Safety profile assessment of drug products used for the pathogenetic treatment of COVID19

Clinical Microbiology and Antimicrobial Chemotherapy. 2021; 23(3):314-329

​ Syraeva G.I., Mishinova S.A., Kolbin A.S., Eremenko E.O.
10.36488/cmac.2021.3.314-329
COVID-19 SARS-CoV-2 drug products pharmacovigilance pharmacotherapy adverse drug reaction adverse event
Section
Personal Experience
Type
Review
Publication
Clinical Microbiology and Antimicrobial Chemotherapy. 2021; 23(3):314-329

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.

Gulnara I. Syraeva

Pavlov First Saint-Petersburg State Medical University, Saint-Petersburg, Russia
Research Center Eco-safety, Saint-Petersburg, Russia

Mishinova S.A.

Pavlov First Saint-Petersburg State Medical University, Saint-Petersburg, Russia

Alexey S. Kolbin

Pavlov First Saint-Petersburg State Medical University, Saint-Petersburg, Russia

Eremenko E.O.

Pavlov First Saint-Petersburg State Medical University, Saint-Petersburg, Russia

  • 1. Coronavirus resource center. Johns Hopkins University and Medicine, 2021. Available at: https://coronavirus.jhu.edu/. Accessed December 01, 2021.
  • 2. Khoseva E.N., Morozova T.E. Problems of development of a pharmacovigilance in Russia at the present stage (Review). Kachestvennaya klinicheskaya praktika. 2013;3:40-45. Russian.
  • 3. Syraeva G.I., Kolbin A.S., Matveev A.V., Panezhina V.S. Сomparative review of methodologies for estimating the cost of adverse drug reactions in the Russian Federation and Brazil. Farmacija i farmakologija. 2020;8(5):336-344. Russian.
  • 4. Adam Lavertu A., Vora B., Giacomini K., Altman R., Rensi S. A new era in pharmacovigilance: toward realworld data and digital monitoring. Clin Pharmacol Ther. 2021;109(5):1197-1202. DOI: 10.1002/cpt.2172
  • 5. Montastruc J.L., Toutain P.L. A new drug-drug interaction between hydroxychloroquine and metformin? A signal detection study. Drug Saf. 2020;43(7):657-660. DOI: 10.1007/s40264-020-00955-y
  • 6. Chouchana L., Preta L.H., Tisseyre M., Terrier B., Treluyer J.M., Montastruc F. Kidney disorders as serious adverse drug reactions of remdesivir in coronavirus disease 2019: a retrospective case-noncase study. Kidney Int. 2021;99(5):1235-1236. DOI: 10.1016/j.kint.2021.02.015
  • 7. Garcia P., Revet A., Yrondi A., Rousseau V., Degboe Y., Montastruc F. Psychiatric disorders and hydroxychloroquine for Coronavirus Disease 2019 (COVID-19): A VigiBase Study. Drug Saf. 2020;43(12):1315-1322. DOI: 10.1007/s40264-020-01013-3
  • 8. Gérard A.O., Laurain A., Fresse A., Parassol N., Muzzone M., Rocher F., et al. Remdesivir and acute renal failure: a potential safety signal from disproportionality analysis of the WHO safety database. Clin Pharmacol Ther. 2021;109(4):1021-1024. DOI: 10.1002/cpt.2145
  • 9. Touafchia A., Bagheri H., Carrié D., Durrieu G., Sommet A., Chouchana L., Montastruc F. Serious bradycardia and remdesivir for coronavirus 2019 (COVID-19): a new safety concerns. Clin Microbiol Infect. 2021;27(5):791.e5-8. DOI: 10.1016/j.cmi.2021.02.013
  • 10. Safety of remdesivir and tocilizumab in COVID-19 Treatment. Bezopasnost' i risk farmakoterapii. 2020;8(3):160-162. Russian (Безопасность применения ремдесивира и тоцилизумаба при лечении COVID-19. Безопасность и риск фармакотерапии. 2020;8(3):160-162.) DOI: 10.30895/2312-7821-2020-8-3-160-162
