="simple">gkb15@zdrav.mos.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3010-755X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Аверков</surname><given-names>О. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Averkov</surname><given-names>O. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Аверков Олег Валерьевич, доктор медицинских наук, профессор.</p><p>Ул. Вешняковская, д. 23, Москва, 111539</p></bio><bio xml:lang="en"><p>Oleg V. Averkov, Dr. Sci. (Med.), Professor.</p><p>23 Veshnyakovskaya St., Moscow 111539</p></bio><email xlink:type="simple">oleg.averkov@gmail.com</email><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Глаголев</surname><given-names>С. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Glagolev</surname><given-names>S. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Глаголев Сергей Владимирович, кандидат медицинских наук.</p><p>Scopus Author ID: <ext-link xlink:href="https://www.scopus.com/authid/detail.uri?authorId=57193931109" ext-link-type="uri">https://www.scopus.com/authid/detail.uri?authorId=57193931109</ext-link></p><p>Рахмановский пер., д. 3, Москва, 127994</p></bio><bio xml:lang="en"><p>Sergey V. Glagolev, Cand. Sci. (Med.).</p><p>Scopus Author ID: <ext-link xlink:href="https://www.scopus.com/authid/detail.uri?authorId=57193931109" ext-link-type="uri">https://www.scopus.com/authid/detail.uri?authorId=57193931109</ext-link></p><p>3 Rakhmanovsky Per., Moscow 127994</p></bio><email xlink:type="simple">press@minzdrav.gov.ru</email><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1242-0833</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Темирбулатов</surname><given-names>И. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Temirbulatov</surname><given-names>I. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Темирбулатов Ильяс Ильдарович.</p><p>Баррикадная ул., 2/1, стр. 1, Москва, 125993;</p><p>Ул. Вешняковская, д. 23, Москва, 111539</p></bio><bio xml:lang="en"><p>Ilyas I. Temirbulatov.</p><p>2/1/1 Barrikadnaya St., Moscow 125993;</p><p>23 Veshnyakovskaya St., Moscow 111539</p></bio><email xlink:type="simple">temirbulatov.ilyas@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9307-4994</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Мирзаев</surname><given-names>К. Б.</given-names></name><name name-style="western" xml:lang="en"><surname>Mirzaev</surname><given-names>K. B.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Мирзаев Карин Бадавиевич, доктор медицинских наук.</p><p>Баррикадная ул., 2/1, стр. 1, Москва, 125993</p></bio><bio xml:lang="en"><p>Karin B. Mirzaev, Dr. Sci. (Med.).</p><p>2/1/1 Barrikadnaya St., Moscow 123242</p></bio><email xlink:type="simple">karin05doc@yandex.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3278-5941</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Денисенко</surname><given-names>Н. П.</given-names></name><name name-style="western" xml:lang="en"><surname>Denisenko</surname><given-names>N. P.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Денисенко Наталья Павловна, кандидат медицинских наук.</p><p>Баррикадная ул., 2/1, стр. 1, Москва, 125993</p></bio><bio xml:lang="en"><p>Natalya P. Denisenko, Cand. Sci. (Med.).</p><p>2/1/1 Barrikadnaya St., Moscow 123242</p></bio><email xlink:type="simple">natalypilipenko3990@gmail.com</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9001-1499</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Абдуллаев</surname><given-names>Ш. П.</given-names></name><name name-style="western" xml:lang="en"><surname>Abdullaev</surname><given-names>Sh. P.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Абдуллаев Шерзод Пардабоевич, кандидат биологических наук</p><p>Баррикадная ул., 2/1, стр. 1, Москва, 125993</p></bio><bio xml:lang="en"><p>Sherzod P. Abdullaev, Cand. Sci. (Biol.).</p><p>2/1/1 Barrikadnaya St., Moscow 123242</p></bio><email xlink:type="simple">abdullaevsp@gmail.com</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4496-3680</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сычев</surname><given-names>Д. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Sychev</surname><given-names>D. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Сычев Дмитрий Алексеевич, академик РАН, доктор медицинских наук, профессор.</p><p>Баррикадная ул., 2/1, стр. 1, Москва, 125993</p></bio><bio xml:lang="en"><p>Dmitry A. Sychev, Academician of the RAS, Dr. Sci. (Med.), Professor.</p><p>2/1/1 Barrikadnaya St., Moscow 123242</p></bio><email xlink:type="simple">dmitry.alex.sychev@gmail.com</email><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Федеральное государственное бюджетное общеобразовательное учреждение дополнительного профессионального образования «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской Федерации; Государственное бюджетное учреждение здравоохранения города Москвы «Городская клиническая больница № 15 имени О.М. Филатова Департамента здравоохранения города Москвы»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Federal State Budgetary Educational Institution of Further Professional Education "Russian Medical Academy of Continuous Professional Education" of the Ministry of Healthcare of the Russian Federation (FSBEI FPE RMACPE MOH Russia); O.M. Filatov City Clinical Hospital No. 15</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Федеральное государственное бюджетное общеобразовательное учреждение дополнительного профессионального образования «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской Федерации</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Federal State Budgetary Educational Institution of Further Professional Education "Russian Medical Academy of Continuous Professional Education" of the Ministry of Healthcare of the Russian Federation (FSBEI FPE RMACPE MOH Russia)</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>Государственное бюджетное учреждение здравоохранения города Москвы «Городская клиническая больница № 15 имени О.