rpcardioRational Pharmacotherapy in CardiologyРациональная Фармакотерапия в Кардиологии1819-64462225-3653«SILICEA-POLIGRAF» LLC10.20996/1819-6446-2024-3088FRSYFUrpcardio-3088Research ArticlePAGES OF RUSSIAN NATIONAL SOCIETY OF EVIDENCE-BASED PHARMACOTHERAPYСТРАНИЦЫ НАЦИОНАЛЬНОГО ОБЩЕСТВА ДОКАЗАТЕЛЬНОЙ ФАРМАКОТЕРАПИИOriginal drugs and generics: are there any differences from the clinician’s point of view?Оригинальные и воспроизведенные лекарственные препараты: есть ли различия с точки зрения клинициста?https://orcid.org/0000-0002-7717-4362МарцевичС. Ю.MartsevichS. Yu.

Марцевич Сергей Юрьевич.

Москва

Sergey Yu. Martsevich.

Moscow

sergeymartsevich@mail.ruhttps://orcid.org/0000-0001-6395-2584КутишенкоН. П.KutishenkoN. P.

Кутишенко Наталья Петровна - руководитель лаборатории фармакоэпидемиологических исследований отдела профилактической фармакотерапии.

Москва

Natalia P. Kutishenko.

Moscow

nkutishenko@gnicpm.ruhttps://orcid.org/0000-0002-4453-8430ДрапкинаО. М.DrapkinaO. M.

Драпкина Оксана Михайловна.

Москва

Oxana M. Drapkina.

Moscow

drapkina@bk.ruНациональный медицинский исследовательский центр терапии и профилактической медицины Минздрава РоссииРоссияNational Medical Research Center for Therapy and Preventive MedicineRussian Federation202426092024204433443Copyright © Martsevich S.Y., Kutishenko N.P., Drapkina O.M., 20242024Марцевич С.Ю., Кутишенко Н.П., Драпкина О.М.Martsevich S.Y., Kutishenko N.P., Drapkina O.M.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/3088

The article defines the original drug (OD) and examines the history of the appearance of generic drugs (GD), as well as the evolution of views to prove their bioequivalence to OD. The question is considered to what extent pharmacokinetic equivalence can guarantee the clinical equivalence of OD and GD. The data on the rules of registration of GD in different countries are provided. A brief overview of various types of studies comparing the clinical efficacy and safety of OD and GD (meta-analyses, randomized controlled trials, observational studies, description of clinical cases) and their main results is given. The results of a number of observational studies on the replacement of OD with GD and its consequences are presented. The existing system of current quality control of GD is described, numerous cases of recall of GD due to detected violations during their production are given. It is mentioned about individual cases of clinical inefficiency of GD and their side effects identified by the practical physicians. It is concluded that a qualitatively produced GD with proven pharmacokinetic equivalence to OD is able to provide therapy of the same quality as OD. However, numerous cases of the appearance of GD on the pharmaceutical market, which does not correspond to the quality of OD, make us somewhat wary of therapy based on VP. Both the practitioner and the patient should know which of the drugs prescribed by the international nonproprietary name is OD and which is GD.

В статье дается определение оригинального препарата (ОЛП) и рассматривается история появления воспроизведенных лекарственных препаратов (ВЛП), а также эволюция взглядов на доказательства их биоэквивалентности ОЛП. Рассматривается вопрос, насколько фармакокинетическая эквивалентность может гарантировать терапевтическую эквивалентность ОЛП и ВЛП, приводятся данные о правилах регистрации ВЛП в разных странах, дается краткий обзор различных видов исследований по сравнению клинической эффективности и безопасности ОЛП и ВЛП (метаанализы, рандомизированные контролируемые исследования, наблюдательные исследование, описание клинических случаев) и их основных результатов. Приводятся результаты ряда наблюдательных исследований по замене ОЛП на ВЛП и их последствиях. Описывается существующая система текущего контроля качества ВЛП, приводятся случаи отзыва ВЛП с рынка фармацевтических препаратов вследствие выявленных нарушений при их производстве, упоминается об отдельных случаях клинической неэффективности ВЛП и побочных действиях, выявленных практическими врачами. Делается вывод о том, что качественно произведенный ВЛП с доказанной фармакокинетической эквивалентностью ОЛП способен обеспечить терапию такого же качества, что и ОЛП. Однако случаи появления на фармацевтическом рынке ВЛП, несоответствующих по качеству ОЛП, заставляют с определенной настороженностью относиться к терапии, основанной на ВЛП. И практический врач, и пациент должны знать, какой из назначенных по международному непатентованному названию препаратов является ОЛП, а какой ВЛП.

