N-Nitrosodimethylamine (NDMA) has recently entered the Food & Drug Administration “FDA” spotlight for its presence in Ranitidine Hydrochloride (“Ranitidine”), originally sold under the trade name Zantac®. Ranitidine is an H2 (histamine-2) blocker developed to decrease stomach acid production, and is used to treat peptic ulcer disease, gastroesophageal reflux disease, and Zollinger-Ellison Syndrome. It is more commonly used over-the-counter and by prescription to prevent and relieve heartburn.
The recent recalls and FDA-withdrawals of Ranitidine products and Zantac® from the U.S. market are directly related to the discovery of dangerous levels of NDMA within these medications. The common Zantac® and Ranitidine products at issue include:
- Zantac® 150 Tablets
- Zantac® 150 Maximum Strength
- Zantac® 150 Maximum Strength Cool Mint
- Zantac® 75 Tablets
- Wal-Zan® 150
- Wal-Zan® 75
- Heartburn Relief (ranitidine)
- Acid Reducer (ranitidine)
- Acid Control (ranitidine)
What Exactly Is NDMA?
NDMA, also known as dimethylnitrosamine, is an organic compound – (CH3)2NNO – that presents as a volatile yellow oil.
NDMA is not currently produced in pure form or commercially used in the United States, except for research purposes. It was formerly used in production of liquid rocket fuel, antioxidants, and as additives for lubricants and softeners. Because of these uses, NDMA caused contamination of air, soil, and water surrounding production facilities. Specifically, NDMA had a high potential of leaching into groundwater, and put certain geographical regions at risk as it permeated aquifers, wells, and other drinking water sources.
According to the Environmental Protection Agency “EPA” and the Agency for Toxic Substances and Disease Registry (ASTDR), the primary sources for human exposure to NDMA are:
- Eating smoked and cured meats (including bacon)
- Eating fatty fish
- Eating certain cheeses
- Using shampoos, soaps, or cleansers that contain the ingredient
- Smoking or chewing tobacco
- Using detergents that contain the ingredient
- Breathing interior air of cars
- Ingesting pesticides
- Eating alkylamine-containing foods
- Using baby-bottle nipples and pacifiers
Although NDMA can be found in these products and food items at varying levels, the FDA has never considered normal levels (below 96ng (nanograms) per day) of ingestion to be toxic to humans.
The Dangerous Link Between NDMA And Ranitidine
NDMA is classified by the FDA as a “B2 probable human carcinogen,” with risks acknowledged in consumption of Ranitidine drugs. On April 1, 2020, the FDA ordered all Ranitidine medications sold under the name Zantac® to be taken off store shelves immediately. The FDA, EPA and World Health Organization “WHO” now all classify NDMA as a probable cancer-causing substance.
The FDA had previously established a permissible daily intake limit of 96ng of NDMA. However, using FDA-approved methods of testing in September of 2019, results concluded that certain Zantac® medications contained levels of NDMA up to 3,000 times greater than the FDA’s daily intake limit, and 26,000 times greater higher than what the FDA has determined “acceptable.” For instance, one 150mg (milligram) tablet of Zantac® was detected to contain more than 2,500,00ng of NDMA. The ordered withdrawal from the FDA was therefore long overdue.
Further, animal testing analyzed by the ASTDR has shown shocking results: “[w]hen rats, mice, hamsters, and other animals ate food, drank water, or breathed air containing lower levels of NDMA for periods more than several weeks, liver cancer and lung cancer as well as non-cancerous liver damage occurred.” Mice that were exposed to NDMA during pregnancy had offspring that were born dead or died shortly after birth. The ASTDR noted that “it is reasonable to expect that exposure by eating, drinking, or breathing could cause cancer in humans.” Similar testing produced the same results in higher primates. The EPA has similarly concluded that NDMA is a “B2 (probable human) carcinogen based on the induction of tumors at multiple sites in different mammal species exposed to NDMA by various routes.” The U.S. Department of Health and Human Services (DHHS) stated that “NDMA caused tumors in numerous species of experimental animals, at several different tissue sites, and by several different routes of exposure,” and that the “[t]umors occurred primarily of the liver, respiratory tract, kidney, and blood vessels.” Finally, the WHO had reviewed studies in 2002 that addressed NDMA’s effects on humans, and reported that “in three of four case-control studies, there was a positive relationship with evidence of exposure—response for the intake of NDMA and gastric cancer.
While the exact cause of NDMA contamination in humans is still under investigation, research has shown a strong link between Ranitidine, the active ingredient in Zantac®, and NDMA. The formation of NDMA in humans is caused by the inherent instability of the Ranitidine molecule, meaning that many different medications containing Ranitidine could generate very high levels of NDMA in the body. Specifically, a chemical reaction occurs when Ranitidine comes into contact with water that causes the formation of NDMA in humans, at dangerous levels.
The types of cancer thus far associated with Zantac® and generic forms of Ranitidine may include:
- Breast cancer
- Bladder cancer
- Esophageal cancer
- Colon and rectal cancer
- Intestinal cancer
- Liver cancer
- Kidney cancer
- Ovarian cancer
- Pancreatic cancer
- Testicular cancer
- Prostate cancer
- Uterine cancer
- Stomach cancer
Other Dangers Associated With NDMA
NDMA is considered hepatotoxic, meaning that it contains destructive agents, or hepatotoxins, which damage the liver. NDMA is linked to drug-induced liver injury, and chemical-driven liver damage. These types of injuries are responsible for 5% of all hospital admissions, and 50% of acute liver failures. Other symptoms of NDMA overexposure include:
- Abdominal cramps
- Enlarged liver
- Reduced function of the liver, kidneys, and lungs
- Nervous system disorders
- Arrhythmia or Tachycardia
- Vitamin B-12 deficiency
- Increased risk of Pneumonia
- Low platelet levels in blood
- Skin rashes
- Hair loss
Recently, the FDA has issued a recall on certain high blood pressure medications due to the NDMA exposure in patients. This includes Angiotensin II Receptor Blocker (ARB) medications containing valsartan, losartan, or irbesartan. These types of medications are being recalled due to the presence of NDMA, described as industrial contaminants suspected to cause cancer in people.
Why Is The Data Important?
Simply put, if companies are aware of inherently dangerous substances within products they market to consumers, and intentionally conceal the risks of those substances, they can be liable to consumers injured by using their products. Ranitidine was introduced to the market in 1981, and quickly rose to the number one selling prescription drug by 1987. Zantac® production in the U.S. was bought and controlled by Boehringer Ingelheim in 2006, and later sold to Sanofi in 2016, with U.S. headquarters in Bridewater, New Jersey, and is known as the top-selling drug in history. In 2016 alone, 15 million prescriptions were written for Zantac® in the U.S. So, how did it go undetected?
NDMA has now been classified as a B2 probable carcinogen. This was not exposed until a third-party lab in Connecticut called Valisure tested drugs that it sold within its own online pharmacy to ensure quality and purity. After uncovering the incredibly high amounts of NDMA in humans, it was reported to the FDA. The issue here is that comprehensive laboratory analysis of pharmaceutical products, when submitted to the FDA, is submitted under parameters that can be set by the manufacturer itself. Apparently, it has been known since the 1980s by independent scientists that there were potential risks of NDMA exposure in Ranitidine, but these studies never made it past manufacturers to regulatory agencies. The question becomes, with such high levels of a carcinogenic NDMA found in Zantac® by todays tests, were manufacturers aware before now? Many believe so, and lawsuits have been filed to hold these companies responsible.