Vonoprazan-related adverse events: a pharmacovigilance study based on the FDA adverse event reporting system

Abstract

This study comprehensively evaluated the safety profile of Vonoprazan using data from the FDA Adverse Event Reporting System (FAERS) from the first quarter (Q1) of 2023 through the first quarter (Q1) of 2025. This analysis was restricted to real-world reports collected after the U. S. approval of vonoprazan, to better reflect its current clinical use pattern in the United States. Reports in which Vonoprazan was designated as the primary suspect(PS) drug were systematically extracted, and duplicate entries were removed using MySQL(version 8.0.42). Adverse events were coded in according tothe Medical Dictionary for Regulatory Activities (MedDRA, version 24.0). To detect potential safety signals, four disproportionality methods were applied: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS). Differences between serious and non-serious adverse events were further examined using Pearson's chi-square test and Fisher's exact test. Temporal patterns of adverse event occurrence were evaluated using Time-to-Onset (TTO) analysis and Weibull Shape Parameter (WSP) modeling. In total, 978 vonoprazan-related cases were included; females accounted 62.0% of reports, and 34.3% of events were classified as serious. Forty seven preferred terms (PTs) met predefined signal criteria, and 16 of these, such as facial paralysis and cholecystitis, were not listed in the current U. S. FDA prescribing information for vonoprazan. Serious adverse events were more often associated with renal impairment and haematemesis, whereas non-serious events were predominantly gastrointestinal. Stratified analyses further revealed several potential high-risk signals, particularly inmale and elderly patients. The median time to onset was 7 days, and most events occurred within the first 30 days after treatment initiation. Weighted Survival Probability (WSP) analysis suggested an "early failure" pattern, and co-administration of aspirin and other acid-suppressing agents was common. In conclusion, this study provides a systematic characterization of Vonoprazan- associated adverse events and highlights several potential new safety signals that are not currently reflected in the drug's labeling, these findings should be interpreted as hypothesis-generating safety signals that may inform future prospective monitoring and clinician counseling.

Keywords: FAERS; TTO; Vonoprazan; WSP; adverse events; signal detection.

Figure 1

Research flowchart.

Figure 2

Analysis of vonoprazan-related adverse events using the faers database. (A) Annual trends in adverse event report frequency from 2023 to 2025. (B) Safety signal evaluation of vonoprazan-associated systemic adverse events by system organ class (SOC), ranked by reporting odds ratio (ROR) and 95% CI. (C) Proportional distribution of reports across different soc categories. (D) Distribution of adverse events by Preferred Term (PT), organized by the number of reported cases.

Figure 3

Multi-Method detection and characterization of vonoprazan-related adverse reactions. (A) Ranking of Preferred Terms (PTs) according to ROR values. (B) Analysis of commonly co-administered drugs with vonoprazan. (C) Cross-validation of vonoprazan-related adverse events using four disproportionality algorithms: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Lower Bound (EBGM), and Bayesian Confidence Propagation Neural Network (BCPNN). (D) Cumulative incidence curve showing a median time-to-onset (TTO) of 7 days (IQR: 2.00–23.00). (E) Gender-stratified cumulative incidence curve showing a median TTO of 6 days (IQR: 2.00–14.00) in females and 14 days (IQR: 2.00–60.00) in males (log-rank test, p = 0.02). (F) Analysis of the time to onset of adverse drug events associated with Vonoprazan.

Figure 4

Signal analysis of Vonoprazan-related adverse events by gender. (A) Top 25 adverse events in male and female subgroups. (B) Top 50 adverse events stratified by gender, compared by Reporting Odds Ratio (ROR) and 95% CI.

Figure 5

Signal intensity analysis of Vonoprazan-related adverse across age subgroups. Reporting Odds Ratio (ROR) and 95% confidence level. ROR and their 95% confidence intervals for adverse events (Preferred Terms, PTs) in three age subgroups: <18 years, 18–64.9 years, and ≥65 years.