With recent warnings from the U.S. Food and Drug Administration (FDA) indicating that the popular heartburn drug Zantac and its generics (ranitidine) may contain a cancer-causing agent, many people have grown concerned that they may be at increased risk for a variety of cancers, including esophageal cancer.

The American Cancer Society (ACS) estimates that in the year 2020, about 18,440 people will be diagnosed with esophageal cancer, and about 16,170 people will die from it. The disease is more common in men than in women, though both may be affected. 

Fortunately, the overall rates of the disease have been fairly stable for many years. Esophageal cancer makes up only about 1 percent of all cancers diagnosed in the U.S., so it’s rare, but unfortunately, it can also be deadly.

It’s unclear at this point how long Zantac may have contained NDMA, but the product has been on the market for decades. Chaffin Luhana is currently investigating cases in which patients took Zantac or generic forms of ranitidine and then suffered serious injuries and/or esophageal cancer.

What is Esophageal Cancer?

The esophagus is the long, hollow tube that runs from the throat to the stomach. Scientists aren’t sure what causes esophageal cancer, but they know it occurs when the cells in the esophagus undergo DNA mutations that lead to cancerous overgrowth. They also know that certain factors can increase the risk of this cancer, including smoking, having gastroesophageal reflux disease (GERD), being obese, drinking alcohol, and undergoing radiation to the chest or upper abdomen.

Symptoms of esophageal cancer may include difficulty swallowing, unintended weight loss, chest pain or pressure, indigestion and heartburn that get worse, coughing or hoarseness, and a burning sensation in the esophagus. In its early stages, however, esophageal cancer typically causes no signs or symptoms.

Treatment for esophageal cancer may include surgery to remove tumors and/or a portion of the esophagus, chemotherapy, and radiation therapy. Doctors may also use targeted drug treatments and immunotherapy.

During the 1960s and 1970s, only about 5 percent of patients survived at least 5 years after being diagnosed with esophageal cancer. Today, the 5-year survival rate is about 20 percent. Survival is largely dependent on how early the disease is discovered and can be much higher in those who are diagnosed while it is still localized only in the esophagus.

What is NDMA?

NDMA belongs to a class of chemicals called “nitrosamines,” most of which are highly carcinogenic. These compounds are used in the manufacturer of cosmetics, pesticides, tobacco products, and most rubber products like tires. They can also form in foods when nitrites and amines combine in acidic places like the human stomach.

Food preparation methods that use high temperatures, such as frying, can increase the formation of nitrosamines, as can meat processing methods used to produce bacon, hot dogs, and other similar items. Nitrites are often added to foods to increase the shelf-life, and they can combine with other chemicals in the stomach to form nitrosamines. Nitrites can also be found in crop fertilizers.

NDMA, in particular, is a known environmental contaminant, and can also be produced in amine manufacturing plants, drinking-water plants, fish processing facilities, foundries, dye manufacturers, rubber and tire manufacturing plants, surfactant industries, and in automobile exhaust.

The U.S. Environmental Protection Agency (EPA) states that NDMA is a probable human carcinogen, based on the fact that in animal studies, exposure to the chemical resulted in cancerous tumors at multiple sites. The U.S. Department of Health and Human Services (DHHS) also states that NDMA is reasonably anticipated to be a human carcinogen, and has caused tumors in numerous species of experimental animals, at several different tissue sites. Tumors occurred primarily in the liver, respiratory tract, kidney, and blood vessels.

The World Health Organization (WHO) states that based on laboratory studies, “NDMA is clearly carcinogenic…potentially at relatively low levels of exposure.” The International Agency for Research on Cancer (IARC) has also qualified NDMA as a probable human carcinogen, based mostly on animal studies and some human studies. 

NDMA Linked with Cancer, Including Esophageal Cancer

Research suggests that exposure to nitrosamines and NDMA can increase the risk of cancer in animals and humans. A human study of nearly 9,000 rubber workers, for example, showed that exposure to nitrosamines was significantly associated with an increased mortality rate from cancers of the esophagus, oral cavity, and pharynx, and non-significantly associated with increased mortality from prostate and brain cancer.

Dietary intake of NDMA has also been connected to cancer. In one animal study, for instance, researchers found that after subjects consumed a solution with NDMA, they experienced cancerous changes in their tissues, including in the liver, esophagus, ovaries, pancreas, bladder, and uterus. In a human study of 23,000 men and women, aged 40-79, dietary intake of NDMA was significantly associated with an increased risk of gastrointestinal cancers, particularly rectal cancer.

Since processed meats contain nitrosamines, scientists have examined how a diet high in these items may affect cancer risk. In a large review of the research, researchers found an association between nitrite and nitrosamine intake and gastrointestinal cancer, with a relatively large number of studies showing consistent results supporting a positive link between processed meat intake and both gastrointestinal and esophageal cancer.

Another review of research on Chinese subjects found similar results. Scientists found several N-nitrosamines, including NDMA, in the gastric juice collected from Lin-Xian inhabitants, and found a correlation between lesions in the lining of the esophagus (which could turn cancerous) and the level of nitrosamines present.

