ORIGINAL ARTICLESInteraction of daptomycin with two recombinant thromboplastin reagents leads to falsely prolonged patient prothrombin time/International Normalized Ratio resultsWebster, Peggy Sa; Oleson, Frederick B Jr.a; Paterson, David Lb; Arkin, Charles Fc; Mangili, Alexandrad; Craven, Donald Ee; Adcock, Dorothy Mf; Lindfield, Kimberly Ca; Knapp, Andrew Ga; Martone, William JaAuthor Information aCubist Pharmaceuticals, Inc., Lexington, Massachusetts, USA bDivision of Infectious Diseases, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA cDepartment of Laboratory Medicine, Lahey Clinic Medical Center, Burlington, USA dDivision of Geographic Medicine and Infectious Diseases, Tufts–New England Medical Center, Boston, USA eDepartment of Infectious Diseases, Lahey Clinic Medical Center, Burlington and Tufts University School of Medicine, Boston, Massachusetts, USA fEsoterix, Inc., Aurora, Colorado, USA Received 12 October, 2006 Revised 31 May, 2007 Accepted 8 August, 2007 Correspondence to Dr Peggy Webster, Cubist Pharmaceuticals, Inc., 65 Hayden Avenue, Lexington, MA 02421, USA Tel: +1 781 860 8690; fax: +1 781 860 1490; e-mail: firstname.lastname@example.org Blood Coagulation & Fibrinolysis: January 2008 - Volume 19 - Issue 1 - p 32-38 doi: 10.1097/MBC.0b013e3282f10275 Buy Metrics Abstract A cluster of patients experiencing elevations of International Normalized Ratio without clinical bleeding in temporal association with daptomycin therapy was identified during postmarketing safety surveillance. A common element was the thromboplastin reagent used for the laboratory assay. The present study evaluated the effect of daptomycin on measured prothrombin time using commercially available thromboplastin reagent kits commonly used in the United States. Thirty reagent kits were obtained. Daptomycin was added to pooled normal human plasma samples to achieve final concentrations of 0–200 μg/ml. Quality control ranges were established for each reagent kit using normal and abnormal control plasmas. Triplicate assays of the prothrombin time were performed on the daptomycin-spiked plasma samples using each of the 30 kits. The activated partial thromboplastin time and thrombin time were also assessed. Statistical comparisons of interest were performed using analysis of variance with the Bonferroni t-test for multiple comparisons; α = 0.05 was used. Addition of daptomycin to human plasma samples dose-dependently prolonged measured prothrombin times when two recombinant thromboplastin reagents were utilized. The findings were statistically and clinically significant. No clinically meaningful effect was observed with the other reagents. The activated partial thromboplastin time and thrombin time were not affected. Prolonged International Normalized Ratio patient values were an artifact caused by the interaction of daptomycin with the in-vitro prothrombin time test reagent; an in-vivo anticoagulant effect was not observed. Healthcare providers should consider a possible drug–laboratory test interaction if prolonged prothrombin time or elevated International Normalized Ratio values are observed in patients receiving daptomycin. © 2008 Lippincott Williams & Wilkins, Inc.