Carcinogen in Heartburn Drug May Build in Storage, Lab Finds

(Bloomberg) -- The heartburn medicine Zantac appears to produce unacceptably high levels of a cancer-causing chemical when exposed to heat for as little as five days, according to a testing laboratory that’s urging the U.S. Food and Drug Administration to recall all forms of the widely used product.

Since at least September, the FDA has been monitoring the presence of a toxic chemical found in some samples of Zantac, which is also sold in generic versions. But the agency has found that levels of the chemical, NDMA, vary from safe to dangerously high. Those discrepancies have created uncertainty about how contamination is happening and whether consumers can safely use some versions of the drug.

New testing by an Alameda, California-based independent laboratory called Emery Pharma found that a combination of heat and time can raise levels of NDMA, potentially while drugs are sitting in packaging well after being analyzed by their manufacturers.

Numerous manufacturers have already pulled products from pharmacy shelves, including Sanofi, which makes the brand-name version of Zantac. A leading oncology hospital, New York’s Memorial Sloan Kettering Cancer Center, has also said it will no longer offer the drug to patients while it reviews the risk. The FDA has yet to push for any widespread recall.

Currently, the FDA asks drugmakers to test Zantac products after production and not release them to the public if they would expose patients to more than 96 nanograms of NDMA per day. But the new analysis suggests that even limited exposure to high heat, such as in a hot car or a delivery truck, could cause problems, said the lab’s chief executive officer.

“The more you heat it, the more NDMA you generate,” Emery CEO Ron Najafi said in a telephone interview. “I am worried that if it just sits at home at room temperature, it could gradually generate NDMA.”

Emery Pharma was originally hired by the pharmacy company Valisure LLC, which markets itself as source of quality-tested drugs and has petitioned the FDA to recall all forms of Zantac. Najafi has also worked as an expert witness in litigation on contamination of drugs with NDMA, including Zantac and its generics.

Recall Request

The agency will review the citizen petition and respond directly to the group that filed it, said Jeremy Kahn, an FDA spokesman. He declined to comment on the substance of the filing, and said the FDA is working with manufacturers to ensure a safe and high-quality drug supply.

The FDA has been investigating whether ranitidine, the active ingredient in Zantac, is converted into NDMA inside the body after it’s been consumed. The agency said its tests have shown levels in the medicine that are naturally found in smoked and grilled meats. While manufacturers conduct stability tests on new medicines in development, Zantac was originally approved in 1983, well before the technology existed to pick up such low levels of NDMA, Najafi said.

On Thursday, Emery filed a Citizen Petition with the FDA, asking the agency to suspend sales of all products containing ranitidine, to recall those that are already on the market and to require stability testing before they can be sold in the future. The medicine should also be shipped in temperature-controlled vehicles and carry warnings that potential cancer-causing byproducts may be produced if it is exposed to heat, the lab said.

The testing by Emery looked at three samples of ranitidine over time. A high dose of the active ingredient surpassed the FDA’s daily 96-nanogram limit of NDMA after just five days at 70 degrees Celsius (158 degrees Fahrenheit). After 12 days at the same temperature, the lab found 142 nanograms of NDMA.

Lower temperatures produced NDMA as well. An identical sample at the lower temperature of 25 degrees Celsius (77 degrees Fahrenheit) steadily rose to 25 nanograms over 12 days.

Some people take multiple doses each day, exposing them to higher levels, Najafi said.

“Manufacturers should have a strong warning on the label that if the product has been heated above a certain temperature, they shouldn’t use it,” he said. “Or else you may be exposing yourself to large quantities of this cancer-causing agent.”

©2020 Bloomberg L.P.

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