Last Updated November 12, 2020

Zantac is the product name for the drug ranitidine. Approved by the U.S. Food and Drug Administration (FDA) in 1984 for the treatment and prevention of ulcers, heartburn, esophagitis, and Zoeller-Ellison syndrome, Zantac quickly rose to become one of the most popular prescriptions and over-the-counter (OTC) H2-blockers on the market. In 2018, Zantac ranked as one of the top-10 antacid tablets in the United States.

In March 2019, laboratories in the United States tested Zantac for the presence of carcinogens and discovered that some forms of Zantac were testing positive for the presence of N-Nitrosodimethylamine, also known as “NDMA” – a potent carcinogen. After further testing and analysis, the FDA ordered all Zantac pulled from shelves in April 2020. Today, more than 500 individuals have filed claims in federal court in Florida alleging that taking Zantac caused their cancer.

NDMA and Zantac Cancer Risk

NDMA is an organic chemical that is both naturally occurring or as a result of industrial processes. NDMA and related compounds can typically be found in tobacco, detergents, and solvents. They may also form in foods such as cured meats as part of a reaction between nitrites and amines.  NDMA is rarely ever produced intentionally in the United States unless it is used for laboratory experiments.

NDMA is classified by the International Agency for Research on Cancer (IARC) as Group 2A – meaning they deem it as “probably carcinogenic to humans”. Its harmful and carcinogenic effects are thought to stem from its propensity to cause irreversible DNA mutations and chemical properties which initiate the development of cancers. Animal studies have revealed that NDMA is acutely toxic to rats and even short-to-medium term exposure in other animals has shown damage to multiple organs. In humans, intentionally poisoned with NDMA,  medical records demonstrate severe liver damage and internal bleeding.

How Did NDMA Contaminate Zantac?

Researchers are not exactly clear on how they believe NDMA came to be found in Zantac. Its presence is not generally believed to be the result of the manufacturing processes. Valisure, the small Connecticut laboratory which first conducted tests of Zantac for NDMA, has stated that it is likely formed as the result of the inherent instability of ranitidine (the drug molecule at the heart of Zantac). In fact, Valisure believes that the NDMA may occur as a natural byproduct of Zantac breaking down over time.

A 2016 study conducted by Stanford University may support the notion that NDMA’s presence in Zantac is a function of the ranitidine molecule itself. The study gave ten healthy volunteers doses of Zantac and found later that their urine contained trace amounts of NDMA. The presence of NDMA in urine also raises the specter that, if ranitidine breaks down into NDMA, it could also be present in sewage systems or contaminate sources of groundwater.

Which Cancers is NDMA Associated With?

There are numerous causes for cancer ranging from infectious agents; to genetic predisposition; to environmental factors and behaviors such as smoking, alcohol use, diet, obesity, and exposure to pollution. Furthermore, studies and research have yet to draw a conclusive link between NDMA in Zantac and cancer. Accordingly, at this time, it is difficult to calculate the specific cancer risk from NDMA contamination.

With that in mind, researchers have theorized that long-term exposure to NDMA contamination in Zantac could be linked with the following cancers:

• Stomach
• Bladder
• Colorectal
• Liver
• Esophageal
• Small Intestinal

Although less prevalent in research, NDMA has also been linked to these types of cancers:

• Prostate
• Ovarian
• Pancreatic
• Lung
• Uterine
• Brain
• Breast
• Thyroid
• Testicular
• Leukemia
• Non-Hodgkin’s Lymphoma
• Multiple Myeloma

FDA Recall

NDMA contamination in Zantac first came to light following the work of a small laboratory in Connecticut known as Valisure. This laboratory was created after one of its founders suffered from a contaminated batch of medication. Valisure began testing Zantac in March 2019 on the founder’s whim after it was prescribed for his infant daughter to combat acid reflux.  The testing immediately revealed abnormal levels of NDMA contamination.

After more testing, Valisure notified the FDA and European drug regulators who each immediately began their own investigations. In October 2019, the FDA ordered all manufacturers of ranitidine products to test for NDMA. That order was followed-up with a broad recall order from the FDA in April 2020, clearing all ranitidine products off the shelves throughout the United States.

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Sources Cited (12)

1) “NDMA, a contaminant found in multiple drugs, has industry seeking sources and solutions” https://cen.acs.org/pharmaceuticals/pharmaceutical-chemicals/NDMA-contaminant-found-multiple-drugs/98/i15

2) “The Zantac problem: What’s NDMA?” https://abcnews.go.com/Health/zantac-problem-whats-ndma/story?id=65799147

3) “Ranitidine Cancer Risk“ https://www.medpagetoday.com/meetingcoverage/ddw/86314

4) “Health Risks Associated with N-Nitrosodimethylamine (NDMA)” https://www.labmanager.com/insights/health-risks-associated-with-n-nitrosodimethylamine-ndma-656

5) “What We Know about the Possible Carcinogen Found in Zantac” https://www.scientificamerican.com/article/what-we-know-about-the-possible-carcinogen-found-in-zantac/#:~:text=In%20its%20petition%2C%20Valisure%20also,break%20down%20to%20form%20NDMA.

6) “The Finding of N‐Nitrosodimethylamine in Common Medicines” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288647/

7) “Oral intake of ranitidine increases urinary excretion of N-nitrosodimethylamine” https://pubmed.ncbi.nlm.nih.gov/26992900/

8) “Formation Mechanism of NDMA from Ranitidine, Trimethylamine, and Other Tertiary Amines during Chloramination: A Computational Study” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123930/

9) “Statement alerting patients and health care professionals of NDMA found in samples of ranitidine” https://www.fda.gov/news-events/press-announcements/statement-alerting-patients-and-health-care-professionals-ndma-found-samples-ranitidine

10) “Clinical Study to Investigate the Urinary Excretion of N-nitrosodimethylamine (NDMA) After Ranitidine Administration” https://clinicaltrials.gov/ct2/show/NCT04397445

11) “FDA asks manufacturers to remove ranitidine from market: What now?” https://www.aappublications.org/news/2020/07/01/focus-ranitidine070120

12) “Concerned about the ranitidine (brand name: Zantac) recall? Here’s what the FDA says” https://www.miamiherald.com/news/health-care/article236067123.html

Tracy Everhart

Tracy Everhart is the Editor for Drug Law Journal. A highly-trained and certified medical professional, Tracy is also an accomplished medical writer. After spending years on the front lines of the medical profession, Tracy now devotes her expertise and skills to researching and reporting on new drugs and devices that enter the market, as well as their side-effects and the real-life stories involved. Prior to joining Drug Law Journal, Tracy wrote for benchmark online healthcare resources focused on families and, in particular, women’s health issues. Tracy holds post-graduate degrees from both the American College of Healthcare Sciences and the Yale School of Nursing. She is also a graduate of both Hampshire College, where she studied microbiology and the University of South Carolina school of nursing.