In September, the FDA announced that samples of ranitidine, an H2 Blocker used for stomach upset, reflux and ulcers sold generically and under the brand name of Zantac, were found to have the contaminant N-nitrosodimethylamine (NDMA). This is one of the chemicals that prompted the generic ARB blood pressure medication recalls last year.
Now drugmakers are mandated to pull all Zantac brand name and generic products off the shelves and stop online sales.
Patients are also urged to stop taking any of the products they currently have and discard them immediately following the FDA’s drug disposal guidelines. Discussions with one’s healthcare provider should be done if consumers need medication alternatives.
Other similar medications in its class such as: famotidine (Pepcid), cimetidine (Tagamet), esomeprazole (Nexium), lansoprazole (Prevacid) or omeprazole (Prilosec), are not believed to have the same risks of NDMA exposure.
We don’t believe there have been reports of consumers becoming ill. In animals, N-nitrosodimethylamine (NDMA) is known to cause liver and lung cancer. It has been linked to tumor production in a variety of human organs, including the tongue, esophagus, lung, pancreas, liver, kidney and bladder (Ciemniak A., 2006). Additionally, the CDC states it may cause liver function impairment and cirrhosis.
The FDA writes:
The agency has determined that the impurity in some ranitidine products increases over time and when stored at higher than room temperatures and may result in consumer exposure to unacceptable levels of this impurity. As a result of this immediate market withdrawal request, ranitidine products will not be available for new or existing prescriptions or OTC use in the U.S.
Hence the FDA believes unsafe levels of NDMA could exist in the medications if the product was stored in higher than normal room temperatures.
They also state:
NDMA is a probable human carcinogen (a substance that could cause cancer). In the summer of 2019, the FDA became aware of independent laboratory testing that found NDMA in ranitidine. Low levels of NDMA are commonly ingested in the diet, for example NDMA is present in foods and in water. These low levels would not be expected to lead to an increase in the risk of cancer. However, sustained higher levels of exposure may increase the risk of cancer in humans. The FDA conducted thorough laboratory tests and found NDMA in ranitidine at low levels. At the time, the agency did not have enough scientific evidence to recommend whether individuals should continue or stop taking ranitidine medicines, and continued its investigation and warned the public in September 2019 of the potential risks and to consider alternative OTC and prescription treatments.
New FDA testing and evaluation prompted by information from third-party laboratories confirmed that NDMA levels increase in ranitidine even under normal storage conditions, and NDMA has been found to increase significantly in samples stored at higher temperatures, including temperatures the product may be exposed to during distribution and handling by consumers. The testing also showed that the older a ranitidine product is, or the longer the length of time since it was manufactured, the greater the level of NDMA. These conditions may raise the level of NDMA in the ranitidine product above the acceptable daily intake limit.
With today’s announcement, the FDA is sending letters to all manufacturers of ranitidine requesting they withdraw their products from the market. The FDA is also advising consumers taking OTC ranitidine to stop taking any tablets or liquid they currently have, dispose of them properly and not buy more; for those who wish to continue treating their condition, they should consider using other approved OTC products. Patients taking prescription ranitidine should speak with their health care professional about other treatment options before stopping the medicine, as there are multiple drugs approved for the same or similar uses as ranitidine that do not carry the same risks from NDMA. To date, the FDA’s testing has not found NDMA in famotidine (Pepcid), cimetidine (Tagamet), esomeprazole (Nexium), lansoprazole (Prevacid) or omeprazole (Prilosec).
The investigation is ongoing and more needs to be looked at when it comes to this manufacturing process suspected to result in these “impurities” being made.
Last year NDEA was also found in the generic blood pressure medications that were the subject of recall, however has not yet been suggested as being present in ranitidine.
N-Nitroso-N-methyl-4-aminobutyric acid (NMBA) was the third chemical detected resulting in the latest two recalls of losartan, an angiotensin receptor blocker commonly used to treat hypertension (high blood pressure). It is believed to have been created during the manufacturing process of the generic drug.
NMBA, according to Toronto Research Chemicals, is a known carcinogen in a wide range of animal species.
Previously, ScieGen Pharmaceuticals, Inc. recalled certain lots of irbesartan, a similar angiotensin receptor blocker used in blood pressure management.
The recalls initially began in 2018 when the FDA recalled a number of lots of valsartan due to an “impurity”, N-nitrosodimethylamine (NDMA) that is known to cause cancer in animals. Weeks later they additionally found traces of N-nitrosodiethylamine (NDEA).
According to Reuters, earlier that year, the MHRA, Medicines and Healthcare Products Regulatory Agency, located in the UK, said the appearance of the impurity, N-nitrosodimethylamine (NDMA), came after a change in the process for making valsartan at one facility owned by Zhejiang Huahai Pharmaceuticals, a company in Linhai, China.
With NDEA, data is limited, but due to its classification as a nitrosamine and its prevalence in tobacco smoke it is classified as a probable human carcinogen.
According to New Jersey Department of Health’s website, NDEA has been linked to liver, lung and gastrointestinal tract cancer in animals.
Losartan, valsartan and irbesartan are medications in the class of angiotensin receptor blockers (ARBs) used for high blood pressure and congestive heart failure.
Those taking either tablet for their blood pressure are urged to not abruptly stop their medication but rather check with their medical provider and pharmacy to see if their particular prescription is involved in the recall.
I suspect more recalls will follow as processes may be similar across multiple pharmaceutical facilities and NMBA, NDMA and NDEA are byproducts that may not be individually unique to just one “brand” of medication manufacturing.