FDA Issues Recall Alert for Metformin ER Products

The recall stems from a recent series of tests that revealed unacceptably high levels of N-nitrosodimethylamine, a probable human carcinogen, in several lots of metformin extended-release products.

"Now that we have identified some metformin products that do not meet our standards, we're taking action, "said Patrizia Cavazzoni, M.D., acting director of the agency's Center for Drug Evaluation and Research, in a press release. "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."

Companies Notified

FDA officials said in a May 29 conference call that the firms that have been contacted are

• Actavis Pharma Inc.,
• Amneal Pharmaceuticals, LLC,
• Apotex Corp.,
  
• Lupin Pharma and
• Marksans Pharma Ltd.

Of those five, the only recall notice listed on the FDA's Recalls, Market Withdrawals & Safety Alerts page at the time of the conference call was for all lots of metformin 500-mg tablets marketed by Apotex, a Canadian firm headquartered in Toronto. During the call, FDA officials said the agency would post additional recall notices as they are published.

Apotex said in a company announcement that the FDA had found elevated NDMA levels in one lot of its metformin ER, USP 500-mg tablets, which prompted the voluntary recall. Apotex noted that the firm stopped selling that particular product in the United States in February 2019 and that it has not received any reports of adverse events related to the product to date.

Amneal has since issued its own press release announcing voluntary withdrawal of all lots of its metformin ER 500- and 750-mg tablets. It also stated that no reports of adverse events had been received.

Additional Direction

The FDA is recommending that clinicians continue to prescribe metformin when clinically appropriate. In addition, the agency recommends that patients continue taking metformin products even after recalls occur until they can consult with their physician to receive a replacement prescription or different treatment option.

All manufacturers of metformin-containing ER products are being asked to evaluate the risk of excessive NDMA in their products and to test each batch before releasing it into the U.S. market. If testing shows NDMA above the acceptable intake limit, the manufacturer should inform the agency and halt release of the batch.

It should be noted that the recall does not apply to immediate-release metformin products.

According to the FDA, several other firms that manufacture extended-release metformin formulations have not had their products recalled. The agency is currently evaluating whether the announced recalls will create shortages in metformin ER products and will work with manufacturers to prevent or reduce the impact of any shortages.

Metformin is one of the most commonly prescribed drugs in the United States and is often the first oral medication prescribed for people newly diagnosed with diabetes. According to the Agency for Healthcare Research and Quality, more than 78 million prescriptions for metformin were written in 2017, with extended-release versions of the drug accounting for about one-quarter of those prescriptions.