This past year a number of blood pressure medications known as angiotensin II receptor blockers (ARBs) or “sartan” drugs have been found to contain two industrial contaminants: N-nitrosodiethylamine (NDEA) and/or N-nitrosodimethylamine (NDMA). This week Torrent Pharmaceuticals Ltd. announced the discovery of a third contaminant in lots of losartan, known as N-Methylnitrosobutyric acid (NMBA).
Last year two ARB drugs, valsartan and irbesartan, were found to be contaminated with NDEA, a chemical used in aviation fuel and industrial lubricants, and NDMA, a byproduct of numerous industrial processes. The contamination was ultimately traced to a Chinese facility and was attributed to a change in the manufacturing process.
The most recently-discovered contaminant, NMBA, is found in tobacco products, including cigarettes, pipe tobacco, cigars, snuff, and chewing tobacco. According to the FDA, the levels of NMBA discovered in the losartan samples exceeded acceptable levels.
The active ingredient in Torrent’s product was manufactured by Hetero Labs, a company located in Hyderabad, India. Hetero was sent a warning letter by the FDA in 2017 after investigations found it to be in violation of current good manufacturing practice regulations. The letter stated that Hetero “does not have an adequate ongoing program for monitoring process control to ensure stable manufacturing operations and consistent drug quality.” Hetero’s U.S. subsidiary Camber Pharmaceuticals issued a voluntary recall of 87 lots of losartan last week on February 28due to NMBA contamination concerns.
All three of the chemical contaminants found in ARB drugs are part of a class known as nitrosamines, which, in addition to industrial applications, are found in smoked and some processed, cooked meats. All of these are considered to be probable carcinogens above certain exposure levels. In a press statement, FDA Commissioner Scott Gottlieb said the FDA is “deeply concerned about the presence of a third nitrosamine impurity in certain ARB medications.” However, he also noted that “…based on the FDA’s initial evaluation, the increased risk of cancer to patients with NMBA exposure appears to be the same for NDMA exposure but less than the risk from NDEA exposure.”
Patients who are on ARBs for blood pressure and have concerns about exposure to these chemicals should consult with the prescribing physician before they stop taking their medications. It is possible that there are other drugs, such as ACE inhibitors and beta blockers, which have not been found to contain chemical contamination.