Research in the Netherlands also showed a connection between the dietary intake of nitrosamines and esophageal cancer. Scientists studied over 120,000 men and women aged 55-69 years, analyzing their diets and cancer occurrence for about 16 years. Results showed a positive association between the intake of NDMA intake, in particular, and the risk of esophageal cancer, as well as the risk of gastric (stomach) cancer.

NDMA Discovered in Zantac and Generic Ranitidine

Online pharmacy Valisure was the first to find NDMA in samples of Zantac tested. The company alerted the FDA to the findings in June 2019, then followed up with a citizen’s petition on September 9, 2013. In it, authors David Light, CEO, and Kaury Kucera, Chief Scientific Officer, urged the FDA to recall all forms of ranitidine from the market.

The FDA followed with a warning to healthcare providers on September 13, 2019. The agency had already been investigating NDMA and “other nitrosamine impurities” in blood pressure and heart failure medications since 2018, recommending numerous recalls for drugs that had unacceptable levels of the cancer-causing agent. The agency traced the source of the carcinogen to certain manufacturing companies and plants that were failing to live up to standard good practices.

At that time of that first warning about Zantac, the FDA did not seem overly concerned, stating that the levels of NDMA found in ranitidine “barely exceeds amounts you might expect to find in common foods.” It did recommend that manufacturers start testing their products and report their results.

Manufacturers complied and started testing, and over the following several months, many of them recalled their medications after finding NDMA in samples. Sanofi, the current manufacturer of Zantac, recalled its products in October 2019.

There were many similarities between the discovery of NDMA in blood pressure drugs and the discovery in ranitidine, but there was one important difference. Whereas the chemical seemed to have gotten into the blood pressure medications because of manufacturing errors, there was some evidence that things were different with ranitidine.

In its petition to the FDA, Valisure suggested that ranitidine was a naturally unstable molecule, and could break down during the digestion process to create NDMA. Light and Kucera wrote: “Valisure’s tests suggest ranitidine can react with itself,” adding that the ranitidine molecule “contains both a nitrite and a dimethylamine (‘DMA’) group which are well known to combine to form NDMA.”

To support this argument, Valisure pointed to a 2016 study conducted at Stanford University in which researchers gave participants ranitidine and measured the NDMA found in urine samples 24 hours later. The results showed that NDMA increased 400-fold from 110 to 47,600 ng after ranitidine intake, while total N-nitrosamine increased 5-fold.

FDA Recalls All Ranitidine from the Market

In January 2020, independent laboratory Emery Pharma sent a citizen’s petition to the FDA. In it, Emery President and CEO Ramin Najafi, Ph.D., noted that a preliminary analysis of ranitidine revealed that while stable at room temperature, the molecule could become unstable under elevated temperatures of about 158 degrees Fahrenheit.

“This was concerning,” wrote Janafi, “since significantly elevated temperatures can occur within closed vehicles during transportation and during storage of the drug, because there is no requirement for ranitidine to be cold-chained, i.e., shipped in temperature-controlled conditions and stored under refrigeration.”

Additional tests showed that NDMA also increased with time. In other words, the older the ranitidine product is, or the longer the time since it was manufactured, the greater the level of NDMA.

Based on these findings, on April 1, 2020, the FDA requested the removal of all ranitidine products from the market. The agency sent letters to all manufacturers directing them to recall their products, and also advised consumers to stop taking ranitidine products and seek other treatment alternatives.

Types of Injuries Associated with Zantac (Ranitidine)

Considering the potential exposure to NDMA, the following injuries may be associated with long-term intake of Zantac and generic ranitidine:

• Bladder cancer
• Stomach or gastric cancer
• Kidney cancer
• Liver cancer
• Esophageal cancer
• Pancreatic cancer
• Prostate cancer
• Breast cancer
• Testicular cancer
• Colorectal cancer (colon or rectal cancer)
• Uterine (endometrial) cancer
• Death

Zantac Esophageal Cancer Lawsuits

Several Zantac cancer lawsuits have already been filed in various courts across the country. In general, the plaintiffs blame the manufacturers for failing to provide adequate warnings about the risks associated with their products, and for failing to take appropriate action as soon as they learned about ranitidine’s toxic potential.

Early studies, for example, showed that ranitidine could encourage changes leading to cancer. A 1983 study published in the scientific journal Toxicology Letters, for instance, explored the potential for ranitidine to react under acidic conditions to form dangerous nitrosamines. In a related study that same year, researchers reported that nitrites (which are found in some foods) could react with ranitidine in human gastric juice to produce a mutagenic response.

On February 6, 2020, the U.S. Judicial Panel on Multidistrict Litigation (JPML) consolidated all federally filed Zantac lawsuits into the Southern District of Florida. District Judge Robin L. Rosenberg was appointed to oversee the proceedings.

If you took Zantac or ranitidine regularly and were later diagnosed with esophageal or other forms of cancer, you may be eligible to file a Zantac lawsuit to recover damages. Chaffin Luhana is now investigating these cases and invites you to call today at 888-480-1123.