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Oritavancin Diphosphate

Class: Glycopeptides
Chemical Name: (4″R)-22-O-(3-Amino-2,3,6-trideoxy-3-C-methyl-α-l-arabino-hexopyranosyl)-N3″-[p-(p-chlorophenyl)benzyl]vancomycin
Molecular Formula: C86H97Cl3N10O26C86H97Cl3N10O26•2H3PO4
CAS Number: 171099-57-3
Brands: Orbactiv

Medically reviewed on April 9, 2018


Antibacterial; lipoglycopeptide; semisynthetic derivative of a naturally occurring glycopeptide.1 7 8

Uses for Oritavancin Diphosphate

Skin and Skin Structure Infections

Treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA; also known as oxacillin-resistant S. aureus or ORSA] and methicillin-susceptible S. aureus), Streptococcus pyogenes (group A β-hemolytic streptococci, GAS), S. agalactiae (group B streptococci, GBS), S. dysgalactiae, S. anginosus group (includes S. anginosus, S. intermedius, and S. constellatus), or vancomycin-susceptible Enterococcus faecalis.1 5 6

Oritavancin Diphosphate Dosage and Administration


Administer by IV infusion.1

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Must reconstitute and further dilute prior to IV infusion.1

Do not administer simultaneously with commonly used IV drugs through a common port.1

If the same IV line or port is used for sequential infusion of other drugs, flush IV line with 5% dextrose injection before and after oritavancin infusion.1

Vials contain no preservatives; for single use only.1


Reconstitute vials containing 400 mg of oritavancin by adding 40 mL of sterile water for injection to provide a solution containing 10 mg/mL.1 Total of 3 vials required to prepare a single 1.2-g dose.1

To avoid foaming, gently swirl vials until contents completely dissolve.1 Reconstituted solution should appear clear and colorless to pale yellow.1


Further dilute reconstituted solution in 5% dextrose injection.1 Before adding oritavancin to a 1-L IV bag of 5% dextrose injection, withdraw and discard 120 mL of the 5% dextrose injection.1 Then, withdraw 40 mL of oritavancin solution from each of the 3 reconstituted vials and add to the IV bag to bring the volume to 1 L.1 Final diluted solution has a concentration of 1.2 mg/mL.1

Rate of Administration

Administer by IV infusion over 3 hours.1


Available as oritavancin diphosphate; dosage expressed in terms of oritavancin.1


Skin and Skin Structure Infections

Single 1.2-g dose.1

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment: Dosage adjustments not needed.1

Severe hepatic impairment: Pharmacokinetics not evaluated.1

Renal Impairment

Mild or moderate renal impairment: Dosage adjustments not needed.1

Severe renal impairment: Pharmacokinetics not evaluated.1

Cautions for Oritavancin Diphosphate


  • Hypersensitivity to oritavancin.1

  • Unfractionated heparin sodium contraindicated for 48 hours after oritavancin;1 aPTT expected to be falsely elevated.1 (See Tests Used to Monitor Coagulation under Cautions.)


Sensitivity Reactions

Serious hypersensitivity reactions reported.1 Median onset of hypersensitivity reactions was 1.2 days and median duration was 2.4 days in clinical studies.1

Because of possibility of cross-sensitivity, question patients about previous hypersensitivity reactions to glycopeptides (e.g., dalbavancin, telavancin, vancomycin).1 Carefully monitor those with a history of glycopeptide allergy for signs of hypersensitivity during oritavancin infusion.1

If acute hypersensitivity reaction occurs during the infusion, immediately discontinue and initiate appropriate supportive care.1

Infusion Reactions

Infusion-related reactions (e.g., pruritus, urticaria, flushing) reported.1

If an infusion-related reaction occurs, consider slowing or interrupting infusion.1

Tests Used to Monitor Coagulation

Artificially prolongs certain tests used to monitor coagulation, including PT, INR, and aPTT;1 also expected to prolong activated clotting time (ACT).1 Oritavancin binds to phospholipid reagents and prevents activation of coagulation in such tests.1 This may complicate laboratory monitoring in patients receiving certain anticoagulants (e.g., heparin, warfarin).1

