There was a time when Zantac (ranitidine) was the world’s most successful drug. This heartburn and anti-ulcer medicine hit the market in 1983. It was a cash cow for Glaxo, earning billions. We heard through the grapevine that an executive at the company described Zantac as the “engine that pulled the train.” But there is growing concern that there could be a connection between ranitidine and cancer (JAMA Network Open, Jan. 29, 2021).
NDMA and Cancer?
The problem is a nitrosamine called NDMA (N-nitrosodimethylamine). It is classified as a potent carcinogen in animal studies and a “probable” human carcinogen. This compound started showing up in “sartan” blood pressure drugs back in the summer of 2018. These medications are also called ARBs (angiotensin receptor blockers).
A Chinese pharmaceutical company (Zhejiang HuaHai) had introduced a contaminant into the manufacturing of valsartan. The European Medicines Agency (EMA) issued a warning about NDMA and its potential for causing cancer.
Eventually, other sartans were found to be contaminated with nitrosamines. Millions of pills containing irbesartan, losartan and valsartan were removed from the market.
Valisure, Ranitidine and Cancer:
A pharmacy in New Haven, Connecticut became quite concerned about the quality of generic drugs.
They had developed a sophisticated testing process to verify that the products they were selling online were safe and of high quality:
“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 Valisure lab discovered that the NDMA problem was not confined to blood pressure medications. The company found this nitrosamine in both Zantac and generic ranitidine. Valisure notified the FDA on September 9, 2019 that this popular over-the-counter heartburn medicine contained NDMA. It took the FDA until April 1, 2020 to:
“request the removal of all ranitidine products (Zantac) from the market.”
Is There A Connection Between Ranitidine and Cancer?
A collaboration between Valisure and Memorial Sloan Kettering Cancer Center in New York City has led to an early online preprint in medRxiv (posted Jan. 29, 2021).
Here are their conclusions:
“Under simulated gastric conditions, ranitidine yields increasing amounts of NDMA over time (up to, and likely beyond 4 hours) and with increasing concentrations of sodium nitrite. In addition, among a cohort of cancer patients reporting use of H2-blockers or PPIs at the time of diagnosis, we found an association between ranitidine use and cancers of the breast, thyroid, bladder and prostate.”
When you look at the preprint, you see what is called an odds ratio or OR. This means the elevated relative risk of thyroid cancer was 89% for those taking ranitidine vs. other acid-suppressing drugs. The increased relative risk for bladder cancer was 58%. The OR for prostate cancer was 80% and for breast cancer the increased relative risk was 58%.
The NDMA Problem “May be Tip of the Iceberg:”
The Invited Commentary in JAMA Network Open (Jan. 29, 2021) notes that NDMA:
“…is a chemical shown to induce tumor formation in the gastrointestinal tract, liver, lungs, and kidneys in animals.”
The author mentions other research in humans:
“…a preliminary observational study by Mathes et al. assessed the association between use of H2 blockers and risk of different types of breast cancer. Current users of ranitidine were found to have a significantly increased risk of ductal carcinoma but neither cimetidine nor famotidine were associated with increased risk.”
Dr. C. Michael White also discusses other drugs that may form NDMA. That’s why his subtitle suggests that ranitidine’s nitrosamine “problem may be the tip of the iceberg.” Another acid-suppressing drug, nizatadine, may also lead to NDMA production.
More Concerns About Ranitidine:
An epidemiologist at the University of Alabama at Birmingham has added to the controversy about ranitidine and cancer.
Writing in the journal Cancers (Dec. 23, 2020), Dr. McGwin notes in the introduction:
“N-nitrosodimethylamine (NDMA) is a carcinogen in experimental animals. It has been classified a probable human carcinogen and has been found in ranitidine. This study sought to evaluate the association between ranitidine use and cancer of the gastrointestinal system.”
What he did was compare cancer rates between ranitidine and other acid-suppressing drugs that were submitted to FDA’s Adverse Events Reporting System (FAERS). He dubbed this Proportional Reporting Ratios or PRRs for short.
Here is what he found:
“The proportion of adverse events for any gastrointestinal system cancer relative to all other events was elevated for ranitidine compared to PPIs and other H2 antagonists (PRR 3.66). Elevated and significant PRRs were observed for pharyngeal (PRR 9.24), esophageal (PRR 3.56), stomach (PRR 1.48), colorectal (PRR 16.31), liver (PRR 2.64), and pancreatic (PRR 2.18) cancers.”
Dr. McGwin describes the significance of his research into ranitidine and cancer this way:
“The results of the current study supported the interpretation that NDMA is carcinogenic in humans, specifically to the gastrointestinal system. This study was unique in that it compared cancer occurrence among ranitidine users to that of a population that uses medications to treat similar conditions, though not known to be contaminated with NDMA.”
Final Words on Ranitidine and Cancer:
Ranitidine is now gone from the marketplace. But what did drug companies know about a potential risk of nitrosamine formation and when did they know it? We found an Italian study that raised concerns about the “Genotoxicity of nitrosated ranitidine” (Carcinogenesis, Jan. 1, 1983). A question of NDMA formation was raised. That was the same year the FDA approved Zantac.
Sadly, we do not have a lot of high-quality epidemiological data to assess the risks of NDMA after long-time exposure to ranitidine. The fact that millions of people could have received unacceptable levels of nitrosamines for decades is worrisome enough. Whether there is a direct link between ranitidine and cancer remains to be determined.
Read more about this sad saga at this link:
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