Перепрофилированные противомикробные и противовирусные препараты для лечения COVID-19: безопасность и побочные эффекты в реальной клинической практике (научный обзор)

Леонова М.В. Перепрофилированные противомикробные и противовирусные препараты для лечения COVID-19: безопасность и побочные эффекты в реальной клинической практике (научный обзор). Consilium Medicum. 2022;24(9): DOI: 10.26442/20751753.2022.9.201763

© ООО «КОНСИЛИУМ МЕДИКУМ», 2022 г.

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Leonova MV. Repurposed antimicrobial and antiviral drugs for COVID-19 treatment: safety and side effects in real clinical practice (scientific review): A review. Consilium Medicum. 2022;24(9):
DOI: 10.26442/20751753.2022.9.201763

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Аннотация

Пандемия COVID-19 бросила вызов новым этиотропным средствам, что привело к экстренному перепрофилированию противомикробных и противовирусных препаратов для лечения новой инфекции по результатам экспериментальных исследований in silico, in vitro, in vivo и клинических исследований. Однако вопросам безопасности перепрофилированных препаратов уделялось меньше внимания. Воздействие перепрофилированных препаратов с ограниченными доказательствами соотношения риск-польза при COVID-19 требовало адаптации мониторинга безопасности, что повлияло на полноту и качество отчетов, а проведение оценки причинно-следственных связей стало самой сложной задачей. Представлен обзор накопленных за период пандемии COVID-19 данных о характере нежелательных реакций, связанных с применением перепрофилированных препаратов (гидроксихлорохина, хлорохина, ремдесивира, фавипиравира, лопинавира/ритонавира, рибавирина), используемых в реальной практике. Использовались результаты рандомизированных контролируемых исследований и наблюдательных исследований, систематических обзоров и метаанализов. Согласно систематизированным данным по безопасности применения гидроксихлорохина и хлорохина у пациентов с COVID-19 при краткосрочном лечении (≤14 дней), включая серию метаанализов, риск развития нежелательных эффектов повышен в 1,5–2 раза; основные проявления – удлинение интервала QT и аритмии (до 25%), расстройства со стороны желудочно-кишечного тракта – ЖКТ (до 50%), повышение уровня билирубина (3%) и трансаминаз (до 10%), дерматологические (до 10%) и нейропсихические побочные эффекты (до 21,7%). Большинство побочных эффектов перепрофилированных противовирусных препаратов группы аналогов нуклеозидов связано с их прямым цитотоксическим действием, что проявляется токсическим поражением ЖКТ, гепатотоксичностью, нефротоксичностью, кардиотоксичностью, гематотоксичностью. Наибольшее количество побочных эффектов со стороны ЖКТ и печени наблюдалось для лопинавира/ритонавира в сравнении с другим препаратами. Выявлены новые побочные эффекты для ремдесивира при использовании в условиях пандемии COVID-19 – кардиотоксичность (брадикардия и тяжелая гипотензия) и нефротоксичность, что расценено регуляторными органами как «сигнал безопасности». Для решения задач по оценке причинно-следственной связи потребуются дальнейшие более тщательные исследования и анализы. Накопленная информация в условиях продолжающейся пандемии COVID-19 должна подвергаться постоянному динамическому анализу и публиковаться в медицинских изданиях для оповещения клиницистов.

Ключевые слова: противовирусные препараты, перепрофилированные препараты, COVID-19, безопасность, побочные эффекты

