Zantac

Studies + Science

How Zantac Works

Ranitidine and nizatidine are both histamine H2 receptor antagonists. These drugs work by blocking histamine from connecting with their receptors and preventing them from triggering. The end result is a decrease in the secretion of stomach acid, and relief from conditions like heartburn, GERD, and stomach ulcers. 

NDMA, also known as dimethylnitrosamine (DMN), is an organic compound that is classified by the FDA and the International Agency for Cancer Research of the World Health Organization as a probable carcinogen for humans. NDMA was labeled as a probable carcinogen after trials on rats demonstrated the development of tumors after long term exposures. NDMA can also be toxic if consumed in extreme amounts. 

When NDMA is consumed by humans, it undergoes a transformation in the liver into a molecule that can damage DNA and with long term exposure lead to the development of cancer. According to a 2016 article published in the Chinese Journal of Epidemiology, NDMA has been linked to both gastric and colorectal cancers.  

NDMA most often occurs as a byproduct of industrial processes. The precursor to NDMA can leach into drinking water sources, where water treatment by chlorination can convert it to NDMA. NDMA does not degrade easily and requires additional careful treatment to remove it from water sources. NDMA can also enter water sources as a pesticide contaminant. 

NDMA is also found in significant levels in tobacco smoke and chewing tobacco products, and in lower levels in cured meats, cheeses, beer, vegetables, and other foods. 

NDMA has not been found in ranitidine and nizatidine products at a high enough level to cause immediate adverse effects, but it has been found in these products beyond the safe daily limit for carcinogenic exposure. Long term exposure to these NDMA contaminated products would place a patient at a higher risk for developing cancer.

However, in the accompanying November 1 release of laboratory testing results, the FDA had collected so far, several ranitidine and nizatidine products had levels of NDMA well above acceptable daily levels. The FDA declined to issue a mandatory recall, instead continuing to rely on voluntary recalls by pharmaceutical companies.  

By April 2020, the FDA had withdrawn all ranitidine products from the stream of commerce immediately.

Next Steps

The FDA so far has only found concerning levels of NDMA in ranitidine and nizatidine products. With a voluntary recall, patients are dependent on manufacturers or distributors to test their products and withdraw them if NDMA contamination is found. Major drugstore chains like Walmart, Walgreens, and CVS have already withdrawn Zantac and generic versions of ranitidine. 

Until the FDA issues new guidance on the state of ranitidine and nizatidine products, the FDA has suggested that patients seek alternatives to treat heartburn, GERD, stomach ulcers, and related conditions.

The FDA currently lists the following drugs as NDMA-free: famotidine (Pepcid), cimetidine (Tagamet), esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec). Due to greater side effects, it is advised that cimetidine not be used as a first choice alternative to ranitidine or nizatidine. 

In addition to drug alternatives, patients might also find it helpful to use antacids such as Tums to help relieve heartburn. Changes to diet like reducing oversized or high-fat meals, alcohol, and spicy foods can also help prevent aggravation of stomach acid-related conditions. 

NDMA can be detected by testing blood and urine samples, and if patients are concerned about exposure to unsafe levels of NDMA they should discuss testing with their physician.