оригинальные лекарственные препаратыдженерикифармацевтическая эквивалентностьбиоэквивалентностьтерапевтическая эквивалентностьэффективностьбезопасностьсистема регистрации дженериковoriginal drugsreproduced medicinesgenericspharmaceutical equivalencebioequivalencetherapeutic equivalenceeffectivenesssafety generic registration systemРабота выполнена при поддержке Национального медицинского исследовательского центра терапии и профилактической медицины Минздрава России.The study was performed with the support of National Medical Research Center for Therapy and Preventive Medicine of the Ministry of Healthсare of the Russian Federation.ReferencesMeredith PA. Potential concerns about generic substitution: bioequivalence versus therapeutic equivalence of different amlodipine salt forms. Curr Med Res Opin. 2009;25(9):2179-89. DOI:10.1185/03007990903116867.Meredith PA. Potential concerns about generic substitution: bioequivalence versus therapeutic equivalence of different amlodipine salt forms. Curr Med Res Opin. 2009;25(9):2179-89. DOI:10.1185/03007990903116867.Meyer GF. History and regulatory issues of generic drugs. Transplant Proc. 1999;31(3A Suppl):10S-12S. DOI:10.1016/s0041-1345(99)00105-0.Meyer GF. History and regulatory issues of generic drugs. Transplant Proc. 1999;31(3A Suppl):10S-12S. DOI:10.1016/s0041-1345(99)00105-0.Bingel U; Placebo Competence Team. Avoiding nocebo effects to optimize treatment outcome. JAMA. 2014;312(7):693-4. DOI:10.1001/jama.2014.8342.Bingel U; Placebo Competence Team. Avoiding nocebo effects to optimize treatment outcome. JAMA. 2014;312(7):693-4. DOI:10.1001/jama.2014.8342.Lindenbaum J, Mellow MH, Blackstone MO, Butler VP Jr. Variation in biologic availability of digoxin from four preparations. N Engl J Med. 1971;285(24):1344-7. DOI:10.1056/NEJM197112092852403.Lindenbaum J, Mellow MH, Blackstone MO, Butler VP Jr. Variation in biologic availability of digoxin from four preparations. N Engl J Med. 1971;285(24):1344-7. DOI:10.1056/NEJM197112092852403.Skelly JP, Knapp G. Biologic availability of digoxin tablets. JAMA. 1973;224(2):243.Skelly JP, Knapp G. Biologic availability of digoxin tablets. JAMA. 1973;224(2):243.Drug bioequivalence. Recommendations from the Drug Bioequivalence Study Panel to the Office of Technology Assessment, Congress of the United States. J Pharmacokinet Biopharm. 1974;2(5):433-66.Drug bioequivalence. Recommendations from the Drug Bioequivalence Study Panel to the Office of Technology Assessment, Congress of the United States. J Pharmacokinet Biopharm. 1974;2(5):433-66.Hogan GF. Repercussions of the Drug Price Competition and Patent Term Restoration Act of 1984. Am J Hosp Pharm. 1985;42(4):849-51.Hogan GF. Repercussions of the Drug Price Competition and Patent Term Restoration Act of 1984. Am J Hosp Pharm. 1985;42(4):849-51.Robertson A. The Future of Patent Protection for Post-FDA-Approved Generics: A Look at the Federal Circuit’s Incongruous Interpretations of the "Safe Harbor" Provision in 35 U.S.C. § 271(e)(1). Seton Hall Circuit Review. 2014;10(2):7.Robertson A. The Future of Patent Protection for Post-FDA-Approved Generics: A Look at the Federal Circuit’s Incongruous Interpretations of the "Safe Harbor" Provision in 35 U.S.C. § 271(e)(1). Seton Hall Circuit Review. 