International – Information Note Nitrosamine impurities

UPDATE ON NITROSAMINE IMPURITIES

Background

Medicine Regulatory Authorities first became aware of the presence of the nitrosamine impurity, Nnitrosodimethylamine (NDMA), in products containing valsartan in July 2018. Valsartan is an Angiotensin II Receptor Blocker (ARB) and belongs to a family of analogue compounds commonly referred to as the sartans.

Further nitrosamine impurities were subsequently detected in other medicines belonging to the sartan family, including: N-nitrosodiethylamine (NDEA), N -nitrosodiisopropylamine (NDIPA), N -nitrosoethylisopropylamine (NEIPA) and N -nitroso-N-methyl-4-aminobutyric acid (NMBA).

More recently, nitrosamine impurities have been reported in pioglitazone and ranitidine containing products.1-3

What are nitrosamines?

Nitrosamines, or more correctly N-nitrosoamines, refer to any molecule containing the nitroso functional group. These molecules are of concern because nitrosamine impurities are probable human carcinogens. Although they are also present in some foods and drinking water supplies, their presence in medicines is nonetheless considered unacceptable…