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The COVID-19 pandemic has posed a challenge for new etiotropic agents, leading to an urgent repurposing of antimicrobial and antiviral drugs to treat a new infection based on the results of in silico, in vitro, in vivo experimental studies, and clinical trials. However, less attention has been paid to the safety of repurposed drugs. Exposure to repurposed drugs with limited risk-benefit evidence in COVID-19 required adaptation of safety monitoring, which affected the completeness and quality of reports, and making causality assessments the most difficult task. A review of data accumulated over the period of the COVID-19 pandemic on the nature of adverse reactions associated with the use of repurposed drugs (hydroxychloroquine, chloroquine, remdesivir, favipiravir, lopinavir/ritonavir, ribavirin) used in real practice is presented. The results of RCTs and observational studies, systematic reviews and meta-analyses were used. Systematized data on the safety of the use of hydroxychloroquine and chloroquine in patients with COVID-19 in short-term treatment (≤14 days), including a series of meta-analyses, the risk of adverse effects was increased by 1.5–2 times; the main manifestations are prolongation of the QT interval and arrhythmias (up to 25%), gastrointestinal disorders (up to 50%), increased levels of bilirubin (3%) and transaminases (up to 10%), dermatological (up to 10%) and neuropsychiatric side effects (up to 21.7%). Most of the side effects of repurposed antiviral drugs of the nucleoside analog group are associated with their direct cytotoxic effect, which is manifested by toxic damage to the gastrointestinal tract, hepatotoxicity, nephrotoxicity, cardiotoxicity, and hematotoxicity. The greatest number of side effects from the gastrointestinal tract and liver were observed for lopinavir/ritonavir in comparison with other drugs. New side effects have been identified for remdesivir when used in the context of the COVID-19 pandemic – cardiotoxicity (bradycardia and severe hypotension) and nephrotoxicity, which was regarded by regulatory authorities as a “safety signal”. To solve the problems of assessing the cause-and-effect relationship, further more thorough research and analysis will be required. The accumulated information in the context of the ongoing COVID-19 pandemic should be subject to ongoing dynamic analysis and published in medical journals to alert clinicians.