PT and INR shown to be artificially prolonged for 24 hours after oritavancin;1 aPTT shown to be artificially prolonged for 48 hours after oritavancin.1

For patients requiring aPTT monitoring within 48 hours of oritavancin administration, use a non-phospholipid-dependent coagulation test (e.g., factor Xa [chromogenic] assay) or consider using alternative anticoagulant not requiring aPTT monitoring.1

Does not affect the coagulation system.1

Concomitant Use with Warfarin

Because of increased warfarin exposure (see Interactions), use oritavancin and chronic warfarin therapy concomitantly only when benefits expected to outweigh risk of bleeding.1

If used concomitantly, frequently monitor for signs of bleeding.1 Consider that laboratory monitoring of anticoagulant effects of warfarin is unreliable for 24 hours after oritavancin.1 (See Tests Used to Monitor Coagulation under Cautions.)


In clinical studies, osteomyelitis reported more frequently in patients receiving oritavancin than in those receiving vancomycin.1

Monitor patients for signs and symptoms of osteomyelitis.1 If osteomyelitis is suspected or diagnosed, initiate appropriate alternative antibacterial therapy.1

Superinfection/Clostridium difficile-associated Diarrhea and Colitis (CDAD)

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.1 Monitor carefully; institute appropriate therapy if superinfection occurs.1

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.1 12 14 15 C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all anti-infectives, including oritavancin, and may range in severity from mild diarrhea to fatal colitis.1 12 14 15 C. difficile produces toxins A and B which contribute to development of CDAD;1 12 hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.1

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.1 12 14 15 Obtain careful medical history since CDAD may occur as late as ≥2 months after anti-infective therapy is discontinued.1

If CDAD suspected or confirmed, discontinue anti-infectives not directed against C. difficile whenever possible.1 12 Initiate appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.1 12 14 15

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of oritavancin and other antibacterials, use only for treatment of infections proven or strongly suspected to be caused by susceptible bacteria.1

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.1 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.1

Specific Populations


Category C.1

Use during pregnancy only if potential benefits justify potential risks to fetus.1

No adequate and well-controlled studies in pregnant women;1 animal studies (rats and rabbits) did not reveal evidence of fetal harm at dosages equivalent to 25% of human dosage, but higher doses not evaluated.1


Distributed into milk in lactating rats;1 not known whether distributed into human milk.1

Use with caution in nursing women.1

Pediatric Use

Safety and efficacy not established in pediatric patients.1

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether they respond differently then younger adults.1 Greater sensitivity in some older individuals cannot be ruled out.1

Hepatic Impairment

Moderate hepatic impairment (Child-Pugh class B): Pharmacokinetics not altered.1

Severe hepatic impairment (Child-Pugh class C): Pharmacokinetics not evaluated.1

Renal Impairment

Mild or moderate renal impairment: Pharmacokinetics not altered.1

Severe renal impairment or undergoing dialysis: Pharmacokinetics not evaluated.1

Common Adverse Effects

GI effects (i.e., diarrhea, nausea, vomiting, constipation),1 5 6 dizziness,1 5 6 headache,1 5 6 infusion site reactions (including phlebitis and extravasation),1 5 6 pruritus,5 6 urticaria,5 pyrexia,5 6 chills,5 abscess (limb or subcutaneous),1 5 6 cellulitis,5 6 increased AST and ALT,1 5 6 tachycardia,1 6 insomnia,5 fatigue.5

Interactions for Oritavancin Diphosphate

Weak inhibitor of CYP2C9 and 2C19; weak inducer of 3A4 and 2D6.1

Not a substrate or inhibitor of the P-glycoprotein (P-gp) efflux transporter.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

If used concomitantly with drugs that are metabolized by CYP2C9, 2C19, 3A4, or 2D6 and have a narrow therapeutic index, use caution and closely monitor for signs of toxicity or lack of efficacy.1

Specific Drugs and Laboratory Tests





Decreased ratio of dextromethorphan to dextrorphan concentrations in urine1

Fluoroquinolones (ciprofloxacin, moxifloxacin)

Ciprofloxacin: In vitro evidence of synergistic antibacterial effects against vancomycin-resistant enterococci (VRE)27

