FDA is announcing that agency laboratory testing has revealed levels of the nitrosamine impurity N-Nitrosodimethylamine (NDMA) above the agency’s acceptable intake limit in several lots of the extended-release (ER) formulation of metformin, a prescription drug used to control high blood sugar in patients with type 2 diabetes. The agency is in contact with five firms to recommend they voluntarily recall their products. There are additional manufacturers of the metformin ER formulation that supply a significant portion of the U.S. market, and their products are not being recalled.
Patients should continue taking metformin tablets even after recalls occur, until they consult with their health care professional who can prescribe a replacement.
FDA testing has not shown NDMA in immediate release (IR) metformin products (the most commonly prescribed type of metformin). The agency is working with manufacturers of the recalled tablets to identify the source of the NDMA impurity. At this time, the elevated levels of NDMA have been found in some finished-dose tablets of the ER formulation but have not been detected NDMA in samples of the metformin active pharmaceutical ingredient.
The agency is also asking all manufacturers of metformin containing ER products to evaluate the risk of excessive NDMA in their product and to test each batch before it is released into the U.S. market. If testing shows NDMA above the acceptable intake limit, the manufacturer should inform the agency and should not release the batch to the U.S. market.
NDMA is a common contaminant found in water and foods including cured and grilled meats, dairy products and vegetables. The FDA’s acceptable intake limit for NDMA in drug formulations is 96 nanograms per day. Nitrosamine impurities may increase the risk of cancer if people are exposed to them at above-acceptable levels over long periods of time.