myrwdРеальная клиническая практика: данные и доказательстваReal-World Data & Evidence2782-3784Publishing House OKI10.37489/2782-3784-myrwd-9FEIPNImyrwd-12Research ArticleБЕЗОПАСНОСТЬ ЛЕКАРСТВDRUG SAFETYАспекты безопасного применения лекарственных препаратов на основе лекарственного растительного сырья при COVID-19Aspects of the safe use of medicinal products based on medicinal plant materials in COVID-19https://orcid.org/0000-0001-5594-4859ТаубэА. А.TaubeA. A.

Таубэ Александра Альбертовна, к. фарм. н. 

Санкт-Петербург

St. Petersburg

aleksandra.taube@pharminnotech.comФГБУ «Научный центр экспертизы средств медицинского применения» Минздрава России; ФГБОУ ВО «Санкт-Петербургский государственный химико-фармацевтический университет» Министерства здравоохранения Российской ФедерацииРоссияFGBU “Scientific Center for Expertise of Medicinal Products” of the Ministry of Health of Russia; FGBOU VO “St. Petersburg State Chemical and Pharmaceutical University” of the Ministry of Health of the Russian FederationRussian Federation202215032022212835Copyright © Таубэ А.А., 20222022Таубэ А.А.Taube A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.myrwd.ru/jour/article/view/12

Согласно данным ряда исследований, лекарственные растения и лекарственные препараты (ЛП) на их основе могут быть использованы в качестве ингибиторов различных вирусных инфекций, включая вирус SARS-CoV-2, на разных стадиях их проявления и развития. В ряде стран разработаны официальные рекомендации по самостоятельной и вспомогательной терапии COVID-19 лекарственными растениями и ЛП на их основе. Однако в сочетании с ЛП, разработанными для лечения COVID-19, могут возникать различные взаимодействия, в том числе неблагоприятные.

Цель

Цель: проведение систематизации и анализа данных по возможным взаимодействиям лекарственных растений и природных биологически активных веществ, являющихся мажорными действующими веществами в растительном сырье, с ЛП, рекомендованными для лечения COVID-19.

Материалы и методы

Материалы и методы. В исследовании были отобраны ЛП, рекомендованные к лечению COVID-19 на различных стадиях и различной степени тяжести, с различным механизмом действия. Использовалась открытая информация о подтверждённых межлекарственных взаимодействиях на сайте международной базы данных https://go.drugbank.com/.

Результаты и обсуждение

Результаты и обсуждение. Выявлены результаты возможных взаимодействий со следующими лекарственными растениями: Зверобой, Наперстянка, Барвинок, Безвременник, Хинное дерево, Строфант, Спорынья, Перец, Лимон, Кофе, Чай, дерево Йохимбе, Чеснок, Примула вечерняя, Мак опийный, Раувольфия змеиная.

Заключение

Заключение. Рассмотрены ЛП, применяемые для лечения COVID-19, разных анатомо-терапевтических групп, выявлены возможные изменения их терапевтической эффективности при одновременном приёме с лекарственными растениями или биологически активными веществами растительного происхождения, содержащимися в продуктах питания и пищевых добавках. Показано, что не все взаимодействия могут быть нежелательными. Влияние лекарственных растений на фармакокинетику ЛП изучено недостаточно и представляется важным и перспективным аспектом деятельности по фармаконадзору. Выявлены интересные взаимодействия: зверобой продырявленный и ЛП на его основе способны вызвать индукцию CYP3A и снижение терапевтического эффекта при совместном применении с ЛП: лопинавиром, ремдесивиром, умифеновиром, нирматрелвиром; кардиотоксический эффект интерферона может быть снижен за счёт применения лекарственного растительного сырья, содержащего сердечные гликозиды; сочетание приёма феруловой кислоты с пэгинтерфероном альфа-2а повышает риск и тяжесть кровотечений. Обнаружено, что база данных Drugbank не содержит сведений о межлекарственных взаимодействиях лекарственных растений с молнупиравиром.

According to a number of studies, medicinal plants and drugs based on them can be used as inhibitors of various viral infections, including the SARS-CoV-2 virus at different stages of their manifestation and development. In a number of countries, official recommendations have been developed for independent and auxiliary therapy of COVID-19 with medicinal plants and drugs based on them. However, in combination with drugs developed for the treatment of COVID-19, various interactions, including adverse ones, may occur.

Purpose

Purpose: to systematize and analyze data on possible interactions of medicinal plants and natural biologically active substances, which are major active substances in plant raw materials, with medicinal products recommended for the treatment of COVID-19.

