Akademik Veri Yönetim Sistemi
13th International Symposium on Pharmaceutical Sciences (ISOPS), Ankara, Türkiye, 22 - 25 Haziran 2021, ss.214
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.