FDA REQUEST RECALL OF ALL ZANTAC/ RANTIDINE PRODUCTS. IS THIS THE TIP OF A MUCH LARGER ICEBERG? By JOHN RAY

John Ray 4/1/2020 5:38:00 PM

On 04/01/2020, the FDA requested that all makers of all ranitidine drugs (Zantac and generics) remove their products from the market. The reasoning citied by the FDA “The FDA has determined that the impurity in some ranitidine products increases over time and when stored at higher than room temperatures may result in consumer exposure to unacceptable levels of this impurity”. See entire press release at this link. The reason the FDA has requested that all ranitidine (Zantac et.al) products be removed from the market go far beyond the reasons currently stated in the FDA press release.

PRIMARY TOPICS COVERED IN THIS ARTICLE

1. The FDA may (and arguably should) demand the recall of all ‘histamine H2-receptor antagonists' (227 approved products in total) as the “contamination issue” is not the primary defect or danger presented by these drugs. In more simple terms, these drugs most likely cause the production of high levels of N-Nitroso compounds when introduced in the human body, especially in individuals with higher than normal levels of acid in their stomach or GI tract. Why? 'Histamine H2-receptor antagonists are nitrosatable.Nitrosatable: Capable of being converted into nitroso compounds also referred to as n-nitroso compounds. (See list of n-nitroso compounds in appendix A below)Nitrosatable Drug: Drugs Capable of being converted into nitroso compound also referred to as n- nitroso compounds.) Generally, the conversion to or production of the n- nitroso compound occurs when the drug interacts with the acidic compounds found in the stomach and gastrointestinal tract.
2. The litigation resulting from the current ranitidine requested recall may dramatically increase in scope over the next year, to include all 'histamine H2-receptor antagonists without regard to whether an individual consumed a product known to have been contaminated.
3. The litigation will be complex as under certain scenarios cases involved ANDA approved products (generics) may be foreclosed on by Pliva v. Mensing, while under other circumstances Pliva v. Mensing may not foreclose on claims involving generics (this subject will be more thoroughly covered in future articles).
4. The injuries or adverse events caused by the n-nitroso compounds, whether through contamination in the production process, aggravated by heat or due to the inherent nitrosatable properties of Histamine H2-receptor antagonists are not limited to cancer, the n-nitroso compounds produced by consumption of these drugs (without regard to contamination, not only are believed to cause cancer. The n-nitroso compounds in question are also known to cause major organ failure, still births and birth defects. The fact that pregnant women often have issues with stomach acidity and consume 'histamine H2-receptor antagonists” to mitigate the pain associated with this ailment, is of significant concern to this researcher. (this subject will be more thoroughly covered in future articles)

THE ELEPHANT IN THE ROOM

The FDAs reasoning behind the requested recall of all ranitidine products being that the level or amount of the N-Nitroso impurity (contamination) increases when exposed to heat higher than room temperatures begs the following question: Why is the FDA only requesting the removal of ranitidine products and not other products such as the various blood pressure medications (ie. Valsartan) that have also been found to be contaminated with N-Nitroso compounds? There may be a simple answer to the question posed. Ranitidine like all other 'histamine H2-receptor antagonists' are nitrosatable while Valsartan et.al. drugs are not nitrosatable. Histamine H2-Receptor Antagonists Histamine H2-Receptor Antagonists also known as H2 blockers are a group of medicines that reduce the amount of acid produced by the cells in the lining of the stomach. They include cimetidine, famotidine, nizatidine and ranitidine, and have various brand names, including Zantac. (See Appendix B1, a list of all FDA approved ranitidine and Appendix B2 for a list of all other FDA approved 'histamine H2-receptor antagonists' (141 products) Individuals take H2-receptor antagonists due to pain caused lower than normal PH Levels (more acidic) stomach and gastrointestinal “juices” than normal. The lining of the stomach and other structures in the gastrointestinal tract are not designed to resist degradation by acids with lower PH (more acidic) than the normal levels found in healthy individuals. The scientific literature supports the conclusion that the introduction of a Nitrosatable Drug in a patient with lower than normal (more acidic) PH levels in their Stomach and GI tract, produces higher levels of as n-nitroso compounds than are produced with that same drug is introduced into the body of an individual with normal PH levels (normal acid levels) in their Stomach and GI tract see: See: N-Nitrosamines in gastric juice of patients with gastric ulcer before and during treatment with histamine H2-receptor antagonists: https://link.springer.com/article/10.1007/BF02776810

REASONABLE CONCLUSION

Reasonable Conclusion: A Nitrosatable Drug designed to treat individuals known to have lower than normal PH levels in their Stomach and GI tract, is defective in concept and design in that the drug will arguably create higher levels of n- nitroso compounds in the group of individuals that the drug is intended to treat, versus a nitrosatable Drug designed to treat individuals not known to have lower than normal PH levels in their Stomach and GI tract (such as Valsartan). More simply stated, the drugs are intended to treat individuals with pre-existing conditions that make these individuals more susceptible to the significant adverse events that can result from consumption of the drug.

THE TIP OF A VERY LARGE ICEBERG

The issue arising from contamination certain lots of Valsartan and certain Ranitidine products was first brought to the attention of the FDA by a small company relatively young company Valisure, LLC (founded in 2015) operating out of New Haven Connecticut. See the record of communications between Valisure, LLC and the FDA at this link. Valisure's Harvard- and Yale-trained scientists have developed laser-based technology to analyze the chemical properties and ingredients of pharmaceutical products. The novel technology employs laser-induced, quantum shift emissions to address the variability and quality problems that pervade many pharmaceutical products throughout the US. On an unrelated note that might be of interest to investors, Valisure, currently a privately held company, filed the required documents to make a public stock offering in 2019 see documents at this link. Shortly after Valisure filed its first petition related to its findings of NDMA and other n-nitroso compounds found in certain lots of blood pressure drugs (Valsartan et.al.) and antacid drugs (Zantac et.al) the FDA began a rapid-fire succession of actions designed to remove certain lots of these products from the market. See the relevant FDA actions at this link. The fact that the FDA has now requested the removal of all ranitidine drugs from the market, (without regard to specific lot contamination) while not requesting the same of those non-nitrosatable drugs (Valsartan) for which contaminated lots have been discovered, lead this researcher to the conclusion that the issue with the ranitidine and other H2 blockers, goes far beyond the fact that a limited number of lots were found to be contaminated with the same harmful compounds the drug produces when introduced into the human body, without regard to additional contamination during the manufacturing process.

APENDIX A LIST OF N-NITOROS COMPOUNDS

APPENDIX B1 LIST OF ALL FDA APPROVED H2 RECEPTOR ANTAGONIST CONTAINING RANITINIDINE or RANITINIDINE HYRDROCHLORIDE ( 86 Products)

APPENDIX B2 LIST OF ALL FDA APPROVED H2 RECEPTOR ANTAGONIST (141 Products)