On Friday, September 13, 2019, the FDA officially acknowledged that “some” ranitidine (Zantac) pills have been found to contain the nitrosamine impurity NDMA (N-nitrosodimethylamine). Nitrosamines are considered potent carcinogens. How did this happen? How long has it been going on? Who discovered this problem? How worrisome is it? What should be done? This People’s Pharmacy Special Health Alert will attempt to answer those questions.
The Snowball That Started the Avalanche:
You may remember that the popular blood pressure drugs called ARBs (Angiotensin II Receptor Blockers) started being recalled over a year ago because of carcinogen contamination. Drugs like irbesartan, losartan and valsartan were found to contain nitrosamines such as NDMA, NDEA (N-nitrosodiethylamine) and NMBA (N-nitroso-N-methyl-4-aminobutyric acid).
We were among the first to notify the public about this disaster. We issued a People’s Pharmacy Health Alert on July 15, 2018, about the blood pressure medicine Valsartan (Diovan). That was 10 days after the European Medicines Agency raised the first red flag about Chinese-made valsartan contaminated with NDMA. We had to keep revising this article as more recalls followed.
Since then we have written about “sartan” recalls so many times we have lost count. Tens of millions of pills have been pulled off pharmacy shelves because of nitrosamine contamination. Here is just one of our many posts:
Another Day Another Losartan Recall | Can We Trust the FDA?
Who Discovered that Ranitidine Is Tainted with a Carcinogen?
Because of concerns about generic drugs in general, and the ARB contamination catastrophe in particular, one pharmacy decided to start testing all the drugs it dispensed. Valisure is an online pharmacy based in New Haven, Connecticut.
The company’s motto:
“Valisure is the only pharmacy that chemically tests every batch of every medication that we sell, at no additional cost.
“Batch-tested medication. Delivered to your door.”
The scientists at Valisure discovered that the ranitidine and Zantac samples it was testing had unexpectedly high levels of the nitrosamine NDMA. This is an extremely popular acid-blocking drug. According to our calculations, over 15 million ranitidine prescriptions are dispensed annually. That does not count all the over-the-counter bottles of Zantac and house brand ranitidine that are sold.
Zantac was first marketed in the U.S. in 1983. By 1988 it was the # 1 most prescribed drug in the world. An executive at GlaxoSmithKline was purported to have said that “Zantac was the engine that pulled the train.” In other words, Zantac was the cash cow at the company.
Valisure’s Citizen Petition on Ranitidine:
On September 9, 2019, Valisure notified the Food and Drug Administration that there was a big problem with ranitidine and Zantac.
That was when it filed a “Citizen Petition” with some startling revelations:
“The drug ranitidine, commonly sold under the brand Zantac, is an antacid, specifically an H2 receptor blocker (“H2 blocker”), which, due to a very high perception of safety, is heavily prescribed to adults and infants and sold over-the-counter. Valisure tests all batches of all its medications for quality and consistency issues and through such tests detected extremely high levels of N-nitrosodimethylamine (“NDMA”), a probable human carcinogen, in every lot tested, across multiple manufacturers and dosage forms of the drug ranitidine. The Food and Drug Administration (“FDA”) has established a permissible daily intake limit for the probable human carcinogen, NDMA, of 96 ng. Valisure has detected NDMA in excess of 3,000,000 ng per tablet when analyzing ranitidine products, likely due to an inherent instability of the ranitidine molecule.”
Yikes! Do the math. If Valisure’s testing procedures are accurate, that’s over 30,000 times the permissible FDA level for NDMA. Valisure calls for the agency to “recall and suspend sale of all lots of all products containing ranitidine.” The pharmacy asks the FDA to investigate the manufacturing processes for this drug and instruct people on the safe disposal of ranitidine.
FDA’s Response:
The initial response from the FDA was surprisingly prompt. On September 13, 2019, Janet Woodcock, MD, Director of the Center for Drug Evaluation and Research (CDER) put out a statement.
It said in part:
“The U.S. Food and Drug Administration has learned that some ranitidine medicines, including some products commonly known as the brand-name drug Zantac, contain a nitrosamine impurity called N-nitrosodimethylamine (NDMA) at low levels.
“The FDA has been investigating NDMA and other nitrosamine impurities in blood pressure and heart failure medicines called Angiotensin II Receptor Blockers (ARBs) since last year. In the case of ARBs, the FDA has recommended numerous recalls as it discovered unacceptable levels of nitrosamines.
“When the agency identifies a problem, it takes appropriate action quickly to protect patients. The FDA is evaluating whether the low levels of NDMA in ranitidine pose a risk to patients. FDA will post that information when it is available.
“Although NDMA may cause harm in large amounts, the levels the FDA is finding in ranitidine from preliminary tests barely exceed amounts you might expect to find in common foods.
“The FDA is not calling for individuals to stop taking ranitidine at this time; however, patients taking prescription ranitidine who wish to discontinue use should talk to their health care professional about other treatment options. People taking OTC ranitidine could consider using other OTC medicines approved for their condition. There are multiple drugs on the market that are approved for the same or similar uses as ranitidine.”
Unanswered Questions About Ranitidine Tainted with a Carcinogen:
- How long has this been going on?
We may never know for sure. According to Valisure, nitrosamine formation may be an inherent characteristic of the ranitidine. That means it could have existed for decades.
- How worrisome is the NDMA in ranitidine and Zantac?
Valisure seems to believe that this is so serious all products containing this molecule should be recalled now. The FDA seems to be saying, don’t worry, be happy. The agency is not calling for a recall and “is not calling for individuals to stop taking ranitidine at this time…”
- What should be done?
We need immediate assessment of the level of risk. Is the amount of nitrosamine contamination as minimal as the FDA suggests or as alarming as Valisure contends?
David Light, CEO of Valisure, is quoted as saying (Bloomberg, September 13, 2019):
“There’s no acceptable cancer risk for a drug like this.”
Until all questions are answered, we tend to err on the side of caution. There are lots of antacids and acid-controlling drugs on the market. H2 antagonists like cimetidine (Tagamet) and famotidine (Pepcid) have not been linked to nitrosamines. Good old-fashioned baking soda (sodium bicarbonate) can serve as an antacid in a pinch. And of course there are products containing calcium carbonate or magnesium hydroxide. These ingredients are found in OTC antacids.
You can read about lots of ways to control indigestion in our eGuide to Digestive Disorders. If you prefer nondrug approaches to heartburn, you will find lots in The People’s Pharmacy Quick & Handy Home Remedy Book.
Final Words:
We used to be among the FDA’s biggest boosters.
In our second book, The People’s Pharmacy-2 (1980), we acknowledged an FDA Commissioner:
“A great many people helped us put this book together. We never could have made it without the assistance of…
“Jere Goyan, the best damn Commissioner of the Food and Drug Administration this country has ever had!”
There are many great scientists at the Food and Drug Administration. That said, we have lost confidence in the agency. Its ability to monitor generic drug quality and safety has been called into questions. You can listen to our free interview with Katherine Eban about her book, Bottle of Lies at this link. Our interview with Rosemary Gibson, author of China Rx: Exposing the Risks of America’s Dependence on China for Medicine can be found here.
Should you wish to learn more about how we discovered flaws in the FDA’s oversight of generic drugs, here is a link to Top Screwups.
What do you think about the possibility that ranitidine is tainted with a carcinogen? Is it all a tempest in a teapot? Only time will tell. Please share your thoughts in the comment section below.
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