S3113 Comparative Safety of the Novel Potassium-Competitive Acid Blocker Vonoprazan vs Proton Pump Inhibitors: A Pharmacovigilance Study

Introduction: Vonoprazan, a novel potassium-competitive acid blocker (P-CAB), has emerged as an alternative to proton pump inhibitors (PPIs) for acid-related conditions. Despite its increasing use, real-world safety data comparing vonoprazan to PPIs remain limited. This study aimed to evaluate and compare adverse event (AE) profiles of vonoprazan vs PPIs using data from a large post-marketing safety database. Methods: We queried the FDA Adverse Event Reporting System database for AEs reported for vonoprazan and the 3 most commonly used PPIs (pantoprazole, omeprazole, and esomeprazole) between 2023 and 2025. AEs were categorized according to seriousness and system organ class (SOC). Univariate logistic regression analyses were used to compare event rates between vonoprazan and PPIs. Results: Out of 2,581 reports, 524 AEs were reported for vonoprazan while 2,057 were reported for PPIs. Vonoprazan was associated with a significantly lower proportion of serious AEs compared to PPIs (38.9% vs 89.3%; P < 0.001), with a markedly lower odds of serious events (odds ratio [OR] 0.077; 95% confidence interval [CI] 0.061-0.096). Death (2.9% vs 14.4%; OR 0.18), life-threatening events (3.4% vs 10.0%; OR 0.32), and disability (2.9% vs 15.8%; OR 0.16) were significantly less frequent in vonoprazan reports (all P < 0.001). Additionally, common gastrointestinal and neurological symptoms were less common with vonoprazan: diarrhea (5.9% vs 30.4%; OR 0.14), nausea/vomiting (6.7% vs 30.1%; OR 0.17), headache (5.5% vs 26.3%; OR 0.16), and fatigue (6.5% vs 28.2%; OR 0.18) (all P < 0.001). Standard-of-care-based analysis revealed significantly lower odds of AEs involving the gastrointestinal (OR 0.15), cardiovascular (OR 0.20), central nervous (OR 0.30), respiratory (OR 0.20), renal/urinary (OR 0.11), endocrine (OR 0.15), and other systems among vonoprazan users (all P < 0.001). Notably, however, urinary tract infections were more frequently reported with vonoprazan (OR 3.06; 95% CI 1.33-7.02; P = 0.008). Conclusion: In this large pharmacovigilance-based comparison, vonoprazan demonstrated a substantially safer AE profile than PPIs across multiple domains, including serious outcomes and system-specific reactions. These findings suggest vonoprazan may offer a favorable safety alternative to PPIs for acid suppression therapy, warranting further prospective evaluation and paving the way for their more widespread use.