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Background: Oritavancin (ORI) is a lipoglycopeptide (LG) antibiotic approved as a single-dose treatment of adults with acute bacterial skin and skin structure infections (ABSSI) caused by gram-positive pathogens. As some LG and lipopeptide (LP) antibiotics are known to interfere with phospholipid (PL)-dependent coagulation tests (CT), we assessed the effects of ORI on common CT and determined the time-to-resolution (TtR) of test interference. Methods: For testing of clinical samples, plasma was obtained from normal healthy volunteers (NHV; n= 20) at defined time intervals following a 3h infusion of a single 1200 mg dose of ORI in a Phase 1 study. The TtR of each test interference was the interval from the start of the ORI infusion to the time the result returned to the normal reference range. For in vitro testing, ORI was spiked into human plasma over a concentration range of 2 to 47 μg/ml. PL-dependent CT included prothrombin time (PT), activated partial thromboplastin time (aPTT), Dilute Russell Viper Venom Test (DRVVT), activated clotting time (ACT), silica clot time (SCT) and activated Protein C Resistance (APCR). PL-independent CT included chromogenic anti-factor Xa (anti-FXa), thrombin time (TT) and an assay to diagnose heparin-induced thrombocytopenia (anti-heparin-PF4). Results: Transient prolongation of PT, aPTT, DRVVT, ACT and SCT occurred in plasma samples obtained from NHVs in the phase 1 study (table). Using ORI-spiked human plasma in vitro, prolongation of coagulation in the affected tests occurred in a concentration-dependent manner. ORI did not interfere with assays for APCR, anti-FXa, TT, or antiheparin-PF4. Conclusion: Although ORI has no effect of the coagulation system, it can cause artificial elevations in some laboratory CT. Because of its single-dose regimen, the transient interference of ORI on these CT does not require further consideration beyond the specified TtR of test interference in contrast to some LG and LP antibiotics that require daily administration. Disclosures Support and funding and for this study was provided by The Medicines Company. Conclusions • A single dose of oritavancin was associated with falsely elevated values of some phospholipid-dependent coagulation tests. The extent of test elevations was concentration-dependent, as demonstrated in in vitro studies using oritavancin-spiked samples (Table 1). • Oritavancin plasma concentrations following a single 1200 mg dose in subjects in this study are comparable to those in patients with ABSSSI (Figure 1). Thus, the estimates of time to resolution of potential lab test interference in normal subjects is expected to match those in infected patients. • A relationship between oritavancin plasma concentrations and increases in PT/INR or aPTT was observed in the phase 1 study (Figure 2). • The estimates of maximum time to resolution of test interference (Table 3) provides information on how to avoid coagulation test interference following a single dose of oritavancin. Jeff Loutit, M.D. The Medicines Company 3033 Science Park Rd, Suite 200 San Diego, CA 92121 Jeff.Loutit@themedco.com

Interference of Oritavancin on Coagulation Tests as Assessed In Vitro and in a Phase 1 Study of Normal Healthy Volunteers