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open access

Vol 29, No 1 (2022)
Review Article
Submitted: 2020-09-02
Accepted: 2020-11-20
Published online: 2020-12-01
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The plague of unexpected drug recalls and the pandemic of falsified medications in cardiovascular medicine as a threat to patient safety and global public health: A brief review

Damian Świeczkowski1, Szymon Zdanowski2, Piotr Merks34, Łukasz Szarpak56, Régis Vaillancourt7, Milosz J. Jaguszewski1
DOI: 10.5603/CJ.a2020.0168
·
Pubmed: 33346374
·
Cardiol J 2022;29(1):133-139.
Affiliations
  1. First Department of Cardiology, Medical University of Gdansk, Poland
  2. Department of Anesthesiology and Intensive Therapy, Medical University of Gdansk, Poland
  3. Medical Department, Cardinal Stefan Wyszynski University in Warsaw, Poland
  4. Department of Pharmaceutical Technology, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Poland
  5. Bialystok Oncology Center, Bialystok, Poland
  6. Maria Sklodowska-Curie Medical Academy, Warsaw, Poland
  7. Children’s Hospital of Eastern Ontario, Ottawa, Canada

open access

Vol 29, No 1 (2022)
Review articles — Clinical cardiology
Submitted: 2020-09-02
Accepted: 2020-11-20
Published online: 2020-12-01

Abstract

Valsartan, losartan, and irbesartan, are widely used in the treatment strategies of cardiovascular medicine diseases, including hypertension and heart failure. Recently, many formulations for the aforementioned diseases contained active pharmaceutical ingredients and had been abruptly recalled from the market due to safety concerns mainly associated with unwanted impurities — nitrosamines, which are highly carcinogenic substances accidentally produced during manufacturing. Along with cardiovascular medications, formulations containing ranitidine were also recalled from the market. This poses a particular threat to public health due to the non-prescription status of these drugs. Regulatory authorities, including the Food and Drug Administration and European Medicines Agency among others, have taken action to minimize patient risk and improve the manufacturing quality as well as re-checking current guidelines and recommendations. While these steps are necessary to avoid further recalls, authorities should remember the growing concerns of patients regarding the safety and efficacy of pharmacotherapy. Apart from the genuine manufacturing mistakes mentioned above, falsified and counterfeit medications should be at the heart of global attention. The lack of a well-accepted definition of falsified/counterfeit medications has impeded political and scientific efforts to mitigate risk of this phenomenon. Falsified Medicines Directive should be considered the most pivotal legislation recently enacted to harmonize international cooperation. In summary, one should remember that only international and direct collaboration between patients, stakeholders, and authorities be considered a remedy for a pandemic of falsified medicines and plague of unexpected recalls due to safety concerns.

Abstract

Valsartan, losartan, and irbesartan, are widely used in the treatment strategies of cardiovascular medicine diseases, including hypertension and heart failure. Recently, many formulations for the aforementioned diseases contained active pharmaceutical ingredients and had been abruptly recalled from the market due to safety concerns mainly associated with unwanted impurities — nitrosamines, which are highly carcinogenic substances accidentally produced during manufacturing. Along with cardiovascular medications, formulations containing ranitidine were also recalled from the market. This poses a particular threat to public health due to the non-prescription status of these drugs. Regulatory authorities, including the Food and Drug Administration and European Medicines Agency among others, have taken action to minimize patient risk and improve the manufacturing quality as well as re-checking current guidelines and recommendations. While these steps are necessary to avoid further recalls, authorities should remember the growing concerns of patients regarding the safety and efficacy of pharmacotherapy. Apart from the genuine manufacturing mistakes mentioned above, falsified and counterfeit medications should be at the heart of global attention. The lack of a well-accepted definition of falsified/counterfeit medications has impeded political and scientific efforts to mitigate risk of this phenomenon. Falsified Medicines Directive should be considered the most pivotal legislation recently enacted to harmonize international cooperation. In summary, one should remember that only international and direct collaboration between patients, stakeholders, and authorities be considered a remedy for a pandemic of falsified medicines and plague of unexpected recalls due to safety concerns.