  • 11. West T.A., Malik S., Nalpantidis A., Tran T., Cannon C., Bhonagiri D., et al. Tocilizumab for severe COVID-19 pneumonia: case series of 5 Australian patients. Int J Rheum Dis. 2020;23(8):1030-1039. DOI: 10.1111/1756-185X.13913
  • 12. Cavalcanti A.B., Zampieri F.G., Rosa R.G., Azevedo L.C.P., Veiga V.C., and Coalition Covid-19 Brazil I Investigators. Hydroxychloroquine with or without azithromycin in mildtomoderate Covid-19. N Engl J Med. 2020 19;383(21): 2041-2052. DOI: 10.1056/NEJMoa2019014
  • 13. Melo J.R.R., Duarte E.C., Moraes M.V., Fleck K., Silva A.S.D.N.E., Arrais P.S.D. Adverse drug reactions in patients with COVID-19 in Brazil: analysis of spontaneous notifications of the Brazilian pharmacovigilance system. Cad Saude Publica. 2021;37(1):e00245820. DOI: 10.1590/0102-311X00245820.
  • 14. Udwadia Z.F., Singh P., Barkate H., Patil S., Rangwala S., Pendse A., et al. Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-tomoderate COVID-19: A randomized, comparative, openlabel, multicenter, phase 3 clinical trial. Int J Infect Dis. 2021;103:62-71. DOI: 10.1016/j.ijid.2020.11.142
  • 15. Vecchio G., Zapico V., Catanzariti A., Carboni Bisso I., Las Heras M. Efectos adversos de lopinavir/ritonavir en enfermedad grave por coronavirus (COVID-19) [Adverse effects of lopinavir/ritonavir in critically ill patients with COVID-19]. Medicina (B Aires). 2020;80(5):439-441. Spanish. PMID: 33048786
  • 16. Ramírez E., Urroz M., Rodríguez A., González-Muñoz M., Martín-Vega A., Villán Y., et al. Incidence of suspected serious adverse drug reactions in Coronavirus Disease-19 patients detected by a pharmacovigilance program by laboratory signals in a tertiary hospital in Spain: cautionary data. Front Pharmacol. 2020;3;11:602841. DOI: 10.3389/fphar.2020.602841
  • 17. Rubio-Rivas M., Ronda M., Padulles A., Mitjavila F., RieraMestre A., García-Forero C., et al. Beneficial effect of corticosteroids in preventing mortality in patients receiving tocilizumab to treat severe COVID-19 illness. Int J Infect Dis. 2020;101:290-297. DOI: 10.1016/j.ijid.2020.09.1486
  • 18. Cantini F., Niccoli L., Matarrese D., Nicastri E., Stobbione P., Goletti D. Baricitinib therapy in COVID-19: a pilot study on safety and clinical impact. J Infect. 2020;81(2):318-356. DOI: 10.1016/j.jinf.2020.04.017
  • 19. Crescioli G., Brilli V., Lanzi C., Burgalassi A., Ieri A., Bonaiuti R., et al. Adverse drug reactions in SARS-CoV-2 hospitalized patients: a case-series with a focus on drugdrug interactions. Intern Emerg Med. 2021;16(3):697-710. DOI: 10.1007/s11739-020-02586-8
  • 20. Cao B., Wang Y., Wen D., Liu W., Wang J., Fan G., et al. Trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020 7;382(19):1787-1799. DOI: 10.1056/NEJMoa2001282
  • 21. Li Y., Xie Z., Lin W., Cai W., Wen C., Guan Y., et al. Efficacy and safety of lopinavir/ritonavir or arbidol in adult patients with mild/moderate COVID-19: an exploratory randomized controlled trial. Med (NY). 2020;18(1):105-113.e4. DOI: 10.1016/j.medj.2020.04.001
  • 22. Chang C., Yi Z., Jianying H., Ping Y., Zhenshun C., Jianyuan W., et al. Favipiravir versus arbidol for COVID-19: a randomized clinical trial. medRxiv 2020;03.17.20037432. DOI: 10.1101/2020.03.17.20037432
  • 23. Hung I.F., Lung K.C., Tso E.Y., Liu R., Chung T.W., Chu M.Y., et al. Triple combination of interferon beta-1b, lopinavirritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet. 2020;30;395(10238):1695-1704. DOI: 10.1016/S0140-6736(20)31042-4
