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Tan E., Baysal E., Coşkun M., Yetkin I.

13th International Symposium on Pharmaceutical Sciences (ISOPS), Ankara, Turkey, 22 - 25 June 2021, pp.214

  • Publication Type: Conference Paper / Summary Text
  • City: Ankara
  • Country: Turkey
  • Page Numbers: pp.214
  • Gazi University Affiliated: Yes


Introduction: Metformin (MET) has been used clinically for many years as a first-line treatment for patients with type 2 diabetes mellitus (T2D) due to its cost-effectiveness, good safety profile and cardiovascular benefits (Flory et al., 2019). Recently, nitrosamines, known to have probably carcinogenic effects, have been detected above the acceptable intake limits in various extendedrelease MET products, so the recall of these drug products in the USA caused concern in physicians and pharmacists (FDA, 2021). Nitrosamines are products formed by the reaction of secondary or tertiary amines between a nitrosating agent. Nitrosamines may cause cancer in animals and humans. Dimethylnitrosamine (NDMA) and diethylnitrosamine (NDEA) are classified as probably carcinogenic to humans by the International Agency for Cancer (IARC) (Erkekoğlu et al., 2010, Zmysłowski et al., 2020). In this review, we aimed to inform the recent events to health care providers and pay attention to the potential risk of nitrosamine impurities in human medical products especially metformin. Materials and Methods: In this review, we compile the scientific data, documents from the European Medicines Agency (EMA), US Food and Drug Administration (FDA) and Turkish Pharmaceuticals and Medical Devices Agency (TITCK) about nitrosamine impurities in human medical products. Results: It was shown that the medicine authorities recalled the products which contain NDMA and other nitrosamine impurity level higher than acceptable intake limits. Additionally, they published guides and reports to inform the industry and healthcare providers. However, there is still limited data available on the causes and consequences of nitrosamine impurity in human medical products. Conclusions: In conclusion, FDA and EMA have stated that despite the possible risk of toxic effects of low level of nitrosamines, MET treatment should continue, considering the risks that may occur as a result of the discontinuation of the drug treatment of the patient. The root cause of NDMA impurity for MET have not been identified so far and the risk evaluation is still processing. The elimination of the danger will only be possible by the strict risk evaluation.