Abstract
In 2018, some sartan medicinal products were reported to be contaminated with nitrosamine compounds, which are potent mutagenic carcinogens. Two nitrosamines received particular attention: N -nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA). These have since been confirmed in different types of medicinal products, including ranitidine and metformin. Consequently, the European Medicines Agency (EMA) started an investigation into the cause of contamination and an assessment of the risk to patients taking contaminated medicinal products. The main source of contamination were changes in production, which involves combinations of amines and nitrogen compounds and the use of specific catalysts and reagents. Withdrawals of medicinal products that took place in Croatia did not lead to a shortage of sartan- or metformin-containing medicines. Moreover, ranitidine had been preventively withdrawn all over the EU, including Croatia, creating shortages at the time, but was subsequently replaced with therapeutic alternatives.
Highlights
In 2018, some sartan medicinal products were reported to be contaminated with nitrosamine compounds, which are potent mutagenic carcinogens
They can be found in water, food, tobacco, pesticides, or plastics, but received public attention in mid-2018, when they were found in medicinal products [1]
Once N-nitrosamines are activated by microsomal liver enzymes, they can react with DNA base pairs to form unstable α-hydroxyalkylnitrosamines and produce alkyldiazonium ions, which alkylate DNA bases and induce carcinogenic response [5]
Summary
In 2018, some sartan medicinal products were reported to be contaminated with nitrosamine compounds, which are potent mutagenic carcinogens. Two nitrosamines received particular attention: N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA). These have since been confirmed in different types of medicinal products, including ranitidine and metformin. Nitrosamines are a group of organic compounds containing the nitroso functional group They can be found in water, food, tobacco, pesticides, or plastics, but received public attention in mid-2018, when they were found in medicinal products [1]. The two best-known nitrosamines, N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA), have been classified by the International Agency for Research on Cancer (IARC) as possible human (class 2A) carcinogens, but they are genotoxic [3, 4]. Once N-nitrosamines are activated by microsomal liver enzymes, they can react with DNA base pairs to form unstable α-hydroxyalkylnitrosamines and produce alkyldiazonium ions, which alkylate DNA bases and induce carcinogenic response [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