Materials and methods

Materials and methods. The study selected drugs recommended for the treatment of COVID-19 at various stages and severity with different mechanisms of action. We used open information on confirmed drug interactions on the website of the international database https://go.drugbank.com/.

Results and discussion

Results and discussion. The results of possible interactions with the following medicinal plants were revealed: St. John’s wort, Digitalis, Periwinkle, Colchicum, Cinchona, Strophant, Ergot, Pepper, Lemon, Coffee, Tea, Yohimbe tree, Garlic, Evening primrose, Poppy opium, Rauwolfia serpentine.

Conclusion

Conclusion. The drugs used for the treatment of COVID-19 of different anatomical and therapeutic groups are considered, possible changes in their therapeutic efficacy are identified when taken simultaneously with medicinal plants or biologically active substances of plant origin contained in food and nutritional supplements. It is shown that not all interactions may be undesirable. The effect of medicinal plants on the pharmacokinetics of drugs has not been studied enough and seems to be an important and promising aspect of pharmacovigilance activities. Interesting interactions have been identified: St. John’s wort and drugs based on it can cause the induction of CYP3A and reduce the therapeutic effect when used together with drugs: lopinavir, remdesivir, umifenovir, nirmatrelvir; the cardiotoxic effect of interferon can be reduced through the use of medicinal plant materials containing cardiac glycosides; the combination of ferulic acid with peginterferon alfa-2a increases the risk and severity of bleeding. It was found that the Drugbank database does not contain information on drug-drug interactions of medicinal plants with molnupiravir.