  • 24. Sun J., Deng X., Chen X., Huang J., Huang S., Li Y., et al. Incidence of adverse drug reactions in COVID-19 patients in China: an active monitoring study by hospital pharmacovigilance system. Clin Pharmacol Ther. 2020;108(4):791-797. DOI: 10.1002/cpt.1866
  • 25. Lozano-Cruz O.A., Jiménez J.V., Olivas-Martinez A., OrtizBrizuela E., Cárdenas-Fragoso J.L., Azamar-Llamas D., et al. Adverse effects associated with the use of antimalarials during the COVID-19 pandemic in a tertiary care center in Mexico city. Front Pharmacol. 2021;3;12:668-678. DOI: 10.3389/fphar.2021.668678
  • 26. Falcão F., Viegas E., Carmo I., Soares J., Falcao M., Solano M., et al. A prospective, observational study to evaluate adverse drug reactions in patients with COVID-19 treated with remdesivir or hydroxychloroquine: a preliminary report. Eur J Hosp Pharm. 2021;28(5):248-253. DOI: 10.1136/ejhpharm-2020-002613
  • 27. Kiselev Yu.Yu., Tsvetov V.M., Mirzaev K.B., Sychev D.A. What are the indications for combined use of hydroxychloroquine and lopinavir/ritonavir, and how should treatment safety monitoring be performed? Kachestvennaya klinicheskaya praktika. 2020;(4S):47-49. Russian. DOI: 10.37489/2588-0519-2020-S4-47-49
  • 28. Kiselev Yu.Yu., Matveev A.V., Mirzaev K.B., Sychev D.A. Monitoring of safety using favipiravir: risk management of adverse drug reactions in clinical practice. Kachestvennaya klinicheskaya praktika. 2020;(4S):115-119. Russian. DOI: 10.37489/2588-0519-2020-S4-115-119
  • 29. Antonov V.N., Ignatova G.L., Pribytkova O.V., Sleptsova S.S., Strebkova E.A., Khudyakova E.A., et al. Experience of olokizumab use in COVID-19 patients. Terapevticheskij arhiv. 2020;92(12):148-154. Russian. DOI: 10.26442/00403660.2020.12.200522
  • 30. Nasonov E., Fatenejad S., Korneva E., Krechikova D., Maslyansky A., Plaksina T., et al. Safety and efficacy of olokizumab in a phase iii trial of patients with moderately to severely active rheumatoid arthritis inadequately controlled by methotrexate – CREDO1 Study. Proceedings of 2019 ACR/ARP Annual Meeting. Arthritis Rheumatol. 2019;71(Suppl. 10).
  • 31. Rosenberg E.S., Dufort E.M., Udo T., Wilberschied L.A., Kumar J., Tesoriero J., et al. Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York state. JAMA. 2020;323(24):2493-2502. DOI: 10.1001/jama.2020.8630
  • 32. Kalil A.C., Patterson T.F., Mehta A.K., Tomashek K.M., Wolfe C.R., Ghazaryan V., et al. ACTT-2 Study Group Members. Baricitinib plus remdesivir for hospitalized adults with Covid-19. N Engl J Med. 2021;4;384(9):795-807. DOI: 10.1056/NEJMoa2031994
  • 33. Furlow B. COVACTA trial raises questions about tocilizumab's benefit in COVID-19. Lancet Rheumatol. 2020;2(10):e592. DOI: 10.1016/S2665-9913(20)30313-1
  • 34. Ip A., Berry D.A., Hansen E., Goy A.H., Pecora A.L., Sinclaire B.A., et al. Hydroxychloroquine and tocilizumab therapy in COVID-19 patients – an observational study. PLoS One. 2020;13;15(8):e0237693. DOI: 10.1371/journal.pone.0237693
  • 35. Chouchana L., Boujaafar S., Gana I., Preta L.H., Regard L., Legendre P., et al. Plasma concentrations and safety of lopinavir/ritonavir in COVID-19 Patients. Ther Drug Monit. 2021;1:43(1):131-135. DOI: 10.1097/FTD.0000000000000838
