Ranitidine, commonly known by the brand name Zantac, was available in tablet form in several milligram strengths, including 75 mg and 150 mg. These dosages were prescribed for conditions such as heartburn, acid indigestion, and gastroesophageal reflux disease (GERD) [1].
Why is Ranitidine no longer available?
Ranitidine was voluntarily withdrawn from the U.S. market by its manufacturer in April 2020 [1]. This action followed concerns raised by the U.S. Food and Drug Administration (FDA) regarding the presence of N-Nitrosodimethylamine (NDMA), a probable human carcinogen, in ranitidine products [2][3]. The NDMA was found to degrade over time and under certain storage conditions, leading to unacceptable levels of the contaminant [3].
What are the alternatives to ranitidine for heartburn?
Following the market withdrawal of ranitidine, individuals seeking relief from heartburn and related conditions have turned to other medications. These alternatives generally fall into two main categories: H2 receptor antagonists and proton pump inhibitors (PPIs) [4].
H2 receptor antagonists, such as famotidine (Pepcid) and cimetidine (Tagamet), work by reducing the amount of acid the stomach produces. Famotidine is available both over-the-counter and by prescription in various strengths [4][5]. Cimetidine is also available over-the-counter [4].
Proton pump inhibitors (PPIs) are generally considered more potent acid reducers than H2 blockers. Common PPIs include omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), and pantoprazole (Protonix). These are available in both over-the-counter and prescription formulations [4].
What are the risks associated with ranitidine?
The primary risk associated with ranitidine that led to its market withdrawal was the contamination with NDMA. Studies indicated that NDMA levels in ranitidine products could increase over time and under elevated temperatures [3]. NDMA is classified as a probable human carcinogen, meaning it is likely to cause cancer in humans. Exposure to NDMA can occur from various sources, including contaminated food and water [6].
What was the manufacturing history of ranitidine?
Ranitidine was first synthesized in the late 1970s and introduced to the market in the early 1980s by GlaxoSmithKline (GSK), then known as Glaxo. It rapidly became one of the most widely prescribed and used medications globally for managing acid-related gastrointestinal disorders [7]. For decades, it was a flagship product for GSK and later became available as a generic medication from numerous manufacturers [8].
When did ranitidine patents expire?
The original patents for ranitidine expired many years ago, allowing for the development and sale of generic versions of the drug. For example, U.S. Patent 3,602,949, which covered ranitidine, expired long before its market withdrawal [9]. The expiration of these patents opened the door for generic competition, making ranitidine more accessible and affordable for patients.
What is NDMA and why is it a concern?
N-Nitrosodimethylamine (NDMA) is a chemical compound that is a common environmental contaminant and a probable human carcinogen [6]. It can form as a byproduct of certain chemical processes and is also found in some foods and water supplies. The concern with NDMA in medications arises from its potential to cause DNA damage and increase cancer risk when present at elevated levels over time [3][6].
Sources:
[1] U.S. Food and Drug Administration. (2020, April 1). FDA Requests Removal of All Ranitidine Products from the U.S. Market. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requests-removal-all-ranitidine-products-us-market
[2] U.S. Food and Drug Administration. (2019, September 26). FDA Investigating Possible NDMA in Ranitidine. https://www.fda.gov/drugs/drug-safety-and-availability/fda-investigating-possible-ndma-ranitidine
[3] U.S. Food and Drug Administration. (2020, April 1). Information about NDMA in Ranitidine. https://www.fda.gov/drugs/drug-safety-and-availability/information-about-ndma-ranitidine
[4] Mayo Clinic. (n.d.). Heartburn. Retrieved from https://www.mayoclinic.org/diseases-conditions/heartburn/diagnosis-treatment/drc-20373232
[5] Healthline. (2023, October 17). Famotidine: Uses, Dosage, Side Effects, and Warnings. https://www.healthline.com/drugs/famotidine
[6] World Health Organization. (2015). Nitrosamines. https://www.who.int/news-room/fact-sheets/detail/nitrosamines
[7] British National Formulary. (n.d.). Ranitidine. Retrieved from https://bnf.nice.org.uk/drugs/ranitidine.html
[8] DrugPatentWatch.com. (n.d.). Ranitidine Drug Information. https://drugpatentwatch.com/ranitidine
[9] U.S. Patent 3,602,949. (1971). Process for the preparation of substituted furfurylguanidines.