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research-article2013

AOPXXX10.1177/1060028013513883Annals of PharmacotherapyConway et al

Research Report

Evaluation of Dabigatran Exposures Reported to Poison Control Centers

Annals of Pharmacotherapy 2014, Vol. 48(3) 354­–360 © The Author(s) 2013 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1060028013513883 aop.sagepub.com

Susan E. Conway, PharmD1, Scott E. Schaeffer, BS Pharm2, and Donald L. Harrison, PhD1

Abstract Background: Dabigatran is a novel oral anticoagulant for which a well-defined range of toxicity and proven antidote has not been established. Objective: The primary objective of this study was to characterize dabigatran exposures reported to poison centers by dose ingested, clinical effects, treatments used, and managment sites to gain a better understanding of patient outcomes. Methods: A retrospective database review was conducted for dabigatran exposures reported to the National Poison Data System for the American Association of Poison Control Centers (AAPCC) over the period October 2010 to December 2012. Results: There were 802 human dabigatran exposures involving adults predominantly (91% of cases). Exposure chronicity was acute in 43%, acute-on-chronic in 46%, and chronic in 11%, with the most common reason for an exposure call being an unintentional therapeutic error (70.6%). The most common management sites were on-site in 72% of cases and within a health care facility for 26%. Bleeding events and coagulopathies were the most commonly observed clinical effects. Treatments administered included activated charcoal, blood and coagulation products, hemodialysis, and supportive measures. Confirmed outcomes included death in 13 patients (1.6%), major effects in 23 (2.9%), and moderate effects in 50 (6.2%). More severe outcomes were significantly associated with adverse drug reactions, patients ≥65 years of age, those treated with blood and coagulation products and/or dialysis, and renal dysfunction (P < .05). Children experienced few moderate effects and no major effects or deaths. Conclusions: Severe outcomes from dabigatran exposures were not common, occurring in approximately 5% of cases. Keywords dabigatran, direct thrombin inhibitor, hemorrhage, overdose

Introduction Dabigatran was approved by the United States Food and Drug Administration (FDA) in October 2010 and was the first in a new drug class of oral anticoagulants that acts through direct thrombin inhibition. The primary advantage of this novel anticoagulant is that it has predictable pharmacokinetics and does not require therapeutic monitoring, unlike warfarin, which requires dose titration and frequent international normalized ratio (INR) testing.1,2 Because of its predominantly renal elimination, dabigatran should be used at a reduced dose of 75 mg twice daily if the creatinine clearance (CrCl) is 15 to 30 mL/min, and dosing recommendations are not available in patients with CrCl 65 years Treatmentb   Supportive care   Blood products and/or hemodialysis Renal function   No documented renal dysfunction   Increased serum creatinine or renal failure

1 (1.3%) 12 (7.0%)

0 (0%) 22 (12.9%)

4 (1.8%) 9 (25.7%)

7 (3.2%) 14 (40%)

10 (4.1%) 3 (18.8%)

18 (7.4%) 5 (31.3%)

P Value   .002  

Evaluation of dabigatran exposures reported to poison control centers.

Dabigatran is a novel oral anticoagulant for which a well-defined range of toxicity and proven antidote has not been established...
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