Korean Journal of Clinical Pharmacy (한국임상약학회지)

Korean College Of Clinical Pharmacy (한국임상약학회)
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Systematic Review on Clinical Equivalence of Generic and Brand-name Drugs in Statin Therapy

Statin 계열 약물의 제네릭 및 브랜드 제품 간 임상 치료결과 비교를 위한 체계적 문헌 고찰

  • Received : 2017.04.10
  • Accepted : 2017.06.20
  • Published : 2017.06.30
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Abstract

Background: Generic medications are approved on the basis of bioequivalence with brand medications in healthy volunteers rather than the target population, there remains a substantial uncertainty regarding their clinical effectiveness and safety. The object of this paper is to compare the clinical equivalence of generic statin drugs in patients. Methods: Literature published before September 2016, which is indexed in PubMed, EMBASE, RISS, comparing generic to brand products in statins. Outcomes included blood lipid level, proportion of days covered (adherence), hospitalization and mortality. Results: 511 citations were screened, of which 11 studies met eligibility criteria (6 randomized clinical trials, 5 observational studies). Generic atorvastatin was clinical equivalent with brand drugs in blood lipid level (3 RCTs) and generic simvastatin was also clinical equivalent with brand drugs (2 RCTs). 2 of 3 studies reported no significant difference in proportion of days covered except 1 study which reported generic statin significantly enhance proportion of days covered (p<0.001). Hospitalization was no significant difference in all studies (p>0.05). 1 study reported that all cause of mortality was significantly low in generic drugs (p<0.0001). Conclusion: Published data on comparing clinical efficacy of generic and brand statins were insufficient in both quantity and quality. This systematic review suggests that additional studies on clinical equivalence and safety of generic medications in patients would be needed.

