Valsartan: Extended investigations – products on Swiss market tested to date give no cause for concern

Over the past month Swissmedic has, as a precautionary measure, been investigating sartan-containing medicinal products that are currently authorised and available on the Swiss market for contamination with N-nitrosodimethylamine (NDMA). The investigations will be continued and extended to the related substance N-nitrosodiethylamine (NDEA).

Since July 2018, Swissmedic's independent in-house laboratory (OMCL, Official Medicines Control Laboratory) has been investigating products that could be affected by the NDMA problem. To this end, the manufacturing documentation was first checked for five different active substances following evidence of the development and presence of NDMA and related compounds, and comprehensive laboratory analyses of the requested samples were subsequently arranged. 

An initial review of finished products with the active substances valsartan, losartan, olmesartan and candesartan available on the Swiss market is now concluded. The measurements showed that none of the medicinal products analysed give any cause for concern in respect of NDMA.

Over the coming weeks, the Swissmedic OMCL control laboratory will be testing medicinal products with the active substance irbesartan for impurities, even though the manufacturing documentation suggests that contamination with nitrosamines is unlikely. The results of these investigations should be available by the end of October 2018.

At the end of September 2018, the European Medicines Agency (EMA) reported that a compound related to NDMA had been discovered in a sartan active substance in Germany: Small quantities of N-nitrosodiethylamine (NDEA) were detected in losartan, manufactured by the company Hetero Labs in India. Both NDEA and NMDA are classed as substances that can probably cause cancer in humans. 

The Swissmedic laboratory has developed additional new analytical methods that can also be used to detect NDEA, and Swissmedic has checked the losartan medicinal products available in Switzerland:

• No preparations from this manufacturer containing the active substance losartan are marketed in Switzerland.
• No elevated NDEA levels were detected in those medicines containing losartan as the active substance that are available on the Swiss market. 

How the impurities arose during the manufacture of sartans has not yet been fully explained. The synthesis routes for sartans will be further evaluated, and those products whose synthesis route could lead to the formation of NDMA or NDEA impurities will be further investigated. To this end, Swissmedic is working closely with national authorities, international partners and the European Directorate for the Quality of Medicines (EDQM).