М. Филатова Департамента здравоохранения города Москвы»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>O.M. Filatov City Clinical Hospital No. 15</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru"><institution>Министерство здравоохранения Российской Федерации</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Ministry of Health of the Russian Federation</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2022</year></pub-date><pub-date pub-type="epub"><day>29</day><month>12</month><year>2022</year></pub-date><volume>10</volume><issue>4</issue><fpage>326</fpage><lpage>344</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Крюков А.В., Жирякова А.С., Шевчук Ю.В., Матвеев А.В., Вечорко В.И., Аверков О.В., Глаголев С.В., Темирбулатов И.И., Мирзаев К.Б., Денисенко Н.П., Абдуллаев Ш.П., Сычев Д.А., 2022</copyright-statement><copyright-year>2022</copyright-year><copyright-holder xml:lang="ru">Крюков А.В., Жирякова А.С., Шевчук Ю.В., Матвеев А.В., Вечорко В.И., Аверков О.В., Глаголев С.В., Темирбулатов И.И., Мирзаев К.Б., Денисенко Н.П., Абдуллаев Ш.П., Сычев Д.А.</copyright-holder><copyright-holder xml:lang="en">Kryukov A.V., Zhiryakova A.S., Shevchuk Y.V., Matveev A.V., Vechorko V.I., Averkov O.V., Glagolev S.V., Temirbulatov I.I., Mirzaev K.B., Denisenko N.P., Abdullaev S.P., Sychev D.A.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.risksafety.ru/jour/article/view/340">https://www.risksafety.ru/jour/article/view/340</self-uri><abstract><p>Актуальность проблемы безопасности фармакотерапии COVID-19 связана в первую очередь с малым опытом использования отдельных препаратов и с использованием препаратов вне показаний. Цель работы: анализ информации о предикторах и возможных нежелательных реакциях (НР) при применении этиотропной и патогенетической терапии COVID-19. По данным литературы, основными клинически значимыми факторами риска развития НР у пациентов с COVID-19 являются длительность пребывания в стационаре, комбинированное использование противовирусных препаратов, полипрагмазия и наличие лекарственной аллергии в анамнезе. Показано, что наиболее частыми НР при применении противовирусных препаратов являются нарушения со стороны желудочно-кишечного тракта и гепатобилиарной системы, вирус-нейтрализующих антител — нарушения со стороны желудочно-кишечного тракта, аллергические реакции и неврологические нарушения. При использовании иммуноглобулина человека против COVID-19 и плазмы реконвалесцентов наиболее часто развиваются трансфузионные реакции (лихорадка, озноб и другие). При проведении патогенетической терапии системными глюкокортикостероидами самой характерной НР является гипергликемия. Применение ингибиторов янус-киназ и ингибиторов интерлейкинов чаще всего сопряжено с желудочно-кишечными нарушениями и гипертрансаминаземией, для ряда ингибиторов интерлейкинов также характерна нейтропения. НР при использовании антикоагулянтов со стороны системы гемостаза зависят от режима дозирования и тяжести состояния пациента. Лекарственные взаимодействия являются распространенной проблемой при терапии COVID-19, наибольшее количество значимых лекарственных взаимодействий отмечается при применении препарата нирматрелвир+ритонавир, что обусловлено его фармакокинетическими особенностями. В настоящий момент есть данные о влиянии фармакогенетических биомаркеров на безопасность и клинический исход терапии COVID-19. Таким образом, для повышения безопасности фармакотерапии COVID-19 необходим комплексный подход, при котором будут учитываться клинико-демографические и фармакогенетические предикторы развития НР, а также риски лекарственных взаимодействий.</p></abstract><trans-abstract xml:lang="en"><p>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 disor ders; 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. Haemo static 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.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>COVID-19</kwd><kwd>нежелательные реакции</kwd><kwd>фармаконадзор</kwd><kwd>межлекарственное взаимодействие</kwd><kwd>фармакогенетика</kwd><kwd>нирматрелвир+ритонавир</kwd><kwd>ингибиторы интерлейкинов</kwd><kwd>моноклональные антитела</kwd></kwd-group><kwd-group xml:lang="en"><kwd>COVID-19</kwd><kwd>adverse drug reactions</kwd><kwd>pharmacovigilance</kwd><kwd>drug-drug interactions</kwd><kwd>pharmacogenetics</kwd><kwd>nirmatrelvir+ritonavir</kwd><kwd>interleukin inhibitors</kwd><kwd>monoclonal antibodies</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Работа выполнена при финансовой поддержке Министерства здравоохранения Российской Федерации. Тематика государственного задания «Разработка системы поддержки принятия врачебных решений для прогнозирования нежелательных лекарственных реакций у пациентов с COVID-19 на основе фармакогенетического тестирования» (ЕГИСУ НИОКТР № 122021800321-2)</funding-statement><funding-statement xml:lang="en">This study was funded by the Ministry of Health of the Russian Federation and carried out under the state assignment “Development of a clinical decision support system for predicting adverse drug reactions in COVID-19 patients on the basis of pharmacogenetic testing” (R&amp;D public accounting No. 122021800321-2)</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Зырянов СК, Затолочина КЭ, Казаков АС. Актуальные вопросы обеспечения безопасности пациентов: роль фармаконадзора. 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