General Information

Orbactiv (oritavancin) is a semisynthetic lipoglycopeptide antibacterial drug. It exerts concentration-dependent bactericidal activity in vitro against S. aureus, S. pyogenes, and E. faecalis.

Orbactiv is specifically indicated for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following Gram-positive microorganisms: Staphylococcus aureus (including methicillin-susceptible and methicillin–resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus anginosus group (includes S. anginosus, S. intermedius, and S. constellatus), and Enterococcus faecalis (vancomycin-susceptible isolates only).

Orbactiv is supplied as a solution for intravenous infusion. The recommended dose is a single 1200 mg dose administered by intravenous infusion over three hours in patients 18 years and older. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Orbactiv and other antibacterial drugs, Orbactiv should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria.

Clinical Results

FDA Approval

The FDA approval of Orbactiv was based on two identically designed, randomized, double-blind, multi-center, multinational, non-inferiority trials (Trial 1 and Trial 2). The trials enrolled 1,987 adults with clinically documented ABSSSI suspected or proven to be due to Gram-positive pathogens. A single 1200 mg intravenous dose of Orbactiv was compared to intravenous vancomycin (1 g or 15 mg/kg every 12 hours) for 7 to 10 days. The primary analysis population (modified intent to treat, mITT) included all randomized patients who received any study drug. The primary endpoint in both trials was early clinical response (responder), defined as cessation of spread or reduction in size of baseline lesion, absence of fever, and no rescue antibacterial drug at 48 to 72 hours after initiation of therapy. Data showed Orbactiv was as effective as Vancomycin in treating the infections. Trial 1: Orbactiv: 82.3% responders and Vancomycin: 78.9% responders. Trial 2: Orbactiv: 80.1% responders and Vancomycin: 82.9% responders.

Side Effects

Adverse effects associated with the use of Orbactiv may include, but are not limited to, the following:

headache

nausea

vomiting

limb and subcutaneous abscesses

diarrhea

Mechanism of Action

Orbactiv (oritavancin) is a semisynthetic lipoglycopeptide antibacterial drug. It exerts concentration-dependent bactericidal activity in vitro against S. aureus, S. pyogenes, and E. faecalis. Oritavancin has three mechanisms of action: (i) inhibition of the transglycosylation (polymerization) step of cell wall biosynthesis by binding to the stem peptide of peptidoglycan precursors; (ii) inhibition of the transpeptidation (crosslinking) step of cell wall biosynthesis by binding to the peptide bridging segments of the cell wall; and (iii) disruption of bacterial membrane integrity, leading to depolarization, permeabilization, and cell death. These multiple mechanisms contribute to the concentration-dependent bactericidal activity of oritavancin.

Additional Information

For additional information regarding Orbactiv or ABSSSI, please visit The Medicines Company website: http://www.themedicinescompany.com/