Dosing and uses of Orbactiv (oritavancin)
Adult dosage forms and strengths
injection, lyophilized powder for reconstitution
- 400mg per 50 mL vial supplied in a package of 3 vials for a 1200mg 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
Susceptible isolates of gram-positive microorganisms
- Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant S aureus [MRSA] isolates)
- Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus anginosus group (includes Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus)
- Enterococcus faecalis (vancomycin-susceptible isolates only)
Dosage modifications
Renal impairment
- Mild-to-moderate: No dosage adjustment required
- Severe: Not evaluated
- Not removed by hemodialysis
Hepatic impairment
- Mild-to-moderate: No dosage adjustment required
- Severe: Not evaluated
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Orbactiv (oritavancin) adverse (side) effects
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%)
Warnings
Contraindications
Hypersensitivity
Use of intravenous unfractionated heparin sodium within 120 hr (5 days) of oritavancin administration
Cautions
Please refer to the patient counseling section of the prescribing information
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 reported, including pruritus, urticaria, and/or flushing; 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
Coagulation test interference
- Artificially prolongs aPTT for up to 120 hr, 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
- Effects on activated clotting time (ACT) are expected since the phospholipid reagents are also used in this coagulation test
- Oritavancin has no effect on the coagulation system
Pregnancy and lactation
Pregnancy category: C
Lactation: Unknown if distributed in human breast milk
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Orbactiv (oritavancin)
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
Absorption
Peak plasma concentration: 138 mcg/mL
AUC, 0-24 hr: 1110 mcg•hr/mL
AUC, 0-infinity: 2800 mcg•hr/mL
Distribution
Protein bound: 85%
Vd: 87.6 L; extensively distributed into tissues
Metabolism
Not metabolized
Weak inhibitor of CYP2C9 and CYP2C19
Weak inducer of CYP3A4 and CYP2D6
Elimination
Half-life, alpha: 2.29 hr
Half-life, beta: 13.4 hr
Half-life, terminal: 245 hr
Clearance: 0.445 L/hr
Excretion: <1% feces; <5% urine; following 2 weeks of collection
Administration
IV Compatibilities
Dextrose 5% in water
IV Incompatibilities
Saline solutions
Drugs formulated at a basic or neutral pH
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
Storage
Unreconstituted vials: Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-to 86ºF)
Diluted IV solution in D5W
- Room temperature: Use within 6 hr
- Refrigerated (2-8°C [36-46°F]): Use within 12 hr
- The combined storage time (reconstituted solution in the vial and diluted solution in the bag) and 3-hr infusion time should not exceed 6 hr at room temperature or 12 hr if refrigerated