2014;10(2):7.Midha KK, McKay G. Bioequivalence; its history, practice, and future. AAPS J. 2009;11(4):66470. DOI:10.1208/s12248-009-9142-z.Midha KK, McKay G. Bioequivalence; its history, practice, and future. AAPS J. 2009;11(4):66470. DOI:10.1208/s12248-009-9142-z.Schall R, Endrenyi L. Bioequivalence: tried and tested. Cardiovasc J Afr. 2010;21(2):69-71.Schall R, Endrenyi L. Bioequivalence: tried and tested. Cardiovasc J Afr. 2010;21(2):69-71.Anderson S, Hauck WW. Consideration of individual bioequivalence. J Pharmacokinet Biopharm. 1990;18(3):259-73. DOI:10.1007/BF01062202.Anderson S, Hauck WW. Consideration of individual bioequivalence. J Pharmacokinet Biopharm. 1990;18(3):259-73. DOI:10.1007/BF01062202.Rheinstein PH. Therapeutic inequivalence. Drug Saf. 1990;5 Suppl 1:114-9. DOI:10.2165/00002018-199000051-00018.Rheinstein PH. Therapeutic inequivalence. Drug Saf. 1990;5 Suppl 1:114-9. DOI:10.2165/00002018-199000051-00018.Lever HM. A Physician’s Perspective on Generic Drug Quality. J Manag Care Spec Pharm. 2020;26(5):592-3. DOI:10.18553/jmcp.2020.26.5.592.Lever HM. A Physician’s Perspective on Generic Drug Quality. J Manag Care Spec Pharm. 2020;26(5):592-3. DOI:10.18553/jmcp.2020.26.5.592.Henwood SQ, de Villiers MM, Liebenberg W, Lötter AP. Solubility and dis­solution properties of generic rifampicin raw materials. Drug Dev Ind Pharm. 2000;26(4):403-8. DOI:10.1081/ddc-100101246.Henwood SQ, de Villiers MM, Liebenberg W, Lötter AP. Solubility and dis­solution properties of generic rifampicin raw materials. Drug Dev Ind Pharm. 2000;26(4):403-8. DOI:10.1081/ddc-100101246.Pruszydlo MG, Quinzler R, Kaltschmidt J, Haefeli WE. Medical problems and risks of switching drugs according to legal requirements of drug discount contracts in Germany. Dtsch Med Wochenschr. 2008;133(27):1423-8 (In German) [Pruszydlo MG, Quinzler R, Kaltschmidt J, Haefeli WE. Medizinische Probleme und Risiken bei der rabattvertragsgerechten Umstellung von Medikationen in Deutschland. Dtsch Med Wochenschr. 2008;133(27):1423-8]. DOI:10.1055/s-2008-1081094.Pruszydlo MG, Quinzler R, Kaltschmidt J, Haefeli WE. Medical problems and risks of switching drugs according to legal requirements of drug discount contracts in Germany. Dtsch Med Wochenschr. 2008;133(27):1423-8 (In German) [Pruszydlo MG, Quinzler R, Kaltschmidt J, Haefeli WE. Medizinische Probleme und Risiken bei der rabattvertragsgerechten Umstellung von Medikationen in Deutschland. Dtsch Med Wochenschr. 2008;133(27):1423-8]. DOI:10.1055/s-2008-1081094.Ревельский И. А. Способ сравнительной физиологической оценки фармацевтических субстанций и препаратов на их основе. Вестник Росздравнадзора 2009;(4):48-51.Revel’skiy IA. Way of comparative physiological assessment of pharmaceutical substances and preparations on their basis. Vestnik Roszdravnadzora. 2009;(4):48-51 (In Russ.)Ревельский А. И., Глазков И. Н., Яшин Ю. С. и др. Новый подход к сопоставлению оригинальных фармпрепаратов и дженериков, основанный на сравнении многомерных профилей примесей с использованием СФЭ, ЖЭ и хромато-масс-спектрометрии. Сверхкритические флюиды: теория и практика. 2011;6(4):51-9.Revelsky AI, Glazkov IN, Yashin YS, et al. A new approach to the comparison of original pharmaceuticals and generics, based on comparison of multi­dimensional impurity profiles using supercritical fluid extraction, liquid extraction and GC-MS. Sverhkriticheskie Flyuidy: Teoriya i Praktika. 