Review article
https://doi.org/10.2478/aiht-2021-72-3491
Presence of nitrosamine impurities in medicinal products
Ilijana Sedlo
orcid.org/0000-0003-1673-5290
; University of Rijeka, Department of Biotechnology, Croatia
Teo Kolonić
orcid.org/0000-0002-4548-2555
; Agency for Medicinal Products and Medical Devices (HALMED), Zagreb, Croatia
Siniša Tomić
orcid.org/0000-0002-3500-9940
; University of Rijeka, Department of Biotechnology, Croatia 2 Agency for Medicinal Products and Medical Devices (HALMED), Zagreb, Croatia
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 Moreover, ranitidine had been preventively withdrawn all over the EU, including Croatia, creating shortages at the time, but was subsequently replaced with therapeutic alternatives.
Keywords
carcinogenicity; metformin; NDEA; NDMA; ranitidine; sartans
Hrčak ID:
253743
URI
Publication date:
16.3.2021.
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