New research has confirmed what many have long suspected: The presence of a cancer-causing chemical in Zantac results from the slow breakdown of ranitidine, the active ingredient in the popular antacid medications.
The study, which appeared this month in the medical journal Organic Process Research & Development, was conducted by scientists in the United Kingdom in cooperation with GlaxoSmithKline. Their root-cause analysis determined that rising levels of N-nitrosodimethylamine (NDMA) in Zantac were the result of degrading ranitidine hydrochloride molecules. The analysis also suggested that heat – including the heat generated by the human body’s digestive process – was among the factors that can trigger the transformation of ranitidine into NDMA.
“Analysis using suitably isotopically labeled ranitidine hydrochloride confirmed the formation of NDMA solely from an intermolecular reaction of ranitidine hydrochloride without involvement of impurities,” the study authors wrote. “Factors that influence the rate of degradation include heat, humidity, and the crystal morphology of ranitidine hydrochloride with the material exhibiting a columnar habit showing a slower rate of degradation.
GlaxoSmithKline was just one of the numerous pharmaceutical companies to recall Zantac and other ranitidine-containing heartburn drugs in 2019 after the online pharmacy Valisure detected excessive levels of NDMA in every sample it tested. Valisure also asserted that the instability of the ranitidine molecule results in the production of NDMA when the drug is subjected to conditions that mimic human digestion.
Emery Pharma later reported that its own testing suggested NDMA was produced when ranitidine products were exposed to high temperatures typically encountered during shipment and storage.
The U.S. Food & Drug Administration (FDA) eventually confirmed those findings in April 2020 and ordered all Zantac and generic ranitidine drugs recalled. But by that time, many pharmaceutical companies had already taken steps to withdraw their ranitidine-containing heartburn drugs from the market. Several major retailers, including Walmart, Walgreens, Rite-Aid, and CVS, had also stopped selling the medications by the time the FDA acted.
NDMA is an organic, environmental contaminant found in water and foods, including meats, dairy, and vegetables. However, animal testing suggests exposure to high levels of NDMA can increase the risk of cancer, especially kidney, liver, and gastrointestinal cancers. Both the World Health Organization and the U.S. Environmental Protection Agency have designated NDMA as a probable human carcinogen.
More than 550 Zantac lawsuits are now pending in a multidistrict litigation underway in the U.S. District Court, Southern District of Florida, all of which allege the ingestion of ranitidine-containing medications contributed to the development of cancer. Plaintiffs further claim that Glaxo and other manufacturers had long known that ranitidine could expose users to dangerous levels of NDMA but failed to disclose this risk to doctors and patients.