2011;4:51-9 (In Russ.)Gozzo L, Caraci F, Drago F. Bioequivalence, Drugs with Narrow Therapeutic Index and The Phenomenon of Biocreep: A Critical Analysis of the System for Generic Substitution. Healthcare (Basel). 2022;10(8):1392. DOI:10.3390/healthcare10081392.Gozzo L, Caraci F, Drago F. Bioequivalence, Drugs with Narrow Therapeutic Index and The Phenomenon of Biocreep: A Critical Analysis of the System for Generic Substitution. Healthcare (Basel). 2022;10(8):1392. DOI:10.3390/healthcare10081392.Genis-Najera L, Sañudo-Maury ME, Moquete T. A Single-blind, Randomized, Single-dose, Two-sequence, Two-period, Crossover Study to Assess the Bioequivalence between Two Oral Tablet Formulations of Rivaroxaban 20 mg in Healthy Mexican Volunteers. Clin Pharmacol Drug Dev. 2022;11(7):826-31. DOI:10.1002/cpdd.1092.Genis-Najera L, Sañudo-Maury ME, Moquete T. A Single-blind, Randomized, Single-dose, Two-sequence, Two-period, Crossover Study to Assess the Bioequivalence between Two Oral Tablet Formulations of Rivaroxaban 20 mg in Healthy Mexican Volunteers. Clin Pharmacol Drug Dev. 2022;11(7):826-31. DOI:10.1002/cpdd.1092.Li X, Liu L, Xu B, et al. Bioequivalence and pharmacodynamics of a generic dabigatran etexilate capsule in healthy Chinese subjects under fasting and fed conditions. Pharmacol Res Perspect. 2020;8(2):e00593. DOI:10.1002/prp2.593.Li X, Liu L, Xu B, et al. Bioequivalence and pharmacodynamics of a generic dabigatran etexilate capsule in healthy Chinese subjects under fasting and fed conditions. Pharmacol Res Perspect. 2020;8(2):e00593. DOI:10.1002/prp2.593.Kesselheim AS, Misono AS, Lee JL, et al. Clinical equivalence of generic and brand-name drugs used in cardiovascular disease: a systematic review and meta-analysis. JAMA. 2008;300(21):2514-26. DOI:10.1001/jama.2008.758.Kesselheim AS, Misono AS, Lee JL, et al. Clinical equivalence of generic and brand-name drugs used in cardiovascular disease: a systematic review and meta-analysis. JAMA. 2008;300(21):2514-26. DOI:10.1001/jama.2008.758.Manzoli L, Flacco ME, Boccia S, et al. Generic versus brand-name drugs used in cardiovascular diseases. Eur J Epidemiol. 2016;31(4):351-68. DOI:10.1007/s10654-015-0104-8.Manzoli L, Flacco ME, Boccia S, et al. Generic versus brand-name drugs used in cardiovascular diseases. Eur J Epidemiol. 2016;31(4):351-68. DOI:10.1007/s10654-015-0104-8.Кутишенко Н. П., Марцевич С. Ю., Вашурина И. В. Что такое терапевтическая эквивалентность воспроизведенного препарата (дженерика) и как её доказать. Рациональная Фармакотерапия в Кардиологии. 2011;7(2):241-5. DOI:10.20996/1819-6446-2011-7-2-241-245.Kutishenko NP, Martsevich SYu, Vashurina IV. What is therapeutic equivalence of generic drug and how to prove it. Rational Pharmacotherapy in Cardiology. 2011;7(2):241-5 (In Russ.) DOI:10.20996/1819-6446-2011-7-2-241-245.Кутишенко Н. П., Марцевич С. Ю., Шальнова С. А. и др. Изучение клинической эквивалентности двух препаратов эналаприла у больных артериальной гипертонией. Российский кардиологический журнал. 2003;(5):68-71.Kutishenko NP, Martsevich SYu, Shalnova SA, et al. A study of clinic equivalence of two drug forms of enalapril in patients with arterial hypertension. Russian Journal of Cardiology. 2003;(5):68-71 (In Russ.)