лекарственное растениелекарственное растительное сырьёCOVID-19лекарственные взаимодействияфармаконадзорбезопасность лекарствфавипиравирмолнупиравирумифеновирлопинавирремдесивирнирматрелвиртоцилизумабmedicinal plantmedicinal plant materialsCOVID-19drug interactionspharmacovigilancedrug safetyfavipiravirmolnupiravirumifenovirlopinavirremdesivirnirmatrelvirtocilizumabРабота выполнена в рамках государственного задания ФГБУ «НЦЭСМП» Минздрава России № 056-00001-22-00 на проведение прикладных научных исследований (номер государственного учёта НИР 121021800098-4).ReferencesChan KW, Wong VT, Tang SCW. COVID-19: an update on the epidemiological, clinical, preventive and therapeutic evidence and guidelines of integrative Chinese–Western medicine for the management of 2019 novel coronavirus disease. Am J Chin Med. 2020;48:737–63. doi: 10.1142/S0192415X20500378Chan KW, Wong VT, Tang SCW. COVID-19: an update on the epidemiological, clinical, preventive and therapeutic evidence and guidelines of integrative Chinese–Western medicine for the management of 2019 novel coronavirus disease. Am J Chin Med. 2020;48:737–63. doi: 10.1142/S0192415X20500378Vellingiri B, Rajagopalan K. COVID-19: a promising cure for the global panic. Science of The Total Environment. 2020;725:138277. https://doi.org/10.1016/j.scitotenv.2020.138277.Vellingiri B, Rajagopalan K. COVID-19: a promising cure for the global panic. Science of The Total Environment. 2020;725:138277. https://doi.org/10.1016/j.scitotenv.2020.138277.Bhuiyan FR, Howlader S, Topu Raihan T, Hasan M. Plants Metabolites: Possibility of Natural Therapeutics Against the COVID-19 Pandemic. Front Med (Lausanne). 2020;7:444. doi: 10.3389/fmed.2020.00444Bhuiyan FR, Howlader S, Topu Raihan T, Hasan M. Plants Metabolites: Possibility of Natural Therapeutics Against the COVID-19 Pandemic. Front Med (Lausanne). 2020;7:444. doi: 10.3389/fmed.2020.00444Yang Y. Use of herbal drugs to treat COVID-19 should be with caution. The Lancet. 2020;395 (10238):1689–90. https://doi.org/10.1016/S0140-6736(20)31143-0.Yang Y. Use of herbal drugs to treat COVID-19 should be with caution. The Lancet. 2020;395 (10238):1689–90. https://doi.org/10.1016/S0140-6736(20)31143-0.Vangeela L, Chiu W, Jonghe SD, Maes P, Slechten B, Raymenants J, André E, Leyssen P, Neytsa J, Jochmans D. Remdesivir, Molnupiravir and Nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern. Antiviral Research 2022;(198):105252. https://doi.org/10.1016/j.antiviral.2022.105252.Vangeela L, Chiu W, Jonghe SD, Maes P, Slechten B, Raymenants J, André E, Leyssen P, Neytsa J, Jochmans D. Remdesivir, Molnupiravir and Nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern. Antiviral Research 2022;(198):105252. https://doi.org/10.1016/j.antiviral.2022.105252.Kimiyasu Shiraki K, Noriaki Sato N, Sakai K, Shirou Matsumoto Sh, Kaszynski RH, Takemoto M. Antiviral therapy for COVID-19: Derivation of optimal strategy based on past antiviral and favipiravir experiences. Pharmacology & Therapeutics. 2022;235:108121. https://doi.org/10.1016/j.pharmthera.2022.108121.Kimiyasu Shiraki K, Noriaki Sato N, Sakai K, Shirou Matsumoto Sh, Kaszynski RH, Takemoto M. Antiviral therapy for COVID-19: Derivation of optimal strategy based on past antiviral and favipiravir experiences. Pharmacology & Therapeutics. 2022;235:108121. https://doi.org/10.1016/j.pharmthera.2022.108121.Bosaeed M, Alharbi A, Mahmoud E, Alrehily S, Bahlaq M, Gaifer Z, Alturkistani H, Alhagan Kh, Alshahrani S, Tolbah A, Musattat A, Alanazi M, Jaha R, Sultana Kh, Alqahtani H, Al Aamer K, Jaser S, Alsaedy A, Alaskar A. Efficacy of favipiravir in adults with mild COVID-19: a randomized, double-blind, multicentre, placebo-controlled clinical trial. Clinical Microbiology and Infection. https://doi.org/10.1016/j.cmi.2021.12.026.Bosaeed M, Alharbi A, Mahmoud E, Alrehily S, Bahlaq M, Gaifer Z, Alturkistani H, Alhagan Kh, Alshahrani S, Tolbah A, Musattat A, Alanazi M, Jaha R, Sultana Kh, Alqahtani H, Al Aamer K, Jaser S, Alsaedy A, Alaskar A. Efficacy of favipiravir in adults with mild COVID-19: a randomized, double-blind, multicentre, placebo-controlled clinical trial. Clinical Microbiology and Infection. https://doi.org/10.1016/j.cmi.2021.12.026.Painter GR, Natchus MG, Cohen O, Holman W, Painter WP. Developing a direct acting, orally available antiviral agent in a pandemic: the evolution of molnupiravir as a potential treatment for COVID-19. Current Opinion in Virology. 2021;50:17–22. https://doi.org/10.1016/j.coviro.2021.06.003.Painter GR, Natchus MG, Cohen O, Holman W, Painter WP. Developing a direct acting, orally available antiviral agent in a pandemic: the evolution of molnupiravir as a potential treatment for COVID-19. Current Opinion in Virology. 