Keywords: antiviral drugs, repurposed drugs, COVID-19, safety, side effects

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Список литературы

1. Статистика распространения коронавируса в мире на 15 июня 2022. Режим доступа: https://coronavirus-monitor.info/. Ссылка активна на 28.06.2022 [Statistics of the spread of coronavirus in the world as of June 15, 2022. Available at: https://coronavirus-monitor.info/. Accessed: 28.06.2022 (in Russian)].
2. World Health Organization. 14.9 million excess deaths associated with the COVID-19 pandemic in 2020 and 2021. Published 5 May 2022. Available at: https://www.who.int/news/item/05-05-2022-14.9-million-excess-deaths-were-associated-with-the-covid-1.... Accessed: 28.06.2022
3. Singh TU, Parida S, Lingaraju MC, et al. Drug repurposing approach to fight COVID-19. Pharmacol Rep. 2020;72:1479-508. DOI:10.1007/s43440-020-00155-6
4. Desai MK. Pharmacovigilance and assessment of drug safety reports during COVID 19. Perspect Clin Res. 2020;11(3):128. DOI:10.4103/picr.PICR_171_20
5. U.S. Food and Drug Administration Coronavirus (COVID-19) Update: Daily Roundup March 30, 2020. Available at: https://www.fda.gov/news-events/pressannouncements/coronavirus-covid-19-update-dailyroundup-march-30.... Accessed: 28.06.2022
6. Li X, Wang Y, Agostinis P, et al. Is hydroxychloroquine beneficial for COVID-19 patients?. Cell Death Dis. 2020;11:512. DOI:10.1038/s41419-020-2721-8
7. Zengin R, Sarikaya ZT, Karadağ N, et al. Adverse cardiac events related to hydroxychloroquine prophylaxis and treatment of COVID-19. Infect Dis Clin Microbiol. 2020;2(1):24-6. DOI:10.36519/idcm.2020.0012
8. Jankelson L, Karam G, Becker ML, et al. QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: a systematic review. Heart Rhythm. 2020;17(9):1472-9. DOI:10.1016/j.hrthm.2020.05.008
9. Deng J, Zhou F, Heybati K, et al. Efficacy of chloroquine and hydroxychloroquine for the treatment of hospitalized COVID-19 patients: a meta-analysis. Future Virol. 2022;17(4):95-118. DOI:10.2217/fvl-2021-0119
10. Eze P, Mezue KN, Nduka CU, et al. Efficacy and safety of chloroquine and hydroxychloroquine for treatment of COVID-19 patients-a systematic review and meta-analysis of randomized controlled trials. Am J Cardiovasc Dis. 2021;11(1):93-107. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012280/. Accessed: 28.06.2022
11. Marin S, Val AM, Peligero MB, et al. Safety of short-term treatments with oral chloroquine and hydroxychloroquine in patients with and without COVID-19: a systematic review. Pharmaceuticals (Basel). 2022;15(5):634. DOI:10.3390/ph15050634
12. Gordon CJ, Tchesnokov EP, Woolner E, et al. Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. J Biol Chem. 2020;295(20):6785-97. DOI:10.1074/jbc.RA120.013679
13. FDA approves first treatment for COVID-19 administration (2020) U.S.F.a.D. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-covid-19. Accessed: 28.06.2022
14. Gupta AK, Parker BM, Priyadarshi V, Parker J. Cardiac adverse events with remdesivir in COVID-19 infection. Cureus. 2020;12(10):e11132. DOI:10.7759/cureus.11132
15. Gubitosa JC, Kakar P, Gerula C, et al. Marked sinus bradycardia associated with remdesivir in COVID-19: a case and literature review. JACC Case Rep. 2020;2(14):2260-4. DOI:10.1016/j.jaccas.2020.08.025
16. Day LB, Abdel-Qadir H, Fralick M. Bradycardia associated with remdesivir therapy for COVID-19 in a 59-year-old man. CMAJ. 2021;193(17):E612-5. DOI:10.1503/cmaj.210300
17. Barkas F, Styla CP, Bechlioulis A, et al. Sinus bradycardia associated with remdesivir treatment in COVID-19: a case report and literature review. J Cardiovasc Dev Dis. 2021;8(2):18.
DOI:10.3390/jcdd8020018
