Oritavancin

J01X - Other antibacterials ATC J01XA05 Small molecule approved 2014 Parenteral Natural product

JFDA label: Orbactiv

Mechanism of Action

Oritavancin is a lipoglycopeptide with concentration-dependent bactericidal activity. It inhibits cell wall biosynthesis by inhibiting the polymerization step by binding to stem peptides of peptidoglycan precursors, by inhibiting crosslinking by binding to bridging segments, and by disrupting bacterial membrane integrity, leading to cell death.

Indications

Approved

Acute bacterial skin and skin structure infections

Antimicrobial Spectrum

Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: EUCAST v16 · curated · openfda-label.

Bacteria

Organism	Activity	MIC
Enterococcus faecalis	Susceptible	0.12 mg/L
Enterococcus faecium	Susceptible	0.12 mg/L
Staphylococcus aureus	Susceptible	0.12 mg/L
Streptococcus A/B/C/G	Susceptible	0.252 mg/L
Streptococcus agalactiae	Active	—
Streptococcus anginosus	Active	—
Streptococcus dysgalactiae	Active	—
Streptococcus pyogenes	Active	—

Class profile

gramStatus	Gram+
spectrumBreadth	Narrow
atypicalCoverage	No
isBactericidal	1
moaCategory	Cell wall synthesis inhibitor (glycopeptide) + membrane depolarization (dual MOA)
pdIndex	Concentration-dependent
postAntibioticEffect	Prolonged
mrsaCoverage	1
resistanceMechanisms	VanA/VanB gene clusters (reduced susceptibility),Membrane phospholipid changes

Contraindications

Source: Lexicomp

Hypersensitivity to oritavancin or any component of the formulation Absolute
use of intravenous unfractionated heparin for 120 hours (5 days) after oritavancin administration (oritavancin falsely elevates aPTT for up to 120 hours (5 days) after administration) Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (2)

Common hypersensitivity angiitis, dizziness · Tachycardia

Blood and lymphatic system disorders (1)

Common Anemia, increased serum AST, increased total serum bilirubin

Skin and subcutaneous tissue disorders (1)

Common Erythema multiforme, vomiting, diarrhea

General disorders and administration site conditions (3)

Common erythema at injection site (Neuromuscular & skeletal: Myalgia (Respiratory: Bronchospasm (Clostridium difficile-associated diarrhea · Injection site phlebitis · injection site reaction

Dosing

Source: Lexicomp

Acute bacterial skin and skin structure infections (ABSSI): IV: 1,200 mg as a single dose

Refer to adult dosing.

CrCl ≥30 mL/minute: No dosage adjustment necessary. CrCl ESRD requiring hemodialysis: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); not removed by hemodialysis.

Mild to moderate hepatic impairment (Child-Pugh class A or B): No dosage adjustment necessary. Severe hepatic impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Warnings & Precautions

Source: Lexicomp

Hypersensitivity

Serious hypersensitivity reactions have been reported (median onset in studies ~1.2 days). If an acute reaction occurs, discontinue infusion immediately and institute appropriate supportive care (median resolution ~2.4 days) Inquire about previous hypersensitivity reactions to glycopeptides; carefully monitor patients with a history of glycopeptide allergy.

Infusion reactions

Infusion related reactions (pruritus, urticaria, flushing) have been reported. If reactions occur, consider slowing or interrupting infusion.

Osteomyelitis

In clinical trials, more cases of osteomyelitis were noted in patients treated with oritavancin. Monitor for signs and symptoms of osteomyelitis and institute appropriate alternate antibacterial therapy if warranted.

Superinfection

Use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse events were not observed in animal reproduction studies.

Lactation

It is not known if oritavancin is excreted into breast milk. The manufacturer recommends that caution be used if administered to a nursing woman.

Monitoring

Efficacy	Culture and susceptibility testing; clinical resolution (temperature, WBC, CRP, procalcitonin)
Toxicity	Renal function (dose adjustment in renal impairment); hepatic function for hepatically cleared agents; signs of C. difficile infection (diarrhoea)
Clinical pearl	Culture results guide de-escalation to narrower-spectrum therapy. Review antibiotic appropriateness at 48–72 h (antimicrobial stewardship).
Counseling	Complete the full course. Report persistent diarrhoea, rash, or lack of improvement after 48–72 h.

Chemistry & Properties

Formula	C86H97Cl3N10O26
Molecular weight	1793.12 g/mol
IUPAC name	(1S,2R,18R,19R,22S,25R,28R,40S)-2-[(2R,4S,5R,6S)-4-amino-5-hydroxy-4,6-dimethyloxan-2-yl]oxy-22-(2-amino-2-oxoethyl)-5,15-dichloro-48-[(2S,3R,4S,5S,6R)-3-[(2S,4S,5R,6S)-4-[[4-(4-chlorophenyl)phenyl]methylamino]-5-hydroxy-4,6-dimethyloxan-2-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-18,32,35,37-tetrahydroxy-19-[[(2R)-4-methyl-2-(methylamino)pentanoyl]amino]-20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentazaoctacyclo[26.14.2.23,6.214,17.18,12.129,33.010,25.034,39]pentaconta-3,5,8,10,12(48),14,16,29(45),30,32,34(39),35,37,46,49-pentadecaene-40-carboxylic acid
CAS	171099-57-3
PubChem CID	16136912
InChIKey	`VHFGEBVPHAGQPI-LXKZPTCJSA-N`

SMILES

CN[C@H](CC(C)C)C(=O)N[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H]2C(=O)N[C@H]3C(=O)N[C@H](C(=O)N[C@H](C(=O)O)c4cc(O)cc(O)c4-c4cc3ccc4O)[C@H](O[C@H]3C[C@](C)(N)[C@@H](O)[C@H](C)O3)c3ccc(c(Cl)c3)Oc3cc2cc(c3O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O[C@H]2C[C@](C)(NCc3ccc(-c4ccc(Cl)cc4)cc3)[C@@H](O)[C@H](C)O2)Oc2ccc(cc2Cl)[C@H]1O

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	7.021 h
Volume of distribution	0.525 L/kg
Protein binding	95.6%
BBB penetrant	No

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Drug–drug interactions (38, DDInter)

Interacting drug	Severity	Management
Heparin	major
Abemaciclib	moderate
Acalabrutinib	moderate
Alpelisib	moderate
Brigatinib	moderate
Cabozantinib	moderate
Cobicistat	moderate
Copanlisib	moderate
Crizotinib	moderate
Darolutamide	moderate
Dasatinib	moderate
Elagolix	moderate
Encorafenib	moderate
Entrectinib	moderate
Ethinylestradiol	moderate
Everolimus	moderate
Fostamatinib	moderate
Gilteritinib	moderate
Glasdegib	moderate
Hydrocodone	moderate
Imatinib	moderate
Larotrectinib	moderate
Macimorelin	moderate
Midostaurin	moderate
Mycophenolic acid	moderate
Nitisinone	moderate
Osilodrostat	moderate
Picosulfuric acid	moderate
Praziquantel	moderate
Ribociclib	moderate
Sorafenib	moderate
Sunitinib	moderate
Temsirolimus	moderate
Ticagrelor	moderate
Toremifene	moderate
Vemurafenib	moderate
Warfarin	moderate
Bortezomib	minor

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Orbactiv	Vial 400 mg	3 vial	/ HIKMA PHARMACEUTICALS.IND/JORDAN / General / / HIKMA PHARMACEUTICALS.IND/JORDAN / General / Genera	—