2021;50:17–22. https://doi.org/10.1016/j.coviro.2021.06.003.Kumar A, Singh Akriti S, Singh R, Misracde A. An updated practical guideline on use of molnupiravir and comparison with agents having emergency use authorization for treatment of COVID-19. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2022;16(2):102396. https://doi.org/10.1016/j.dsx.2022.102396.Kumar A, Singh Akriti S, Singh R, Misracde A. An updated practical guideline on use of molnupiravir and comparison with agents having emergency use authorization for treatment of COVID-19. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2022;16(2):102396. https://doi.org/10.1016/j.dsx.2022.102396.Kumar A, Singh Akriti S, Singh R, Misracde A. Molnupiravir in COVID-19: A systematic review of literature. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2021;15(6):102329. https://doi.org/10.1016/j.dsx.2021.102329.Kumar A, Singh Akriti S, Singh R, Misracde A. Molnupiravir in COVID-19: A systematic review of literature. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2021;15(6):102329. https://doi.org/10.1016/j.dsx.2021.102329.Abdelnabi R, Foo Caroline S, Kaptein Suzanne JF. The combined treatment of Molnupiravir and Favipiravir results in a potentiation of antiviral efficacy in a SARS-CoV-2 hamster infection model. eBioMedicine 2021;72:103595. https://doi.org/10.1016/j.ebiom.2021.103595.Abdelnabi R, Foo Caroline S, Kaptein Suzanne JF. The combined treatment of Molnupiravir and Favipiravir results in a potentiation of antiviral efficacy in a SARS-CoV-2 hamster infection model. eBioMedicine 2021;72:103595. https://doi.org/10.1016/j.ebiom.2021.103595.Focosi D, Maggi F, McConnell S, Casadevall. A Very low levels of remdesivir resistance in SARS-COV-2 genomes after 18 months of massive usage during the COVID19 pandemic: A GISAID exploratory analysis. Antiviral Research. 2022; 198:105247. https://doi.org/10.1016/j.antiviral.2022.105247.Focosi D, Maggi F, McConnell S, Casadevall. A Very low levels of remdesivir resistance in SARS-COV-2 genomes after 18 months of massive usage during the COVID19 pandemic: A GISAID exploratory analysis. Antiviral Research. 2022; 198:105247. https://doi.org/10.1016/j.antiviral.2022.105247.Falcone Marco, Suardi Lorenzo Roberto, Tiseo Giusy. Early Use of Remdesivir and Risk of Disease Progression in Hospitalized Patients With Mild to Moderate COVID-19. Clinical Therapeutics. Available online 17 January 2022. https://doi.org/10.1016/j.clinthera.2022.01.007.Falcone Marco, Suardi Lorenzo Roberto, Tiseo Giusy. Early Use of Remdesivir and Risk of Disease Progression in Hospitalized Patients With Mild to Moderate COVID-19. Clinical Therapeutics. Available online 17 January 2022. https://doi.org/10.1016/j.clinthera.2022.01.007.Choudhary S, Silakari O. Scaffold morphing of arbidol (umifenovir) in search of multi-targeting therapy halting the interaction of SARS-CoV-2 with ACE2 and other proteases involved in COVID-19. Virus Research. 2020;289:198146. https://doi.org/10.1016/j.virusres.2020.198146.Choudhary S, Silakari O. Scaffold morphing of arbidol (umifenovir) in search of multi-targeting therapy halting the interaction of SARS-CoV-2 with ACE2 and other proteases involved in COVID-19. Virus Research. 2020;289:198146. https://doi.org/10.1016/j.virusres.2020.198146.Kiselev YuYu, Zagorodnikova KA, Ivashchenko DV, Krykov AV, Sychev IN, Matveev AS, Mirzaev KB, Otdelenov VA, Tsvetov VM, Dmitriev AV, Poroikov VV, Sychev DA. Current and future use of umifenovir in patients with COVID-19. Kachestvennaya klinicheskaya praktika = Good Clinical Practice. 2020;(4S):75–80. (In Russ.). https://doi.org/10.37489/2588-0519-2020-S4-75-80.Kiselev YuYu, Zagorodnikova KA, Ivashchenko DV, Krykov AV, Sychev IN, Matveev AS, Mirzaev KB, Otdelenov VA, Tsvetov VM, Dmitriev AV, Poroikov VV, Sychev DA. Current and future use of umifenovir in patients with COVID-19. Kachestvennaya klinicheskaya praktika = Good Clinical Practice. 2020;(4S):75–80. (In Russ.). https://doi.org/10.37489/2588-0519-2020-S4-75-80.Ramachandran Ravishankar, Bhosale Vivek, Reddy Himanshu. Phase III, Randomized, Double-blind, Placebo controlled trial of Efficacy, Safety and Tolerability of Antiviral drug Umifenovir vs Standard care of therapy in non-severe COVID-19 patients. International Journal of Infectious Diseases. 2022;115:62–9. https://doi.org/10.1016/j.ijid.2021.11.025.Ramachandran Ravishankar, Bhosale Vivek, Reddy Himanshu. Phase III, Randomized, Double-blind, Placebo controlled trial of Efficacy, Safety and Tolerability of Antiviral drug Umifenovir vs Standard care of therapy in non-severe COVID-19 patients. International Journal of Infectious Diseases. 