Ranitidine recalled due to detection of impurity

In response to the detection of N-nitrosodimethylamine, a probable carcinogen, several companies have recalled the histamine H2 receptor antagonist, although FDA testing has found that levels detected are low.

The FDA has announced recalls of several forms of over-the-counter (OTC) ranitidine, including products branded as Zantac, due to potential contamination.

Over the past several weeks, the FDA has been investigating the detection of an impurity known as N-nitrosodimethylamine (NDMA) in the medications. NDMA is classified as a probable human carcinogen. The FDA summarized results of its investigation in a Nov. 1 update, saying that the levels of NDMA detected in ranitidine are low, “similar to the levels you would expect to be exposed to if you ate common foods like grilled or smoked meats.” In addition, simulation tests concluded that NDMA is not formed after it has been exposed to a small intestine environment or exposed to acid in the stomach with a normal diet.

Still, the agency has asked manufacturers to recall ranitidine if product lots contain NDMA levels above the acceptable limits (96 nanograms/d or 0.32 ppm). It has also asked companies to recall nizatidine, a chemically similar histamine H2 receptor antagonist, if NDMA is detected above the acceptable level. On Oct. 18, Sanofi recalled all OTC ranitidine branded as Zantac (Zantac 150, Zantac 150 Cool Mint, and Zantac 75) due to this issue. Perrigo Company, Dr. Reddy's Laboratories Ltd., and Novitium Pharma LLC have also recalled all pack sizes of ranitidine. In addition, American Health Packaging recalled eight lots of ranitidine oral solution USP (15 mg/mL), and Lannett Company, Inc., recalled all lots of ranitidine oral solution USP (15 mg/mL). Finally, Aurobindo Pharma USA, Inc., recalled one lot of ranitidine tablets (150 mg) and 37 lots of ranitidine capsules (150 mg and 300 mg) and ranitidine oral solution USP (15 mg/mL), and Amneal Pharmaceuticals, LLC, recalled 11 lots of ranitidine tablets (150 mg and 300 mg) and one lot of ranitidine oral solution USP (15 mg/mL).

In the meantime, the FDA's recommendations have remained consistent. Those taking OTC ranitidine or nizatidine can consider using other OTC products approved for their condition. So far, FDA and industry testing of H2 blockers and proton-pump inhibitors has only identified NDMA in ranitidine and nizatidine. Alternative medicines, such as famotidine, cimetidine, esomeprazole, lansoprazole, and omeprazole, have not tested positive for NDMA impurities. Patients taking prescription ranitidine who wish to stop should speak to their clinicians about other treatment options, the FDA said.