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Regulatory Focus™ > News Articles > 2019 > 12 > FDA to Heartburn Drug Manufacturers: Do Not Release Lots if NDMA is Above Acceptable Levels

FDA to Heartburn Drug Manufacturers: Do Not Release Lots if NDMA is Above Acceptable Levels

Posted 05 December 2019 | By Zachary Brennan 

FDA to Heartburn Drug Manufacturers: Do Not Release Lots if NDMA is Above Acceptable Levels

As manufacturers of popular heartburn drugs, like Zantac, continue to pull their products from shelves, the US Food and Drug Administration is now telling the companies to test their drugs for an impurity, known as N-nitrosodimethylamine (NDMA), before making them available.

The new requirement comes as earlier last month FDA noted that although many of these NDMA levels observed via FDA testing are much lower than the levels some third-party scientists first claimed, “some levels still exceed what the FDA considers acceptable for these medicines,” said Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research.

So the agency late Wednesday said it has asked manufacturers of ranitidine and nizatidine products to expand their testing for NDMA to include all lots of the medication before making them available to consumers.

“If testing shows NDMA above the acceptable daily intake limit (96 nanograms per day or 0.32 parts per million for ranitidine), the manufacturer must inform the agency and should not release the lot for consumer use,” the agency said.

Back in October, FDA recommended certain testing methods for companies to identify NDMA in their products. To date, FDA’s testing has not found NDMA in alternative treatments such as Pepcid (famotidine), Tagamet (cimetidine), Nexium (esomeprazole), Prevacid (lansoprazole) or Prilosec (omeprazole).

“Our scientists have determined ranitidine does not form NDMA in typical stomach conditions. However, we need further investigation to fully test how ranitidine and nizatidine behave in the human body and have plans to study this. There is also some evidence that there may be a link between the presence of nitrites and the formation of NDMA in the body if ranitidine or nizatidine is also present. Because of this, consumers who wish to continue taking these drugs should consider limiting their intake of nitrite-containing foods, e.g. processed meats and preservatives like sodium nitrite,” the agency added.

Meanwhile, across the pond, the European Medicines Agency (EMA) is calling on companies, by 26 April 2020, to conduct a risk evaluation to identify products at risk of N-nitrosamine formation or (cross-) contamination and report the outcome and fill out either the template indicating “no risk identified” or “risk identified.”

EMA said it plans to complete this exercise by 26 September 2022, although “this timeline should be shortened in case of findings indicating higher risk to public health and that may require further risk minimisation measures,” the agency said.

FDA Updates and Press Announcements on NDMA in Zantac (ranitidine)

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