rpcardioRational Pharmacotherapy in CardiologyРациональная Фармакотерапия в Кардиологии1819-64462225-3653«SILICEA-POLIGRAF» LLC10.20996/1819-6446-2018-14-4-621-628rpcardio-1734Research ArticleCURRENT QUESTIONS OF CLINICAL PHARMACOLOGYАКТУАЛЬНЫЕ ВОПРОСЫ КЛИНИЧЕСКОЙ ФАРМАКОЛОГИИHepatotoxicity of New Oral AnticoagulantsГепатотоксичность новых оральных антикоагулянтовКасимоваА. Р.KasimovaA. R.

Касимова Алина Рашидовна – аспирант, кафедра клинической фармакологии и доказательной медицины, Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова; врач-клинический фармаколог, отделение клинической фармакологии, РНИИТО им. Р.Р. Вредена 

197022, Санкт-Петербург, ул. Льва Толстого, 6-8; 195427, Санкт-Петербург, ул. Академика Байкова, 8

Alina R. Kasimova – Post-Graduate Student, Chair of Clinical Pharmacology and Evidence-Based Medicine, Pavlov First Saint Petersburg State Medical University; Clinical Pharmacologist, Department of Clinical Pharmacology, Russian Scientific Research Institute of Traumatology and Orthopedics named after R.R. Vreden 

L'va Tolstogo ul. 6-8, Saint Petersburg, 197022; Academica Baykova ul. 8, Saint Petersburg, 195427

kasi-alina@yandex.ruФилиппова (Гурьянова)А. В.Philippova (Guryanova)A. V.

Филиппова (Гурьянова) Анастасия Владимировна – аспирант, кафедра клинической фармакологии и доказательной медицины 

197022, Санкт-Петербург, ул. Льва Толстого, 6-8

Anastasia V. Philippova (Guryanova) – Post-Graduate Student, Chair of Clinical Pharmacology and Evidence-Based Medicine

L'va Tolstogo ul. 6-8, Saint Petersburg, 197022

КолбинА. С.KolbinA. S.

Колбин Алексей Сергеевич – доктор медицинских наук, профессор,зав. кафедрой клинической фармакологии и доказательной медицины

197022, Санкт-Петербург, ул. Льва Толстого, 6-8

Alexey S. Kolbin – MD, PhD, Professor, Head of Chair of Clinical Pharmacology and Evidence-Based Medicine

L'va Tolstogo ul. 6-8, Saint Petersburg, 197022

Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова; Российский научно-исследовательский институт травматологии и ортопедии им Р.Р. ВреденаРоссияPavlov First Saint Petersburg State Medical University; Russian Scientific Research Institute of Traumatology and Orthopedics named after R.R. VredenRussian FederationПервый Санкт-Петербургский государственный медицинский университет им. акад. И.П. ПавловаРоссияPavlov First Saint Petersburg State Medical UniversityRussian Federation201804092018144621628Copyright © Kasimova A.R., Philippova (Guryanova) A.V., Kolbin A.S., 20182018Касимова А.Р., Филиппова (Гурьянова) А.В., Колбин А.С.Kasimova A.R., Philippova (Guryanova) A.V., Kolbin A.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rpcardio.online/jour/article/view/1734Aim

Aim. To summarize and systematize the information published in open sources on the development of various manifestations of liver damage in the use of the new oral anticoagulants (NOAC) for the registered indications and to analyze the published clinical cases of drug induced liver injury (DILI) development.

Material and methods

Material and methods. Search queries for keywords were made in the PubMed (MEDLINE), Scopus, Elibrary and Kiberleninka databases. The search query was composed of the name of the medicinal product (international non-proprietary and commercial name) or the common name of the group and words describing the different variants of the liver damage.

Results

Results. As a result of the search 1497 articles were found. Duplicate articles, articles that do not match the review topic, and articles whose full-text version is not available were removed from the search results. Articles that do not describe specific clinical cases have also been excluded. The review includes 14 articles, published from 2007 to March 2018 in Russian and English and one article in French describing clinical cases of different types of hepatotoxicity in the application of NOAC.

Conclusions

Conclusions. Published clinical cases suggest that NOAC cause undesirable phenomena such as hepatotoxicity, the mechanism and frequency of which remain unclear.

Цель

Цель. Обобщить и систематизировать опубликованную в открытых источниках информацию о развитии различных проявлений повреждений печени при применении лекарственных средств из группы новых оральных антикоагулянтов (НОАК) по зарегистрированным показаниям, и проанализировать опубликованные клинические случаи развития лекарственно индуцированных поражений печени.

