Zantac (ranitidine) has been on the market since 1983 when the U.S. Food and Drug Administration (FDA) approved it for the treatment of gastric ulcers, heartburn, acid indigestion, sour stomach, and other gastrointestinal conditions. Millions of people have taken it to treat these conditions, believing it was safe to ingest.

Now, there is concern that these medications could increase the risk of cancer, including stomach cancer. On September 13, 2019, the FDA warned that some batches of these medications had tested positive for the presence of N-nitrosodimethylamine (NDMA), a probable human carcinogen. It is unclear how long the drugs may have contained this chemical, and consumers are understandably worried.

The American Cancer Society (ACS) estimates that in the year 2020, about 27,600 men and women will be diagnosed with stomach cancer, and about 11,000 will die from it. Fortunately, the incidence of stomach cancer has decreased in the United States by 1.5 percent every year over the last decade, but it remains a dangerous disease, with an overall 5-year survival rate of 32 percent. (Cases that are diagnosed before the cancer spreads beyond the stomach have a 5- year survival rate of 69 percent.)

Chaffin Luhana is currently investigating cases in which patients took Zantac or generic forms of ranitidine and then suffered serious injuries and/or stomach cancer.

What is Stomach Cancer?

Stomach cancer, also called gastric cancer, is any type of cancer that develops in the stomach. Though we often refer to the stomach as the entire area between the chest and pelvis, the medical definition is more localized to just the sac-like organ that holds food and starts the digestion process. It’s shaped like the letter “J,” and is a muscular organ that is connected to the esophagus on the top side, and the small intestine on the bottom.

The stomach has three main jobs:

1. Store food temporarily
2. Mix and breakdown the food through contraction and relaxation of the muscle layers
3. Begin the digestive process

Cells in the stomach produce acid and enzymes that help break down food so the nutrients can be absorbed. Once the food resembles a thick, soupy mixture, the stomach moves it into the small intestine, where most of the nutrients are absorbed. The stomach itself doesn’t play a big role in absorption—it mainly stores and breaks down foods.

Stomach cancer tends to develop slowly over many years, beginning as pre-cancerous changes in the inner lining of the sac. During this stage of the disease, there are usually no symptoms, so most people are unaware of the danger. The different types of stomach cancer are defined by the section of the stomach in which they begin.

The most common type of stomach cancer is called “adenocarcinoma,” and begins in the cells that form the innermost lining of the stomach (the mucosa). While these types of cancers have been declining, another type of stomach cancer that develops where the top part of the stomach (cardia) meets the lower end of the esophagus has become more common. Those who have gastrointestinal reflux disease (GERD) are more at risk for this type of cancer.

It’s never clear exactly what causes cancerous changes to begin in the stomach, but scientists know that the following factors can increase the risk that they will:

• Smoking
• Obesity
• GERD
• Diet high in smoked and salted foods
• Family history of stomach cancer
• Infection with Helicobacter pylori (the same bacteria that causes ulcers)
• Chronic inflammation in the stomach
• Stomach polyps

Though symptoms rarely develop in the early stages of the disease, when they do occur, they may include:

• Unusual fatigue
• Unintentional weight loss
• Severe, persistent heartburn
• Feeling bloated or full after eating small amounts of food
• Severe indigestion that never goes away
• Unexplained, persistent nausea
• Stomach pain
• Persistent vomiting

Treatments for stomach cancer include surgery to remove tumors or diseased portions of the stomach, radiation therapy, chemotherapy, and targeted drug therapy.

What is NDMA?

NDMA belongs to a class of chemicals called “nitrosamines,” most of which are carcinogenic. It’s found in the environment as a byproduct of industrial processes and water disinfection. It can also be found in many processed foods and beverages like beer, smoked and processed meats, bacon, and some cheeses, though levels of NDMA in many foods has declined over the past several years because of improvements in food processing.

Workplace exposure to NDMA can occur at tanneries, pesticide manufacturing plants, and rubber and tire plants. Breathing in cigarette smoke will expose a person to NDMA, as will using certain cosmetics and detergents that may contain it.

NDMA and other nitrosamines are not added to these products on purpose, but they can form as a result of the interaction of other chemicals within them. Manufacturers add nitrites to processed meat, for example, to increase its shelf-life, flavor, and texture. These nitrites can combine with other chemicals in the meat during high-temperature cooking (like frying), or in the stomach during digestion, to form nitrosamines. Nitrites can also be found in crop fertilizers.

The harmful effects of NDMA are due in part to its role as a mutagenic compound, as it can create irreversible damage to DNA, initiating cancerous changes in cells and tissues.

The World Health Organization (WHO), the International Agency for Research on Cancer (IARC), and the U.S. Environmental Protection Agency (EPA) all agree that NDMA is a probable human carcinogen based on the results of animal studies. The U.S. Department of Health and Human Services (DHHS) agrees, noting that NDMA caused tumors in numerous species of experimental animals.

NDMA Linked with Stomach (Gastric) Cancer

Several animal studies have demonstrated the toxic effects of NDMA exposure. Short- and medium-term exposures ranging from 1-12 weeks have been associated with cancerous tumors and DNA damage in many species, while some animal studies have shown after several weeks of exposure, subjects suffered from gastrointestinal bleeding and harmful effects in other organs like the heart, kidneys, lungs, and spleen.

In a 2002 report from the WHO, the authors noted that based on studies conducted with laboratory animals, “ingested NDMA is absorbed rapidly and extensively…primarily from the lower intestinal tract.” They added that animal subjects exposed to NDMA through their diet suffered from gastrointestinal hemorrhages.

