The Food and Drug Administration has called for the withdrawal of all prescription and over-the-counter forms of the heartburn drug ranitidine, commonly known by its brand name Zantac, due to concerns of contamination with a probable human carcinogen.The carcinogen, NDMA, increases over time and when the drug is stored at higher than room temperature, which “may result in consumer exposure to unacceptable levels of this impurity,” the agency said in a statement Wednesday.Numerous drugmakers and pharmacies had already suspended distribution of ranitidine because of the contamination. More than 20 manufacturers have licenses to sell various forms of the drug, although most have discontinued it.
The FDA’s request for manufacturers to pull ranitidine from market nationwide is a notable escalation in a months-long investigation into NDMA contamination, and suggests a higher level of concern from the regulator.
The World Health Organization has linked NDMA, or N-nitrosodimethylamine, to gastric and colorectal cancer, although at elevated levels. The FDA on Wednesday said the levels that NDMA reaches in ranitidine formulations with age or higher temperatures “may result in consumer exposure to unacceptable levels of this impurity.”
The decision to order the recall came 10 months after online pharmacy Valisure told the FDA that its laboratory had detected NDMA at high levels, and nearly seven months after the pharmacy filed a citizen’s petition asking for a recall.
The FDA initially argued that the testing method, which uses high temperatures, artificially generated NDMA at high levels. The agency said in November its own testing revealed NDMA contamination at levels that patients would be exposed to through diet, like the consumption of grilled meats.
Wednesday’s announcement was based on additional testing. “New FDA testing and evaluation prompted by information from third-party laboratories confirmed that NDMA levels increase in ranitidine even under normal storage conditions, and NDMA has been found to increase significantly in samples stored at higher temperatures, including temperatures the product may be exposed to during distribution and handling by consumers,” the regulator said.
The agency recommended patients needing heartburn relief switch to drugs like famotidine or omeprazole, which have not been shown to contain NDMA. Due to the coronavirus pandemic, the FDA warned against returning unused ranitidine to drug take-back locations, and instead recommended following manufacturers’ instructions for safe in-home disposal.
The FDA’s investigation into ranitidine contamination grew out of a larger examination of heart drugs like valsartan and losartan that began in summer 2018. The finding of unacceptable contaminant levels in drugs taken by millions of Americans has put further scrutiny on a drug supply chain that’s now spread across the globe.
