All About N-Nitrosodimethylamine (NDMA)
N-nitrosodimethylamine, more commonly known as NDMA, is an extremely hazardous substance and a known carcinogen in the human body. NDMA was formerly used as a key ingredient in rocket fuel and is found at high levels in groundwater supplies near rocket launch sites. NDMA is so toxic it is used by scientists to induce cancer in lab rats when necessary for research purposes. NDMA is a yellow liquid with faint characteristic or no distinct odor.
According to Wikipedia, NDMA is found at low levels in numerous items of human consumption including cured meat, fish, beer and cheese because of the cooking and fermentation process. The pathway for NDMA formation involves nitrous acid produced from sodium nitrate, which is used to cure meat.
NDMA is a semi-volatile organic chemical that can form in nature or during certain industrial processes. NDMA is created as an unintended byproduct of the chlorination of wastewater and drinking water at treatment plants that use chloramines for disinfection. NDMA can also be formed through processes that occur naturally such as digestion. Ranitidine, which is the main ingredient in Zantac, has a molecular structure that makes it susceptible to creating NDMA in the human body once ingested. Ranitidine contains nitrate and dimethylamine which can combine to form N-nitrosodimethylamine or NDMA.
How is NDMA Harmful to the Body?
According to the Agency for Toxic Substances & Disease Registry, NDMA is very harmful to the liver of humans and other animals. People who are poisoned by ingesting NDMA die of severe liver damage accompanied by severe internal bleeding. Animals that ingest food or water or breath air containing high levels of NDMA over a period of days or several weeks can also develop liver disease, liver cancer or lung cancer. These conditions are accompanied by internal bleeding and typically cause death. Mice that were fed NDMA during pregnancy had offspring that were born dead or died shortly after birth.
NDMA and Drug Contamination
In 2018, and again in 2019, various brands of valsartan were recalled because of contamination with NDMA. In 2019, Zantac and ranitidine were recalled across the world due to NDMA contamination. In December 2019 the FDA began testing samples of the diabetes drug metformin for the carcinogen NDMA. The FDA’s announcement followed a recall of three versions of metformin in Singapore.
In the past few years, private pharmaceutical and regulatory agency labs have found NDMA and other N-nitrosamine contaminants in various drugs. In 2018, the first discovery was made in a drug containing the active pharmaceutical ingredient valsartan by the drug’s maker Novartis. Valsartan is an angiotensin II receptor blocker (ARB) used to treat high blood pressure. Since the first discovery in 2018, NDMA and similar contaminants have been found in at least six drugs that are taken by tens of millions of patients every year.
Due to the carcinogenic nature of NDMA, many regulatory agencies and consumer advocacy groups have deemed the drugs unsafe for people to ingest and recalled the drugs from store shelves. Valsartan was recalled in July 2018, followed later in the year by two other ARBs irbesartan and losartan.
In September 2019, the FDA alerted the public to the presence of NDMA in Zantac and other ranitidine-based products. Ranitidine manufacturers quickly pulled the products from store shelves over the next few months.
Another heartburn medication, Nizatidine, was recalled by manufacturer Mylan Pharmaceuticals in January 2020. Since then, the FDA recommended that ranitidine manufacturers recall all lots and all types of ranitidine medications. NDMA has also been found in diabetes drug metformin which is taken by almost 16 million people worldwide. Since May 2020, various companies have recalled more than 170 products containing metformin.
According to one expert, “these contaminants may have been present in our drugs for years, but we didn’t know to look for them.”
Drug companies and regulatory agencies are working to determine how NDMA ended up in such a wide range of medicines and how to prevent further contamination. Experts are considering several points of failure including side reactions from drug synthesis, the breakdown of unstable drug compounds and contamination from recycled solvents in the manufacturing process.