18. Attena E, Albani S, Maraolo AE, et al. Remdesivir-induced bradycardia in COVID-19: a single center prospective study. Circ Arrhythm Electrophysiol. 2021;14(7):e009811. DOI:10.1161/CIRCEP.121.009811
19. Gupte V, Hegde R, Sawant S, et al. Safety and clinical outcomes of remdesivir in hospitalised COVID-19 patients: a retrospective analysis of active surveillance database. BMC Infect Dis. 2022;22:1. DOI:10.1186/s12879-021-07004-8
20. Rafaniello C, Ferrajolo C, Sullo MG, et al. Cardiac events potentially associated to remdesivir: an analysis from the European Spontaneous Adverse Event Reporting System. Pharmaceuticals (Basel). 2021;14(7):611. DOI:10.3390/ph14070611
21. Pimentel J, Laurie C, Cockcroft A, Andersson N. Clinical studies assessing the efficacy, effectiveness and safety of remdesivir in management of COVID-19: a scoping review. Br J Clin Pharmacol. 2021;87(7):2663-84. DOI:10.1111/bcp.14677
22. Jung SY, Kim MS, Li H, et al. Cardiovascular events and safety outcomes associated with remdesivir using a World Health Organization international pharmacovigilance database. Clin Transl Sci. 2022;15(2):501-13. DOI:10.1111/cts.13168
23. Choi SW, Shin JS, Park SJ, et al. Antiviral activity and safety of remdesivir against SARS‐CoV‐2 infection in human pluripotent stem cell‐derived cardiomyocytes. Antiviral Res. 2020;184:104955. DOI:10.1016/j.antiviral.2020.104955
24. Nabati M, Parsaee H. Potential cardiotoxic effects of remdesivir on cardiovascular system:a literature review. Cardiovasc Toxicol. 2022;22(3):268-72.
DOI:10.1007/s12012-021-09703-9
25. Silva NAO, Zara ALSA, Figueras A, Melo DO. Potential kidney damage associated with the use of remdesivir for COVID-19: analysis of a pharmacovigilance database. Cad Saude Publica. 2021;37(10):e00077721. DOI:10.1590/0102-311X00077721
26. European Medicines Agency. Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 28 September – 1 October 2020. Available at: https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-pra.... Accessed: 28.06.2022
27. Gérard AO, Laurain A, Fresse A, et al. Remdesivir and acute renal failure: a potential safety signal fromdDisproportionality analysis of the WHO safety database. Clin Pharmacol Ther. 2021;109(4):1021-4. DOI:10.1002/cpt.2145
28. Lee S, Yang JW, Jung SY, et al. Neuropsychological adverse drug reactions of Remdesivir: analysis using VigiBase, the WHO global database of individual case safety reports. Eur Rev Med Pharmacol Sci. 2021;25(23):7390-7. DOI:10.26355/eurrev_202112_27435
29. Agrawal U, Raju R, Udwadia ZF. Favipiravir:aA new and emerging antiviral option in COVID-19. Med J Armed Forces India. 2020;76(4):370-6. DOI:10.1016/j.mjafi.2020.08.004
30. Hase R, Kurata R, Ishida K, et al. Acute gouty arthritis during favipiravir treatment for coronavirus disease 2019. Intern Med. 2020;59(18):2327-9.
DOI:10.2169/internalmedicine.5377-20
31. Udwadia ZF, Singh P, Barkate H, et al. Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: a randomized, comparative, open-label, multicenter, phase 3 clinical trial. Int J Infect Dis. 2021;103:62-71. DOI:10.1016/j.ijid.2020.11.142
32. Pilkington V, Pepperrell T, Hill A. A review of the safety of favipiravir – a potential treatment in the COVID-19 pandemic? J Virus Erad. 2020;6(2):45-51.
DOI:10.1016/S2055-6640(20)30016-9
33. Zhao H, Zhang C, Zhu Q, et al. Favipiravir in the treatment of patients with SARS-CoV-2 RNA recurrent positive after discharge: A multicenter, open-label, randomized trial. Int Immunopharmacol. 2021;97:107702. DOI:10.1016/j.intimp.2021.107702
34. Yamazaki S, Suzuki T, Sayama M, et al. Suspected cholestatic liver injury induced by favipiravir in a patient with COVID-19. J Infect Chemother. 2021;27(2):390-2. DOI:10.1016/j.jiac.2020.12.021