We have limited studies on humans so far, but in cases where there was intentional poisoning with NDMA, it resulted in severe liver damage and internal bleeding. There was one recent human study published in the British Medical Journal (BMJ) that examined the potential relationship between taking blood pressure medications contaminated with NDMA and cancer. Results showed no short-term increased risk for cancer overall but did find an increased risk for colorectal and uterine cancer.

We do have human studies on the dietary intake of nitrosamines, however, including NDMA. In a human study of 23,000 men and women aged 40-79, for example, dietary intake of NDMA was significantly associated with an increased risk of gastrointestinal cancers, particularly rectal cancer. In another study, researchers followed about 10,000 Finnish men and women for 24 years. By the end of the study, 189 had been diagnosed with gastrointestinal cancer.

In a 2016 review, Chinese scientists analyzed seven different studies on the relationship between NDMA and the risk of digestive tract cancers. Results showed that NDMA could significantly increase the risk of gastric cancer. In an earlier study, researchers found that compared with subjects with the lowest intake of NDMA-containing foods, those with the highest intake were at a significantly higher risk of gastric cancer.

Processed meats are one of the main items in the human diet that contain nitrosamines, and scientists continue to find that a high intake of these items can lead to digestive cancers. In a large review, 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 gastrointestinal cancer.

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

NDMA Discovered in Zantac and Generic Ranitidine

As far back as the 1980s, there was evidence that ranitidine could form NDMA. In a 1981 article in the scientific journal The Lancet, an Italian researcher wrote about laboratory experiments he’d conducted on cimetidine (another H2 blocker) and ranitidine in human gastric fluid. Results showed that when ranitidine was exposed to gastric fluid in combination with nitrites, it created “toxic and mutagenic effects.” He recommended patients taking ranitidine should consider a diet “low in nitrates and nitrites,” and that doctors may want to suggest that patients not take these medications with meals.

In response, researchers from GlaxoSmithKline (GSK)—the company that originally developed Zantac—noted they were concerned about the potential formation of nitrosamines during the digestion of ranitidine, but argued that such a conversion would not likely occur in real-world experiences.

Meanwhile, GSK enjoyed substantial profits from its sale of Zantac, which reached $1 billion in total sales in December 1986, just three years after its release. In 1996, the drug became available without a prescription, and a year later, generic forms appeared on the market.

Despite additional studies questioning the safety of ranitidine, the manufacturers continued to advertise Zantac and generic ranitidine as perfectly safe for consumer use. Then in June 2019, online pharmacy Valisure discovered NDMA in samples of Zantac during its routine testing of products sold. The company notified the FDA of its findings and continued to investigate.

Meanwhile, the FDA was dealing with the carcinogen in blood pressure drugs like valsartan and losartan. NDMA had been discovered in samples of these drugs, and the FDA was overseeing a variety of recalls of the affected medications. The agency traced the problem back to certain manufacturing plants that were not adhering to the appropriate safety standards. 

On September 9, 2013, Valisure sent a citizen’s petition to the FDA, urging it to recall lots of Zantac and ranitidine that had been found to contain NDMA and to require manufacturers to conduct additional tests. The FDA followed with a safety communication on September 13, 2019, but the agency stopped short of recommending consumers stop using the product.

The agency did encourage companies to test their ranitidine drugs. Most followed that recommendation and many found NDMA. Those that did issued recalls for the affected products, and over the following months, many different brands of Zantac and generic ranitidine disappeared from store shelves. Current Zantac manufacturer Sanofi recalled the drug in October 2019.

The FDA investigated the issue as it had with the blood-pressure drugs, looking for the source of the NDMA, but didn’t find any manufacturing error or contamination problem that could explain it. Valisure believed it had the answer. In its petition, authors David Light, CEO, and Kaury Kucera, Chief Scientific Officer, 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.

The FDA has so far found no evidence to corroborate Valisure’s findings. In a statement dated November 2019, FDA Director for the Center for Drug Evaluation and Research Janet Woodcock, M.D. wrote that FDA tests simulating ranitidine digestion in the human stomach indicated that NDMA was not formed through this process. Woodcock added that “we still must test the drugs in the human body to fully understand if ranitidine forms NDMA.”

To date, the FDA maintains that determining the source of NDMA in ranitidine is “an ongoing investigation.”

FDA Recalls All Ranitidine from the Market

By the end of 2019, many companies had recalled their ranitidine products, but some remained on the market. The FDA did not recommend anything different until April 1, 2020, when it requested the withdrawal of all ranitidine products. This move was made in response to third-party studies that found the NDMA in ranitidine increased over time and with exposure to high temperatures.

In January 2020, independent laboratory Emery Pharma sent a citizen’s petition to the agency. Emery President and CEO Ramin Najafi, Ph.D. revealed 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—the older the ranitidine product, the greater the level of NDMA.

Based on these findings, the FDA took the final action of requesting the recall of all remaining ranitidine products. The agency advised consumers to stop taking the medication 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
• Intestinal 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 Stomach Cancer Lawsuits

In February 2020, an Illinois woman filed a new Zantac lawsuit in the U.S. District Court for the District of New Jersey. She claimed that after taking Zantac for about 18 years, she was diagnosed with gastric cancer. She stated in her complaint that she believed her cancer was caused by her exposure to NDMA in Zantac.

There are many other consumers out there who feel the same. Several have been diagnosed with cancer and have filed lawsuits against Zantac manufactures. Others are simply concerned about their risk, and now feel they must undergo additional medical monitoring.

As more consumers become aware of the fact that Zantac may have contained NDMA for years or even decades, the number of lawsuits is expected to continue to increase. 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 stomach 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.