November 10, 2019 – The FDA issued warnings about cancer risks associated with Zantac after finding unacceptable levels of the probable carcinogen NDMA while testing it and its generic, ranitidine, earlier in September. Zantac had been prescribed more than 15 million times a year without safety concerns prior to the FDA’s announcement. The agency wanted manufacturers to test and recall drugs to see if NDMA levels exceeded standards. Investigations still sought to determine if Zantac and ranitidine users faced greater cancer risk, but in the interim, the agency recommended that consumers might want to choose different medications. The FDA found no NDMA in over-the-counter alternatives such as Pepcid, Tagamet, Nexium, Prevacid, and Prilosec.
The FDA was still working to determine how the carcinogen is formed.
Valisure, an independent online laboratory and pharmacy, tested Zantac in stomach-like fluids with added nitrates commonly found in the body and in foods. With nitrates added, Valisure found one tablet of Zantac exceeded the FDA’s NDMA threshold 3,100 times.
Following the agency’s announcement, many retailers and drugmakers had taken action. Health Canada stopped distributing the drug. Sanofi, a French drugmaker, recalled the drug from retail shelves and drugstores. Germany, Italy, and Switzerland did the same. Taiwan instituted a fine for any pharmacy with ranitidine on its shelves, and Pakistan banned the drug’s distribution and manufacturing. In the U.S., eight companies pulled ranitidine from their shelves. These included pharmaceutical companies and generic ranitidine drugs from Kroger and Walgreens. Despite the voluntary recalls, the FDA took a more conservative approach, asking manufacturers to recall the drugs only if NDMA exceeds standards after testing.
Zantac had been approved for mass markets in 1984, and the researchers at Valisure had said that the drug’s potential risks could be found in medical studies all the way back to close to the date of its inception. Valisure CEO David Light said the risk appears to be in the drug itself, instead of as a manufacturing byproduct, and he confirmed that the problem had existed since its development in the 1980s. In a petition to the FDA, Valisure cited concerns about the validity of the 1987 study on ranitidine conducted by Glaxo Research Group, Zantac’s original research group. The 1987 Glaxo study examined the stomach contents of people who took Zantac. The study found no significant increase in NDMA in users, but Light claimed the study was not accurate. Light said researchers discarded stomach samples that contained ranitidine and used less accurate testing methods. According to Light, the researchers would not have found NDMA without those samples.
While researchers and other agencies sought to determine if Zantac contained unsafe levels of NDMA, the FDA extended voluntary recalls to nizatidine, a similar drug sold under the brand name Axid, if testing showed that it exceeded NDMA daily limits. Of note, NDMA was also the carcinogen that led to the July 2018 recall of valsartan and losartan, two popular blood-pressure-lowering medications.
At this point in investigations, the FDA was not calling for patients to stop taking ranitidine and it had not requested a manufacturer recall. Some companies had voluntarily suspended Zantac sales while waiting for results from ongoing tests and research. NDMA had been classified as a probable carcinogen, but it did not seem that NDMA levels were high enough in Zantac to cause cancer. However, ranitidine was not recommended for long-term use and the FDA suggested that patients talked to a health care professional about alternative treatment options.
Reference: Johnson, Carolyn Y. “A Tiny Pharmacy Is Identifying Big Problems with Common Drugs, Including Zantac.” The Washington Post, WP Company, 8 Nov. 2019, https://www.washingtonpost.com/science/a-tiny-pharmacy-is-identifying-big-problems-with-common-drugs-including-zantac/2019/11/08/6dd009ca-eb76-11e9-9c6d-436a0df4f31d_story.html.