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Keywords

drug recalls, counterfeit drugs, pharmacovigilance, public health, angiotensin II type 1 receptor blockers

About this article
Title

The plague of unexpected drug recalls and the pandemic of falsified medications in cardiovascular medicine as a threat to patient safety and global public health: A brief review

Journal

Cardiology Journal

Issue

Vol 29, No 1 (2022)

Article type

Review Article

Pages

133-139

Published online

2020-12-01

Page views

6586

Article views/downloads

1573

DOI

10.5603/CJ.a2020.0168

Pubmed

33346374

Bibliographic record

Cardiol J 2022;29(1):133-139.

Keywords

drug recalls
counterfeit drugs
pharmacovigilance
public health
angiotensin II type 1 receptor blockers

Authors

Damian Świeczkowski
Szymon Zdanowski
Piotr Merks
Łukasz Szarpak
Régis Vaillancourt
Milosz J. Jaguszewski

References (54)
  1. Mogielnicki M, Swieczkowski D, Bachorski W, et al. The Food and Drug Administration (FDA) and the European Medicines Agency (EMA) perspective on cardiovascular Polypill: A multidimensional concept. Cardiol J. 2016; 23(5): 515–517.
    CrossRefPubMed
  2. ISPE. 2013. Report on the ISPE Drug Shortages Survey. http://ispe.org/ (Accessed 2 April 2020).
  3. Vaida AJ. Drug shortages: A patient safety crisis that affects everyone. http://www.npsf.org/ (Accessed 2 April 2020).
  4. Ornes L, Hendrix TJ. Prescription drug re-importation: a balanced look. J Gerontol Nurs. 2006; 32(8): 15–19.
    CrossRefPubMed
  5. Mantovani A, Naghavi A. Parallel imports and innovation in an emerging economy: the case of Indian pharmaceuticals. Health Econ. 2012; 21(11): 1286–1299.
    CrossRefPubMed
  6. Bhosle MJ, Balkrishnan R. Drug reimportation practices in the United States. Ther Clin Risk Manag. 2007; 3(1): 41–46.
    CrossRefPubMed
  7. Price R. EU: Falsified Medicines Directive 'Delegated Act' accepted by European Parliament. Eur J Hosp Pharm. 2016; 23(3): 183–186.
    CrossRefPubMed
  8. Borup R, Traulsen J. Falsified medicines-bridging the gap between business and public health. Pharmacy (Basel). 2016; 4(2): 16.
    CrossRefPubMed
  9. Sessler DI, Imrey PB. Clinical research methodology 3: randomized controlled trials. Anesth Analg. 2015; 121(4): 1052–1064.
    CrossRefPubMed
  10. Bhagat S, Kapatkar V, Katare S, et al. Potential risks and mitigation strategies during the conduct of a clinical trial: an industry perspective. Rev Recent Clin Trials. 2018; 13(1): 52–60.
    CrossRefPubMed
  11. Gavrielov-Yusim N, Bidollari I, Kaplan S, et al. Challenges of post-authorization safety studies: Lessons learned and results of a French study of fentanyl buccal tablet. Pharmacoepidemiol Drug Saf. 2018; 27(5): 457–463.
    CrossRefPubMed
  12. Mogielnicki M, Swieczkowski D, Bachorski W, et al. The Food and Drug Administration (FDA) and the European Medicines Agency (EMA) perspective on cardiovascular Polypill: A multidimensional concept. Cardiol J. 2016; 23(5): 515–517.
    CrossRefPubMed
  13. Nagaich U, Sadhna D. Drug recall: An incubus for pharmaceutical companies and most serious drug recall of history. Int J Pharm Investig. 2015; 5(1): 13–19.
    CrossRefPubMed
  14. Willborn RJ. Pharmacy's influence and opportunity in public health. Am J Health Syst Pharm. 2016; 73(12): 868–871.
    CrossRefPubMed
  15. Moorhead SA, Hazlett DE, Harrison L, et al. A new dimension of health care: systematic review of the uses, benefits, and limitations of social media for health communication. J Med Internet Res. 2013; 15(4): e85.
    CrossRefPubMed
  16. Working Definitions Document approved by the Seventieth World Health Assembly. https://www.who.int/medicines/regulation/ssffc/definitions/en/ (Accessed 2 April 2020).
