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Generic drugs: benefit/risk ratio

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The review discusses the interchangeability of medications, approaches to the registration of original and generic drugs, and types of their equivalence, as well as problems with generics in clinical practice. Results of pharmacoepidemiological studies, which have been widely carried out recently, speak of insufficient understanding of the impact of generics on remote outcomes of chronic diseases, including mortality. The longterm economic prospects of generic drug administration continue to remain unclear. Among the primary differences between generics and brandname drugs are the differences in active ingredient synthesis methods and the composition of adjuvants and additives. Comparative studies on the therapeutic equivalence of generics with their originals or between themselves are rarely conducted. They are often affected by methodological flaws, which cannot ensure their comparable efficacy and safety. In this regard, automatic replacement of drugs containing the same active ingredient should be avoided without the participation of the attending physician.

About the Authors

E. A. Ushkalova
Peoples' Friendship University of Russia (RUDN University)
Russian Federation

 6, Miklukho-Maklai St., Moscow 117198, Russia 

S. K. Zyryanov
Peoples' Friendship University of Russia (RUDN University) City Clinical Hospital Twenty-Four, Moscow Healthcare Department
Russian Federation

 6, Miklukho-Maklai St., Moscow 117198, Russia 

 10, Pistsovaya St., Moscow 127015, Russia 

I. A. Gopienko
Peoples' Friendship University of Russia (RUDN University)
Russian Federation

 6, Miklukho-Maklai St., Moscow 117198, Russia 


1. Straka RJ, Keohane DJ, Liu LZ. Potential Clinical and Economic Impact of Switching Branded Medications to Generics. Am J Ther. 2017 May;24(3):e278-e289. doi: 10.1097/MJT.0000000000000282

2. Atlas S. How to Reduce Prescription Drug Prices: First, Do No Harm. Mo Med. 2020 JanFeb;117(1):14-5.

3. Leclerc J, Blais C, Rochette L, et al Public Health Outcomes May Differ After Switching from Brand-Name to Generic Angiotensin II Receptor Blockers. Drugs R D. 2020 Jun;20(2): 135-45. doi: 10.1007/s40268-020-00307-2

4. Mishuk AU, Fasina I, Qian J. Impact of U.S. federal and state generic drug policies on drug use, spending, and patient outcomes: A systematic review. Res Social Adm Pharm. 2020 Jun;16(6):736-45. doi: 10.1016/j.sapharm.2019.08.031

5. Chaplenko AA, Vlasov VV, Gil'deyeva GN. Innovative drugs in the Russian pharmaceutical market: key players and main areas of development. Remedium. 2020;(10):4-9. doi: 10.21518/1561-5936-2020-10-4-9 (In Russ.).

6. Videau J-Y. Generic drugs: the hidden issues of quality and cost: general policy issues. WHO Drug Inform. 2000;14(2):77-81. Available from:

7. Закон от 12.04.2010 №61-ФЗ «Об обращении лекарственных средств». [Federal law of the Russian Federation of April 12, 2010 No. 61-FZ «About drug circulation» (In Russ.)].

8. WHO Technical Report Series, No. 937, 2006. Annex 7: Multisource (Generic) Pharmaceutical Products: Guidelines on Registration Requirements to Establish Interchangeability. Available from:

9. World Health Organization, 1996, WHO Expert Expert Committee on Specifications for Pharmaceutical Preparations: thirty-fourth report. WHO Technical Report Series No. 863. Geneva, 1996. P. 114-54.

10. Chow SC, Song F, Chen M. Some thoughts on drug interchangeability. J Biopharm Stat. 2016;26(1):178-86. doi: 10.1080/10543406.2015.1092027

11. Carbon M, Correll CU. Rational use of generic psychotropic drugs. CNS Drugs. 2013 May;27(5):353-65. doi: 10.1007/s40263-013-0045-2

12. Resolution of the Government of the Russian Federation of September 5, 2020 No. 1360 «About procedure for determining interchangeability of medicinal products for medical use» (In Russ.).

13. Niyazov RR, Rozhdestvenskiy DA, Vasiliev AN, et al. Regulatory aspects of marketing authorization of generic and hybrid medicinal products in the Eurasian Economic Union. Remedium. 2018;(7-8):6-19. doi: 10.21518/1561-5936-2018-7-8-6-19 (In Russ.).

14. Zyryanov SK, Fitilev SB, Shkrebneva II, Vozzhaev AV. Drug interchangeability: Clinical efficacy and safety. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2017;(S1):4-10. doi: 10.14412/2074-2711-2017-1S-4-10 (In Russ.).

15. Martinovich AA, Edelstein MV, Tzuman YuP, Kozlov RS. Comparative Quality of Parenteral Formulations of Azithromycin Original and Generic Products. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya = Clinical Microbiology and Antimicrobial Chemotherapy. 2011;13(4):335-45 (In Russ.).

