Oritavancin

Identification

Name

Oritavancin

Accession Number

DB04911

Description

Oritavancin is a glycopeptide antibiotic used for the treatment of skin infections. It was developed by The Medicines Company (acquired by Novartis).¹⁰ Oritavancin was initially approved by the FDA in 2014 and formulated to combat resistant Staphylococcus, Streptococcus, and other gram-positive bacteria that cause skin infections. It boasts the option of single-dose administration that has been proven as non-inferior to a full course of vancomycin therapy.^8,9

Type

Small Molecule

Groups

Approved, Investigational

Structure

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MOLSDFPDBSMILESInChI

Similar Structures

Structure for Oritavancin (DB04911)

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Weight

Average: 1793.101
Monoisotopic: 1790.564106447

Chemical Formula

C₈₆H₉₇Cl₃N₁₀O₂₆

Synonyms

• Chlorobiphenyl-chloroeremomycin
• Oritavancin

External IDs

• LY-333328
• LY333328

Pharmacology

Indication

Oritavancin is indicated for the treatment of adult patients with acute bacterial skin and skin structure (including subcutaneous) infection. It is used for confirmed/suspected infections with designated and susceptible gram-positive organisms.⁹

As antimicrobial susceptibility patterns are geographically distinct, local antibiograms should be consulted to ensure adequate coverage of relevant pathogens prior to use.

Associated Conditions

• Skin and Subcutaneous Tissue Bacterial Infections

Contraindications & Blackbox Warnings

Learn about our commercial Contraindications & Blackbox Warnings data.

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Pharmacodynamics

Oritavancin interferes with bacterial cell wall synthesis and integrity, treating susceptible skin and subcutaneous tissue infections with gram-positive bacteria.^3,9 This drug is known to artifically increase INR and aPTT, interfering with coagulation testing. Cases of infusion reactions have also been reported.⁹

Mechanism of action

The cell wall is vital for the survival and replication of bacteria, making it a primary target for antibiotic therapy.⁴ Oritavancin works against susceptible gram-positive organisms via three separate mechanisms. Firstly, it binds to the stem peptide of peptidoglycan precursors, inhibiting transglycosylation (polymerization). This process normally occurs during cell wall synthesis. Secondly, oritavancin inhibits crosslinking during bacterial cell wall biosynthesis via binding to cell wall pentaglycyl peptide bridging segments. Finally, this drug also acts by disrupting the bacterial cell membrane, interfering with its integrity, which eventually leads to cell death by various mechanisms.^5,6,9

Target	Actions	Organism
APeptidoglycan precursors	binder
ABacterial cell wall peptide bridging segments	inhibitor	Staphylococcus aureus
APentaglycyl bridging segment	disruptor	Staphylococcus aureus

Absorption

Pharmacokinetic analysis of oritavancin revealed a Cmax of 138 and μg/mL and an AUC0-∞ of 2800 μg•h/mL.⁹ The AUC0-t in a study of healthy volunteers after an 800 mg dose 1,1111 μg•h/mL.¹ was also be Another pharmacokinetic study reported a Cmax of 4.7-7.6 micrograms/mL, generally achieved within 24 hours of administration.²

Volume of distribution

The volume of distribution of oritavancin is estimated at 87.6 L, suggesting extensive tissue distribution.⁹

Protein binding

Oritavancin is about 85% bound to plasma proteins.⁹

Metabolism

In vitro studies on human hepatocytes suggest that oritavancin is not metabolized, and is excreted unchanged.^7,9

Route of elimination

Oritavancin is excreted as unchanged drug in both the urine and feces. Less than 5% has been recovered in the urine, and 1% has been recovered in the feces.^2,9

Half-life

The average terminal half-life of oritavancin is about 245 hours.⁹ A pharmacokinetic study revealed a terminal half-life ranging from 135.8-273.8 hours.²

Clearance

The clearance of oritavancin is approximately 0.445 L/h.⁹ One study revealed a renal clearance of 0.457 mL/min.²

Adverse Effects

Learn about our commercial Adverse Effects data.

