The recent recall of sartan-based blood pressure medications has been expanded yet again. Torrent Pharmaceuticals Ltd. has put out a notice for 36 lots of losartan potassium and losartan potassium with hydrochlorothiazide after testing revealed traces of a carcinogenic chemical. The current recall affects over 1 million bottles. Since the problem was discovered in July of 2018, there have been well over 20 such recalls affecting losartan, irbesartan, and valsartan.
The contaminant in question this time is N-methylnitrosobutyric acid (NMBA), the latest of three toxic chemicals that have been discovered in anti-hypertension drugs containing sartan manufactured in India and China. The other two are N-Nitroso-dimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA). All three of these compounds are part of a class known as nitrosamines. Highly carcinogenic, these chemicals have been used in the production of liquid rocket and jet fuel, gasoline, and various industrial lubricants. NDMA is no longer produced or used in the US except for research.
As well as being manufactured, nitrosamines can be produced accidentally as the result of chemical reactions during industrial processes. This appears to be the case for the Chinese source of sartan, at a plant located in the city of Linhai. In 2012, the plant upgraded its manufacturing process in order to reduce waste and increase production. These changes apparently resulted in an unintended chemical reaction, causing the formation of nitrosamines.
This was not the case for Hetero Labs, the production facility in India where Torrent Pharmaceuticals obtains its sartan supplies. In 2017, the FDA sent a warning letter to the company due to its lack of “an adequate ongoing program for monitoring process control to ensure stable manufacturing operations and consistent drug quality.” In addition to Torrent, Hetero Labs supplies sartan to Mylan and Teva Pharmaceuticals.
Sartan-based medications, also known as “angiotensin II receptor blockers,” or ARBs, disable the activity of angiotensin, a hormone that causes the muscles surrounding blood vessels to constrict.
Patients who have been prescribed ARBs and are concerned about nitrosamine contamination should not stop taking their medication until they have discussed their concerns with their primary care physicians. There are alternatives, such as beta blockers and angiotensin-converting enzyme (ACE) inhibitors, the latter of which prevents the production of angiotensin altogether.
The FDA states that it will continue to test ARB drugs. A complete and regularly-updated list of recalled products is available on the FDA website.