Материал и методы

Материал и методы. В базах данных PubMed (MEDLINE), Scopus, Elibrary и Киберленинка были сделаны поисковые запросы по ключевым словам. Поисковый запрос составлялся из названия лекарственного средства (международное непатентованное и торговое наименование) или общего названия группы и слов, описывающих различные варианты поражения печени.

Результаты

Результаты. В результате поиска было найдено 1497 статей. Из результатов поиска удалены повторяющиеся статьи, статьи, не соответствующие теме обзора, а также статьи, полнотекстовая версия которых недоступна. Также были исключены статьи, в которых не приводятся описания конкретных клинических случаев. В обзор включено 14 статей, опубликованных с 2007 по март 2018 гг. на русском и английском языках, и одна статья на французском языке, в которых приводится описание клинических случаев развития различных видов гепатотоксичности при применении НОАК.

Заключение

Заключение. Опубликованные клинические случаи позволяют предположить, что НОАК вызывают такое нежелательное явление, как гепатотоксичность, механизм и частота развития которого остаются неясными.

гепатотоксичностьлекарственно-индуцированные поражения печенидабигатранривароксабанапиксабанновые оральные антикоагулянтыhepatotoxicitydrug-induced liver injurydabigatranrivaroxabanapixabannew oral anticoagulantsReferencesKvasnicka T., Malikova I., Zenahlikova Z., et al. Rivaroxaban metabolism, pharmacologic properties and drug interactions. Curr Drug Metab. 2017;18(7):636-42. doi: 10.2174/1389200218666170518165443.Kvasnicka T., Malikova I., Zenahlikova Z., et al. Rivaroxaban metabolism, pharmacologic properties and drug interactions. Curr Drug Metab. 2017;18(7):636-42. doi: 10.2174/1389200218666170518165443.Lassen M.R., Raskob G.E., Gallus A., et al. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Eng J Med. 2009;361:594-604. doi: 10.1056/NEJMoa1006885.Lassen M.R., Raskob G.E., Gallus A., et al. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Eng J Med. 2009;361:594-604. doi: 10.1056/NEJMoa1006885.Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285-295. doi: 10.2165/00003088200847050-00001.Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285-295. doi: 10.2165/00003088200847050-00001.Tajiri K., Shimizu Y. Practical guidelines for diagnosis and early management of druginduced liver injury. World J Gastroenterol. 2008;14(44):6774-85. doi: 10.3748/wjg.14.6774.Tajiri K., Shimizu Y. Practical guidelines for diagnosis and early management of druginduced liver injury. World J Gastroenterol. 2008;14(44):6774-85. doi: 10.3748/wjg.14.6774.Goldberg D.S., Forde K.A., Carbonari D.M., et al. Population-representative incidence of drug-induced acute liver failure based on an analysis of an integrated health care system. Gastroenterology. 2015;148:1353-61. doi: 10.1053/j.gastro.2015.02.050.Goldberg D.S., Forde K.A., Carbonari D.M., et al. Population-representative incidence of drug-induced acute liver failure based on an analysis of an integrated health care system. Gastroenterology. 2015;148:1353-61. doi: 10.1053/j.gastro.2015.02.050.Björnsson E.S., Bergmann O.M., Björnsson H.K., et al. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology. 2013;144:1419-25. doi: 10.1053/j.gastro.2013.02.006.Björnsson E.S., Bergmann O.M., Björnsson H.K., et al. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology. 2013;144:1419-25. doi: 10.1053/j.gastro.2013.02.006.Wysowski D.K., Swartz L. Adverse drug event surveillance and drug withdrawals in the United States, 1969-2002: the importance of reporting suspected reactions. Arch Intern Med. 2005;165:13639. doi: 10.1001/archinte.165.12.1363.Wysowski D.K., Swartz L. Adverse drug event surveillance and drug withdrawals in the United States, 1969-2002: the importance of reporting suspected reactions. Arch Intern Med. 2005;165:13639. doi: 10.1001/archinte.165.12.1363.Lauschke V., Ingelman-Sundberg M. The importance of patient-specific factors for hepatic drug response and toxicity. Int J Mol Sci. 2016;17:1714. doi: 10.3390/ijms17101714.Lauschke V., Ingelman-Sundberg M. The importance of patient-specific factors for hepatic drug response and toxicity. Int J Mol Sci. 2016;17:1714. doi: 10.3390/ijms17101714.Kaplowitz N. Idiosyncratic drug hepatotoxicity. Nat Rev Drug Discov. 