35. Nasa P, Shrivastava PK, Kulkarni A, et al. Favipiravir induced nephrotoxicity in two patients of COVID-19. J Assoc Physicians India. 2021;69(6):11-2.
36. Shrestha DB, Budhathoki P, Khadka S, et al. Favipiravir versus other antiviral or standard of care for COVID-19 treatment: a rapid systematic review and meta-analysis. Virol J. 2020;17(1):141. DOI:10.1186/s12985-020-01412-z
37. Hassanipour S, Arab-Zozani M, Amani B, et al. The efficacy and safety of favipiravir in treatment of COVID-19: a systematic review and meta-analysis of clinical trials. Sci Rep. 2021;11:11022. DOI:10.1038/s41598-021-90551-6
38. Hung DT, Ghula S, Aziz JMA, et al. The efficacy and adverse effects of favipiravir on patients with COVID-19: a systematic review and meta-analysis of published clinical trials and observational studies. Int J Infect Dis. 2022;120:217-27. DOI:10.1016/j.ijid.2022.04.035
39. Kaur RJ, Charan J, Dutta S, et al. Favipiravir use in COVID-19: analysis of suspected adverse drug events reported in the WHO database. Infect Drug Resist. 2020;13:4427-38.
DOI:10.2147/IDR.S287934
40. Qu J, Li GH, Wang JJ, et al. Comparative effectiveness of lopinavir/ritonavir-based regimens in COVID-19. Clin Exp Pharmacol Physiol. 2021;48(2):203-10.
DOI:10.1111/1440-1681.13425
41. Magro P, Zanella I, Pescarolo M, et al. Lopinavir/ritonavir: repurposing an old drug for HIV infection in COVID-19 treatment. Biomed. J. 2021;44(1):43-53. DOI:10.1016/j.bj.2020.11.005
42. Cao B, Wang Y, Wen D, et al. Trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020;382(19):1787-99. DOI:10.1056/NEJMoa2001282
43. Li Y, Xie Z, Lin W, et al. Efficacy and safety of lopinavir/ritonavir or arbidol in adult patients with mild/moderate COVID-19: an exploratory randomized controlled trial. Med (N Y). 2020;1(1):105-13.e4. DOI:10.1016/j.medj.2020.04.001
44. Liu F, Xu A, Zhang Y, et al. Patients of COVID-19 may benefit from sustained lopinavir-combined regimen and the increase of eosinophil may predict the outcome of COVID-19 progression. Int J Infect Dis. 2020;95:183-91. DOI:10.1016/j.ijid.2020.03.013
45. Diaz-Arocutipa C, Brañez-Condorena A, Hernandez AV. QTc prolongation in COVID-19 patients treated with hydroxychloroquine, chloroquine, azithromycin, or lopinavir/ritonavir: a systematic review and meta-analysis. Pharmacoepidemiol Drug Saf. 2021;30(6):694-706. DOI:10.1002/pds.5234
46. Liu W, Zhou P, Chen K, et al. Efficacy and safety of antiviral treatment for COVID-19 from evidence in studies of SARS-CoV-2 and other acute viral infections: a systematic review and meta-analysis. CMAJ. 2020;192(27):E734-44. DOI:10.1503/cmaj.200647
47. Bhattacharyya A, Kumar S, Sarma P, et al. Safety and efficacy of lopinavir/ritonavir combination in COVID-19: a systematic review, meta-analysis, and meta-regression analysis. Indian J Pharmacol. 2020;52(4):313-23. DOI:10.4103/ijp.IJP_627_20
48. Deng J, Zhou F, Hou W, et al. Efficacy of lopinavir–ritonavir combination therapy for the treatment of hospitalized COVID-19 patients: a meta-analysis. Future Virol. 2022;17(3):169-89. DOI:10.2217/fvl-2021-0066
49. Khalili JS, Zhu H, Mak NSA, et al. Novel coronavirus treatment with ribavirin: groundwork for an evaluation concerning COVID‐19. J Med Virol. 2020;92:740-6. DOI:10.1002/jmv.25798
50. Muller MP, Dresser L, Raboud J, et al. Canadian SARS Research Network. Adverse events associated with high-dose ribavirin: evidence from the Toronto outbreak of severe acute respiratory syndrome. Pharmacotherapy. 2007;27(4):494-503. DOI:10.1592/phco.27.4.494
51. Zhong H, Wang Y, Zhang ZL, et al. Efficacy and safety of current therapeutic options for COVID-19 – lessons to be learnt from SARS and MERS epidemic: a systematic review and meta-analysis. Pharmacol Res. 2020;157:104872. DOI:10.1016/j.phrs.2020.104872