Кутишенко Н. П., Якусевич В. В., Деев А. Д. и др. Оценка терапевтической эквивалентности оригинального индапамида и индапамида — дженерика у больных артериальной гипертонией с помощью рандомизированого, перекрестного исследования. Рациональная фармакотерапия в кардиологии 2007;3(2):26-30.Kutishenko NP, Yakusevich VV, Deev AD, Martsevich SY. Assessment of therapeutical equivalency of original and generic indapamide in hypertensive patients by randomized cross-over study. Rational Pharmacotherapy in Cardiology. 2007;3(2):26-30 (In Russ.)Kakamad FH, Baqi DH, Hassan MN, et al. The clinical safety of generic and brand clopidogrel in patients undergoing carotid endarterectomy: a randomized controlled trial. Ann Med Surg (Lond). 2023;85(6):2708-13. DOI:10.1097/MS9.0000000000000827.Kakamad FH, Baqi DH, Hassan MN, et al. The clinical safety of generic and brand clopidogrel in patients undergoing carotid endarterectomy: a randomized controlled trial. Ann Med Surg (Lond). 2023;85(6):2708-13. DOI:10.1097/MS9.0000000000000827.Kharasch ED, Neiner A, Kraus K, et al. Bioequivalence and Therapeutic Equivalence of Generic and Brand Bupropion in Adults With Major Depression: A Randomized Clinical Trial. Clin Pharmacol Ther. 2019;105(5):1164-74. DOI:10.1002/cpt.1309.Kharasch ED, Neiner A, Kraus K, et al. Bioequivalence and Therapeutic Equivalence of Generic and Brand Bupropion in Adults With Major Depression: A Randomized Clinical Trial. Clin Pharmacol Ther. 2019;105(5):1164-74. DOI:10.1002/cpt.1309.Марцевич С. Ю., Кутишенко Н. П., Гинзбург М. Л. и др. Исследование КАРДИОКАНОН: способ решения вопроса о клинической эквивалентности оригинальных и воспроизведенных препаратов. Рациональная Фармакотерапия в Кардиологии. 2012;8(2):179-84. DOI:10.20996/1819-6446-2012-8-2-54-55.Martsevich SYu, Kutishenko NP, Ginzburg ML, et al. The KARDIOKANON study: a way to settle the subject of clinical equivalence of generic and original drugs. Rational Pharmacotherapy in Cardiology. 2012;8(2):179-184 (In Russ.) DOI:10.20996/1819-6446-2012-8-2-54-55.Марцевич С. Ю., Кутишенко Н. П., Лукина Ю. В., и др. Доказательная фармакотерапия в кардиологии. Нацио­нальное руководство. Рациональная Фармакотерапия в Кардиологии. 2024;20(1):105-70. DOI:10.20996/1819-6446-2024-2992.Martsevich SYu, Kutishenko NP, Lukina YuV, et al. Evidence-based pharmaco­therapy in cardiology. National guideline. Rational Pharmacotherapy in Cardiology. 2024;20(1):105-70 (In Russ.) DOI:10.20996/1819-6446-2024-2992.Chan CC, Tung YC, Lee KT, et al. Clinical outcomes of generic versus brand-name clopidogrel for secondary prevention in patients with acute myocardial infarction: A nationwide cohort study. Clin Transl Sci. 2023;16(9):1594-605. DOI:10.1111/cts.13590.Chan CC, Tung YC, Lee KT, et al. Clinical outcomes of generic versus brand-name clopidogrel for secondary prevention in patients with acute myocardial infarction: A nationwide cohort study. Clin Transl Sci. 2023;16(9):1594-605. DOI:10.1111/cts.13590.Huang T, Bai L, Wushouer H, et al. Clinical Outcome and Medical Cost of Origina­tor and Generic Antihypertensive Drugs: A Population-Based Study in Yinzhou, China. Front Pharmacol. 2022;13:757398. DOI:10.3389/fphar.2022.757398.Huang T, Bai L, Wushouer H, et al. Clinical Outcome and Medical Cost of Origina­tor and Generic Antihypertensive Drugs: A Population-Based Study in Yinzhou, China. Front Pharmacol. 