Craig Rosenbaum | December 10, 2019 | Defective Drugs
As of September of 2019, the popular heartburn medicine Zantac (ranitidine) has been recalled and taken off shelves in pharmacies after the Food and Drug Administration announced that it had found the cancer-causing chemical N-nitrosodimethylamine (NDMA) in some batches of Zantac. Major pharmaceutical companies such as Sanofi-Aventis, Chattem, Inc., Boehringer Ingelheim, Pfizer, and GlaxoSmithKline have been listed as defendants in the recently filed lawsuit.
High Levels of NDMA Detected
The online pharmacy Valisure discovered the NDMA contamination during a “routine analysis of drug products in its pharmacy,” according to the company’s September 9, 2019 citizen petition to the FDA. Based on its findings, Valisure asked the FDA to “recall and suspend the sale of all lots of all products containing ranitidine.” In response, the FDA conducted its own testing on the products and agreed that levels of NDMA were higher than what was deemed to be safe. As a result, on September 13, 2019, the FDA issued a statement alerting patients and health care professionals that NDMA had been found in samples of ranitidine.
The FDA has determined that daily intake of NDMA should not exceed 96 nanograms- one billionth of a gram. When Valisure tested individual tablets, it found 2,511,469 of NDMA in Zantac OTC and 3,267,968 ng of NDMA in Zantac Cool Mint from CVS. The FDA has said that Valisure’s method of high-temperature testing may have increased the levels of NDMA in samples, but still reported unacceptable levels of the contaminate after “early, limited testing” of the samples using a low-heat method.
In the following weeks, the FDA released several statements alerting the public to product recalls starting with those from generic ranitidine manufacturers, On October 22, 2019, Zantac manufacturer Sanofi recalled brand-name Zantac products.
The FDA has published its suggestions for approved testing methods meant to detect nitrosamine impurities in ranitidine drug samples. The agency recommended non-heating methods to produce quality results.
Dangers of NDMA
NDMA is a “probable human carcinogen.” This means it is a potent carcinogen in animals, but there aren’t enough studies to verify its carcinogen effects on humans. In humans, the most common signs of acute NDMA poisoning are stomach cramps, nausea and vomiting that can occur within hours, according to studies from the U.S. National Library of Medicine’s Toxicology Data Network. Headaches, fever and weakness may occur, followed by jaundice and enlargement of the liver. Organs potentially affected by the ingestion of NDMA include the bladder, kidneys, liver, lungs, pancreas and stomach.
There is debate as to why Zantac and generic ranitidine contain NDMA. The FDA has labeled it as an “impurity,” but Valisure asserted that the product itself, when it breaks down in the digestive system, naturally releases NDMA as it is metabolized in the body. Valisure’s website posted that their research, “along with that of Stanford University and others, found that NDMA was the result of the ‘inherent instability’ of the ranitidine molecule. This means that all manufacturers, brand or generic, and all lots of ranitidine-containing medications are affected and could generate high levels of NDMA in the human body.”
In a 2016 study on oral intake of ranitidine, scientists examined urine samples from five healthy female and five healthy male volunteers over 24-hour periods before and after consumption of 150 mg of ranitidine. Following intake, the urinary NDMA excreted over 24 hours increased 400-hold from 110 to 47,600 ng, while total N-nitrosamines increased by 5-fold. “NDMA excretion rates after ranitidine intake equaled or exceeded those observed previously in patients with schistosomiasis,” the researchers wrote, “a disease wherein N-nitrosamines are implicated as the etiological agents for bladder cancer.”
Current State of Litigation
A group of plaintiffs recently filed a motion with the U.S. Judicial Panel on Multidistrict Litigation (JPML) to consolidate all federally filed Zantac lawsuits into one court for pre-trial proceedings. The plaintiffs assert that all the pending actions involve common factual questions- namely, that plaintiffs purchased ranitidine and were exposed to the carcinogen NDMA. Zantac has been sold in the United States for more than 30 years and the plaintiffs state that “every one of the millions of the drug’s consumers have been exposed to dangerous levels of NDMA and many thousands of those consumers have contracted cancer as a result.” The plaintiffs who filed the initial petition suggest the U.S. District Court for the District of New Jersey as the location for the proposed MDL, mainly because lawsuits involving valsartan contamination with NDMA- which the plaintiffs see as very similar to the lawsuits involving Zantac and NDMA- are consolidated there.