If you have been reading this newsletter you know that one of the most popular acid-reducing drugs in the world has become embroiled in a carcinogen controversy. Several weeks ago a pharmacy in New Haven, Connecticut, Valisure, ran a routine test on ranitidine to check for nitrosamines. Here are links to the initial ranitidine weirdness:
Popular Heartburn Drug (Zantac/Ranitidine) Tainted with a Carcinogen
FDA Flip-Flops on Nitrosamines in Zantac and Ranitidine
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 last Saturday’s 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.
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.”
Stanford researchers reported in the journal Carcinogenesis (June, 2016):
“In this work, we confirmed the production of N-nitrosodimethylamine (NDMA), a potent carcinogen, by nitrosation of ranitidine under stomach-relevant pH conditions in vitro. We also evaluated the urinary NDMA excretion attributable to ingestion of clinically used ranitidine doses. Urine samples collected from five female and five male, healthy adult volunteers over 24-h periods before and after consumption of 150mg ranitidine were analyzed for residual ranitidine, ranitidine metabolites, NDMA, total N-nitrosamines and dimethylamine. Following ranitidine intake, the urinary NDMA excreted over 24h increased 400-folds from 110 to 47 600ng, while total N-nitrosamines increased 5-folds.”
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 suspect that the ranitidine weirdness will continue for weeks or even months. Stay tuned for updates.
In the meantime, our advice to this reader is:
Talk with your primary care provider about an alternative to ranitidine. You may wish to consult our Guide to Digestive Disorders for nondrug approaches to controlling heartburn. You can find it in our Health Guide section at this link.