2022;13:757398. DOI:10.3389/fphar.2022.757398.Desai RJ, Sarpatwari A, Dejene S, et al. Comparative effectiveness of generic and brand-name medication use: A database study of US health insurance claims. PLoS Med. 2019;16(3):e1002763. DOI:10.1371/journal.pmed.1002763.Desai RJ, Sarpatwari A, Dejene S, et al. Comparative effectiveness of generic and brand-name medication use: A database study of US health insurance claims. PLoS Med. 2019;16(3):e1002763. DOI:10.1371/journal.pmed.1002763.Tian Y, Reichardt B, Dunkler D, et al. Comparative effectiveness of branded vs. generic versions of antihypertensive, lipid-lowering and hypoglycemic substances: a population-wide cohort study. Sci Rep. 2020;10(1):5964. DOI:10.1038/s41598-020-62318-y.Tian Y, Reichardt B, Dunkler D, et al. Comparative effectiveness of branded vs. generic versions of antihypertensive, lipid-lowering and hypoglycemic substances: a population-wide cohort study. Sci Rep. 2020;10(1):5964. DOI:10.1038/s41598-020-62318-y.Wang H, Zhong G, Ji H, et al. Contrastive analysis on the safety of brand and generic nebivolol: a real-world pharmacovigilance study based on the FDA adverse event reporting system. Front Pharmacol. 2024;15:1280201. DOI:10.3389/fphar.2024.1280201.Wang H, Zhong G, Ji H, et al. Contrastive analysis on the safety of brand and generic nebivolol: a real-world pharmacovigilance study based on the FDA adverse event reporting system. Front Pharmacol. 2024;15:1280201. DOI:10.3389/fphar.2024.1280201.Alatawi Y, Rahman MM, Cheng N, et al. Brand vs generic adverse event repor­ting patterns: An authorized generic-controlled evaluation of cardiovascular medications. J Clin Pharm Ther. 2018;43(3):327-35. DOI:10.1111/jcpt.12646.Alatawi Y, Rahman MM, Cheng N, et al. Brand vs generic adverse event repor­ting patterns: An authorized generic-controlled evaluation of cardiovascular medications. J Clin Pharm Ther. 2018;43(3):327-35. DOI:10.1111/jcpt.12646.Faasse K, Cundy T, Gamble G, et al. The effect of an apparent change to a bran­ded or generic medication on drug effectiveness and side effects. Psychosom Med. 2013;75(1):90-6. DOI:10.1097/PSY.0b013e3182738826.Faasse K, Cundy T, Gamble G, et al. The effect of an apparent change to a bran­ded or generic medication on drug effectiveness and side effects. Psychosom Med. 2013;75(1):90-6. DOI:10.1097/PSY.0b013e3182738826.Lever HM. A Physician’s Perspective on Generic Drug Quality. J Manag Care Spec Pharm. 2020;26(5):592-3. DOI:10.18553/jmcp.2020.26.5.592.Lever HM. A Physician’s Perspective on Generic Drug Quality. J Manag Care Spec Pharm. 2020;26(5):592-3. DOI:10.18553/jmcp.2020.26.5.592.Romanelli RJ, Jukes T, Segal JB. Compliance after switching from branded to generic statins. Pharmacoepidemiol Drug Saf. 2014;23(10):1093-100. DOI:10.1002/pds.3630.Romanelli RJ, Jukes T, Segal JB. Compliance after switching from branded to generic statins. Pharmacoepidemiol Drug Saf. 2014;23(10):1093-100. DOI:10.1002/pds.3630.Rathe J, Søndergaard J, Jarbøl DE, et al. Patients’ concern about their medicine after a generic switch: a combined cross-sectional questionnaire and register study. Pharmacoepidemiol Drug Saf. 2014;23(9):965-73. DOI:10.1002/pds.3671.Rathe J, Søndergaard J, Jarbøl DE, et al. Patients’ concern about their medicine after a generic switch: a combined cross-sectional questionnaire and register study. Pharmacoepidemiol Drug Saf. 2014;23(9):965-73. DOI:10.1002/pds.3671.Tharavichitkun J, Yadee T, Angkaow P, Suansanae T. Evaluating Therapeutic Equivalence of Generic and Original Levetiracetam in Patients with Epilepsy: A Retrospective Study. Neurol Int. 