  17. World Health Organization. WHO Global Surveillance and Monitoring System for substandard and falsified medical products. 2017, WHO, Geneva, Switzerland.
  18. Krumholz HM, Ross JS, Presler AH, et al. What have we learnt from Vioxx? BMJ. 2007; 334(7585): 120–123.
    CrossRefPubMed
  19. World Health Organization (WHO). Counterfeit Drugs: Guidelines for the Development of Measures to Combat Counterfeit Drugs. 2009;15-17. Geneva, Switzerland.
  20. Seiter A. Health and economic consequences of counterfeit drugs. Clin Pharmacol Ther. 2009; 85(6): 576–578.
    CrossRefPubMed
  21. Mackey T, Liang B. The global counterfeit drug trade: Patient safety and public health risks. J Pharmaceutical Scien. 2011; 100(11): 4571–4579.
    CrossRef
  22. Borup R, Kaae S, Minssen T, et al. Fighting falsified medicines with paperwork - a historic review of Danish legislation governing distribution of medicines. J Pharm Policy Pract. 2016; 9: 30.
    CrossRefPubMed
  23. Kagan R. Editor's Introduction: Understanding Regulatory Enforcement. Law Policy. 1989; 11(2): 89–119.
    CrossRef
  24. Bogaert PBC. The mysteries of the Falsified Medicines Directive- where is the logic on safety features? Script Regulatory Affairs, London 2015: 1–3.
  25. Howell EH, Cameron SJ. Neprilysin inhibition: A brief review of past pharmacological strategies for heart failure treatment and future directions. Cardiol J. 2016; 23(6): 591–598.
    CrossRefPubMed
  26. Jankowski P, Czarnecka D, Wolfshaut-Wolak R, et al. Secondary prevention of coronary artery disease in contemporary clinical practice. Cardiol J. 2015; 22(2): 219–226.
    CrossRefPubMed
  27. MHRA. Drug alert. Class 2 medicines recall (action within 48 hours): Counterfeit product: Lipitor Tablets 20mg. EL(05)A/11. www.mhra.gov.uk/home/idcplg?IdcService= GET_FILE&dID=12253&noSaveAs=0& (Accessed 2 April 2020).
  28. MHRA. Class 1 drug alert (action now – including out of hours): Counterfeit parallel distributed product – Waymade plc – Plavix tablets 75mg film coated tablets (clopidogrel). www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&ssDoc Name=CON2031345&ssSourceNodeId =387&ssTargetNodeId=364 (Accessed 2 April 2020).
  29. Chaplin S. Counterfeit medicines: a cause for concern in the UK? https://onlinelibrary.wiley.com/doi/pdf/10.1002/psb.106 (Accessed 2 April 2020).
  30. Heparin's Deadly Side Effects. https://web.archive.org/web/20081121194220/http://www.time.com/time/magazine/article/0%2C9171%2C1858870%2C00.html (Accessed 2 April 2020).
  31. Chinese Heparin Manufacturer again involved in Falsification and GMP Non-Compliance. https://www.gmp-compliance.org/gmp-news/chinese-heparin-manufacturer-again-involved-in-falsification-and-gmp-non-compliance (Accessed 2 April 2020).
  32. Antignac M, Diop BI, Do B, et al. Quality assessment of 7 cardiovascular drugs in 10 sub-saharan countries: the SEVEN study. JAMA Cardiol. 2017; 2(2): 223–225.
    CrossRefPubMed
  33. Fake cardiovascular medicine in Kenya. https://www.gphf.org/en/minilab/hintergrund_cardiovascular_kenya.htm (Accessed 2 April 2020).
  34. Valsartan concerns: Experts warn of risks of stopping blood-pressure medication. https://timesofmalta.com/articles/view/valsartan-concerns-experts-warn-of-risks-of-stopping-blood-pressure.684166 (Accessed 2 April 2020).
  35. Available from: https://www.chemistryworld.com/news/nitrosamine-contamination-withdrawals-spread-to-new-drugs/4010505. (Accessed 2 April 2020).
  36. Nitrosamine contamination withdrawals spread to new drugs. https://www.thetimes.co.uk/article/widely-taken-blood-pressure-drug-valsartan-recalled-m2cd37s9x (Accessed 2 April 2020).
