This week the FDA reported they would investigate if metformin, a popular diabetic drug, contained NDMA within the US market.
NDMA, N-nitrosodimethylamine, is a known carcinogen in a wide range of animal species. It’s in the class of nitrosamines, which may be genotoxic (altering the genetic material in cells causing them to mutate) and cancer-causing in those who are exposed to unacceptable levels for long periods of time. The “acceptable range” according the FDA is 96 ng per day.
The FDA on their website states the following:
The FDA is aware that some metformin diabetes medicines in other countries were reported to have low levels of NDMA. Based on the information we have available, the levels of NDMA seen outside the U.S. are within the range that is naturally occurring in some foods and in water. While we are aware that some regulatory agencies outside the U.S. may be recalling some metformin drugs, there are no metformin recalls affecting the U.S. market at this time. The FDA is investigating whether metformin in the U.S. market contains NDMA, and whether it is above the acceptable daily intake limit of 96 nanograms. The agency will also work with companies to test samples of metformin sold in the U.S. and will recommend recalls as appropriate if high levels of NDMA are found. If as part of our investigation, metformin drugs are recalled, the FDA will provide timely updates to patients and health care professionals.
So no recalls have been initiated at this time.
According to Reuters, earlier last summer, 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.
I suspect more investigations or recalls will follow as processes may be similar across multiple pharmaceutical facilities and NMBA, NDMA and NDEA (discussed below) are byproducts that may not be individually unique to just one “brand” of medication manufacturing.
Generic Zantac Being Investigated for NDMA
The FDA has 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 NDMA. This is one of the chemicals that prompted the generic ARB blood pressure medication recalls last year.
There have been no reports of users becoming ill and no recall has been suggested at this time. In animals, NDMA is known to cause liver and lung cancer. In humans its carcinogenic risk is unknown, however the CDC states it may cause liver function impairment and cirrhosis.
The FDA writes:
THE FDA IS NOT CALLING FOR INDIVIDUALS TO STOP TAKING RANITIDINE AT THIS TIME; HOWEVER, PATIENTS TAKING PRESCRIPTION RANITIDINE WHO WISH TO DISCONTINUE USE SHOULD TALK TO THEIR HEALTH CARE PROFESSIONAL ABOUT OTHER TREATMENT OPTIONS. PEOPLE TAKING OTC RANITIDINE COULD CONSIDER USING OTHER OTC MEDICINES APPROVED FOR THEIR CONDITION. THERE ARE MULTIPLE DRUGS ON THE MARKET THAT ARE APPROVED FOR THE SAME OR SIMILAR USES AS RANITIDINE.
CONSUMERS AND HEALTH CARE PROFESSIONALS SHOULD REPORT ANY ADVERSE REACTIONS WITH RANITIDINE TO THE FDA’S MEDWATCH PROGRAM TO HELP THE AGENCY BETTER UNDERSTAND THE SCOPE OF THE PROBLEM:
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 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.
Last Fall, ScieGen Pharmaceuticals, Inc. recalled certain lots of irbesartan, a similar angiotensin receptor blocker used in blood pressure management.
The recalls initially began last summer when 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).
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, stomach acid issues, or diabetes 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 or investigation.