ZANTAC AND RANITIDINE: EARLY HISTORY OF CANCER-CAUSING DRUG CONTAINING NDMA
Written By: David B. Rheingold, Esq. Senior Zantac Litigation Partner
Zantac was invented by Glaxo Holdings Ltd (now known as GSK or GlaxoSmithKline) and first sold in 1983. Technically known as a histamine H 2 -receptor antagonist, this H 2 blocker drug reduces acid produced by stomach cells. Zantac and ranitidine have been marketed for long-term maintenance use. But can this extended use cause cancer? As a litigation firm, we are digging deep into the history of Zantac and have found some startling facts that the public was not aware of.
Zantac Was First Approved Only for Short-Term Use
Part of the FDA approval was based on Zantac being a short-term drug. This was uncovered in a Reuters article[i] and is documented in Glaxo’s early submission documents. As lawyers, we find this very interesting and would like to investigate if the FDA had cancer concerns. For instance, the recent Valisure Citizen’s Petition cited many studies which showed that the dimethylamine in Zantac can be converted to the carcinogenic compound NDMA when exposed to stomach acids containing nitrates. In fact, to this day, some of the indications (active and duodenal ulcers) in the FDA-approved package insert are for short-term use. [ii]
The 1983 Italian Medical Studies Warning that Zantac Should Not Be Taken with Certain Foods
Two Italian medical studies completed in 1983 uncovered the potential link between ranitidine, the generic chemical name for Zantac, and the carcinogenic molecule NDMA. Zantac contains “DMA” (dimethylamine”) which can combine with the “N” in common foods known as nitrosamines, nitrites and nitrates. In fact, some early investigators warned that Zantac should not be taken with food, even though the drug always is.
The first study “Genotoxicity of Nitrosated Ranitidine,” found that the acid in stomachs caused the “NDMA” to appear in rat, mouse and human livers. [iii] Of note, this did not occur in fasting test subjects.
The second study “Genotoxic Effects in Rodents Given High Oral Doses of Ranitidine and Sodium Nitrite” confirmed the findings of the first study.[iv] They noted that the cellular DNA of gastric cells were damaged. This means the DNA strands were mutated and could become cancer cells. This is known as genotoxicity.
Could Vitamin C Have Prevented the Carcinogenic Dangers?
The scientists in the second study noted that “Simultaneous administration of ascorbic acid reduced the damage of gastric DNA.” That means that in 1983, 36 years before the recall, scientists were so concerned about the creation of the NDMA[v] compound that they suggested including Vitamin C in the Zantac to prevent cancer. By 1979, ascorbic was known as a nitrate “scavenger,” meaning that it neutralizes nitrates.[vi] As lawyers, we will certainly question company representatives as to why they did not add vitamin C to the drug. What do you think their answers will be?
[iii] Genotoxicity of nitrosated ranitidine; Silvio De Flora, Carlo Bennicelli, Anna Camoirano, Patrizia Zanacchi; Carcinogenesis, Volume 4, Issue 3, 1983, Pages 255–260, https://doi.org/10.1093/carcin/4.3.255
[iv] Genotoxic effects in rodents given high oral doses of ranitidine and sodium nitrite
Carcinogenesis, Volume 4, Issue 10, October 1983, Pages 1281–1285, https://doi.org/10.1093/carcin/4.10.1281
[v] NDMA was first invented as rocket fuel, but environmental contamination resulted in a ban of its use. https://www.atsdr.cdc.gov/phs/phs.asp?id=882&tid=173