  • 36. Gatti M., Fusaroli M., Caraceni P., Poluzzi E., De Ponti F., Raschi E. Serious adverse events with tocilizumab: pharmacovigilance as an aid to prioritize monitoring in COVID-19. Br J Clin Pharmacol. 2021;87(3):1533-1540. DOI: 10.1111/bcp.14459
  • 37. Salama C., Han J., Yau L., Reiss W.G., Kramer B., Neidhart J.D., et al. Tocilizumab in patients hospitalized with Covid19 pneumonia. N Engl J Med. 2021;7:384(1):20-30. DOI: 10.1056/NEJMoa2030340
  • 38. Annie F.H., Sirbu C., Frazier K.R., Broce M., Lucas B.D. Jr. Hydroxychloroquine in hospitalized patients with COVID-19: real-world experience assessing mortality. Pharmacotherapy. 2020;40(11):1072-1081. DOI: 10.1002/phar.2467
  • 39. Biran N., Ip A., Ahn J., Go R.C., Wang S., Mathura S., et al. Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study. Lancet Rheumatol. 2020;2(10):e603-e612. DOI: 10.1016/S2665-9913(20)30277-0
  • 40. Singh A.P., Tousif S., Umbarkar P., Lal H. A pharmacovigilance study of hydroxychloroquine cardiac safety profile: potential implication in COVID-19 mitigation. J Clin Med. 2020;15:9(6):1867. DOI: 10.3390/jcm9061867
  • 41. Diaby V., Almutairi R.D., Chen Z., Moussa R.K., Berthe A. A pharmacovigilance study to quantify the strength of association between the combination of antimalarial drugs and azithromycin and cardiac arrhythmias: implications for the treatment of COVID-19. Expert Rev Pharmacoecon Outcomes Res. 2021;21(1):159-168. DOI: 10.1080/14737167.2021.1851600
  • 42. Peng L., Xiao K., Ottaviani S., Stebbing J., Wang Y.J. A real-world disproportionality analysis of FDA Adverse Event Reporting System (FAERS) events for baricitinib. Expert Opin Drug Saf. 2020;19(11):1505-1511. DOI: 10.1080/14740338.2020.1799975
  • 43. Goldman A., Bomze D., Dankner R., Hod H., Meirson T., Boursi B., et al. Cardiovascular adverse events associated with hydroxychloroquine and chloroquine: a comprehensive pharmacovigilance analysis of pre-COVID-19 reports. Br J Clin Pharmacol. 2021;87(3):1432-1442. DOI: 10.1111/bcp.14546
  • 44. Dörks M., Jobski K., Hoffmann F., Douros A. Global COVID-19 pandemic and reporting behavior – an analysis of the Food and Drug Administration adverse events reporting system. Pharmacoepidemiol Drug Saf. 2021;30(6):707-715. DOI: 10.1002/pds.5217
  • 45. Sato K., Mano T., Iwata A., Toda T. Neuropsychiatric adverse events of chloroquine: a real-world pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS) database. Biosci Trends. 2020;14(2):139-143. DOI: 10.5582/bst.2020.03082
  • 46. Yuan J., Li M., Yu Y., Lee T.Y., Lv G., Han B., et al. Pharmacotherapy management for COVID-19 and cardiac safety: a data mining approach for pharmacovigilance evidence from the FDA Adverse Event Reporting System (FAERS). Drugs Real World Outcomes. 2021;8(2):131-140. DOI: 10.1007/s40801-021-00229-8
  • 47. Sarayani A., Cicali B., Henriksen C.H., Brown J.D. Safety signals for QT prolongation or Torsades de Pointes associated with azithromycin with or without chloroquine or hydroxychloroquine. Res Social Adm Pharm. 2021;17(2):483-486. DOI: 10.1016/j.sapharm.2020.04.016
  • 48. Dauner D.G., Dauner K.N. Summary of adverse drug events for hydroxychloroquine, azithromycin, and chloroquine during the COVID-19 pandemic. J Am Pharm Assoc (2003). 2021;61(3):293-298. DOI: 10.1016/j.japh.2021.01.007
