Nitrosamines: All the Alerts
June 2018
US manufacturer Prinston Pharmaceuticals Inc. had contacted FDA’s Center for drug Evaluation and Research to inform the agency that it had stopped manufacturing valsartan products because it had detected trace amounts of a nitrosamines impurity called NDMA (N-nitrosodimethylamine) in valsartan API supplied by Chinese manufacturer Zhejiang Huahai.
July 2018
Authorities in Europe became aware of the presence of NDMA in valsartan manufactured at a facility based in China. Subsequently, another nitrosamine NDEA (N-nitrosodiethylamile) was detected and other sartans from more API manufacturers were implicated.
Late 2018 – early 2019
Companies that make sartan blood pressure medicines (also known as angiotensin II receptor blockers) are being required to review their manufacturing processes so that they do not produce nitrosamine impurities and many valsartan recalls continued both in EU and US.
September – November 2019
FDA has learned that some ranitinide medicines contain a nitrosamines impurity called NDMA (N-nitrosodimethylamine). FDA has detected that also some nizatidine (which is chemically similar to ranitidine) medicines, contain NDMA impurities.
December 2019
EMA and FDA are aware concerning the presence of low levels of NDMA in some metformin diabetes medicines outside the Europe and United States. At this point, there are no data indicating that US and EU metformin medicines are affected, but authorities are in the process of working with companies to test medicines and provide more information.
February 2020
Ranbaxy Pharmaceuticals Canada Inc. recalled six lots of its RAN-Metformin prescription drug from the Canadian market.
March 2020
After questioning about the suitability of the FDA LC-HRMS method reported in the guidance document FY20-058-DPA-S, Valisure detected high levels of NDMA in several metformin drugs.
August 2020
In EU and USA, new nitrosamine impurities in antibacterial drugs based on rifampicin: new investigations have permitted to detect the presence of nitrosamine impurities (1-nitroso-4-methyl piperazine, MeNP) in certain samples of Rifampicin. Rifampicin is antibacterial drugs used to treat tuberculosis, and it is also used to treat other serious infections.
