Postmarketing Safety Analysis of Nebivolol in Real-World Settings Using Bioinformatics and Disproportionality Analysis With FDA Adverse Event Reporting System (FAERS) Data
Author(s)
Shravanth R M, MPH1, Ajoshson John, PharmD1, Rakshitha N, .2, Dr. Maheswari Eswar, .1.
1Department of Pharmacy Practice, Faculty of Pharmacy, M S Ramaiah University of Applied Sciences, Bangalore, India, 2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M S Ramaiah University of Applied Sciences, Bangalore, India.
1Department of Pharmacy Practice, Faculty of Pharmacy, M S Ramaiah University of Applied Sciences, Bangalore, India, 2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M S Ramaiah University of Applied Sciences, Bangalore, India.
OBJECTIVES: Cardiovascular diseases remain a leading global health concern, with beta-blockers like nebivolol playing a vital role in hypertension management. Despite widespread clinical use, real-world safety data on nebivolol remain underexplored. This study aims to investigate post-marketing adverse events associated with nebivolol using FDA Adverse Event Reporting System (FAERS) data and bioinformatics techniques.
METHODS: A retrospective pharmacovigilance analysis was conducted using FAERS reports. Signal detection metrics included Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR), with thresholds set at PRR ≥ 2, ROR ≥ 2, and a minimum of 2 reported cases. Additionally, gene and protein interactions were evaluated using the PubMed Gene database and STRING. Molecular docking simulations were performed using PyRX to assess nebivolol’s binding affinities with inflammatory and regulatory proteins.
RESULTS: Among 29,661,136 total FAERS entries, 4,651 adverse event reports were associated with nebivolol. Signal detection analysis revealed six notable adverse events: epistaxis (128 cases, PRR 2.481), melaena (96 cases, PRR 6.197), sopor (70 cases, PRR 5.895), diplopia (39 cases, PRR 2.165), bradyphrenia (12 cases, PRR 2.306), and pemphigoid (4 cases, PRR 5.03). Molecular docking revealed strong binding affinities between nebivolol and proteins such as IL6 (-8.9 kcal/mol), IL1B (-9.1 kcal/mol), and P53 (-8.7 kcal/mol), suggesting possible pathways for these adverse effects.
CONCLUSIONS: This real-world post-marketing analysis identified multiple potentially serious adverse reactions to nebivolol, emphasizing the importance of continued pharmacovigilance. The integration of bioinformatics enhances understanding of underlying molecular mechanisms. Further pharmacogenetic studies are warranted to confirm causality and support safer prescribing practices.
METHODS: A retrospective pharmacovigilance analysis was conducted using FAERS reports. Signal detection metrics included Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR), with thresholds set at PRR ≥ 2, ROR ≥ 2, and a minimum of 2 reported cases. Additionally, gene and protein interactions were evaluated using the PubMed Gene database and STRING. Molecular docking simulations were performed using PyRX to assess nebivolol’s binding affinities with inflammatory and regulatory proteins.
RESULTS: Among 29,661,136 total FAERS entries, 4,651 adverse event reports were associated with nebivolol. Signal detection analysis revealed six notable adverse events: epistaxis (128 cases, PRR 2.481), melaena (96 cases, PRR 6.197), sopor (70 cases, PRR 5.895), diplopia (39 cases, PRR 2.165), bradyphrenia (12 cases, PRR 2.306), and pemphigoid (4 cases, PRR 5.03). Molecular docking revealed strong binding affinities between nebivolol and proteins such as IL6 (-8.9 kcal/mol), IL1B (-9.1 kcal/mol), and P53 (-8.7 kcal/mol), suggesting possible pathways for these adverse effects.
CONCLUSIONS: This real-world post-marketing analysis identified multiple potentially serious adverse reactions to nebivolol, emphasizing the importance of continued pharmacovigilance. The integration of bioinformatics enhances understanding of underlying molecular mechanisms. Further pharmacogenetic studies are warranted to confirm causality and support safer prescribing practices.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO182
Topic
Clinical Outcomes, Medical Technologies, Real World Data & Information Systems
Topic Subcategory
Clinician Reported Outcomes, Performance-based Outcomes
Disease
Cardiovascular Disorders (including MI, Stroke, Circulatory), Gastrointestinal Disorders, Mental Health (including addition), Sensory System Disorders (Ear, Eye, Dental, Skin)