Following reports of low-level contamination of N-nitrosodimethylamine (NDMA) in metformin medicines in other countries, the FDA released a statement addressing the levels of NDMA in the U.S. metformin supply. This comes after a recent statement regarding NDMA contamination in ranitidine and widespread recalls of generic angiotensin II receptor blockers (ARBs) as a result of NDMA contamination. The FDA is evaluating whether the level of NDMA, considered a probable carcinogen, poses a risk to patients.
A recall has not been recommended at this point.
"Patients should continue taking metformin to keep their diabetes under control. It could be dangerous for patients with this serious condition to stop taking their metformin without first talking to their health care professional. The FDA recommends prescribers continue to use metformin when clinically appropriate, as the FDA investigation is still ongoing, and there are no alternative medications that treat this condition in the same way," said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.
Metformin is the first-line drug control of high blood sugar levels in patients with type 2 diabetes.
Levels of NDMA found in metformin supplies in other countries have been within the range generally seen in food and water, according to the FDA. The FDA and international scientific community do not consider low levels of NDMA—commonly found in foods such as cured and grilled meats, dairy products, and vegetables—to cause harm.
According to Woodcock, “The acceptable daily intake limit for NDMA is the U.S. is 96 nanograms. Genotoxic substances such as NDMA may increase the risk of cancer if people are exposed to them above acceptable levels and over long periods of time, but a person taking a drug that contains NDMA at-or-below the acceptable daily intake limit every day for 70 years is not expected to have an increased risk of cancer.”
With more advanced testing methodology and better knowledge of what manufacturing processes may increase the formation of nitrosamines, the FDA is systematically evaluating the U.S. drug supply in search of medicines with nitrosamines above acceptable limits and removing them from the market.
“Our investigations, including our current investigation of metformin, take into account the medical necessity of the drug, how many Americans may take it, and whether there may be alternative treatments available,” Woodcock noted. “We understand that these issues affect patients’ health and well-being in many ways, and the FDA’s goal is to provide patients and health care providers as much clarity and as many answers as possible to inform their health care decisions.”
Should the ongoing investigation result in a recall of metformin, the FDA “will communicate any information we have scientifically confirmed to ensure the public knows as much as possible as soon as possible.”
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