Many lots of the drug Valsartan were recalled last year due to the contamination of n-nitrosodimethylamine (NDMA), a known animal carcinogen and a probable human carcinogen. More recently, a number of manufacturers recalled their Zantac and ranitidine products due to the belief that the drugs can naturally produce high levels of NDMA as a byproduct of the digestion process. In May 2020, the Food and Drug Administration (FDA) announced it had found high levels NDMA in certain batches of the type-2 diabetes drug Metformin. Many individuals don’t know what NDMA is or how it can impact their health and lifestyle. Here we’ll explore what it is and why the recall was necessary.
What Is NDMA?
NDMA is a semi-volatile organic chemical that can form naturally or unintentionally through industrial processes. Unintentional NDMA can form as a byproduct of the chlorination of wastewater and drinking water. This process led NDMA to be found in Valsartan tablets produced by four different facilities: Zhejiang Huahai Pharmaceuticals in China, Hetero Labs Limited in India, Aurobindo Pharma in India, and Mylan Laboratories, Ltd. in India.
NDMA can also be formed through natural processes. Ranitidine, the active ingredient in Zantac, has a molecular structure that makes it susceptible to naturally creating NDMA once it is ingested. Specifically, the ranitidine compound contains the two elements that are required to form NDMA: nitrite (“N”) and dimethylamine (“DMA”). The presence of both nitrite and dimethylamine in ranitidine’s chemical structure renders it highly capable of producing NDMA under the right conditions.
A recent independent study conducted by Valisure Online Pharmacy sought to understand how capable ranitidine was of naturally producing NDMA. During the testing, Valisure simulated the conditions that ranitidine is exposed to in the human stomach to see how the ranitidine would react; namely, they mixed ranitidine with the gastric fluid and sodium nitrites that stimulate the digestion process. They found that when the ranitidine interacts with the gastric fluid and sodium nitrites found in the stomach, high amounts of NDMA are produced. In fact, when exposed to the simulated stomach conditions, the ranitidine produced approximately 304,500 nanograms (ng) of NDMA per tablet. This is an alarming amount of NDMA, considering the FDA-approved acceptable amount of NDMA intake is 96 ng per day.
Concerns about the molecular generation of NDMA associated with ranitidine have led to several recalls of ranitidine products.
In September 2019, there were voluntary recalls by Sandoz, Inc. and Apotex Corp. The Sandoz ranitidine recall involves 14 lots of prescription capsules, while the Apotex ranitidine recall involves all of its 75mg and 150mg over-the-counter capsules. Many of the Apotex capsules were labeled and sold by popular pharmacies Walgreens, Wal-Mart, and Rite-Aid.
In October 2019, numerous additional voluntary recalls have been announced. On October 23rd, it was announced the Dr. Reddy’s Laboratories Ltd and Sanofi would be recalling ranitidine products. The Dr. Reddy’s recall involves all prescription and over-the-counter capsules manufactured by the company, while Sanofi issued a recall of its over-the-counter ranitidine. On October 28th, it was announced that Perrigo Company, Novitium Pharma LLC, and Lannett Company, Inc. would be recalling ranitidine products as well due to the presence of NDMA. Perrigo Company is recalling all over-the- counter ranitidine tablets; Novitium Pharma is recalling all ranitidine hydrochloride capsules; and, the Lannett Company recall involves all lots of prescription ranitidine syrup.
While several recalls have already occurred, several other countries, including Canada, have taken further action by ordering complete recalls of all Zantac and ranitidine products.
In December 2019, the regulators for multiple global health organizations began testing samples of the type 2 diabetes drug metformin for NDMA contamination. As of December 5, 2019, there has been no metformin recall in the United States. The FDA said in a statement that it has not confirmed any NDMA contamination of metformin sold in the United States, but that any contamination detected beyond the acceptable daily intake limit will lead to recommended recalls. Singapore’s Health Sciences Authority announced on December 4 that is was recalling three metformin medications due NDMA contamination.
In March 2020, Valisure filed a citizen petition with the FDA after it found high levels of NDMA in certain batches of metformin. The citizen petition described Valisure’s testing protocols that improved the accuracy of its tesdting and requested the agency recall the contaminated metformin. On May 27, 2020, the FDA announced it had found high levels of NDMA in some versions of metformin. The agency said it would be in contact with the manufacturers of the contaminated batches to determine the appropriate next steps.
Metformin is manufactured as a generic by multiple global pharmaceutical companies. Popular brand name drugs sold in the United States that contain metformin include Fortamet, Glucophage, Glucophage XR, Glumetza, and Riomet.
What Are the Effects?
NDMA can contaminate drinking water and humans often get NDMA exposure from consuming food or drink that was contaminated with NDMA. Exposure to NDMA in Valsartan can cause prostate cancer, lower esophageal cancer, non-hodgkins lymphoma, leukemia, multiple myeloma, colon, stomach, intestinal, or pancreatic cancer. Even small amounts of exposure can lead to liver damage. Exposure to NDMA in ranitidine has been linked to a number of cancers including stomach cancer, cancer in the small and large intestines, colorectal cancer, esophageal cancer, kidney cancer, bladder cancer, liver cancer, prostate cancer, pancreatic cancer, leukemia, non-hodgkin’s lymphoma, and multiple myeloma.
Classified as a Carcinogen
The EPA classifies NDMA as a B2 carcinogen, meaning it is a probable human carcinogen. B2 carcinogens do not have enough human data but have a sufficient amount of animal data to conclude that it’s a potential carcinogen. Many animal studies were done to test NDMA, and they found that various species, including rats and mice, developed tumors in the liver, respiratory tract, and blood vessels after exposure to NDMA. The U.S. Department of Health and Human Services believes that NDMA is “reasonably anticipated to be a human carcinogen.”
If you or a loved one contracted cancer after taking Valsartan, ranitidine, or metformin, contact the dangerous drug attorneys at GoldenbergLaw. We are committed to promoting safety through accountability.