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Major bleeding events in octagenarians associated with drug interactions between dabigatran and P-gp inhibitors

Journal of Geriatric Cardiology 2019年第11期16卷 806-811页

作者： marjorie bernier Sarah-Line Lancrerot Fanny Rocher Elise K Van-Obberghen Pierre Olivier Thibaud Lavrut Nadège Parassol-Girard Milou-Daniel Drici Department of Pharmacology and Toxicology PharmacoVigilance CenterUniversity of Nice Côte d'Azur Medical CenterHôpital de Cimiez4 Avenue Reine VictoriaBP 117906003NiceFrance Emergency Department Short Stay Unit University of Nice Côte d'Azur Medical CenterHôpital Pasteur 230Voie Romaine 06001NiceFrance

Background The direct oral anticoagulant dabigatran does not require any routine therapeutic drug ***,concerns about possible drug interactions susceptible to increase its inherent bleeding risk,especially in very elderly patients,have been raised *** aim of our study was to evaluate to what extent the co-prescription of P-gp inhibitors with dabigatran may increase its plasma levels and lead to bleeding complications,in usual conditions of care of the very *** Fifty-eight patients over 85 years old with non valvular atrial fibrillation receiving dabigatran were included in a prospective *** were screened for the presence of P-gp inhibitors(Group A)or not(Group B).Results Patients from Group A had increased dabigatran mean plasma concentrations as compared with patients from Group B(A vs.B:182.2±147.3 vs.93.7±64.9 ng/m L).One third of the patients from Group A had dabigatran concentrations that were deemed"out of range"versus none in Group B(P=0.05).This was associated with more frequent bleeding complications in Group A(A:30.4%,B:8.6%,P=0.04).Conclusion In our cohort of very elderly patients,at least,the co-prescription of dabigatran with P-gp inhibitors in usual conditions of care resulted in higher dabigatran plasma concentrations and more frequent bleeding occurrences.

关键词： Dabigatran Drug interaction Hemorrhage P-gp inhibitors,The elderly

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