Outrage of the Month: FDA Foot-Dragging on Tainted Heartburn Drug Endangers Public Health

Health Letter, February 2020

By Michael Carome, M.D.

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On Sept. 13, 2019, the Food and Drug Administration (FDA) first announced that some medications containing the commonly used histamine-2 (H2) blocker ranitidine, which suppresses acid in the stomach, had been found to be contaminated with N-nitrosodimethylamine (NDMA), a probable human carcinogen (a substance that could cause cancer).

Nevertheless, despite growing evidence that many ranitidine products contain amounts of NDMA that exceed federal safety standards and uncertainty about the potential harm, the FDA still has not requested a recall of all ranitidine products from the U.S. market or advised consumers taking ranitidine to switch to available alternative treatments. Instead, the agency has taken only half measures.

Ranitidine is available over-the-counter (OTC) under the brand name ZANTAC for prevention and treatment of heartburn due to acid indigestion and by prescription in generic form for treatment and prevention of ulcers in the stomach and intestines, gastroesophageal reflux disease and other conditions. Of note, there are many other OTC and prescription medications available to treat these conditions.

Regulators in other countries have acted with more appropriate caution than the FDA to address the public health risks posed by NDMA-containing ranitidine medications. For example, Health Canada on Sept. 17 announced that at its request, companies marketing ranitidine products in Canada had stopped further distribution of these medications “until evidence is provided to demonstrate that they do not contain NDMA above acceptable levels.” Canadian regulators noted that NDMA may be found in ranitidine products, regardless of the manufacturer. Likewise, according to the Los Angeles Times, drug regulators in France in late September ordered a recall of all ranitidine products available in pharmacies.

STAT reported that the online pharmacy Valisure first alerted the FDA about NDMA contamination of ranitidine in June. Valisure, which tests batches of each medicine it sells for impurities, detected the carcinogen in every ranitidine product it analyzed. The company believes the problem is inherent to ranitidine itself because the drug appears to degrade into NDMA. In fact, the head of Valisure expressed concern that such degradation may even occur in the human body after the drug is ingested.

On Sept. 18, Novartis, one of several makers of generic ranitidine, announced it was halting worldwide distribution of its ranitidine products as a precaution. Novartis and multiple other companies subsequently voluntarily recalled their ranitidine products from pharmacies in the U.S. The FDA has passively publicized these drug-company-initiated recalls.

The FDA did conduct laboratory tests to measure NDMA levels in ranitidine products and issued the results on Nov. 1. The agency found unacceptable levels of NDMA in one or more prescription and over-the-counter ranitidine products manufactured by nine of 13 companies. For several products, the amount of NDMA detected in a single tablet or dose of ranitidine was more than five times higher than the acceptable daily amount of NDMA ingestion.

The FDA also reported that no additional NDMA was detected when ranitidine was exposed to conditions like those found inside the stomach and intestines. However, Dr. Janet Woodcock, the director of the FDA’s Center for Drug Evaluation and Research, noted that “we still must test the drugs in the human body to fully understand if ranitidine forms NDMA.”

The FDA downplayed the significance of its findings, stating that the levels of NDMA that it detected in ranitidine products were “similar to the levels you would expect to be exposed to if you ate common foods like grilled or smoked meats.” Rather than request a recall of all ranitidine products, the FDA only said on Nov. 1 that it was asking manufacturers of ranitidine products with NDMA levels above the acceptable daily intake limit to recall such products.

On Dec. 4, the FDA asked manufacturers of ranitidine products to expand their testing for NDMA to include all new lots of the medications and instructed them not to distribute any lots of the medication found to have levels of NDMA above the acceptable daily intake limit. However, there remains significant uncertainty regarding whether ranitidine will degrade into NDMA over time, particularly if stored in warm temperatures, or be converted to NDMA in the body after ingestion.

In the case of ranitidine products, the FDA once again has recklessly ignored the precautionary principle of public health by not taking appropriate action to mitigate potential harm despite a lack of definitive scientific evidence. Given the availability of many alternative treatments for heartburn, ulcers and stomach-acid-related conditions — including antacids, other H2 blockers and proton pump inhibitors — the FDA should direct all manufacturers of ranitidine products to recall and cease further distribution of these products and should advise patients who are using ranitidine to consult with their health care professionals about switching to other available alternatives.