A carcinogen is a substance or material capable of causing cancer.
NDMA (n-nitrosodimethylamine) is the probable human carcinogen behind a number of recent drug recalls. As of July 2020, NDMA has been found in blood pressure, heartburn, and diabetes medications. All unexpired drugs known to contain unsafe levels of NDMA have been recalled, but investigations into this issue are ongoing.
What is NDMA?
NDMA belongs to a class of molecules called nitrosamines. It is an oily, yellow molecule found in low levels in smoked meats and certain vegetables. It is combustible and releases toxic fumes when heated. NDMA was historically used to make rocket fuel. It is now used for research purposes only, typically to create tumors in laboratory animals.
Researchers have meticulously documented NDMA's ability to cause cancer in animals. NDMA has not been as thoroughly studied in humans. Still, two regulatory agencies classify NDMA as a probable human carcinogen due to its behavior in animals:
- The U.S. Environmental Protection Agency (EPA)
- The International Agency for Research on Cancer (IARC)
The U.S. Food and Drug Administration (FDA) set a maximum daily exposure level for NDMA in drugs. The FDA says humans can ingest 96 nanograms of NDMA per day without significant health effects. 96 nanograms is about 600 times smaller than a grain of salt.
All unexpired drugs found to contain more than 96 nanograms of NDMA have been recalled. These recalls were done at the retail level, meaning some consumers may not know their medication was recalled. Recall information can be found on the FDA's recall page or at the appropriate link below.
Was your drug recalled? Click the relevant link below to find out:
How is NDMA Getting into Prescription and OTC Drugs?
NDMA was first discovered in the blood pressure medication valsartan. It has since been identified in several other drugs. Regulators in the U.S. and Europe have investigated the issue.
Manufacturers also mounted their own internal investigations. Together, they found several potential explanations for NDMA's unexpected presence in multiple drugs.
1: Accidental NDMA Formation Conditions
The investigations found several manufacturing steps with potential NDMA formation conditions. These conditions could occur if certain amine molecules are present with nitrite molecules. These molecules can combine to form NDMA.
2: Cross-Contamination of Equipment
Pharmaceutical manufacturers often reuse equipment when manufacturing different types of drugs. One manufacturing process can create NDMA, leaving it behind on the equipment. NDMA can then be passed into the next drug manufactured on the equipment.
Manufacturers typically have rigorous cleaning protocols. In spite of that, it is still possible for this type of cross-contamination to occur.
3: Cross-Contamination of Manufacturing Fluids
Manufacturers use a number of costly fluids when making prescription and OTC drugs. They commonly recover and reuse these fluids for multiple rounds of manufacturing to save money. If NDMA were created or left behind in these fluids, it could easily be passed into the next manufacturing run.
Can Zantac Form NDMA in the Stomach?
Unlike other NDMA-contaminated drugs, Zantac (a heartburn medication) presented an additional source of NDMA. Under certain conditions, the drug itself can be an NDMA source.
Zantac's active ingredient, ranitidine, can break down into smaller molecules. Those smaller molecules can combine to form NDMA in some environments.
Online pharmacy Valisure initially discovered NDMA in Zantac. They notified the FDA in a citizen petition. The petition claimed Zantac could break down and allow the formation of NDMA in the human stomach. According to Valisure's data, this process could produce dangerous amounts of NDMA.
When the FDA investigated this issue, they determined Zantac would not create NDMA in the normal human stomach. However, agency officials admitted that nitrites in the stomach could allow the formation of NDMA after taking Zantac. They issued this statement because they did not consider nitrites in the human stomach to be a normal or average condition.
In February 2021, independent researchers published their investigation on this topic. The study indicated ranitidine could in fact form substantial, unsafe levels of NDMA in the human stomach. The FDA has not commented on this study.
FDA officials did call for additional studies of Zantac breakdown in the human body in 2020. No concrete plans for those studies had been announced as of February 2021. However, all Zantac and ranitidine products have been recalled as of April 2020.
How Many Drugs are at Risk of NDMA Contamination?
Drugs containing a structure called a tetrazole ring may be at risk of NDMA contamination. The risk depends on how the drug is manufactured. At this time, the following drugs have been investigated or recalled for NDMA contamination:
|Zantac (ranitidine)||Nexium (esomeprazole)|
Many other prescription and OTC drugs contain tetrazole rings. The FDA will announce any additional recalls of NDMA-contaminated drugs on its Recalls, Market Withdrawals, & Safety Alerts page.
What Is NDMA's Cancer Risk?
The FDA has not determined the exact cancer risk posed by NDMA. Agency officials did estimate the cancer risk for NDMA-contaminated valsartan. If 8,000 people took the maximum dose of tainted valsartan for four full years, the FDA predicts one additional case of cancer.
Cancers Linked to NDMA Exposure
Stomach cancer (gastric cancer)
Cancer of the nasopharynx
Despite this seemingly low risk, many people have filed lawsuits after taking NDMA-contaminated drugs. Learn more about NDMA-contaminated drug lawsuits by selecting the relevant link below: