Oritavancin

Indications

Oritavancin is used for: Indicated for treatment of acute bacterial skin and skin structure infections

Adult Dose

Skin & Skin Structure Infections Indicated for treatment of acute bacterial skin and skin structure infections A single 1200-mg dose administered IV over 3 hr Hepatic impairment Mild-to-moderate: No dosage adjustment required Severe: Not evaluated

Child Dose

Renal Dose

Renal impairment Mild-to-moderate: No dosage adjustment required Severe: Not evaluated Not removed by hemodialysis

Administration

IV Preparation For IV infusion, only after reconstitution and dilution Three 400-mg vials need to be reconstituted and diluted to prepare a single 1200-mg IV dose Reconstitution Add 40 mL of sterile water for injection to reconstitute each vial to provide a 10-mg/mL solution per vial Gently swirl vials to avoid foaming and ensure that all powder is completely reconstituted in solution Inspect each vial visually for particulate matter after reconstitution Solution should appear to be clear and colorless to pale yellow Dilution Use only 5% dextrose in sterile water (D5W) for dilution; do NOT use 0.9% NaCl for dilution, as it is incompatible with oritavancin and may cause precipitation of the drug Use aseptic technique to: -Withdraw and discard 120 mL from a 1000-mL IV bag of D5W -Withdraw 40 mL from each of the 3 reconstituted vials and add to D5W IV bag to bring the bag volume to 1000 mL -This yields a final concentration of 1.2 mg/mL IV Administration Infuse IV over 3 hr Do not administer simultaneously with other IV drugs through a common IV port or Y-site If the same IV line is used for sequential infusion of additional medications, flush the line before and after infusing oritavancin with D5W

Contra Indications

Hypersensitivity Use of intravenous unfractionated heparin sodium within 120 hr (5 days) of oritavancin administration

Precautions

Shown to artificially prolong PT/INR for up to 12 hr (5.1); coadministration with warfarin may result in higher exposure of warfarin and increase risk for bleeding; monitor frequently for signs of bleeding shown to artificially prolong aPTT for up to 120 hours, and may prolong PT and INR for up to 12 hr and ACT for up to 24 hr; for patients who require aPTT monitoring within 120 hr of dosing, consider a non-phospholipid dependent coagulation test such as a Factor Xa (chromogenic) assay or an alternative anticoagulant not requiring aPTT Hypersensitivity reported, including possible cross-sensitivity to other glycopeptides (eg, dalbavancin, telavancin, vancomycin); discontinue infusion if signs of acute hypersensitivity occur; monitor closely patients with known hypersensitivity to glycopeptides Infusion-related reactions, that resemble “Red- man Syndrome”, including flushing of the upper body, urticaria, pruritus and/or rash reported; consider slowing infusion rate or interrupting infusion Clostridium difficile-associated diarrhea (CDAD) has been reported for nearly all systemic antibacterial drugs and may range from mild diarrhea to fatal colitis; evaluate patients if diarrhea occurs In clinical trials, more cases of osteomyelitis were reported with oritavancin compared with vancomycin; if osteomyelitis suspected, institute appropriate alternate antibacterial therapy To reduce development of drug-resistant bacteria and maintain effectiveness, use only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria

Pregnancy-Lactation

Pregnancy Category: C Lactation: Unknown if distributed in human breast milk

Interactions

Adverse Effects

Side effects of Oritavancin : 1-10% Nausea (9.9%) Headache (7.1%) Vomiting (4.6%) Abscess, limb and subcutaneous (3.8%) Diarrhea (3.7%) Increased ALT (2.8%) Dizziness (2.7%) Infusion site phlebitis (2.5%) Tachycardia (2.5%) Infusion site reactions (1.9%) Increased AST (1.8%)

Mechanism of Action

Lipoglycopeptide antibiotic that exerts concentration-dependent bactericidal activity Elicits 3 mechanisms of action: 1. Inhibits the transglycosylation (polymerization) step of cell wall biosynthesis by binding to the stem peptide of peptidoglycan precursors 2. Inhibits the transpeptidation (cross-linking) step of cell wall biosynthesis by binding to the peptide-bridging segments of the cell wall 3. Disrupts bacterial membrane integrity, leading to depolarization, permeabilization, and cell death