After 5 Years, Zantac Back on the Market

 The FDA has approved a reformulated version of ranitidine (Zantac), more than 5 years after requesting the antacid be pulled from shelves over concerns that it could break down into a carcinogen.

Federal regulators announced that they okayed VKT Pharma's ranitidine tablets in 150-mg and 300-mg strengths while also outlining stronger recommendations for storing the medication.

The FDA said in April 2020 that all prescription and over-the-counter ranitidine products should be removed from the market immediately over concerns about the formation of the probable human carcinogen N-Nitrosodimethylamine (NDMA) during storage, particularly when kept at higher than room temperatures.

The FDA credited safety testing and manufacturing improvements for addressing concerns related to the histamine-2 receptor antagonist used to treat gastroesophageal reflux and to help prevent gastric and intestinal ulcers. The agency advised healthcare providers and patients that the reformulated version of ranitidine has the same therapeutic effectiveness as previously approved products.

In its announcement, the FDA advised that tablets should be kept away from moisture and in the original container. They should be discarded after 90 days of first opening or by the expiration date, whichever is sooner. Only one bottle should be opened at a time, with one tablet removed at a time. The bottle should then be closed immediately and tightly, keeping the desiccant inside.

Safety questions emerged in June 2019 after the online pharmacy Valisure, which tests the drugs it carries, alerted the FDA to contamination issues. Valisure filed a Citizen Petition 3 months later, stating that specific lots of the medication contained NDMA or could convert to NDMA in humans, urging federal regulators to pull all ranitidine products from the market.

The FDA subsequently determined some lots contained small amounts of NDMA, prompting some manufacturers of generic ranitidine to voluntarily halt distribution until the contamination issue could be resolved.

A 2016 study linking the use of ranitidine with roughly 400-fold and 2.5-fold increases in 24-hour urinary excretion of NDMA and dimethylamine, respectively, was retracted by its authors in 2021 after they said further research rendered their NDMA measurements unreliable. Also in 2021, two small FDA studies found the nitrosamine impurities in ranitidine do not appear to convert to NDMA in the body, with one finding no statistically significant difference in 24-hour urinary excretion of NDMA with an oral 300-mg dose compared with placebo.

A large 2023 study found that people who took ranitidine for at least a month were no more likely to develop cancer than people who took other histamine-2 receptor antagonists.

https://www.medpagetoday.com/gastroenterology/generalgastroenterology/118711