Nitrosamine in drug products: an open discussion


Chemsafe, Colleretto Giacosa (TO), Italy

Nitrosamines have become a focus of global regulatory agencies, including FDA, due to the discovery of trace amounts of these compounds in a class of drugs known as angiotensin II receptor blockers (ARB), frequently referred to as “sartans”. The “sartan” molecules involved include valsartan, losartan, irbesartan, azilsartan, olmesartan, eprosartan, candesartan, and telmisartan. Valsartan and losartan were the most severely affected due to their market share when several lots were recalled.


The genotoxic and carcinogenic potential of N-nitrosamines raises a serious of safety concerns, and in September 2020, the FDA issued guidance for the pharmaceutical industry regarding the control of nitrosamines in drug products.


The FDA database shows that >1400 product lots have been recalled from the market due to the presence of carcinogenic N-nitrosamine impurities at levels beyond the acceptable intake limit of 26.5 ng/day. The drugs that were present in recalled products include valsartan, irbesartan, losartan, metformin, ranitidine, and nizatidine. This perspective provides a critical account of these product recalls with an e ...