Abstract
Background: Ranitidine (RAN) is one of the common drugs associated with idiosyncratic adverse drug reactions (IADRs) in humans. It was found to be associated with severe adverse drug reactions due to the presence of contaminants such as N-Nitrosodimethylamine (NDMA) which is claimed to be carcinogenic. As a consequence, on April 1, 2020, United States Food and Drug Administration (USFDA) had decided to call off all the RAN products from the market. The exact cause of RAN associated idiosyncratic hepatotoxicity is not clear yet. Purpose: To summarize and analyze the reason behind the withdrawal of RAN products from the market and whether ranitidine will be available again in future or will FDA withdraw approvals of ranitidine National Drug Authority (NDA) and an abbreviated new drug application (ANDA)? Methods: We performed a systematic PubMed/MEDLINE search of studies investigating the reason behind the withdrawal of RAN products and explored the possible mechanism associated with RAN induced hepatotoxicity. Conclusion: RAN induced liver injury is difficult to diagnose and study because of its relative rarity and unpredictive occurrence. Recent studies suggest that most of the RAN associated idiosyncratic reactions may lead to hepatocyte damage, followed by a series of events, such as activation of specific T- and B-cells, release of proinflammatory mediators like TNFα, interleukins, various cytokines and chemokines. The exact cause of RAN associated idiosyncratic hepatotoxicity is not clear yet. More studies must be carried out on this to know about the exact reason behind RAN associated hepatotoxicity.
Highlights
Drug induced liver injury (DILI) is a primary safety concern during drug discovery and those drugs which are found to be associated with severe adverse drug reactions (ADRs) are mainly withdrawn from the market
Recent studies suggest that most of the RAN associated idiosyncratic reactions may lead to hepatocyte damage, followed by a series of events, such as activation of specific T- and B-cells, release of proinflammatory mediators like Tumour Necrosis Factor α (TNFα), interleukins, various cytokines and chemokines
Recent studies suggest that most of the RAN associated idiosyncratic reactions may lead to hepatocyte damage, followed by a series of events, such as activation of specificT- and B-cells, release of proinflammatory mediators like TNFα, interleukins, various cytokines and chemokines
Summary
Drug induced liver injury (DILI) is a primary safety concern during drug discovery and those drugs which are found to be associated with severe adverse drug reactions (ADRs) are mainly withdrawn from the market. RAN induced liver injury may be an associated factor for its withdrawal from pharmaceutical market (Kaplowitz et al, 2005). Majority of RAN associated liver injury cases are not recognized during clinical trials, later on they are reported in post marketing surveillance. 3. 77 year old with 150 mg Elevated ALT ad alkaline phosphatase liver biopsy 3 days 2weeks 4. 58 year old man 150 mg mild elevations in serum alanine with duodenal ulcer daily aminotransferase (ALT) and alkaline phosphatase. 6. 73 year old 150 mg hyperbilirubinemia (15.6 mg/dL) with diffuse twice daily conjugated bilirubin, a 2.5-fold elevation canalicular of alkaline phosphatase and moderate cholestasis increase in aspartate aminotransferase and alanine aminotransferase
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