2005; 4(6):489-99. doi: 10.1038/nrd1750.Kaplowitz N. Idiosyncratic drug hepatotoxicity. Nat Rev Drug Discov. 2005; 4(6):489-99. doi: 10.1038/nrd1750.Benichou C. Criteria of drug-induced liver disorders. Report of an international consensus meeting. J Hepatol. 1990;11(2):272-6. doi: 10.1016/0168-8278(90)90124-A.Benichou C. Criteria of drug-induced liver disorders. Report of an international consensus meeting. J Hepatol. 1990;11(2):272-6. doi: 10.1016/0168-8278(90)90124-A.Aithal G.P., Watkins P.B., Andrade R.J., et al. Case definition and phenotype standardization in druginduced liver injury. Clin Pharmacol Ther. 2011;89(6):806-15. doi: 10.1038/clpt.2011.58.Aithal G.P., Watkins P.B., Andrade R.J., et al. Case definition and phenotype standardization in druginduced liver injury. Clin Pharmacol Ther. 2011;89(6):806-15. doi: 10.1038/clpt.2011.58.Tajiri K., Shimizu Y. Practical guidelines for diagnosis and early management of drug-induced liver injury. World J Gastroenterol. 2008;14(44):6774-85. doi: 10.3748/wjg.14.6774.Tajiri K., Shimizu Y. Practical guidelines for diagnosis and early management of drug-induced liver injury. World J Gastroenterol. 2008;14(44):6774-85. doi: 10.3748/wjg.14.6774.Harder S., Graff J. Novel oral anticoagulants: clinical pharmacology, indications and practical considerations. Eur J Clin Pharmacol. 2013; 69:1617-33. doi: 10.1007/s00228-013-1510-z.Harder S., Graff J. Novel oral anticoagulants: clinical pharmacology, indications and practical considerations. Eur J Clin Pharmacol. 2013; 69:1617-33. doi: 10.1007/s00228-013-1510-z.Lee W.M., Larrey D., Olsson R., et al. Hepatic findings in long-term clinical trials of ximelagatran. Drug Saf. 2005; 28:351-70. doi: 10.1007/978-3-642-00663-0_13.Lee W.M., Larrey D., Olsson R., et al. Hepatic findings in long-term clinical trials of ximelagatran. Drug Saf. 2005; 28:351-70. doi: 10.1007/978-3-642-00663-0_13.Keisu M., Andersson T. Drug-induced liver injury in humans: the case of ximelagatran. Handb Exp Pharmacol. 2010; 196:407-18. doi: 10.1007/978-3-642-00663-0_13.Keisu M., Andersson T. Drug-induced liver injury in humans: the case of ximelagatran. Handb Exp Pharmacol. 2010; 196:407-18. doi: 10.1007/978-3-642-00663-0_13.Xarelto. Summary of product characteristics. [cited by August 23, 2018. Available from: https://www.xarelto.com/en/congress-materials/pdf/SPC_Oct_2017.pdf.Xarelto. Summary of product characteristics. [cited by August 23, 2018. Available from: https://www.xarelto.com/en/congress-materials/pdf/SPC_Oct_2017.pdf.Watkins P.B., Desai M., Berkowitz S.D., et al. Evaluation of drug-induced serious hepatotoxicity (eDISH): application of this data organization approach to phase III clinical trials of rivaroxaban after total hip or knee replacement surgery. Drug Saf. 2011;34:243-52. doi: 10.2165/11586600000000000-00000.Watkins P.B., Desai M., Berkowitz S.D., et al. Evaluation of drug-induced serious hepatotoxicity (eDISH): application of this data organization approach to phase III clinical trials of rivaroxaban after total hip or knee replacement surgery. Drug Saf. 2011;34:243-52. doi: 10.2165/11586600000000000-00000.Licata A., Puccia F., Lombardo V., et al. Rivaroxaban-induced hepatotoxicity: review of the literature and report of new cases. Eur J Gastroenterol Hepatol. 2018;30(2):226-232. doi: 10.1097/MEG.0000000000001030.Licata A., Puccia F., Lombardo V., et al. Rivaroxaban-induced hepatotoxicity: review of the literature and report of new cases. Eur J Gastroenterol Hepatol. 