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1. Statistics of the spread of coronavirus in the world as of June 15, 2022. Available at: https://coronavirus-monitor.info/. Accessed: 28.06.2022 (in Russian).
2. World Health Organization. 14.9 million excess deaths associated with the COVID-19 pandemic in 2020 and 2021. Published 5 May 2022. Available at: https://www.who.int/news/item/05-05-2022-14.9-million-excess-deaths-were-associated-with-the-covid-1.... Accessed: 28.06.2022
3. Singh TU, Parida S, Lingaraju MC, et al. Drug repurposing approach to fight COVID-19. Pharmacol Rep. 2020;72:1479-508. DOI:10.1007/s43440-020-00155-6
4. Desai MK. Pharmacovigilance and assessment of drug safety reports during COVID 19. Perspect Clin Res. 2020;11(3):128. DOI:10.4103/picr.PICR_171_20
5. U.S. Food and Drug Administration Coronavirus (COVID-19) Update: Daily Roundup March 30, 2020. Available at: https://www.fda.gov/news-events/pressannouncements/coronavirus-covid-19-update-dailyroundup-march-30.... Accessed: 28.06.2022
6. Li X, Wang Y, Agostinis P, et al. Is hydroxychloroquine beneficial for COVID-19 patients?. Cell Death Dis. 2020;11:512. DOI:10.1038/s41419-020-2721-8
7. Zengin R, Sarikaya ZT, Karadağ N, et al. Adverse cardiac events related to hydroxychloroquine prophylaxis and treatment of COVID-19. Infect Dis Clin Microbiol. 2020;2(1):24-6. DOI:10.36519/idcm.2020.0012
8. Jankelson L, Karam G, Becker ML, et al. QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: a systematic review. Heart Rhythm. 2020;17(9):1472-9. DOI:10.1016/j.hrthm.2020.05.008
9. Deng J, Zhou F, Heybati K, et al. Efficacy of chloroquine and hydroxychloroquine for the treatment of hospitalized COVID-19 patients: a meta-analysis. Future Virol. 2022;17(4):95-118. DOI:10.2217/fvl-2021-0119
10. Eze P, Mezue KN, Nduka CU, et al. Efficacy and safety of chloroquine and hydroxychloroquine for treatment of COVID-19 patients-a systematic review and meta-analysis of randomized controlled trials. Am J Cardiovasc Dis. 2021;11(1):93-107. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012280/. Accessed: 28.06.2022
11. Marin S, Val AM, Peligero MB, et al. Safety of short-term treatments with oral chloroquine and hydroxychloroquine in patients with and without COVID-19: a systematic review. Pharmaceuticals (Basel). 2022;15(5):634. DOI:10.3390/ph15050634
12. Gordon CJ, Tchesnokov EP, Woolner E, et al. Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. J Biol Chem. 2020;295(20):6785-97. DOI:10.1074/jbc.RA120.013679
13. FDA approves first treatment for COVID-19 administration (2020) U.S.F.a.D. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-covid-19. Accessed: 28.06.2022
14. Gupta AK, Parker BM, Priyadarshi V, Parker J. Cardiac adverse events with remdesivir in COVID-19 infection. Cureus. 2020;12(10):e11132. DOI:10.7759/cureus.11132
15. Gubitosa JC, Kakar P, Gerula C, et al. Marked sinus bradycardia associated with remdesivir in COVID-19: a case and literature review. JACC Case Rep. 2020;2(14):2260-4. DOI:10.1016/j.jaccas.2020.08.025
16. Day LB, Abdel-Qadir H, Fralick M. Bradycardia associated with remdesivir therapy for COVID-19 in a 59-year-old man. CMAJ. 2021;193(17):E612-5. DOI:10.1503/cmaj.210300
17. Barkas F, Styla CP, Bechlioulis A, et al. Sinus bradycardia associated with remdesivir treatment in COVID-19: a case report and literature review. J Cardiovasc Dev Dis. 2021;8(2):18.
DOI:10.3390/jcdd8020018
18. Attena E, Albani S, Maraolo AE, et al. Remdesivir-induced bradycardia in COVID-19: a single center prospective study. Circ Arrhythm Electrophysiol. 2021;14(7):e009811. DOI:10.1161/CIRCEP.121.009811
19. Gupte V, Hegde R, Sawant S, et al. Safety and clinical outcomes of remdesivir in hospitalised COVID-19 patients: a retrospective analysis of active surveillance database. BMC Infect Dis. 2022;22:1. DOI:10.1186/s12879-021-07004-8
