Oritavancin is a lipoglycopeptide antibiotic approved for the treatment of acute bacterial skin and skin structure infections caused by gram-positive bacteria in adults. It has a long half-life of 245 hours, allowing for single dose administration. Phase III clinical trials found that a single 1200 mg dose of oritavancin was non-inferior to 7-10 days of vancomycin therapy for treating these infections. Oritavancin is recommended for use in cases of vancomycin resistance or intolerance. It has drug-drug interactions with warfarin and aripiprazole that require caution.

1. New Drug Review Amy Yeh APPE Internal Medicine II
Drug Orbactiv® (oritavancin)
Class Lipoglycopeptide antibiotic
MOA
Inhibits bacterial cell wall synthesis (polymerization and cross-linking)
Disrupts cell membrane integrity
*Has 2 cell-wall binding sites; also inhibits RNA synthesis
Indication Treatment of ABSSSI caused by gram (+) bacteria in adults
Activity
Bactericidal, concentration-dependent killing
Long post-antibiotic effect
Synergistic with gentamicin, moxifloxacin, rifampin, and linezolid
Active against Gram (+) organisms: Staphylococcus aureus including MRSA
Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae
Streptococcus anginosus, Enterococcus faecalis
Pharmacokinetics
Half-life: 245 hours; 85% protein-binding; extensive tissue distribution
Not metabolized; excreted in feces and urine as unchanged drug
Dosing/Admin
Administer 1200 mg IV in D5W as a single infusion over 3 hrs
Renal: regular dosing for CrCl ≥ 30 ml/min; not studied in CrCl < 30 ml/min
Hepatic: regular dosing for Child-Pugh Class A-B; not studied in Child-Pugh Class C
ADRs
N/V/D (4-10%), headache (7%), limb abscess (< 4%), dizziness (3%),
elevated ALT/AST/bilirubin (2-3%), infusion reaction (2%)
< 2%: myalgia, osteomyelitis, bronchospasm, angioedema, anemia
< 1%: Super-infection (C. difficile), prolonged INR/PT
Contraindications
Hypersensitivity to oritavancin
Use of unfractionated heparin 48 hrs after administration (oritavancin falsely elevates aPTT)
Concomitant use of warfarin  increased bleed risk, elevated INR/PT  use with caution
DDIs
Oritavancin is a weak CYP3A4/CYP2D6 inducer, weak CYP2C19/CYP2C9 inhibitor
Decreases concentration of aripiprazole  avoid concomitant use
Increases concentration of warfarin  increased bleed risk  use with caution
Binds to reagents in coagulation tests  artificially prolonged aPTT/PT/INR
Compatibility Only stable in D5W. Incompatible with saline solutions and other medications.
Pregnancy Category C; use caution in lactation
Monitoring
Safety
 Baseline BUN, SCr, AST, ALT, bilirubin
 Hypersensitivity (discontinue infusion if acute reaction occurs)
 Infusion reaction (slow/interrupt infusion)
 Osteomyelitis (switch to a different antibiotic)
 C. difficile infection
Efficacy
 Temperature, WBC, lesion size, culture results
Evidence:
SOLO I and SOLO II
Phase III Clinical
Trials
A single dose of IV 1200 mg oritavancin was non-inferior to 7-10 days of IV vanco (1 g or 15
mg/kg q12 hrs) for the treatment of adult ABSSSI.
Outcomes
 Early clinical response at 48-72 hrs
o cessation of growth/reduction in lesion
o absence of fever
o no use of rescue antibiotics
 Clinical cure assessed 7-14 days after tx
 At least a 20% reduction in lesion size at 48-72 hrs
ADRs as compared to vanco
 Higher incidence of GI distress, fatigue, ALT elevation, limb abscess
 Lower incidence of pruritus/infusion reaction/extravasation, headache
Cost 400 mg vial for IV infusion: $1160
Most Likely Place in
Therapy
Reserve for the treatment of adult gram (+) ABSSSI in vanco resistance or intolerance

2. References
 Oritavancin package insert. Revised September 2014. Accessed April 4, 2015 at
www.orbactive.com/pdfs/orbactiv-prescribing-information.pdf
 Kmeid J, Kanafani ZA. Oritavancin for the treatment of acute bacterial skin and skin structure
infections: an evidence-based review. Core Evidence. 2015;10:39-47.
 Rodvold KA, McConeghy KW. Methicillin-resistant Staphylococcus aureus therapy: past, present, and
future. CID. 2014;58(Suppl 1):S20-27.
 Corey GR, Kabler H, Mehra P, et al. Single-dose oritavancin in the treatment of acute bacterial skin
infections. NEJM. 2014;370(23):2180-90.
 Corey GR, Good S, Jiang H, et al. Single-dose oritavancin versus 7-10 days of vancomycin in the
treatment of gram-positive acute bacterial skin and skin structure infections: the SOLO II
noninferiority study. CID. 2015;60(2):254-62.
 Lexi-Comp website. Oritavancin. Accessed April 4, 2015 at http://online.lexi.com.proxy.pba.edu/.