Comparative Reporting Patterns of Rabeprazole and Other Proton Pump Inhibitors in EudraVigilance: A System Organ...

Rabeprazole differs from other proton pump inhibitors (PPIs) in its activation and lower dependence on CYP2C19. We compared its System Organ Class (SOC)-level reporting profile with those of esomeprazole, pantoprazole, omeprazole and lansoprazole in EudraVigilance individual case safety reports (ICSRs).

Aggregated ICSR counts were retrieved from adrreports.eu (data lock point 4 October 2026). Rabeprazole was compared head-to-head with each comparator using reporting odds ratios (RORs) with 95% confidence intervals across 27 MedDRA SOCs, with Benjamini-Hochberg false discovery rate control over all 108 tests. Bonferroni correction and serious-only analyses were sensitivity analyses; female-only and male-only analyses were exploratory.

Of 232,045 ICSRs, 7960 involved rabeprazole. Hepatobiliary disorders were the only SOC reported more often with rabeprazole than with all four comparators (ROR 1.29-1.96); the excess met the Bonferroni threshold and persisted among serious reports (ROR 1.19-1.97) and in both sexes. Skin and subcutaneous tissue disorders were reported more often than with three comparators and, among serious reports, than with all four (ROR 1.14-1.83). Eight SOCs showed consistently lower reporting odds, alongside fewer SOCs per rabeprazole ICSR and a different reporter mix.

Rabeprazole showed a consistent hepatobiliary reporting signal within the PPI class, in line with earlier FAERS findings. This is a reporting signal, not a clinical signal: without exposure data, the results describe relative reporting, not incidence, comparative risk or causality, and lower reporting odds do not imply lower clinical risk.