20. Rafaniello C, Ferrajolo C, Sullo MG, et al. Cardiac events potentially associated to remdesivir: an analysis from the European Spontaneous Adverse Event Reporting System. Pharmaceuticals (Basel). 2021;14(7):611. DOI:10.3390/ph14070611
21. Pimentel J, Laurie C, Cockcroft A, Andersson N. Clinical studies assessing the efficacy, effectiveness and safety of remdesivir in management of COVID-19: a scoping review. Br J Clin Pharmacol. 2021;87(7):2663-84. DOI:10.1111/bcp.14677
22. Jung SY, Kim MS, Li H, et al. Cardiovascular events and safety outcomes associated with remdesivir using a World Health Organization international pharmacovigilance database. Clin Transl Sci. 2022;15(2):501-13. DOI:10.1111/cts.13168
23. Choi SW, Shin JS, Park SJ, et al. Antiviral activity and safety of remdesivir against SARS‐CoV‐2 infection in human pluripotent stem cell‐derived cardiomyocytes. Antiviral Res. 2020;184:104955. DOI:10.1016/j.antiviral.2020.104955
24. Nabati M, Parsaee H. Potential cardiotoxic effects of remdesivir on cardiovascular system:a literature review. Cardiovasc Toxicol. 2022;22(3):268-72.
DOI:10.1007/s12012-021-09703-9
25. Silva NAO, Zara ALSA, Figueras A, Melo DO. Potential kidney damage associated with the use of remdesivir for COVID-19: analysis of a pharmacovigilance database. Cad Saude Publica. 2021;37(10):e00077721. DOI:10.1590/0102-311X00077721
26. European Medicines Agency. Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 28 September – 1 October 2020. Available at: https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-pra.... Accessed: 28.06.2022
27. Gérard AO, Laurain A, Fresse A, et al. Remdesivir and acute renal failure: a potential safety signal fromdDisproportionality analysis of the WHO safety database. Clin Pharmacol Ther. 2021;109(4):1021-4. DOI:10.1002/cpt.2145
28. Lee S, Yang JW, Jung SY, et al. Neuropsychological adverse drug reactions of Remdesivir: analysis using VigiBase, the WHO global database of individual case safety reports. Eur Rev Med Pharmacol Sci. 2021;25(23):7390-7. DOI:10.26355/eurrev_202112_27435
29. Agrawal U, Raju R, Udwadia ZF. Favipiravir:aA new and emerging antiviral option in COVID-19. Med J Armed Forces India. 2020;76(4):370-6. DOI:10.1016/j.mjafi.2020.08.004
30. Hase R, Kurata R, Ishida K, et al. Acute gouty arthritis during favipiravir treatment for coronavirus disease 2019. Intern Med. 2020;59(18):2327-9.
DOI:10.2169/internalmedicine.5377-20
31. Udwadia ZF, Singh P, Barkate H, et al. Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: a randomized, comparative, open-label, multicenter, phase 3 clinical trial. Int J Infect Dis. 2021;103:62-71. DOI:10.1016/j.ijid.2020.11.142
32. Pilkington V, Pepperrell T, Hill A. A review of the safety of favipiravir – a potential treatment in the COVID-19 pandemic? J Virus Erad. 2020;6(2):45-51.
DOI:10.1016/S2055-6640(20)30016-9
33. Zhao H, Zhang C, Zhu Q, et al. Favipiravir in the treatment of patients with SARS-CoV-2 RNA recurrent positive after discharge: A multicenter, open-label, randomized trial. Int Immunopharmacol. 2021;97:107702. DOI:10.1016/j.intimp.2021.107702
34. Yamazaki S, Suzuki T, Sayama M, et al. Suspected cholestatic liver injury induced by favipiravir in a patient with COVID-19. J Infect Chemother. 2021;27(2):390-2. DOI:10.1016/j.jiac.2020.12.021
35. Nasa P, Shrivastava PK, Kulkarni A, et al. Favipiravir induced nephrotoxicity in two patients of COVID-19. J Assoc Physicians India. 2021;69(6):11-2.
36. Shrestha DB, Budhathoki P, Khadka S, et al. Favipiravir versus other antiviral or standard of care for COVID-19 treatment: a rapid systematic review and meta-analysis. Virol J. 2020;17(1):141. DOI:10.1186/s12985-020-01412-z
