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

作　　者：Marjorie Bernier Sarah-Line Lancrerot Fanny Rocher Elise K Van-Obberghen Pierre Olivier Thibaud Lavrut Nadège Parassol-Girard Milou-Daniel Drici 

机构地区：[1]Department of Pharmacology and Toxicology,PharmacoVigilance Center,University of Nice Côte d'Azur Medical Center,Hôpital de Cimiez,4 Avenue Reine Victoria,BP 1179,06003,Nice,France [2]Emergency Department Short Stay Unit,University of Nice Côte d'Azur Medical Center,Hôpital Pasteur 2,30,Voie Romaine 06001,Nice,France

出　　处：《Journal of Geriatric Cardiology》2019年第11期806-811,共6页老年心脏病学杂志（英文版）

摘　　要：Background The direct oral anticoagulant dabigatran does not require any routine therapeutic drug monitoring.Yet,concerns about possible drug interactions susceptible to increase its inherent bleeding risk,especially in very elderly patients,have been raised recently.The 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 elderly.Methods Fifty-eight patients over 85 years old with non valvular atrial fibrillation receiving dabigatran were included in a prospective cohort.Prescriptions 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.Background The direct oral anticoagulant dabigatran does not require any routine therapeutic drug monitoring. Yet, concerns about possible drug interactions susceptible to increase its inherent bleeding risk, especially in very elderly patients, have been raised recently. The 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 elderly. Methods Fifty-eight patients over 85 years old with non valvular atrial fibrillation receiving dabigatran were included in a prospective cohort. Prescriptions 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 

分 类 号：R73[医药卫生—肿瘤]