Agency recommends voluntary recall of some extended release pills

WASHINGTON —The FDA recommended that five manufacturers voluntarily recall several lots of the extended-release (ER) formulation of metformin after laboratory testing found unacceptable levels of N-Nitrosodimethylamine (NDMA) impurity in the drugs.

Metformin, a prescription drug used to control high blood sugar in patients with type 2 diabetes, is the latest in a series of products affected by alarmingly high levels of NDMA, a possible human carcinogen. Nitrosamine contamination has plagued the pharmaceutical industry since 2018 — NDMA first triggered several recalls of the angiotensin II receptor blockers valsartan, losartan, and irbesartan through 2018-2019 before the impurity was found in several ranitidine products, prompting the FDA to request that manufacturers remove all lots of the heartburn drug from the market.

“The FDA has strict standards for safety, effectiveness and quality, and the agency makes every effort based on science and data to help keep the U.S. drug supply safe,” said Patrizia Cavazzoni, MD, acting director of the FDA’s Center for Drug Evaluation and Research, in a statement. “We understand that patients may have concerns about possible impurities in their medicines, and want to assure the public that we have been looking closely at this problem over many months in order to provide patients and health care professionals with clear and accurate answers. Now that we have identified some metformin products that do not meet our standards, we’re taking action. As we have been doing since this impurity was first identified, we will communicate as new scientific information becomes available and will take further action, if appropriate.”

The FDA first became aware of the presence of NDMA in certain ER metformin products in the U.S. via a citizen petition filed by a private laboratory, after which the agency conducted its own testing on the same lots the laboratory reported.

“The agency confirmed unacceptable NDMA levels in some, but not all, of those lots,” the agency explained. “In other instances, our laboratory detected NDMA in lots that the private laboratory did not. The agency also found that the levels of NDMA, when present, were generally lower than reported by the private laboratory. Given FDA scientists’ deep experience quantifying these impurities in drugs, the agency is confident in the reliability of the FDA’s testing method and results and will continue to take action based on the latest scientific information. The results have also been consistent with the findings of other regulatory agencies’ laboratories around the world.”

While the FDA is working with manufacturers to remove the impacted lots from the market and asking all other ER metformin manufacturers to test each batch for NDMA impurities before sending them to store shelves, the agency also warned that patients should continue to take their metformin tablets until they are able to consult with their physician to receive a replacement.

“Patients with type 2 diabetes could face dangerous health risks if they stop taking their prescribed metformin,” the agency wrote. “The FDA recommends that health care professionals continue to prescribe metformin when clinically appropriate; FDA testing has not shown NDMA in immediate release (IR) metformin products (the most commonly prescribed type of metformin).”

John McKenna, Associate Editor, BreakingMED™

Cat ID: 183

Topic ID: 70,183,183,730,13,192,669,725,918