Moxifloxacin: In vitro evidence of synergistic antibacterial effects against methicillin-susceptible S. aureus1 9

No in vitro evidence of antagonism1 27


In vitro evidence of synergistic antibacterial effects against methicillin-susceptible S. aureus, vancomycin-intermediate S. aureus (VISA), heterogeneous VISA (hVISA), and vancomycin-resistant S. aureus (VRSA)1 9

In vitro evidence of synergistic antibacterial effects against VRE16

No in vitro evidence of antagonism1


aPTT expected to be falsely elevated for 48 hours after oritavancin administration1

Contraindicated for 48 hours after oritavancin administration1


In vitro evidence of synergistic antibacterial effects against VISA, hVISA, and VRSA1 9

No in vitro evidence of antagonism1


Decreased midazolam AUC1


Increased ratio of omeprazole to 5-hydroxyomeprazole concentrations1


In vitro evidence of synergistic antibacterial effects against methicillin-susceptible S. aureus and VRSA1 9

No in vitro evidence of antagonism1

Tests, coagulation

Artificially prolongs PT, INR, and aPTT;1 also expected to prolong ACT;1 binds to phospholipid reagents and prevents activation of coagulation in these tests1

PT and INR artificially prolonged for 24 hours; aPTT artificially prolonged for 48 hours1

Does not affect coagulation system1

Patients requiring aPTT monitoring within 48 hours of oritavancin: Use non-phospholipid-dependent coagulation test (e.g., factor Xa [chromogenic] assay) or consider alternative anticoagulant not requiring aPTT monitoring1


Increased warfarin AUC;1 possible increased risk of bleeding1

Due to artificial prolongation of PT and INR, monitoring of anticoagulant effects of warfarin unreliable for 24 hours after oritavancin administration1

Use concomitantly only when benefits expected to outweigh risk of bleeding;1 monitor frequently for signs of bleeding1

Oritavancin Diphosphate Pharmacokinetics


Plasma Concentrations

Linear, dose-dependent pharmacokinetics following IV administration.1 28



Extensively distributed into tissues, including skin blister fluid,1 19 extracellular lung fluid,2 and alveolar macrophages.2 Mean oritavancin concentrations in skin blister fluid approximately 20% of those in plasma after a single 800-mg dose in healthy individuals.1 19

Plasma Protein Binding

Approximately 85%.1



Not metabolized.1

Elimination Route

Slowly eliminated unchanged in feces and urine;1 <1 and 5% of a single IV dose recovered in feces and urine, respectively, by 2 weeks after dose.1

Not removed by hemodialysis or continuous renal replacement therapy (CRRT).1 25


Approximately 10 days (245 hours).1

Special Populations

Moderate hepatic impairment (Child-Pugh class B): No clinically important effect on pharmacokinetics.1

Mild or moderate renal impairment: No clinically important effect on pharmacokinetics.1




Powder for Injection

20–25°C (may be exposed to 15–30°C).1

Following reconstitution and further dilution, store at room temperature or refrigerate at 2–8°C.1

Combined total storage time and 3-hour infusion time should not exceed 6 hours at room temperature or 12 hours at 2–8°C.1


For information on systemic interactions resulting from concomitant use, see Interactions.


May be incompatible with drugs formulated at an alkaline or neutral pH.1

Solution Compatibility1


Dextrose 5% in water


Sodium chloride 0.45 or 0.9%

Drug Compatibility
Y-Site Compatibility26


Calcium gluconate

Cimetidine hydrochloride

Ciprofloxacin lactate


Dobutamine hydrochloride

Epinephrine hydrochloride


Fentanyl citrate


Gentamicin sulfate

Haloperidol lactate

Insulin, regular


Midazolam hydrochloride

Morphine sulfate


Norepinephrine bitartrate

Pancuronium bromide

Phenylephrine hydrochloride

Potassium chloride

Ranitidine hydrochloride

Tobramycin sulfate



Amphotericin B


Clindamycin phosphate



Heparin sodium

Hydrocortisone sodium succinate


Sodium nitroprusside



Actions and Spectrum

  • Semisynthetic lipoglycopeptide antibacterial derived from chloroeremomycin, a naturally occurring glycopeptide.1 7 8 Structurally similar to vancomycin, but has side chains that enhance antibacterial activity.7 8