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Toxicity

The LD50 of oritavancin in rats is >500m mg/kg.¹² Prescribing information indicates no experience with overdose during the clinical program for oritavancin, however, an overdose is likely to result in an increased risk of adverse effects, such as headache, nausea vomiting, and diarrhea. This drug is not dialyzable, and in the case of an overdose, supportive measures should be undertaken.⁹

Affected organisms

• Gram-positive Bacteria
• Streptococcus pyogenes
• Streptococcus pneumoniae
• Staphylococcus aureus
• Enterococcus faecalis

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Abiraterone	The metabolism of Abiraterone can be increased when combined with Oritavancin.
Acalabrutinib	The metabolism of Acalabrutinib can be increased when combined with Oritavancin.
Acebutolol	The metabolism of Acebutolol can be decreased when combined with Oritavancin.
Acenocoumarol	The risk or severity of bleeding can be increased when Oritavancin is combined with Acenocoumarol.
Acetaminophen	The metabolism of Acetaminophen can be decreased when combined with Oritavancin.
Acetohexamide	The metabolism of Acetohexamide can be decreased when combined with Oritavancin.
Acetylsalicylic acid	The metabolism of Acetylsalicylic acid can be decreased when combined with Oritavancin.
Albendazole	The metabolism of Albendazole can be decreased when combined with Oritavancin.
Alectinib	The metabolism of Alectinib can be increased when combined with Oritavancin.
Almotriptan	The metabolism of Almotriptan can be decreased when combined with Oritavancin.

Additional Data Available

Extended Description
Extended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
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Severity
Severity
A severity rating for each drug interaction, from minor to major.
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Evidence Level
Evidence Level
A rating for the strength of the evidence supporting each drug interaction.
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Action
Action
An effect category for each drug interaction. Know how this interaction affects the subject drug.
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Food Interactions

No interactions found.

Products

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Oritavancin diphosphate	VL1P93MKZN	192564-14-0	PWTROOMOPLCZHB-BHYQHFGMSA-N

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Unlock Additional Data
Orbactiv	Injection, powder, lyophilized, for solution	400 mg/1	Intravenous	The Medicines Company	2014-09-01	2021-06-30
Orbactiv	Injection, powder, lyophilized, for solution	400 mg/1	Intravenous	Melinta Therapeutics, Inc.	2014-09-01	Not applicable
Orbactiv	Injection, powder, lyophilized, for solution	400 mg/1	Intravenous	The Medicines Company	2014-09-01	2014-08-12

Additional Data Available

Application Number
Application Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
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Product Code
Product Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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Categories

ATC Codes

J01XA05 — Oritavancin

• J01XA — Glycopeptide antibacterials
• J01X — OTHER ANTIBACTERIALS
• J01 — ANTIBACTERIALS FOR SYSTEMIC USE
• J — ANTIINFECTIVES FOR SYSTEMIC USE

Drug Categories

• Amino Acids, Peptides, and Proteins
• Anti-Bacterial Agents
• Anti-Infective Agents
• Antibacterials for Systemic Use
• Antiinfectives for Systemic Use
• Carbohydrates
• Cytochrome P-450 CYP2C19 Inhibitors
• Cytochrome P-450 CYP2C19 Inhibitors (weak)
• Cytochrome P-450 CYP2C9 Inhibitors
• Cytochrome P-450 CYP2C9 Inhibitors (weak)
• Cytochrome P-450 CYP2D6 Inhibitors
• Cytochrome P-450 CYP2D6 Inhibitors (weak)
• Cytochrome P-450 CYP3A Inducers
• Cytochrome P-450 CYP3A Inhibitors
• Cytochrome P-450 CYP3A4 Inducers
• Cytochrome P-450 CYP3A4 Inducers (weak)
• Cytochrome P-450 CYP3A4 Inhibitors
• Cytochrome P-450 CYP3A4 Inhibitors (weak)
• Cytochrome P-450 Enzyme Inducers
• Cytochrome P-450 Enzyme Inhibitors
• Glycoconjugates
• Glycopeptide Antibacterials
• Glycopeptides
• Lipids
• Lipoglycopeptide Antibacterial
• Lipopeptides
• Peptides