16. Sokolov AV, Kukes VG, Buniatian ND, et al. Therapeutic equivalence, bioequivalence and interchangeability of medicinal products. Vrach. 2015;(10):32-5 (In Russ.).

17. Andre M, Canon JL, Levecque P, et al. Eosinophilia-myalgia syndrome associated with L-tryptophan. A case report with pulmonary manifestations and review of the literature. Acta Clin Belg. 1991;46(3):178-82. doi: 10.1080/17843286.1991.11718161

18. Varga J, Uitto J, Jimenez SA. The cause and pathogenesis of the eosinophilia-myalgia syndrome. Ann Intern Med. 1992 Jan 15;116(2):140-7. doi: 10.7326/0003-4819-116-2-140

19. Montpas N, Desormeaux A, Keire D, Adam A. Les reactions anaphylactoides associees a l'heparine d'origine chinoise [Anaphylactoid reactions associated with contaminated heparin from China]. Ann Pharm Fr. 2011 Sep;69(5):258-64. doi: 10.1016/j.pharma.2011.06.007 (In French)].

20. White CM. Understanding and Preventing (N-Nitrosodimethylamine) NDMA Contamination of Medications. Ann Pharmacother. 2020 Jun;54(6):611-4. doi: 10.1177/1060028019892222

21. Ray A, Atal S, Sadasivam B. Understanding the molecular-pharmaceutical basis of sartan recalls focusing on valsartan. Glob Cardiol Sci Pract. 2020 Nov 30;2020(2):e202025. doi: 10.21542/gcsp.2020.25

22. Angeli DG, Trezza C. Quality and stability of ramipril generics/copies versus reference ramipril (Tritace): a 3-month stability comparative study. Clin Drug Investig. 2009;29(10):667-76. doi: 10.2165/11315270-000000000-00000

23. Attorrese G, Massi-Benedetti M. Quality and behavior of glimepiride generics versus amaryl under stressed conditions. Diabetes Technol Ther. 2007 Jun;9(3):287-96. doi: 10.1089/dia.2006.0029

24. Gomez Y, Adams E, Hoogmartens J. Analysis of purity in 19 drug product tablets containing clopidogrel: 18 copies versus the original brand. J Pharm Biomed Anal. 2004 Feb 4;34(2):341-8. doi: 10.1016/S0731-7085(03)00533-8

25. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations, 38th ed. U. S. Food and Drug Administration; 2018. Available from:

26. Alcocer L. Quality of low-cost drugs: the frailty of costs savings. J Hypertens. 2018 Feb;36(2):230-3. doi: 10.1097/HJH.0000000000001579

27. Romodanovsky DP, Goryachev DV, Solovieva AP, Eremenko NN. Principles of statistical evaluation of bioequivalence studies in the context of current regulatory requirements and legal acts. Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo primeneniya = The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. 2018;8(2):92-8. doi: 10.30895/1991-2919-2018-8-2-92-98 (In Russ.).

28. National standard of Russian Federation GOST R 57679-2017 «Medicines for Medical applications. Investigation bioequivalence of medications» (In Russ.).

29. Romodanovsky DP. Relevant issues of planning bioequivalence studies of drugs with a narrow therapeutic range. Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo primeneniya = The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. 2020;10(3):201-10. doi: 10.30895/1991-2919-2020-10-3-201-210 (In Russ.).

30. Romodanovsky DP, Eremenkova TV, Dranitsyna MA, et al. Highly variable medicines – specific aspects of bioequivalence studies. Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo primeneniya = The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. 2015;(4):5-10 (In Russ.).

31. Kesselheim AS, Polinski JM, Fulchino LA, et al. Modified Regulatory Pathways to Approve Generic Drugs in the US and a Systematic Review of Their Outcomes. Drugs. 2015 Apr;75(6):633-50. doi: 10.1007/s40265-015-0382-1

32. Torshin IYu, Gromova OA, Sardaryan IS, et al. Comparative chemoreactome analysis of mexidol. Farmakokinetika i farmakodinamika = Pharmacokinetics and Pharmacodynamics. 2016;(4):19-30 (In Russ.).

33. Khubieva MYu, Yurgel NV, Ushkalova EA, et al. Problems of quality and therapeutic equivalence of generics. Zdravookhraneniye = Healthcare. 2010;(11):15-22 (In Russ.).

34. Holman A. Is Bioequivalence a Sufficient Measure of Equivalence? J Leg Med. 2019 JulSep;39(3):247-61. doi: 10.1080/01947648.2019.1653800

35. Desmarais JE, Beauclair L, Margolese HC. Switching from brand-name to generic psychotropic medications: a literature review. CNS Neurosci Ther. 2011 Dec;17(6):750-60. doi: 10.1111/j.1755-5949.2010.00210.x. Epub 2010 Nov 30.

