Ranitidine Induced Hepatotoxicity: A Review

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.

Download Full-text

Abbreviated New Drug Application Process: A Gift for The Industry and The Patients

Asian Journal of Research in Chemistry ◽

10.52711/0974-4150.2021.00056 ◽

2021 ◽

pp. 331-335

Author(s):

Hindustan Abdul Ahad ◽

Haranath Chinthaginjala ◽

Gangireddy Jayasimha Reddy ◽

Pasupuleti Dheeraj Krishna ◽

Syed Rahamathulla ◽

...

Keyword(s):

Drug Application ◽

The United States ◽

New Drugs ◽

Brand Name ◽

Application Process ◽

Drug Products ◽

Federal Food ◽

United States Food ◽

States Food ◽

New Drug Application

The United States Food and Drug Administration (USFDA) is one of the main regulated agencies wherein the submission and approval of the new drugs is done. This review is based on the process of submission to the ANDA as per FDA norms as described in paragraph IV submission in Federal Food, Drug, and Cosmetic Act (FD and C Act). No drug would exist in the market until it gets accepted by regulatory authorities. The ANDA submission is for those firms seeking to copy branded drugs before running out of patents to get profit on them. A generic applicant must provide in its application a "certification" that a patent submitted to FDA by the brand-name drug's sponsor and scheduled in FDA's Approved Drug Products with Therapeutic Equivalence Evaluations (the Orange Book). A Generic Product must meet the standards recognized by FDA in Reference listed drugs (RLD). This study concludes the process of ANDA submission to FDA and acts correlated to the submission in paragraph IV, the details of ANDA filling in the eCTD format and overview of the review process the checklist to the applicant.

Download Full-text

Risk Analysis of Lurasidone in Patients with Schizophrenia and Bipolar Depression

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527319666200303120147 ◽

2020 ◽

Vol 19 (2) ◽

pp. 109-114

Author(s):

Harika Modugula ◽

Anoop Kumar

Keyword(s):

Adverse Drug Reactions ◽

Causality Assessment ◽

Bipolar Depression ◽

Large Population ◽

The United States ◽

Drug Reactions ◽

Restless Leg Syndrome ◽

Exclusion Criteria ◽

United States Food ◽

States Food

Lurasidone was approved by the United States Food and Drug Administration (FDA) for the treatment of schizophrenia, as well as for the treatment of bipolar depression. However, emerging reports have indicated various adverse drug reactions with the use of lurasidone. Thus, in this article, we have analyzed the risk profile of lurasidone in the established therapeutic indication. A total of 419 studies were published from October 2010-July 2019 regarding lurasidone. After the inclusion and exclusion criteria, 17 studies were selected for the analysis of risk. The adverse drug reactions (ADRs) of these studies were categorized as per the innovator summary of product characteristics (SmPC). Finally, the unlisted ADRs were analyzed by using the Naranjo probability algorithm. Telogen effluvium, thrombocytopenia, restless leg syndrome and hypersexuality were found with the use of lurasidone and fall under the unlisted category. The causality assessment has shown a probable correlation of lurasidone with hypersexuality, restless leg syndrome, thrombocytopenia and possible relation with telogen effluvium. In conclusion, lurasidone is a novel and efficacious pharmacological treatment for bipolar depression and schizophrenia. However, more data regarding the safety of this drug in a large population is needed.

Download Full-text

Adverse Drug Reactions in the Orofacial Region

Critical Reviews in Oral Biology & Medicine ◽

10.1177/154411130401500405 ◽

2004 ◽

Vol 15 (4) ◽

pp. 221-239 ◽

Cited By ~ 126

Author(s):

C. Scully ◽

J.-V. Bagan

Keyword(s):

Drug Therapy ◽

Adverse Drug Reactions ◽

Wide Spectrum ◽

Case Reports ◽

Drug Reactions ◽

Double Blind ◽

Medline Search ◽

Mucosal Ulceration ◽

Small Series ◽

Orofacial Region

A wide spectrum of drugs can sometimes give rise to numerous adverse orofacial manifestations, particularly dry mouth, taste disturbances, oral mucosal ulceration, and/or gingival swelling. There are few relevant randomized double-blind controlled studies in this field, and therefore this paper reviews the data from case reports, small series, and non-peer-reviewed reports of adverse drug reactions affecting the orofacial region (available from a MEDLINE search to April, 2003). The more common and significant adverse orofacial consequences of drug therapy are discussed.

Download Full-text