Chemical TaxonomyProvided by Classyfire

Description

This compound belongs to the class of organic compounds known as oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Amino acids, peptides, and analogues

Direct Parent

Oligopeptides

Alternative Parents

Cyclic peptides / Aminoglycosides / Phenolic glycosides / Leucine and derivatives / Chlorinated biphenyls / N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / Diarylethers / Disaccharides / O-glycosyl compounds / Benzylamines / Phenylmethylamines / Aralkylamines / Chlorobenzenes / 1-hydroxy-2-unsubstituted benzenoids / 1-hydroxy-4-unsubstituted benzenoids / Aryl chlorides / Oxanes / N-acyl amines / Amino acids / Secondary carboxylic acid amides / 1,2-aminoalcohols / Primary carboxylic acid amides / Secondary alcohols / Lactams / Acetals / Oxacyclic compounds / Dialkylamines / Polyols / Carboxylic acids / Azacyclic compounds / Monocarboxylic acids and derivatives / Carbonyl compounds / Hydrocarbon derivatives / Monoalkylamines / Organic oxides / Organochlorides / Organopnictogen compounds / Primary alcohols

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Substituents

1,2-aminoalcohol / 1-hydroxy-2-unsubstituted benzenoid / 1-hydroxy-4-unsubstituted benzenoid / Acetal / Alcohol / Alpha-amino acid amide / Alpha-amino acid or derivatives / Alpha-oligopeptide / Amine / Amino acid / Amino acid or derivatives / Amino saccharide / Aminoglycoside core / Aralkylamine / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Benzylamine / Biphenyl / Carbonyl group / Carboxamide group / Carboxylic acid / Chlorinated biphenyl / Chlorobenzene / Cyclic alpha peptide / Diaryl ether / Disaccharide / Ether / Fatty acyl / Fatty amide / Glycosyl compound / Halobenzene / Hydrocarbon derivative / Lactam / Leucine or derivatives / Monocarboxylic acid or derivatives / Monocyclic benzene moiety / N-acyl-alpha amino acid or derivatives / N-acyl-amine / N-substituted-alpha-amino acid / O-glycosyl compound / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organochloride / Organohalogen compound / Organoheterocyclic compound / Organonitrogen compound / Organooxygen compound / Organopnictogen compound / Oxacycle / Oxane / Phenolic glycoside / Phenylmethylamine / Polyol / Primary alcohol / Primary aliphatic amine / Primary amine / Primary carboxylic acid amide / Secondary alcohol / Secondary aliphatic amine / Secondary amine / Secondary carboxylic acid amide

show 55 more

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

disaccharide derivative, glycopeptide (CHEBI:82699)

Chemical Identifiers

UNII

PUG62FRZ2E

CAS number

171099-57-3

InChI Key

VHFGEBVPHAGQPI-LXKZPTCJSA-N

InChI

InChI=1S/C86H97Cl3N10O26/c1-35(2)22-51(92-7)77(110)98-67-69(105)42-15-20-55(49(88)24-42)120-57-26-44-27-58(73(57)125-84-74(71(107)70(106)59(34-100)122-84)124-62-32-86(6,76(109)37(4)119-62)93-33-38-8-10-39(11-9-38)40-12-17-45(87)18-13-40)121-56-21-16-43(25-50(56)89)72(123-61-31-85(5,91)75(108)36(3)118-61)68-82(115)97-66(83(116)117)48-28-46(101)29-54(103)63(48)47-23-41(14-19-53(47)102)64(79(112)99-68)96-80(113)65(44)95-78(111)52(30-60(90)104)94-81(67)114/h8-21,23-29,35-37,51-52,59,61-62,64-72,74-76,84,92-93,100-103,105-109H,22,30-34,91H2,1-7H3,(H2,90,104)(H,94,114)(H,95,111)(H,96,113)(H,97,115)(H,98,110)(H,99,112)(H,116,117)/t36-,37-,51+,52-,59+,61-,62-,64+,65+,66-,67+,68-,69+,70+,71-,72+,74+,75-,76-,84-,85-,86-/m0/s1