2022;115:62–9. https://doi.org/10.1016/j.ijid.2021.11.025.Alavi Darazam I, Shokouhi Sh, Mardani M, Pourhoseingholi MA, Rabiei MM, Hatami F, Shabani M, Moradi O, Gharehbagh FJ, Irvani SSN, Amirdosara M, Hajiesmaeili M, Rezaei O, Khoshkar A, Lotfollahi L, Gachkar L, Dehbsneh HSh, Khalili N, Soleymaninia A, Kusha AH, Shoushtari MT, Torabinavid P. Umifenovir in hospitalized moderate to severe COVID-19 patients: A randomized clinical trial. International Immunopharmacology. 2021;99:107969. https://doi.org/10.1016/j.intimp.2021.107969.Alavi Darazam I, Shokouhi Sh, Mardani M, Pourhoseingholi MA, Rabiei MM, Hatami F, Shabani M, Moradi O, Gharehbagh FJ, Irvani SSN, Amirdosara M, Hajiesmaeili M, Rezaei O, Khoshkar A, Lotfollahi L, Gachkar L, Dehbsneh HSh, Khalili N, Soleymaninia A, Kusha AH, Shoushtari MT, Torabinavid P. Umifenovir in hospitalized moderate to severe COVID-19 patients: A randomized clinical trial. International Immunopharmacology. 2021;99:107969. https://doi.org/10.1016/j.intimp.2021.107969.Ader F, Peiffer-Smadja N, Poissy J. An open-label randomized controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with COVID-19. Clinical Microbiology and Infection. 2021;27(12):1826–37. https://doi.org/10.1016/j.cmi.2021.05.020.Ader F, Peiffer-Smadja N, Poissy J. An open-label randomized controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with COVID-19. Clinical Microbiology and Infection. 2021;27(12):1826–37. https://doi.org/10.1016/j.cmi.2021.05.020.Patel Tejas K, Patel Parvati B, Barvaliya M. Efficacy and safety of lopinavir-ritonavir in COVID-19: A systematic review of randomized controlled trials. Journal of Infection and Public Health. 2021;14(6): 740–8. https://doi.org/10.1016/j.jiph.2021.03.015.Patel Tejas K, Patel Parvati B, Barvaliya M. Efficacy and safety of lopinavir-ritonavir in COVID-19: A systematic review of randomized controlled trials. Journal of Infection and Public Health. 2021;14(6): 740–8. https://doi.org/10.1016/j.jiph.2021.03.015.Owa Adewale Bayode, Owa Olufunke Tolulope. Lopinavir/ritonavir use in Covid-19 infection: is it completely non-beneficial? Journal of Microbiology, Immunology and Infection. 2020;53(5):674–5.Owa Adewale Bayode, Owa Olufunke Tolulope. Lopinavir/ritonavir use in Covid-19 infection: is it completely non-beneficial? Journal of Microbiology, Immunology and Infection. 2020;53(5):674–5.Li Hui, Xiong Nian, Li Changjun. Efficacy of ribavirin and interferon-α therapy for hospitalized patients with COVID-19: A multicenter, retrospective cohort study. International Journal of Infectious Diseases. 2021;104:641–8. https://doi.org/10.1016/j.ijid.2021.01.055.Li Hui, Xiong Nian, Li Changjun. Efficacy of ribavirin and interferon-α therapy for hospitalized patients with COVID-19: A multicenter, retrospective cohort study. International Journal of Infectious Diseases. 2021;104:641–8. https://doi.org/10.1016/j.ijid.2021.01.055.Bhushan BLS, Wanve S, Koradia P. Efficacy and safety of pegylated interferon-α2b in moderate COVID-19: a phase 3, randomized, comparator-controlled, open-label study. International Journal of Infectious Diseases. 2021;111:281–7. https://doi.org/10.1016/j.ijid.2021.08.044.Bhushan BLS, Wanve S, Koradia P. Efficacy and safety of pegylated interferon-α2b in moderate COVID-19: a phase 3, randomized, comparator-controlled, open-label study. International Journal of Infectious Diseases. 2021;111:281–7. https://doi.org/10.1016/j.ijid.2021.08.044.Mushtaq Muhammad Z, Mahmood Saad BZ, Almas A. Tocilizumab in critically ill COVID-19 patients: An observational study. International Immunopharmacology. 2022;102:108384. https://doi.org/10.1016/j.intimp.2021.108384.Mushtaq Muhammad Z, Mahmood Saad BZ, Almas A. Tocilizumab in critically ill COVID-19 patients: An observational study. International Immunopharmacology. 2022;102:108384. https://doi.org/10.1016/j.intimp.2021.108384.Klopfenstein T, Zayet S, Lohse A. Impact of tocilizumab on mortality and/or invasive mechanical ventilation requirement in a cohort of 206 COVID-19 patients. International Journal of Infectious Diseases. 2020;99:491–5. https://doi.org/10.1016/j.ijid.2020.08.024.Klopfenstein T, Zayet S, Lohse A. Impact of tocilizumab on mortality and/or invasive mechanical ventilation requirement in a cohort of 206 COVID-19 patients. International Journal of Infectious Diseases. 2020;99:491–5. https://doi.org/10.1016/j.ijid.2020.08.024.Murav’eva DA, Samylina IA, Yakovlev GP. Farmakognoziya. M.: Medicina, 2002:656.Murav’eva DA, Samylina IA, Yakovlev GP. Farmakognoziya. M.: Medicina, 2002:656.

The authors declare that there are no conflicts of interest present.