37. Hassanipour S, Arab-Zozani M, Amani B, et al. The efficacy and safety of favipiravir in treatment of COVID-19: a systematic review and meta-analysis of clinical trials. Sci Rep. 2021;11:11022. DOI:10.1038/s41598-021-90551-6
38. Hung DT, Ghula S, Aziz JMA, et al. The efficacy and adverse effects of favipiravir on patients with COVID-19: a systematic review and meta-analysis of published clinical trials and observational studies. Int J Infect Dis. 2022;120:217-27. DOI:10.1016/j.ijid.2022.04.035
39. Kaur RJ, Charan J, Dutta S, et al. Favipiravir use in COVID-19: analysis of suspected adverse drug events reported in the WHO database. Infect Drug Resist. 2020;13:4427-38. DOI:10.2147/IDR.S287934
40. Qu J, Li GH, Wang JJ, et al. Comparative effectiveness of lopinavir/ritonavir-based regimens in COVID-19. Clin Exp Pharmacol Physiol. 2021;48(2):203-10.
DOI:10.1111/1440-1681.13425
41. Magro P, Zanella I, Pescarolo M, et al. Lopinavir/ritonavir: repurposing an old drug for HIV infection in COVID-19 treatment. Biomed. J. 2021;44(1):43-53. DOI:10.1016/j.bj.2020.11.005
42. Cao B, Wang Y, Wen D, et al. Trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020;382(19):1787-99. DOI:10.1056/NEJMoa2001282
43. Li Y, Xie Z, Lin W, et al. Efficacy and safety of lopinavir/ritonavir or arbidol in adult patients with mild/moderate COVID-19: an exploratory randomized controlled trial. Med (N Y). 2020;1(1):105-13.e4. DOI:10.1016/j.medj.2020.04.001
44. Liu F, Xu A, Zhang Y, et al. Patients of COVID-19 may benefit from sustained lopinavir-combined regimen and the increase of eosinophil may predict the outcome of COVID-19 progression. Int J Infect Dis. 2020;95:183-91. DOI:10.1016/j.ijid.2020.03.013
45. Diaz-Arocutipa C, Brañez-Condorena A, Hernandez AV. QTc prolongation in COVID-19 patients treated with hydroxychloroquine, chloroquine, azithromycin, or lopinavir/ritonavir: a systematic review and meta-analysis. Pharmacoepidemiol Drug Saf. 2021;30(6):694-706. DOI:10.1002/pds.5234
46. Liu W, Zhou P, Chen K, et al. Efficacy and safety of antiviral treatment for COVID-19 from evidence in studies of SARS-CoV-2 and other acute viral infections: a systematic review and meta-analysis. CMAJ. 2020;192(27):E734-44. DOI:10.1503/cmaj.200647
47. Bhattacharyya A, Kumar S, Sarma P, et al. Safety and efficacy of lopinavir/ritonavir combination in COVID-19: a systematic review, meta-analysis, and meta-regression analysis. Indian J Pharmacol. 2020;52(4):313-23. DOI:10.4103/ijp.IJP_627_20
48. Deng J, Zhou F, Hou W, et al. Efficacy of lopinavir–ritonavir combination therapy for the treatment of hospitalized COVID-19 patients: a meta-analysis. Future Virol. 2022;17(3):169-89. DOI:10.2217/fvl-2021-0066
49. Khalili JS, Zhu H, Mak NSA, et al. Novel coronavirus treatment with ribavirin: groundwork for an evaluation concerning COVID‐19. J Med Virol. 2020;92:740-6. DOI:10.1002/jmv.25798
50. Muller MP, Dresser L, Raboud J, et al. Canadian SARS Research Network. Adverse events associated with high-dose ribavirin: evidence from the Toronto outbreak of severe acute respiratory syndrome. Pharmacotherapy. 2007;27(4):494-503. DOI:10.1592/phco.27.4.494
51. Zhong H, Wang Y, Zhang ZL, et al. Efficacy and safety of current therapeutic options for COVID-19 – lessons to be learnt from SARS and MERS epidemic: a systematic review and meta-analysis. Pharmacol Res. 2020;157:104872. DOI:10.1016/j.phrs.2020.104872

Авторы

М.В. Леонова*

МОО «Ассоциация клинических фармакологов», Волгоград, Россия
*anti23@mail.ru

________________________________________________

Marina V. Leonova*

Association of Clinical Pharmacologists, Volgograd, Russia
*anti23@mail.ru

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