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-(carbamoylmethyl)-5,47-dichloro-48-{[(2S,3R,4S,5S,6R)-3-{[(2S,4S,5R,6S)-4-[({4'-chloro-[1,1'-biphenyl]-4-yl}methyl)amino]-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)pentanamido]-20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentaazaoctacyclo[26.14.2.2^{3,6}.2^{14,17}.1^{8,12}.1^{29,33}.0^{10,25}.0^{34,39}]pentaconta-3,5,8,10,12(48),14,16,29(45),30,32,34,36,38,46,49-pentadecaene-40-carboxylic acid

SMILES

CN[[email protected]](CC(C)C)C(=O)N[[email protected]@H]1[[email protected]](O)C2=CC=C(OC3=C(O[[email protected]@H]4O[[email protected]](CO)[[email protected]@H](O)[[email protected]](O)[[email protected]]4O[[email protected]]4C[[email protected]](C)(NCC5=CC=C(C=C5)C5=CC=C(Cl)C=C5)[[email protected]@H](O)[[email protected]](C)O4)C4=CC(=C3)[[email protected]@H](NC(=O)[[email protected]](CC(N)=O)NC1=O)C(=O)N[[email protected]@H]1C3=CC(=C(O)C=C3)C3=C(O)C=C(O)C=C3[[email protected]](NC(=O)[[email protected]@H](NC1=O)[[email protected]](O[[email protected]]1C[[email protected]](C)(N)[[email protected]@H](O)[[email protected]](C)O1)C1=CC(Cl)=C(O4)C=C1)C(O)=O)C(Cl)=C2

References

Synthesis Reference

Adel Rafai Far, Gopal Krishna, Min Ding, Sanjay R, Chemburkar Carl M, Knable James, J. PETZEL, Julie J Pruyne, Douglas M. Reamer.2015. High purity oritavancin and method of producing same.Patent WO2016011245A1

General References

1. Fetterly GJ, Ong CM, Bhavnani SM, Loutit JS, Porter SB, Morello LG, Ambrose PG, Nicolau DP: 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 Jan;49(1):148-52. [PubMed:15616289]
2. Bhavnani SM, Owen JS, Loutit JS, Porter SB, Ambrose PG: Pharmacokinetics, safety, and tolerability of ascending single intravenous doses of oritavancin administered to healthy human subjects. Diagn Microbiol Infect Dis. 2004 Oct;50(2):95-102. [PubMed:15474317]
3. Kmeid J, Kanafani ZA: Oritavancin for the treatment of acute bacterial skin and skin structure infections: an evidence-based review. Core Evid. 2015 Feb 11;10:39-47. doi: 10.2147/CE.S51284. eCollection 2015. [PubMed:25709561]
4. Schuerholz T, Domming S, Hornef M, Dupont A, Kowalski I, Kaconis Y, Heinbockel L, Andra J, Garidel P, Gutsmann T, David S, Sanchez-Gomez S, Martinez de Tejada G, Brandenburg K: Bacterial cell wall compounds as promising targets of antimicrobial agents II. Immunological and clinical aspects. Curr Drug Targets. 2012 Aug;13(9):1131-7. doi: 10.2174/138945012802002438. [PubMed:22664073]
5. Kim SJ, Cegelski L, Stueber D, Singh M, Dietrich E, Tanaka KS, Parr TR Jr, Far AR, Schaefer J: Oritavancin exhibits dual mode of action to inhibit cell-wall biosynthesis in Staphylococcus aureus. J Mol Biol. 2008 Mar 14;377(1):281-93. doi: 10.1016/j.jmb.2008.01.031. Epub 2008 Jan 17. [PubMed:18258256]
6. Zhanel GG, Schweizer F, Karlowsky JA: Oritavancin: mechanism of action. Clin Infect Dis. 2012 Apr;54 Suppl 3:S214-9. doi: 10.1093/cid/cir920. [PubMed:22431851]
7. Cada DJ, Baker DE: Oritavancin diphosphate. Hosp Pharm. 2014 Dec;49(11):1049-60. doi: 10.1310/hjp4911-1049. [PubMed:25673895]
8. Corey GR, Kabler H, Mehra P, Gupta S, Overcash JS, Porwal A, Giordano P, Lucasti C, Perez A, Good S, Jiang H, Moeck G, O'Riordan W: Single-dose oritavancin in the treatment of acute bacterial skin infections. N Engl J Med. 2014 Jun 5;370(23):2180-90. doi: 10.1056/NEJMoa1310422. [PubMed:24897083]
9. FDA Approved Drug Products: Orbactiv (oritavancin) for intravenous injection [Link]
10. Novartis successfully completes acquisition of The Medicines Company, adding a potentially first-in-class, investigational cholesterol-lowering therapy inclisiran [Link]
11. DailyMed: Orbactiv (oritavancin) powder for injection [Link]
12. Mckesson: Oritavancin diphosphate MSDS [Link]
13. Orbactiv website [Link]