  • 49. Beyzarov E., Chen Y., Julg R., Naim K., Shah J., Gregory W.W., et al. Global safety database summary of COVID-19-related drug utilization-safety surveillance: a sponsor's perspective. Drug Saf. 2021;44(1):95-105. DOI: 10.1007/s40264-020-01035-x
  • 50. Tanriverdİ E., Çörtük M., Yildirim B.Z., Uğur Chousein E.G., Turan D., Çinarka H., et al. Hydroxychloroquine plus azithromycin and early hospital admission are beneficial in COVID-19 patients: Turkish experience with real-life data. Turk J Med Sci. 2021;51(1):10-15. DOI: 10.3906/sag-2005-82
  • 51. Bessière F., Roccia H., Delinière A., Charrière R., Chevalier P., Argaud L., Cour M. Assessment of QT Intervals in a case series of patients with coronavirus disease 2019 (COVID-19) infection treated with hydroxychloroquine alone or in combination with azithromycin in an intensive care unit. JAMA Cardiol. 2020;5(9):1067-1069. DOI: 10.1001/jamacardio.2020.1787
  • 52. Fresse A., Viard D., Romani S., Gérard A., Lepelley M., Rocher F., et al. French Network of Pharmacovigilance Centers. Spontaneous reported cardiotoxicity induced by lopinavir/ritonavir in COVID-19. An alleged pastresolved problem. Int J Cardiol. 2021;324:255-260. DOI: 10.1016/j.ijcard.2020.10.028
  • 53. Gérard A., Romani S., Fresse A., Viard D., Parassol N., Granvuillemin A., et al. French Network of Pharmacovigilance Centers. «Off-label» use of hydroxychloroquine, azithromycin, lopinavir-ritonavir and chloroquine in COVID-19: a survey of cardiac adverse drug reactions by the French Network of Pharmacovigilance Centers. Therapie. 2020;75(4):371-379. DOI: 10.1016/j.therap.2020.05.002
  • 54. Giaime P., Guenoun M., Pedinielli N., Narbonne H., Bergounioux J.P., Solas C., et al. Hydroxychloroquine and azithromycin tolerance in haemodialysis patients during COVID-19 infection. Nephrol Dial Transplant. 2020;35(8):1346-1353. DOI: 10.1093/ndt/gfaa191
  • 55. Romani S., Gérard A., Fresse A., Viard D., VanObberghen É., Micallef J., et al. French Pharmacovigilance Network. Insights on the evidence of cardiotoxicity of hydroxychloroquine prior and during COVID-19 epidemic. Clin Transl Sci. 2021;14(1):163-169. DOI: 10.1111/cts.12883
  • 56. Fusetti M., Eibenstein A., Corridore V., Hueck S., ChitiBatelli S. Meflochina ed ototossicità: descrizione di tre casi [Mefloquine and ototoxicity: a report of 3 cases]. Clin Ter. 1999;150(5):379-382.
  • 57. U.S. National Library of Medicine. Efficacy of mefloquine as prophylaxis against COVID-19: a placebo-control, randomized clinical trial, 2021. Available at: https://clinicaltrials.gov/ct2/show/study/NCT04847661?term=Mefloquine&draw=2&rank=1#wrapper. Accessed July 12, 2021.
  • 58. Instructions for the medical use of the drug Plaquenil, 2019. Available at: www.sanofi.ru/-/media/Project/One-SanofiWeb/Websites/Europe/Sanofi-RU/Home/healthcaresolutions/immunology/Plaquenil-hydroxychloroquineapprovedSPC-L-2019-10-14.pdf?la=ru. Accessed July 12, 2021. Russian.
  • 59. Gautret P., Lagier J.C., Parola P., Hoang V.T., Meddeb L., Mailhe M., et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an openlabel non-randomized clinical trial. Int J Antimicrob Agents. 2020;56(1):105949. DOI: 10.1016/j.ijantimicag.2020.105949
  • 60. Leonova M.V. Cardiotoxicity of chloroquine and hydroxychloroquine in the treatment of COVID-19 infection. Consilium Medicum. 2020;22(10):15-21. Russian. DOI: 10.26442/20751753.2020.10.200270
