Istradefylline Safety Profiles: Examination of Individual Case Safety Reports in the FDA Adverse Event Reporting System (FAERS) Database

Abstract

Abstract Background Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, affecting more than 6 million people annually, and its prevalence is increasing as the population ages. To date, levodopa remains a cornerstone therapy, but prolonged use often leads to complications such as wear-and-tear phenomena and switching phenomena. As an adenosine A2A receptor antagonist, Istradefylline, marketed in the United States after approval in 2019, has emerged as an adjunctive therapy to levodopa, aiming to alleviate motor fluctuations and reduce off periods. In this study, post-marketing adverse event (ADE) data related to Istradefylline for Parkinson's disease were reviewed and analyzed using the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) for clinical safety assessment. Methods ADE data linked to Istradefylline were gathered from the fourth quarter of 2019 to the fourth quarter of 2023. After standardizing the data, the analysis will be carried out using a range of signal quantification techniques including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Results In 3872 ADE reports involving Istradefylline as the primary suspected drug, 65 Preferred Terms (PTs) for adverse reactions were identified, covering 21 different System Organ Classifications (SOCs). Specifically, neurological disorders and psychiatric disorders were the most common Adverse Events (AEs) associated with Istradefylline, both in terms of frequency of occurrence and signal intensity. All of the aforementioned effects are documented in the official drug insert. Among the top 30 PTs in terms of signal intensity, 4 were linked to neurological disorders, 16 to psychiatric disorders, general disorders, administration site conditions, and metabolism and nutrition disorders. The most frequently reported AEs are the most common. The top 3 AEs reported were Parkinsonism Hyperpyrexia Syndrome (PHS), dyskinesia, and sleep talking, in that order. Some PTs were not described in the specification, such as sleep talking, fear of falling, somnambulism, PHS, among others. Conclusions Istradefylline demonstrates therapeutic advantages despite the potential occurrence of diverse adverse reactions. In clinical settings, it is imperative for healthcare professionals to vigilantly observe patients for the onset of neurological and psychiatric conditions, as well as other related events.