  37. Huang QF, Li Y, Wang JG. Overview of clinical use and side effect profile of valsartan in Chinese hypertensive patients. Drug Des Devel Ther. 2013; 8: 79–86.
    CrossRefPubMed
  38. Al-Salmi Z, Al-Raisi F, Al-Harbi A, et al. A study of prescribing valsartan in Out-patient Clinics at the Royal Hospital, Muscat, Oman. Oman Med J. 2009; 24(1): 17–21.
    CrossRefPubMed
  39. Recall Of Valsartan Due To Contamination. https://www.nafdac.gov.ng/recall-of-valsartan-due-to-contamination/ (Accessed 2 April 2020).
  40. Pottegård A, Kristensen KB, Ernst MT, et al. Use of N-nitrosodimethylamine (NDMA) contaminated valsartan products and risk of cancer: Danish nationwide cohort study. BMJ. 2018; 362: k3851.
    CrossRefPubMed
  41. Valsartan recall: 4 things patients should know. https://edition.cnn.com/2018/07/19/health/valsartan-recall-explainer/index.html (Accessed 2 April 2020).
  42. Update on medicines containing valsartan from Zhejiang Tianyu: company no longer authorised to manufacture valsartan active substance for EU medicines due to presence of NDMA. https://www.ema.europa.eu/en/news/update-medicines-containing-valsartan-zhejiang-tianyu-company-no-longer-authorised-manufacture (Accessed 2 April 2020).
  43. Statement alerting patients and health care professionals of NDMA found in samples of ranitidine. https://www.fda.gov/news-events/press-announcements/statement-alerting-patients-and-health-care-professionals-ndma-found-samples-ranitidine (Accessed 2 April 2020).
  44. Questions and Answers: NDMA impurities in ranitidine (commonly known as Zantac). https://www.fda.gov/drugs/drug-safety-and-availability/questions-and-answers-ndma-impurities-ranitidine-commonly-known-zantac (Accessed 2 April 2020).
  45. FDA Updates and Press Announcements on Angiotensin II Receptor Blocker (ARB) Recalls (Valsartan, Losartan, and Irbesartan). https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-and-press-announcements-angiotensin-ii-receptor-blocker-arb-recalls-valsartan-losartan (Accessed 2 April 2020).
  46. Health Canada assessing NDMA in ranitidine. https://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2019/70989a-eng.php (Accessed 2 April 2020).
  47. EMA to provide guidance on avoiding nitrosamines in human medicines. https://www.ema.europa.eu/en/news/ema-provide-guidance-avoiding-nitrosamines-human-medicines (Accessed 2 April 2020).
  48. Rasheed H, Hoellein L, Bukhari KS, et al. Regulatory framework in Pakistan: situation analysis of medicine quality and future recommendations. J Pharm Policy Pract. 2019; 12: 23.
    CrossRefPubMed
  49. Ferrario A, Sautenkova N, Bezverhni Z, et al. An in-depth analysis of pharmaceutical regulation in the Republic of Moldova. J Pharm Policy Pract. 2014; 7: 4.
    CrossRefPubMed
  50. FDA: New Nitrosamine Impurity Detected in Certain Losartan Lots. https://www.pharmacytimes.com/resource-centers/cardiovascular-health/fda-new-nitrosamine-impurity-detected-in-certain-losartan-lots (Accessed 2 April 2020).
  51. More blood pressure medicines recalled over possible cancer-causing impurity. https://eu.usatoday.com/story/news/health/2019/09/23/losartan-recall-fda-says-more-blood-pressure-medicine-has-cancer-risk/2418140001/ (Accessed 2 April 2020).
  52. Valsartan, Losartan & Other BP Med Recalls 2018-19. https://www.webmd.com/hypertension-high-blood-pressure/valsartan-losatran-bp-med-recalls-2018-19 (Accessed 2 April 2020).
  53. Losartan FDA Alerts. https://www.drugs.com/fda-alerts/1489-0.html (Accessed 2 April 2020).
  54. SSFFC medical products. https://www.youtube.com/watch?v=5B85z7Y2KNM (Accessed 2 April 2020).

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