  • Mechanism of action similar to that of other glycopeptides (e.g., dalbavancin, telavancin, vancomycin).7 Binds to d-alanyl-d-alanine terminus of growing peptidoglycan chains, thereby inhibiting bacterial cell wall synthesis;1 4 7 8 binds to peptide bridging segments of the cell wall, thereby inhibiting transpeptidation (crosslinking) step of cell wall biosynthesis; dimerizes and anchors into bacterial cell membrane, which improves binding to target.1 4 7 8 10 11

  • Bactericidal in vitro against certain gram-positive bacteria, including staphylococci, streptococci, and enterococci.1 7 8 10 13

  • Active in vitro and in clinical studies against S. aureus (including methicillin-resistant S. aureus [MRSA; also known as oxacillin-resistant S. aureus or ORSA]),1 4 5 6 13 20 24 S. pyogenes (group A β-hemolytic streptococci, GAS),1 4 5 6 21 S. agalactiae (group B streptococci, GBS),1 4 5 6 S. dysgalactiae,1 5 6 S. anginosus group (includes S. anginosus, S. intermedius, and S. constellatus),1 5 6 and vancomycin-susceptible E. faecalis.1 4 5 6 13

  • Active in vitro against vancomycin-susceptible E. faecium,1 4 Clostridium perfringens,4 C. difficile,4 22 23 Peptostreptococcus,4 Propionibacterium acnes,4 S. pneumoniae,18 vancomycin-intermediate S. aureus (VISA),24 vancomycin-resistant S. aureus (VRSA),18 and daptomycin-nonsusceptible S. aureus (DNSSA).24 However, safety and efficacy in treating clinical infections due to these bacteria not established.1

  • Reduced susceptibility or resistance to oritavancin produced in vitro by serial passage of S. aureus and E. faecalis in the presence of increasing concentrations of the drug.1

Advice to Patients

  • Advise patients that antibacterials (including oritavancin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1

  • Importance of completing full course of therapy, even if feeling better after a few days.1

  • Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with oritavancin or other antibacterials in the future.1

  • Advise patients that allergic reactions, including serious allergic reactions, could occur and require immediate treatment.1 Importance of informing clinician about any previous hypersensitivity reactions to oritavancin or other glycopeptides (e.g., dalbavancin, telavancin, vancomycin).1

  • Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.1 Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Oritavancin Diphosphate


Dosage Forms


Brand Names



For injection, for IV infusion

400 mg (of oritavancin)


Medicines Company

AHFS DI Essentials. © Copyright 2018, Selected Revisions April 7, 2015. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.


1. Orbactiv. The Medicines Company (oritavancin) for injection prescribing information. Parsippany, NJ; 2014 Sep.

2. US Food and Drug Administration. Center for Drug Evaluation and Research: Application number 206334Orig1s000: Summary review. 2014 Aug 6. From FDA website.

4. Karaoui LR, El-Lababidi R, Chahine EB. Oritavancin: an investigational lipoglycopeptide antibiotic. Am J Health Syst Pharm. 2013; 70:23-33.

5. Corey GR, Kabler H, Mehra P et al. Single-dose oritavancin in the treatment of acute bacterial skin infections. N Engl J Med. 2014; 370:2180-90.

6. Corey GR, Good S, Jiang H et al. Single-dose Oritavancin Compared to 7-10 days of Vancomycin in the Treatment of Gram-Positive Acute Bacterial Skin and Skin Structure Infections; the SOLO II Non-inferiority Study. Clin Infect Dis. 2014; :.

7. Zhanel GG, Schweizer F, Karlowsky JA. Oritavancin: mechanism of action. Clin Infect Dis. 2012; 54 Suppl 3:S214-9.

8. Allen NE. From vancomycin to oritavancin: the discovery and development of a novel lipoglycopeptide antibiotic. Anti-Infect Agents Med Chem. 2010; 9:23-47.

9. Belley A, Neesham-Grenon E, Arhin FF et al. Assessment by time-kill methodology of the synergistic effects of oritavancin in combination with other antimicrobial agents against Staphylococcus aureus. Antimicrob Agents Chemother. 2008; 52:3820-2.

