Withdrawn medicines included in the essential medicines lists of 136 countries

Autoři: Onella Charles aff001;  Igho Onakpoya aff002;  Simran Benipal aff001;  Hannah Woods aff001;  Anjli Bali aff001;  Jeffrey K. Aronson aff002;  Carl Heneghan aff002;  Nav Persaud aff001
Působiště autorů: MAP Centre for Urban Health Solutions, St. Michael’s Hospital, Toronto, Canada aff001;  Centre for Evidence-Based Medicine, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom aff002;  Department of Family and Community Medicine, St. Michael’s Hospital, Toronto, Ontario aff003
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0225429



Essential medicines lists and related policies are intended to meet the priority health needs of populations and their implementation is associated with more appropriate use of medicines. The World Health Organization (WHO) recommends that countries carefully select the medicines to be included in their national essential medicines lists. Lists that are used to prioritize access to important treatments should not include medicines that have been withdrawn elsewhere because of an unfavourable benefit-to-harm balance; however, countries still list and use medicines that have been withdrawn worldwide. The objective of this study was to determine whether the national essential medicines lists of 137 countries include medicines that have been withdrawn in other countries.

Methods and findings

We performed an audit of national essential medicines lists for medicines that had been withdrawn. Medicines withdrawn from worldwide markets between 1953 and 2014 were identified using a systematic review of published literature and regulatory documents. The reviewers used sources including the WHO’s database of drugs, PubMed, and the websites of regulatory agencies to obtain information regarding adverse effects associated with the medicines, the year of first withdrawal, markets of withdrawal, and the level of evidence supporting each withdrawal. We recorded the number of countries with a withdrawn medicine included in their national medicines list, the number of withdrawn medicines included in each nation’s list, and the number of national essential medicines including each withdrawn medicine. 97 medicines were withdrawn in at least one country but still included in one more national essential medicines list. Of 137 countries with a national essential medicines list, 136 lists included at least one withdrawn medicine, with 54% of the lists containing 5 or fewer withdrawn medicines, and 27% including 10 or more withdrawn medicines. 11 medicines were withdrawn worldwide but still included on at least one national essential medicines list. Countries with longer essential medicines lists had more withdrawn medicines included in their lists.


This study found that withdrawn medicines are included in all but one national essential medicines list, representing a need for more stringent processes for selecting and removing medicines on these lists. Countries may wish to apply special scrutiny to medicines withdrawn in other nations when selecting medicines to include on their lists.

Klíčová slova:

Adverse reactions – Cardiology – Database searching – Drugs – Europe – Global health – Marketing – Systematic reviews


1. Wirtz VJ, Hogerzeil HV, Gray AL, Bigdeli M, de Joncheere CP, Ewen MA, et al. Essential medicines for universal health coverage. Lancet (London, England). 2017;389(10067):403–76. Epub 2016/11/12. doi: 10.1016/s0140-6736(16)31599-9 27832874.

2. Persaud N, Ahmad H. Canadian list of essential medications: Potential and uncertainties. Canadian family physician Medecin de famille canadien. 2017;63(4):266–8. Epub 2017/04/14. 28404694

3. Holloway KA, Henry D. WHO Essential Medicines Policies and Use in Developing and Transitional Countries: An Analysis of Reported Policy Implementation and Medicines Use Surveys. PLOS Medicine. 2014;11(9):e1001724. doi: 10.1371/journal.pmed.1001724 25226527

4. Holloway KA, Rosella L, Henry D. The Impact of WHO Essential Medicines Policies on Inappropriate Use of Antibiotics. PLOS ONE. 2016;11(3):e0152020. doi: 10.1371/journal.pone.0152020 27002977

5. World Health Organization. Essential medicines selection—national medicines list/formulary/standard treatement guidelines: World Health Organization; c2018 [cited 2018 July 20]. http://www.who.int/selection_medicines/country_lists/en/#B.

6. Onakpoya IJ, Heneghan CJ, Aronson JK. Delays in the post-marketing withdrawal of drugs to which deaths have been attributed: a systematic investigation and analysis. BMC Med. 2015;13:26. Epub 2015/02/06. doi: 10.1186/s12916-014-0262-7 25651859

7. Topol EJ. Failing the public health—rofecoxib, Merck, and the FDA. The New England journal of medicine. 2004;351(17):1707–9. Epub 2004/10/08. doi: 10.1056/NEJMp048286 15470193.

