Last month, Drug Safety News featured a story about Valisure, a small, independent pharmaceutical testing lab in Connecticut that discovered carcinogenic NDMA in Zantac. It wasn't outside contamination – it was a problem with the molecule at the heart of the formulation. Like all reputable researchers, the people at Valisure went to an outside lab, Emery Pharma, in order to confirm their results. What they discovered was alarming. It turns out that ranitidine, the active ingredient in Zantac, can actually transform itself into NDMA just by being exposed to warm temperatures.
NDMA (n-nitrosodimethylamine or dimethylnitrosamine) is an oily, yellowish colored substance that is a byproduct of a number of industrial processes. It is found in smoked meats and tobacco products among other consumables. This chemical was discovered in the blood pressure medication valsartan in 2018. Since then, traces of NDMA have been found in other drugs of the ARB class as well as the antidepressant Xanax and, outside the U.S., metformin, the first-line treatment for type-2 diabetes.
After Valisure reported its findings to the FDA, the government agency ran its own tests. Last September, it announced that “low levels” of NDMA had been discovered. Although the FDA did not advise patients to stop taking the medication (and in fact has been minimizing the risks), several drug manufacturers – including Novartis, the original developer of Zantac – moved ahead with their own recalls of the brand name and generic products.
Now, Emery Pharma has found evidence to indicate that NDMA levels in ranitidine can rise on their own when exposed to high temperatures. During tests in which ranitidine was heated to nearly 160 degrees Fahrenheit, the amount of NDMA increased from 25 to 142 nanograms – well above the “safe” level of 96 nanograms established by the FDA.
In an interview on CBS This Morning, Emery founder and CEO Ron Najafi, a chemist, said, “If someone were to keep their Zantac in their car in the middle of summertime, that product is going to get heated up and it's going to generate this compound. NDMA...is not an impurity in the drug, it's being formed from the drug itself.” This exposure to heat can also occur during shipping, he noted.
FDA research director Dr. Janet Woodcock acknowledged the findings, but said, “...these are pretty high temperatures. The question about whether ranitidine would need to be kept cold to keep it from converting is something that still hasn't been answered.”