  • 61. Nguyen L.S., Dolladille C., Drici M.D., Fenioux C., Alexandre J., Mira J.P., et al. Cardiovascular toxicities associated with hydroxychloroquine and azithromycin: an analysis of the World Health Organization Pharmacovigilance Database. Circulation. 2020;142(3):303-305. DOI: 10.1161/CIRCULATIONAHA.120.048238
  • 62. Chandwani A., Shuter J. Lopinavir/ritonavir in the treatment of HIV-1 infection: a review. Ther Clin Risk Manag. 2008;4(5):1023-1033. DOI: 10.2147/TCRM.S3285
  • 63. 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
  • 64. Nagata T., Lefor A., Hasegawa M., Ishii M. Favipiravir: a new medication for the Ebola virus disease pandemic. Disaster Med Public Health Prep. 2015;9(1):79-81. DOI: 10.1017/dmp.2014.151
  • 65. Sychev D.A. Information Center on Pharmacotherapy in Patients with New Coronavirus Infection COVID-19 «PharmaCOVID», Russia, 2020. Available at: http://onrrussia.ru.u5993.moko.vps-private.net/sites/default/files/final-favipiravir_update_ver6.pdf. Accessed July 12, 2021. Russian.
  • 66. Order of the Federal Service for Surveillance in Healthcare February 15, 2017 № 1071 «On approval of the Procedure for the implementation of pharmacovigilance», 2017. Available at: www.garant.ru/products/ipo/prime/doc/71534896/. Accessed July 12, 2021. Russian.
  • 67. Penman S.L., Kiy R.T., Jensen R.L., Beoku-Betts C., Alfirevic A., Back D., et al. Safety perspectives on presently considered drugs for the treatment of COVID-19. Br J Pharmacol. 2020;177(19):4353-4374. DOI: 10.1111/bph.15204
  • 68. Nasonov E.L., Aleksandrova E.N., Avdeeva A.S., Panasyuk E.Yu. Interleukin 6 inhibition: new possibilities of pharmacotherapy for immunoinflammatory rheumatic diseases. Nauchno-prakticheskaja revmatologija. 2013;51(4):416-427. Russian. DOI: 10.14412/1996-7012-2013-04
  • 69. U.S. National Library of Medicine. Study of the efficacy and safety of a single administration of olokizumab and RPH104 with standard therapy in patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (COVID-19), 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT04380519. Accessed July 12, 2021.
  • 70. U.S. National Library of Medicine. Dapagliflozin effects on cardiovascular events in patients with an acute heart attack (DAPA-MI), 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT04564742. Accessed July 12, 2021.
  • 71. Keystone E.C., Taylor P.C., Drescher E., Schlichting D.E., Beattie S.D., Berclaz P.Y., et al. Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate. Ann Rheum Dis. 2015;74(2):333-340. DOI: 10.1136/annrheumdis-2014-206478
  • 72. Josef S.S., Mark C.G., Tsutomu T., David L.H., William L.M., Terence R., et al. Safety profile of baricitinib in patients with active rheumatoid arthritis with over 2 years median time in treatment. J Rheumatol. 2019; 46 (1):7-18. DOI: 10.3899/jrheum.171361
  • 73. Glagolev S.V. Good pharmacovigilance practice of the Russian Federation and the Eurasian Economic Union, harmonization with international approaches and practices. Proceedings of the International scientific and practical conference «Pharmacovigilance. Modern challenges and opportunities». Russia, 2012. Russian.
  • 74. Mishinova S.A., Zhuravkov A.A., Zhuravko V.K. Use of unlicensed drugs and off-label drug use: focus on COVID-19. Kachestvennaya klinicheskaya praktika. 2020;(4S):120-129. Russian. DOI: 10.37489/2588-0519-2020-S4-120-129
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