10. Belley A, McKay GA, Arhin FF et al. Oritavancin disrupts membrane integrity of Staphylococcus aureus and vancomycin-resistant enterococci to effect rapid bacterial killing. Antimicrob Agents Chemother. 2010; 54:5369-71.

11. Patti GJ, Kim SJ, Yu TY et al. Vancomycin and oritavancin have different modes of action in Enterococcus faecium. J Mol Biol. 2009; 392:1178-91.

12. Cohen SH, Gerding DN, Johnson S et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol. 2010; 31:431-55.

13. McKay GA, Beaulieu S, Arhin FF et al. Time-kill kinetics of oritavancin and comparator agents against Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium. J Antimicrob Chemother. 2009; 63:1191-9.

14. Fekety R for the American College of Gastroenterology Practice Parameters Committee. Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis. Am J Gastroenterol. 1997; 92:739-50.

15. American Society of Health-System Pharmacists Commission on Therapeutics. ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of Clostridium difficile-associated disease. Am J Health-Syst Pharm. 1998; 55:1407-11.

16. Zelenitsky SA, Booker B, Laing N et al. Synergy of an investigational glycopeptide, LY333328, with once-daily gentamicin against vancomycin-resistant Enterococcus faecium in a multiple-dose, in vitro pharmacodynamic model. Antimicrob Agents Chemother. 1999; 43:592-7.

18. Coyle EA, Rybak MJ. Activity of oritavancin (LY333328), an investigational glycopeptide, compared to that of vancomycin against multidrug-resistant Streptococcus pneumoniae in an in vitro pharmacodynamic model. Antimicrob Agents Chemother. 2001; 45:706-9.

19. Fetterly GJ, Ong CM, Bhavnani SM et al. Pharmacokinetics of oritavancin in plasma and skin blister fluid following administration of a 200-milligram dose for 3 days or a single 800-milligram dose. Antimicrob Agents Chemother. 2005; 49:148-52.

20. Arhin FF, Sarmiento I, Moeck G. In vitro activities of oritavancin and comparators against meticillin-resistant Staphylococcus aureus (MRSA) isolates harbouring the novel mecC gene. Int J Antimicrob Agents. 2014; 44:65-8.

21. Arhin FF, McKay GA, Beaulieu S et al. Time-kill kinetics of oritavancin and comparator agents against Streptococcus pyogenes. Int J Antimicrob Agents. 2009; 34:550-4.

22. O'Connor R, Baines SD, Freeman J et al. In vitro susceptibility of genotypically distinct and clonal Clostridium difficile strains to oritavancin. J Antimicrob Chemother. 2008; 62:762-5.

23. Baines SD, O'Connor R, Saxton K et al. Comparison of oritavancin versus vancomycin as treatments for clindamycin-induced Clostridium difficile PCR ribotype 027 infection in a human gut model. J Antimicrob Chemother. 2008; 62:1078-85.

24. Saravolatz LD, Pawlak J, Johnson LB. In vitro activity of oritavancin against community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), vancomycin-intermediate S. aureus (VISA), vancomycin-resistant S. aureus (VRSA) and daptomycin-non-susceptible S. aureus (DNSSA). Int J Antimicrob Agents. 2010; 36:69-72.

25. Kumar A, Mann HJ, Keshtgarpour M et al. In vitro characterization of oritavancin clearance from human blood by low-flux, high-flux, and continuous renal replacement therapy dialyzers. Int J Artif Organs. 2011; 34:1067-74.

26. Kumar A, Mann HJ. Visual compatibility of oritavancin diphosphate with selected coadministered drugs during simulated Y-site administration. Am J Health Syst Pharm. 2010; 67:1640-4.

27. Noviello S, Ianniello F, Esposito S. In vitro activity of LY333328 (oritavancin) against Gram-positive aerobic cocci and synergy with ciprofloxacin against enterococci. J Antimicrob Chemother. 2001; 48:283-6.

28. Bhavnani SM, Owen JS, Loutit JS et al. Pharmacokinetics, safety, and tolerability of ascending single intravenous doses of oritavancin administered to healthy human subjects. Diagn Microbiol Infect Dis. 2004; 50:95-102.