If you have been reading this newsletter, you know that one of the most popular acid-reducing drugs in the world became embroiled in a carcinogen controversy over two years ago. That’s when a pharmacy in New Haven, Connecticut, Valisure, ran a routine test on ranitidine to check for nitrosamines. On September 9, 2019, this testing organization filed a Citizen Petition with the FDA requesting a recall and suspension of sales of ranitidine (Zantac). Not long after that the ranitidine weirdness hit the fan!
Eventually ranitidine disappeared from the market along with the initial brand Zantac. You can read about the bizarre flip-flop-flip history in the following articles.
Here are some links to ranitidine weirdness:
And then there was this:
Zantac Was GONE…But Now It’s BACK!
We recently received a question from a reader who missed Zantac.
Then he saw it on pharmacy shelves and wondered what the heck was going on:
“Zantac helped my heartburn for years when other medications didn’t. Proton pump inhibitors (PPIs) like omeprazole caused me serious side effects.
“I was very disappointed when Zantac was pulled off the market. Frankly, I’d rather be given the choice to continue with the Zantac rather than wonder what to do for heartburn.
“Yesterday in the drugstore I saw a product labeled Zantac 360. Are they bringing it back? What’s the deal?”
What’s the Zantac Flip-Flop-Flip-Flop All About?
The Food and Drug Administration requested removal of Zantac (ranitidine) more than a year ago. That’s because tests showed it and generic ranitidine products could contain NDMA (N-nitrosodimethylamine), a probable human carcinogen.
“The agency has determined that the impurity in some ranitidine products increases over time and when stored at higher than room temperatures and may result in consumer exposure to unacceptable levels of this impurity.”
Zantac was a popular brand name, originally as a prescription anti-ulcer medicine. Later it was sold over the counter for heartburn.
The drug company that sold Zantac prior to the recall is now reintroducing the brand as Zantac 360°™. This nonprescription heartburn medicine now contains a different ingredient, famotidine. It was originally sold under the brand name Pepcid and is now also available OTC as Pepcid AC. There is no NDMA problem with famotidine.
Ranitidine Weirdness vs Zantac Reintroduction:
With such ranitidine reports it is not surprising that readers might be a bit confused.
This person wants to know about a ranitidine recall:
Q. I have been on ranitidine to control acid reflux for four years. Ranitidine has been in the news, but I cannot find out if my medicine has been recalled. It is made by Strides Pharma. My pharmacist has been no help. Do you have any info?
A. Strides Pharma Science Limited, based in Bangalore, India, stopped US sales of ranitidine in late September. Your pharmacist should have been able to check on this for you.
From the Horse’s Mouth:
We consulted David Light, head of Valisure, the Connecticut pharmacy that discovered the carcinogen NDMA in ranitidine (Zantac).
He told us:
“Many, if not most, ranitidine products have now been recalled. It is the view of Valisure that the chemical, biological and clinical data strongly suggest that all ranitidine products are easily susceptible to forming the carcinogen NDMA. Valisure tested other medications in the same drug class, H2 blockers, that do not have the same inherent ability to form NDMA. These include famotidine (Pepcid) and cimetidine (Tagamet). It’s important to note that another H2 blocker, nizatidine, also formed NDMA in Valisure’s chemical tests.”
Listen to David Light describe in greater detail how Valisure discovered the nitrosamine problem with ranitidine and other options people with heartburn might have on our podcast. The Light interview occurs about two-thirds of the way into the podcast, after our discussion with Dr. Tieraona Low Dog about dietary supplements. Here is a link to our interview: “Are Supplements Really A Waste of Time?”
Another FDA Flip-Flop on Ranitidine:
This is what we call triple whiplash. First, the FDA said “some” ranitidine pills contained the nitrosamine impurity NDMA. That was on September 13, 2019. The agency was responding to a September 9, 2019 “Citizen Petition” from Valisure, the pharmacy that discovered the problem. The FDA downplayed the risk and did not call for individuals to stop taking ranitidine.
