FDA seeks withdrawal of heartburn drugs due to new carcinogen concerns
The FDA on Wednesday requested that all manufacturers of drugs containing ranitidine (commonly known as Zantac and used for heartburn) remove all prescription and over-the-counter (OTC) versions from the market because the carcinogen N-Nitrosodimethylamine (NDMA) has now been found to increase significantly in samples stored at higher temperatures.
The announcement is the most serious in a chain of FDA safety advisories related to NDMA in ranitidine medicines following a series of recalls of Zantac and other ranitidine drugs, and as the agency said last November that the NDMA levels in such drugs “are similar to the levels you would expect to be exposed to if you ate common foods like grilled or smoked meats.”
Now, 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,” FDA said.
“The testing also showed that the older a ranitidine product is, or the longer the length of time since it was manufactured, the greater the level of NDMA. These conditions may raise the level of NDMA in the ranitidine product above the acceptable daily intake limit,” the agency added.
FDA also previously told companies to voluntarily withdraw ranitidine and nizatidine products that do not meet the agency’s NDMA threshold (96 nanograms per day or 0.32 ppm).
But now FDA is issuing this immediate market withdrawal request for all manufacturers, which means ranitidine products will not be available for new or existing prescriptions or OTC use in the US.
“Ranitidine products will stay off the market unless a manufacturer can show that their product is stable while stored and does not generate excess NDMA,” CDER Director Janet Woodcock said on Twitter.
As far as other heartburn medicines, FDA says that its testing has not found NDMA in famotidine (Pepcid), cimetidine (Tagamet), esomeprazole (Nexium), lansoprazole (Prevacid) or omeprazole (Prilosec).
FDA and the European Medicines Agency began investigating the presence of NDMA in ranitidine medicines last September.
RAPS: First published in Regulatory Focus™ by the Regulatory Affairs Professionals Society, the largest global organization of and for those involved with the regulation of healthcare products. Click here for more information.