FDA calls for market removal of ranitidine


A problem with probable human carcinogen N-nitrosodimethylamine (NDMA) contamination in ranitidine, commonly known by the brand name Zantac, has led the Food and Drug Administration to call for manufacturers of the drug to remove all product, both branded and generic over-the-counter and prescription forms, from the market.

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The NDMA contamination does not stem from a manufacturing concern, but rather the levels have been found to increase over time depending on how the ranitidine is stored.

In particular, the FDA found through product testing that the NDMA impurity developed over time when the ranitidine was stored above room temperature.

“The testing also showed that the older a ranitidine product is, or the longer the length of time since it was manufactured, the greater the level of NDMA,” FDA said in a statement announcing the call for product withdrawal.

The FDA has been investigating NDMA contamination since September 2019 when the agency first announced the contamination in ranitidine. Manufacturers have been withdrawing their products from the market since the first reports of contamination surfaced. Despite these recalls, there were still ranitidine products on the market, according to an FDA spokesperson, necessitating the further action taken by the agency.

In addition to products being removed from the market, FDA is asking consumers to discard any ranitidine products they may have.

“There are still questions about how the impurity is formed in ranitidine over time during storage,” Janet Woodcock, MD, director of the FDA Center for Drug Evaluation and Research, said during an April 1 conference call with reporters announcing the withdrawal request. “For example, what impact does the drug packaging have on the development or the specific formulation have on the development of NDMA.”

Dr. Janet Woodcock, director, FDA's Center for Drug Evaluation and Research.

Dr. Janet Woodcock

She said the issue may be fixable over time, and the agency is open to reformulations that demonstrate that ranitidine is stable over time and under various storage conditions.

Dr. Woodcock stressed that the products at the point of manufacture do not have unacceptable levels of NDMA.

“This is a market withdrawal, this is not a recall because technically the products are okay. They met all their specs,” she said. “It is only when they are subjected generally to heat stress do they manifest higher levels” of NDMA.

“Clearly, we can’t have products on the market that if they are stored under conditions consumers might store them under that they would become unacceptable.”

Dr. Woodcock said FDA is not withdrawing approvals for the products, but manufacturers would need to show the product remains stable under normal storage conditions.

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