2022;14(1):271-83. DOI:10.3390/neurolint14010022.Tharavichitkun J, Yadee T, Angkaow P, Suansanae T. Evaluating Therapeutic Equivalence of Generic and Original Levetiracetam in Patients with Epilepsy: A Retrospective Study. Neurol Int. 2022;14(1):271-83. DOI:10.3390/neurolint14010022.Desai RJ, Sarpatwari A, Dejene S, et al. Differences in rates of switchbacks after switching from branded to authorized generic and branded to generic drug products: cohort study. BMJ. 2018;361:k1180. DOI:10.1136/bmj.k1180.Desai RJ, Sarpatwari A, Dejene S, et al. Differences in rates of switchbacks after switching from branded to authorized generic and branded to generic drug products: cohort study. BMJ. 2018;361:k1180. DOI:10.1136/bmj.k1180.Wang CY, Pham PN, Kim S, et al. Predicting Cost-Effectiveness of Generic vs. Brand Dabigatran Using Pharmacometric Estimates Among Patients with Atrial Fibrillation in the United States. Clin Transl Sci. 2020;13(2):352-61. DOI:10.1111/cts.12719.Wang CY, Pham PN, Kim S, et al. Predicting Cost-Effectiveness of Generic vs. Brand Dabigatran Using Pharmacometric Estimates Among Patients with Atrial Fibrillation in the United States. Clin Transl Sci. 2020;13(2):352-61. DOI:10.1111/cts.12719.Духанин А. С. Актуальные вопросы клинической фармакологии амлодипина: предпочесть оригинальный или генерический препарат? КардиоСоматика. 2016;7(3-4):104-9.Dukhanin AS. Actual questions of clinical pharmacology by amlodipine: should we prefer the original or a generic drug? Cardiosomatics. 2016;7(3-4):104-9. (In Russ) [Духанин А. С. Актуальные вопросы клинической фармакологии амлодипина: предпочесть оригинальный или генерический препарат? КардиоСоматика. 2016;7(3-4):104-9].Okie S. Multinational medicines-ensuring drug quality in an era of global manufacturing. N Engl J Med. 2009;361(8):737-40. DOI:10.1056/NEJMp0903870.Okie S. Multinational medicines-ensuring drug quality in an era of global manufacturing. N Engl J Med. 2009;361(8):737-40. DOI:10.1056/NEJMp0903870.Mahase E. Europe suspends hundreds of generic drugs over serious data concerns. BMJ. 2023;383:2981. DOI:10.1136/bmj.p2981.Mahase E. Europe suspends hundreds of generic drugs over serious data concerns. BMJ. 2023;383:2981. DOI:10.1136/bmj.p2981.Лепахин В. К., Переверзев А. П., Романов Б. К. Cравнительная оценка количества сообщений о нежелательных реакциях на лекарственные средства. Безопасность и риск фармакотерапии. 2015;(1):30-6.Lepakhin VK, Pereverzev AP, Romanov BK. Comparative evaluation of infor­mation on adverse reactions to medicines. Safety and Risk of Pharmacotherapy. 2015;(1):30-6 (In Russ.)Kesselheim AS, Avorn J, Greene JA. Risk, responsibility, and generic drugs. N Engl J Med. 2012;367(18):1679-81. DOI:10.1056/NEJMp1208781.Kesselheim AS, Avorn J, Greene JA. Risk, responsibility, and generic drugs. N Engl J Med. 2012;367(18):1679-81. DOI:10.1056/NEJMp1208781.White CM. Generic Drugs Not as Safe as FDA Wants You to Believe. Ann Pharmacother. 2020;54(3):283-6. DOI:10.1177/1060028019881692.White CM. Generic Drugs Not as Safe as FDA Wants You to Believe. Ann Pharmacother. 2020;54(3):283-6. DOI:10.1177/1060028019881692.Eban K. Bottle of Lies: The Inside Story of the Generic Drug Boom. New York:HarperCollins Publishers; 2019.Eban K. Bottle of Lies: The Inside Story of the Generic Drug Boom. New York:HarperCollins Publishers; 2019.

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