8. Vaithianathan R, Hockey PM, Moore TJ, Bates DW. Iatrogenic effects of COX-2 inhibitors in the US population: findings from the Medical Expenditure Panel Survey. Drug safety. 2009;32(4):335–43. Epub 2009/04/25. doi: 10.2165/00002018-200932040-00007 19388724.

9. Friedman MA, Woodcock J, Lumpkin MM, Shuren JE, Hass AE, Thompson LJ. The safety of newly approved medicines: do recent market removals mean there is a problem? Jama. 1999;281(18):1728–34. Epub 1999/05/18. doi: 10.1001/jama.281.18.1728 10328074.

10. Onakpoya IJ, Heneghan CJ, Aronson JK. Post-marketing withdrawal of 462 medicinal products because of adverse drug reactions: a systematic review of the world literature. BMC medicine. 2016;14:10-. doi: 10.1186/s12916-016-0553-2 26843061.

11. Centre for Evidence-Based Medicine. OCEBM Levels of Evidence Centre for Evidence-Based Medicine, University of Oxford2016 [updated May 1, 2016; cited 2018 November 28]. https://www.cebm.net/2016/05/ocebm-levels-of-evidence/.

12. Aronson JK, Ferner RE. Clarification of terminology in drug safety. Drug safety. 2005;28(10):851–70. Epub 2005/09/27. doi: 10.2165/00002018-200528100-00003 16180936.

13. Persaud N, Jiang M, Shaikh R, Bali A, Oronsaye E, Woods H, et al. Similarities and Differences in Essential Medicines Lists of 137 Countries: a quantitative analysis. Bulletin of the World Health Organization 2019;Accepted for publication.

14. Nations United. Consolidated List of Products—Whose Consumption and/or Sale Have Been Banned, Withdrawn, Severly Restricted or Not Approved by Governments. Pharmaceuticals—Economic & Social Affairs. 2005;(12th):1–598.

15. Nations United. Consolidated List of Products—Whose Consumption and/or Sale Have Been Banned, Withdrawn, Severely Restricted or not Approved by Governments. Pharmaceuticals—Economic & Social Affairs. 2008;(14).

16. Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, et al. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic acids research. 2018;46(D1):D1074–d82. Epub 2017/11/11. doi: 10.1093/nar/gkx1037 29126136

17. WHO Collaborating Centre for Drug Statistics Methodology. ATC/DDD Index 2018: Norwegian Institute of Public Health; 2018 [updated December 20, 2017; cited 2018 May 14]. https://www.whocc.no/atc_ddd_index/.

18. Juni P, Nartey L, Reichenbach S, Sterchi R, Dieppe PA, Egger M. Risk of cardiovascular events and rofecoxib: cumulative meta-analysis. Lancet (London, England). 2004;364(9450):2021–9. Epub 2004/12/08. doi: 10.1016/s0140-6736(04)17514-4 15582059.

19. Sibbald B. Rofecoxib (Vioxx) voluntarily withdrawn from the market. CMAJ. 2004;171(9):1027–8. doi: 10.1503/cmaj.1041606 15505253

20. Lee KH, Kim GJ, Kim JH. Correlation between Drug Market Withdrawals and Socioeconomic, Health, and Welfare Indicators Worldwide. Journal of Korean medical science. 2015;30(11):1567–76. Epub 2015/11/06. doi: 10.3346/jkms.2015.30.11.1567 26538999

21. Ninan B, Wertheimer AI. Withdrawing Drugs in the U.S. Versus Other Countries. Innovations in Pharmacy. 2012;3(3):1–13.

22. Mahmic-Kaknjo M, Jelicic-Kadic A, Utrobicic A, Chan K, Bero L, Marusic A. Essential medicines availability is still suboptimal in many countries: a scoping review. Journal of clinical epidemiology. 2018;98:41–52. Epub 2018/02/17. doi: 10.1016/j.jclinepi.2018.02.006 29452222.

23. Den Norske Legeforening. Diclofenac 2006 [cited 2019]. https://legeforeningen.no/Fagmed/Norsk-revmatologisk-forening/Pasientinformasjon/pasientinformasjon-om-legemidler/diclofenac-tbl/.

24. McGettigan P, Henry D. Use of Non-Steroidal Anti-Inflammatory Drugs That Elevate Cardiovascular Risk: An Examination of Sales and Essential Medicines Lists in Low-, Middle-, and High-Income Countries. PLOS Medicine. 2013;10(2):e1001388. doi: 10.1371/journal.pmed.1001388 23424288

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2019 Číslo 12
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