Second, the FDA did a U turn. The agency initially stated that the nitrosamines in Zantac and ranitidine “barely exceed amounts you might expect to find in common foods.” Then it stated that:
“To date, the agency’s early, limited testing has found unacceptable levels of NDMA in samples of ranitidine.”
Many pharmaceutical companies announced voluntary recalls for ranitidine.
Third, on November 1, 2019 the FDA once again downplayed the danger of nitrosamines in ranitidine.
Here is part of the statement from Dr. Janet Woodcock, the FDA executive who has tremendous authority at the agency:
“Through our testing so far, we have found levels of NDMA in ranitidine that are similar to the levels you would expect to be exposed to if you ate common foods like grilled or smoked meats… Although many of these levels of NDMA observed through FDA testing are much lower than the levels some third-party scientists first claimed, some levels still exceed what the FDA considers acceptable for these medicines…. If we or the manufacturers find NDMA levels above the acceptable limits (96 nanograms per day or 0.32 ppm), we’re now asking companies to voluntarily recall ranitidine. We would also ask manufacturers to voluntarily recall nizatidine, commonly known as Axid, if they found NDMA above the acceptable daily intake level because it is chemically similar to ranitidine.”
Trying to Make Sense of Ranitidine Weirdness
Permit us to try to summarize the FDA’s position and a contrary assessment from David Light:
- Yes, some, perhaps most, ranitidine products contain the nitrosamine N-nitrosodimethylamine (NDMA). It is a “probable carcinogen.”
- Some of the ranitidine/Zantac the FDA tested had nine times the “acceptable limit” for NDMA.
- Do not worry, though. Dr. Woodcock says “Through our testing so far, we have found levels of NDMA in ranitidine that are similar to the levels you would expect to be exposed to if you ate common foods like grilled or smoked meats.” In other words, do not worry, be happy.
- Some scientists have suggested that ranitidine can be converted to nitrosamines inside the human body because the chemical structure of the acid-suppressing drug is inherently unstable. The FDA responded: “We also conducted tests that simulate what happens to ranitidine after it has been exposed to acid in the stomach with a normal diet and results of these tests indicate that NDMA is not formed through this process.”
- David Light of Valisure responds: “… these are overly simplistic conditions that do not properly evaluate a real-world stomach.”
A study published in JAMA (July 20, 2021) concluded:
“In this trial that included 18 healthy participants, oral ranitidine (300 mg), compared with placebo, did not significantly increase 24-hour urinary excretion of NDMA when participants consumed noncured-meats or cured-meats diets. The findings do not support that ranitidine is converted to NDMA in a general, healthy population.”
But…the FDA also noted (April 1, 2020):
“The agency has determined that the impurity [NDMA] in some ranitidine products increases over time and when stored at higher than room temperatures and may result in consumer exposure to unacceptable levels of this impurity. As a result of this immediate market withdrawal request, ranitidine products will not be available for new or existing prescriptions or OTC use in the U.S.”
The Fourth and Final Flop on Zantac:
And now, Zantac is back…but not as ranitidine. It has returned as famotidine. Companies recognize the power of brand loyalty. We suspect that most shoppers do not bother to read label ingredients. They don’t know what’s in their pain pills, their allergy medicine or their laxative. All they know is that they take a familiar medicine and it works to relieve their symptoms. If it’s famotidine instead of ranitidine to relieve heartburn they could care less. And as David Light stated above, famotidine is not a problem when it comes to nitrosamines.
Our Bottom Line on Ranitidine Weirdness:
The FDA says there are unacceptable levels of nitrosamines in ranitidine, but don’t worry, it’s really not a problem. We’re not sure the story is over. We predicted back in November, 2019, that the ranitidine weirdness might continue for weeks or even months. Now that Zantac is back as famotidine, we would say that prediction sort of came true.
You can learn more about these histamine-blocking medications and many other ways to treat heartburn in our eGuide to Overcoming Digestive Disorders. This online resource may be found under the Health eGuides tab. You will also learn about nondrug approaches to controlling heartburn, constipation, celiac disease, diarrhea and IBS.