1954. Lack of Effect of Oritavancin on Warfarin Pharmacokinetics in Healthy Adult Subjects
Session: Poster Abstract Session: Antimicrobial Pharmacokinetics and Pharmacodynamics
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • IDWeek 2016 Bellibas -- Lack of Effect of ORI on Warfarin PK v03a.pdf (292.8 kB)
  • Background: Oritavancin (ORI) is a novel semisynthetic lipoglycopeptide antibiotic administered as a single intravenous (IV) dose for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus(MRSA). A previous screening study using a cocktail design showed that warfarin clearance may be reduced with a single dose of ORI. Since warfarin is a drug with a narrow therapeutic index and some patients with ABSSSI may receive ORI while on warfarin treatment, this study was conducted to determine warfarin PK at varying intervals following a single ORI dose. Methods: This was an open-label study evaluating the effects of ORI on the pharmacokinetics (PK) of warfarin in 36 healthy subjects enrolled in 3 cohorts at a single center. Subjects were administered with a single 25-mg oral dose of warfarin in the first treatment period of the study. On Day 8, the beginning of the second period of the study, subjects received a single 1200-mg IV infusion of ORI over 3 hours. Warfarin was administered with ORI (Cohort 1), 24 hours after ORI (Cohort 2), or 72 hours after ORI (Cohort 3). Serial blood samples were collected up to 144 hours post-warfarin dose to assess warfarin PK profiles (measured as S-warfarin) alone and when co-administered with ORI. The effect of ORI on warfarin exposure was evaluated within each cohort by comparing the S-warfarin PK parameters of Cmax, AUC0-last, and AUC0-inf using 90% confidence intervals for the geometric mean ratios. Results: The 90% CIs lie completely within the range of 80% to 125%; thus, ORI had no effect on the PK of warfarin for up to 72 hours after the start of ORI infusion. Overall, ORI infusion, when administered with warfarin, was generally well tolerated and no AEs of bleeding were reported. There were no clinically meaningful changes in clinical labs, vital signs, 12-lead ECG results, or physical examination findings. Conclusion: ORI did not affect the PK of warfarin when it was administered concurrently with and up to 72 hours after the start of an ORI infusion and no signs of bleeding were observed. Thus, ORI may be considered for use in patients receiving warfarin without any concern for interaction.
    S. Eralp Bellibas, MD, PhD1, Carlos Sanabria, MD2, Brooke Lohse, BA3, Karen Fusaro, BA4, Jeff Loutit, MBChB3 and Michael N. Dudley, Pharm.D.3, (1)Clinical Pharmacology, The Medicines Company, Parsippany, NJ, (2)Spaulding Clinical, West Bend, WI, (3)The Medicines Company, San Diego, CA, (4)The Medicines Company, Parsippany, NJ

    Disclosures:

    S. E. Bellibas, The Medicines Company: Employee and Shareholder , Salary and stock options

    C. Sanabria, None

    B. Lohse, The Medicines Company: Employee , Salary and stock options

    K. Fusaro, The Medicines Company: Employee , Salary and stock options

    J. Loutit, The Medicines Company: Employee , Salary and stock options

    M. N. Dudley, The Medicines Company: Employee , Salary and stock options

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.