36. Contin M, Alberghini L, Candela C, et al. Intrapatient variation in antiepileptic drug plasma concentration after generic substitution vs stable brand-name drug regimens. Epilepsy Res. 2016 May;122:79-83. doi: 10.1016/j.eplepsyres.2016.02.012

37. Ushkalova EA, Zyryanov SK, Zatolochina KE. Generic substitutions of antiepileptic drugs: Is it possible to put an end to the discussion? Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2018;10(1S):75-80. doi: 10.14412/2074-2711-2018-1S-75-80 (In Russ.).

38. Resolution of the meeting of the working group of the Russian Antiepileptic League. Epilepsiya i paroksizmal'nyye sostoyaniya = Epilepsy and Paroxysmal Conditions. 2016;8(4):109-11 (In Russ.).

39. Romodanovsky DP, Goryachev DV, Khokhlov AL, Miroshnikov AE. Influence of sex differences on pharmacokinetics of drugs within the framework of bioequivalence studies of generic medicinal products. Acta Biomedica Scientifica. 2018;3(5):94-105. doi: 10.29413/ABS.2018-3.5.15 (In Russ.).

40. Romodanovsky DP, Miroshnikov AE. Sex differences of pharmacokinetics of drugs within the framework of bioequivalence studies and their influence on consumers' risk. Meditsinskaya etika = Medical Ethics. 2018;7(2):35-9 (In Russ.).

41. Unterecker S, Proft F, Riederer P, et al. The comparison of brand-name and generic formulations of venlafaxine: a therapeutic drug monitoring analysis. Ther Drug Monit. 2014 Apr;36(2):269-72. doi: 10.1097/FTD.0000000000000008

42. Lima DM, dos Santos LD, Lima EM. Stability and in vitro release profile of enalapril maleate from different commercially available tablets: possible therapeutic implications. J Pharm Biomed Anal. 2008 Aug 5;47(4-5):934-7. doi: 10.1016/j.jpba.2008.02.030. Epub 2008 Mar 4.

43. Sicras-Mainar A, Sanchez-Alvarez L, Navarro-Artieda R, Darba J. Treatment persistence and adherence and their consequences on patient outcomes of generic versus brandname statins routinely used to treat high cholesterol levels in Spain: a retrospective costconsequences analysis. Lipids Health Dis. 2018 Dec 6;17(1):277. doi: 10.1186/s12944-018-0918-y

44. Mehdi MM, Solanki P, Singh P. Oxidative stress, antioxidants, hormesis and calorie restriction: The current perspective in the biology of aging. Arch Gerontol Geriatr. 2021 JulAug;95:104413. doi: 10.1016/j.archger.2021.104413

45. Neha K, Haider MR, Pathak A, Yar MS. Medicinal prospects of antioxidants: A review. Eur J Med Chem. 2019 Sep 15;178:687-704. doi: 10.1016/j.ejmech.2019.06.010

46. Меn'shikova ЕB, Zenkov N., Lankin VZ, et al. Okislitel'nyy stress: Patologicheskiye sostoyaniya I zabolevaniya [Oxidative stress: Pathological conditions and diseases]. Novosibirsk: ARTA; 2008 (In Russ.).

47. Skvortsova VI, Stakhovskaya LV, Nartsyssov YaR, et al. The randomized double-blind placebocontrolled study of efficacy and safety of mexidol in the complex therapy of ischemic stroke in the acute period. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2006;106(18):47-54 (In Russ.).

48. Stakhovskaya LV, Shamalov NA, Khasanova DR, et al. Results of a randomized double blind multicenter placebo-controlled, in parallel groups trial of the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (EPICA). Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2017;117(3):55-65. doi: 10.17116/jnevro20171173255-65 (In Russ.).

49. Stakhovskaya LV, Mkhitaryan EA, Tkacheva ON, et al. Efficacy and safety of mexidol across age groups in the acute and early recovery stages of hemispheric ischemic stroke (results of additional sub-analysis of a randomized double blind multicenter placebo-controlled study, in parallel groups trial EPICA). Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2020;120(8-2):49-57. doi: 10.17116/jnevro202012008249 (In Russ.).

50. Shchul'kin AV, Iakusheva EN, Chernykh IV. A comparative study of mexidol and ethylmethylhydroxypyridine succinate pharmacokinetic parameters. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2014;114(11-2):40-3 (In Russ.).

51. Nasrollahi S, Meera NK, Boregowda S. Pharmaceutical Excipient Exposure in a Neonatal Intensive Care Unit. Indian Pediatr. 2020 Sep 15;57(9):801-804.

For citation:

Ushkalova E.A., Zyryanov S.K., Gopienko I.A. Generic drugs: benefit/risk ratio. Neurology, Neuropsychiatry, Psychosomatics. 2021;13(6):98-104. (In Russ.)

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