2018;30(2):226-232. doi: 10.1097/MEG.0000000000001030.Glenn K., Chen P., Musleh M., et al. A Rare Case of Rivaroxaban Causing Delayed Symptomatic Hepatocellular Injury and Hyperbilirubinemia. Case Rep Gastrointest Med. 2017;2017:5678187. doi: 10.1155/2017/5678187.Glenn K., Chen P., Musleh M., et al. A Rare Case of Rivaroxaban Causing Delayed Symptomatic Hepatocellular Injury and Hyperbilirubinemia. Case Rep Gastrointest Med. 2017;2017:5678187. doi: 10.1155/2017/5678187.Aslan A.N., Sari C., Baştuğ S., et al. Severe jaundice due to intrahepatic cholestasis after initiating anticoagulation with rivaroxaban. Blood Coagul Fibrinolysis. 2016;27(2):226-7. doi: 10.1097/MBC.0000000000000442.Aslan A.N., Sari C., Baştuğ S., et al. Severe jaundice due to intrahepatic cholestasis after initiating anticoagulation with rivaroxaban. Blood Coagul Fibrinolysis. 2016;27(2):226-7. doi: 10.1097/MBC.0000000000000442.Lee W.M., Larrey D., Olsson R., et al. Hepatic findings in long-term clinical trials of ximelagatran. Drug Saf. 2005; 28:351-70. doi: 10.1016/j.ijcard.2015.11.147.Lee W.M., Larrey D., Olsson R., et al. Hepatic findings in long-term clinical trials of ximelagatran. Drug Saf. 2005; 28:351-70. doi: 10.1016/j.ijcard.2015.11.147.Cordeanu M., Lambert A., Gaertner S., et al. Apixaban-induced hepatotoxicity. Int J Cardiol. 2016;1;204:4-5. doi: 10.1136/bcr-2016-216744.Cordeanu M., Lambert A., Gaertner S., et al. Apixaban-induced hepatotoxicity. Int J Cardiol. 2016;1;204:4-5. doi: 10.1136/bcr-2016-216744.Clarke S.A., Alsaad A.A., Mack A., et al. Apixaban-induced liver injury. BMJ Case Rep. 2016. doi: 10.1136/bcr-2016-216744.Clarke S.A., Alsaad A.A., Mack A., et al. Apixaban-induced liver injury. BMJ Case Rep. 2016. doi: 10.1136/bcr-2016-216744.Pradaxa.Summaryofproductcharacteristics.[citedbyAugust23,2018.Availablefrom:http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000829/WC500041059.pdf.Pradaxa.Summaryofproductcharacteristics.[citedbyAugust23,2018.Availablefrom:http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000829/WC500041059.pdf.Rochwerg B., Xenodemetropoulos T., Crowther M., et al. Dabigatran-induced acute hepatitis. Clin Appl Thromb Hemost. 2012;18(5):549-50. doi: 10.1177/1076029611435840.Rochwerg B., Xenodemetropoulos T., Crowther M., et al. Dabigatran-induced acute hepatitis. Clin Appl Thromb Hemost. 2012;18(5):549-50. doi: 10.1177/1076029611435840.Fulcrand J., Lerooy A., Giraud J., et al. le réseau des Centres régionaux de Pharmacovigilance. [Cytolysis in an elderly patient treated with dabigatran etexilate. Therapie. 2013 Sep-Oct;68(5):3324. doi: 10.2515/therapie/2013053.Fulcrand J., Lerooy A., Giraud J., et al. le réseau des Centres régionaux de Pharmacovigilance. [Cytolysis in an elderly patient treated with dabigatran etexilate. Therapie. 2013 Sep-Oct;68(5):3324. doi: 10.2515/therapie/2013053.Caldeira D., Barra M., Santos A.T., et al. Risk of drug-induced liver injury with the new oral anticoagulants: systematic review and meta-analysis. Heart. 2014;100 (7):550-6. doi: 10.2515/therapie/2013053.Caldeira D., Barra M., Santos A.T., et al. Risk of drug-induced liver injury with the new oral anticoagulants: systematic review and meta-analysis. Heart. 2014;100 (7):550-6. doi: 10.2515/therapie/2013053.Liakoni E., Rätz Bravo A.E., Krähenbühl S. Hepatotoxicity of New Oral Anticoagulants (NOACs). Drug Saf. 2015;38 (8):711-20. doi: 10.1136/heartjnl-2013-305288.Liakoni E., Rätz Bravo A.E., Krähenbühl S. Hepatotoxicity of New Oral Anticoagulants (NOACs). Drug Saf. 2015;38 (8):711-20. doi: 10.1136/heartjnl-2013-305288.Raschi E. Poluzzi E, Koci A, et al. Liver injury with novel oral anticoagulants: assessing post-marketing reports in the US Food and Drug Administration adverse event reporting system. Br J Clin Pharmacol. 2015;80(2):285-93. doi: 10.1111/bcp.12611.Raschi E. Poluzzi E, Koci A, et al. Liver injury with novel oral anticoagulants: assessing post-marketing reports in the US Food and Drug Administration adverse event reporting system. Br J Clin Pharmacol. 2015;80(2):285-93. doi: 10.1111/bcp.12611.

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