Oral anticoagulant-proton pump inhibitor interactions: A pharmacovigilance assessment using disproportionality and interaction analyses

Abstract

Objective: Oral anticoagulants operate within a narrow therapeutic window, with upper gastrointestinal bleeding representing a significant safety concern. While proton pump inhibitors (PPIs) have demonstrated gastroprotective properties, existing literature presents conflicting evidence regarding their interactions with oral anticoagulants. Methods: A detailed analysis was conducted using the United States Food and Drug Administration Adverse Event Reporting System (USFDA AERS) database. The study examined interactions between five oral anticoagulants (warfarin, apixaban, dabigatran, edoxaban, and rivaroxaban) and six PPIs (lansoprazole, dexlansoprazole, omeprazole, esomeprazole, pantoprazole, and rabeprazole). A case-non-case disproportionality analysis was employed, utilizing both frequentist and Bayesian data mining algorithms. Interaction Signal Scores were calculated to evaluate interaction strengths. Results: Of 29,163,222 initial reports, 5,222 met inclusion criteria. Significant interactions were identified across multiple anticoagulant-PPI combinations. Notably, dabigatran combined with omeprazole or pantoprazole, and apixaban with most PPIs, demonstrated increased hemorrhagic event risks. Gastrointestinal hemorrhage interactions were most extensive, with significant signals across multiple drug combinations. Certain combinations, like rivaroxaban-esomeprazole, showed protective effects, while others, such as rivaroxaban-rabeprazole, exhibited increased venous thromboembolic event risks. Conclusion: This pharmacovigilance analysis reveals complex interactions between oral anticoagulants and PPIs, highlighting the need for individualized risk assessment. Healthcare providers should carefully monitor patients receiving these combinations, considering potential hemorrhagic complications and patient-specific risk factors.