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References

  1. OECD. Pharmaceutical spending 2017. Available from https://data.oecd.org/healthres/pharmaceutical-spending.htm. Accessed March 2, 2017.
  2. Simoens, S. Sustaining generic medicines markets in europe. Research Centre for Pharmaceutical Care and Pharmaco-economics 2006.
  3. Generic Pharmaceutical Assoociation. The 2015 generic drug savings in the U.S. Report 2015 seventh annual edition: 2015.
  4. Canadian generic pharmaceutical association. The value of generic prescription medicines. 2016. Available from http://canadiangenerics.ca/resources/reports-submissions/ Accessed April 3, 2017.
  5. FDA. Facts about generic drugs. 2016. Available from http://www.fda.gov/Drugs/Resources For You/Consumers/Buying Using Medicine Safely/Understanding Generic Drugs/ucm167991.htm. Accessed October 27, 2016.
  6. Ministry of food and drug safety. Guideline for bioequivalence studies of generic products. 2016. Available from http://www.mfds.go.kr/ index.do?mid=1161&seq=11145&cmd=v. Accessed September 18, 2016.
  7. FDA. Review of therapeutic equivalence generic bupropion xl 300 mg and wellbutrinxl 300 mg 2013. Available from https://www.fda.gov/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/ucm153270.htm. Accessed March 30, 2017.
  8. FDA. Methylphenidate hydrochloride extended release tablets (generic concerta) made by mallinckrodt and kudco 2016. Available from https://www.fda.gov/Drugs/DrugSafety/ucm422568.htm. Accessed March 30, 2017.
  9. Dunne, S. S. and Dunne, C. P. What do people really think of generic medicines? A systematic review and critical appraisal of literature on stakeholder perceptions of generic drugs. BMC Med 2015;13:173. https://doi.org/10.1186/s12916-015-0415-3
  10. Wilner, A. N. Therapeutic equivalency of generic antiepileptic drugs: Results of a survey. Epilepsy & behavior : E&B 2004;5:995-8 https://doi.org/10.1016/j.yebeh.2004.05.011
  11. Chong, C. P., Hassali, M. A., Bahari, M. B. and Shafie, A. A. Exploring community pharmacists' views on generic medicines: A nationwide study from malaysia. Int Journal Clin phar2011;33:124-31. https://doi.org/10.1007/s11096-010-9470-1
  12. HIRA. Disease statistics by korea informative classification of disease (2017) Available from http://opendata.hira.or.kr/op/opc/olap4thDsInfo.do. Accessed March 3, 2017.
  13. Pharmscore. Hyperlipidemia medicine markets are close to 100biliion won. Available from http://www.pharmscore.com/news/articleView. html?idxno=607. Accessed April 1, 2017.
  14. Kesselheim, A. S., Misono, A. S., Lee, J. L., Stedman, M. R., Brookhart, M. A., Choudhry, N. K., et al. Clinical equivalence of generic and brandname drugs used in cardiovascular disease: A systematic review and meta-analysis. JAMA 2008;300:2514-26. https://doi.org/10.1001/jama.2008.758
  15. Higgins, J. P., Altman, D. G., Gotzsche, P. C., Juni, P., Moher, D., Oxman, A. D., et al. The cochrane collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928. https://doi.org/10.1136/bmj.d5928
  16. Sterne, J. A., Hernan, M. A., Reeves, B. C., Savovic, J., Berkman, N. D., Viswanathan, M., et al. Robins-i: A tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919
  17. Assawawitoontip, S. and Wiwanitkit, V. A randomized crossover study to evaluate ldl-cholesterol lowering effect of a generic product of simvastatin (unison company) compared to simvastatin ($zocor^{TM}$) in hypercholesterolemic subjects. J Med Associ Thailand 2002;85:S118-4.
  18. Solangi, N. A., Ahmed, S. P. and Soomro, K. Cholesterol, triglycerides and ldl lowering effects of generic products of simvastatin and hdl effect as compared to original brand of simvastatin in hypercholesterolemic subjects - a randomized study. Medical Channel 2012;18:41-4
  19. Wiwanitkit, V., Wangsaturaka, D. and Tangphao, O. Ldl-cholesterol lowering effect of a generic product of simvastatin compared to simvastatin ($zocor^{TM}$) in thai hypercholesterolemic subjects - a randomized crossover study, the first report from thailand. BMC Clinical Pharmacology. 2002;2.
  20. Boh, M., Opolski, G., Poredos, P., Ceska, R. and Jezovnik, M. Therapeutic equivalence of the generic and the reference atorvastatin in patients with increased coronary risk. International angiology : a journal of the International Union of Angiology 2011;30:366-4
  21. Kim, S. H., Park, K., Hong, S. J., Cho, Y. S., Sung, J. D., Moon, G. W., et al. Efficacy and tolerability of a generic and a branded formulation of atorvastatin 20 mg/d in hypercholesterolemic korean adults at high risk for cardiovascular disease: A multicenter, prospective, randomized, double-blind, double-dummy clinical trial. Clinical Therapeutics 2010;32:1896-905. https://doi.org/10.1016/j.clinthera.2010.10.004
  22. Kim, S. H., Seo, M. K., Yoon, M. H., Choi, D. H., Hong, T. J. and Kim, H. S. Assessment of the efficacy and tolerability of 2 formulations of atorvastatin in korean adults with hypercholesterolemia: A multicenter, prospective, open-label, randomized trial. Clinical Therapeutics 2013;35:77-86. https://doi.org/10.1016/j.clinthera.2012.11.009
  23. Jackevicius, C. A., Tu, J. V., Krumholz, H. M., Austin, P. C., Ross, J. S., Stukel, T. A., et al. Comparative effectiveness of generic atorvastatin and lipitor in patients hospitalized with an acute coronary syndrome. J Am Heart Assoc 2016;5:e003350. https://doi.org/10.1161/JAHA.116.003350
  24. Gagne, J. J., Choudhry, N. K., Kesselheim, A. S., Polinski, J. M., Hutchins, D., Matlin, O. S., et al. Comparative effectiveness of generic and brand-name statins on patient outcomes: A cohort study. Ann Intern Med 2014;161:400-407. https://doi.org/10.7326/M13-2942
  25. O'Brien, E. C., McCoy, L. A., Thomas, L., Peterson, E. D. and Wang, T. Y. Patient adherence to generic versus brand statin therapy after acute myocardial infarction: Insights from the can rapid stratification of unstable angina patients suppress adverse outcomes with early implementation of the american college of cardiology/american heart association guidelines registry. American Heart Journal 2015;170:55-61. https://doi.org/10.1016/j.ahj.2015.04.011
  26. Colombo, G. L., Agabiti-Rosei, E., Margonato, A., Mencacci, C., Montecucco, C. M. and Trevisan, R. Off-patent generic medicines vs. Offpatent brand medicines for six reference drugs: A retrospective claims data study from five local healthcare units in the lombardy region of italy. PLoS One 2013;8:e82990. https://doi.org/10.1371/journal.pone.0082990
  27. Mano, Y., Fukushima, S., Kuroda, H., Ohshima, H., Kato, Y., Ohuchi, K., et al. Adherence to changing from brand-name to generic atorvastatin in newly treated patients: A retrospective cohort study using health insurance claims. J Pharm Health Care Sci 2015;1:12. https://doi.org/10.1186/s40780-015-0013-8
  28. Cameron, A., Mantel-Teeuwisse, A. K., Leufkens, H. G. and Laing, R. O. Switching from originator brand medicines to generic equivalents in selected developing countries: How much could be saved? Value in Health 2012;15:664-73. https://doi.org/10.1016/j.jval.2012.04.004
  29. Kwon, H. Y. and Yang, B. M. Do generics really create savings on drug expenditures? Korean J Health EconPol 2011;17:23-42.
  30. Kwon, H. Y. and Godman, B. Do newly marketed generic medicines expand markets using descriptive time series analysis and mixed logit models? Korea as an exemplar and its implications. BMC Health Serv Res 2016;16:130. https://doi.org/10.1186/s12913-016-1356-z
  31. Kim, D. S., Bae, S. J. and Jang, S. M. Lessons from generic promotion policies in other countries. Health Policy and Management 2013;23: 210-23. https://doi.org/10.4332/KJHPA.2013.23.3.210
  32. Duncan, D. Generic prescribing and substitution: The big issues. Brit J com nursing 2010;15:248-9. https://doi.org/10.12968/bjcn.2010.15.5.47951