External Links

KEGG Compound

C12034

PubChem Compound

16136912

PubChem Substance

175426900

ChemSpider

17286443

RxNav

1547611

ChEBI

82699

ChEMBL

CHEMBL1688530

Wikipedia

Oritavancin

FDA label

Download (527 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Completed	Other	Skin Diseases, Bacterial	1
4	Completed	Treatment	Acute acute bacterial skin and skin structure infections	1
4	Recruiting	Treatment	Staphylococcus Aureus Bacteraemia / Staphylococcus Aureus Endocarditis	1
3	Completed	Treatment	Abscesses / Cellulitis / Systemic Inflammation / Wound Infections	2
2	Completed	Treatment	Abscesses / Cellulitis / Staphylococcal Skin Infections / Streptococcal Infections / Wounds and Injuries	1
1	Completed	Not Available	Healthy Volunteers	3
1	Completed	Basic Science	Acute acute bacterial skin and skin structure infections	1
1	Completed	Treatment	Healthy Volunteers	3
1	Recruiting	Treatment	Gram Positive Bacterial Infections / Infections, Gram-Positive Bacterial	1
Not Available	Completed	Not Available	Infections, Gram-Positive Bacterial	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection, powder, for solution	Intravenous	400 MG
Injection, powder, lyophilized, for solution	Intravenous	400 mg/1

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
Unlock Additional Data
US8420592	No	2013-04-16	2029-08-29
US5840684	No	1998-11-24	2016-11-24
US5998581	No	1999-12-07	2017-11-12
US9649352	No	2017-05-16	2035-07-16
US9682061	No	2017-06-20	2030-04-26

Additional Data Available

Filed On
Filed On
The date on which a patent was filed with the relevant government.
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Properties

State

Solid

Experimental Properties

Property	Value	Source
boiling point (°C)	810.3	http://www.demechem.com/English/productshow.asp?id=49
water solubility	10 mg/mL	https://www.sigmaaldrich.com/catalog/product/sigma/sml1586?lang=fr®ion=CA
logP	4.1	PMID: 18375379
pKa	2.93±0.7	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB92451283.htm

Predicted Properties

Property	Value	Source
Water Solubility	0.0588 mg/mL	ALOGPS
logP	1.92	ALOGPS
logP	0.2	ChemAxon
logS	-4.5	ALOGPS
pKa (Strongest Acidic)	2.98	ChemAxon
pKa (Strongest Basic)	9.96	ChemAxon
Physiological Charge	2	ChemAxon
Hydrogen Acceptor Count	27	ChemAxon
Hydrogen Donor Count	20	ChemAxon
Polar Surface Area	560.98 Å2	ChemAxon
Rotatable Bond Count	19	ChemAxon
Refractivity	441.59 m3·mol-1	ChemAxon
Polarizability	178.55 Å3	ChemAxon
Number of Rings	13	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	-	0.6087
Blood Brain Barrier	-	0.9905
Caco-2 permeable	-	0.7039
P-glycoprotein substrate	Substrate	0.9233
P-glycoprotein inhibitor I	Non-inhibitor	0.8502
P-glycoprotein inhibitor II	Non-inhibitor	0.9262
Renal organic cation transporter	Non-inhibitor	0.9503
CYP450 2C9 substrate	Non-substrate	0.8721
CYP450 2D6 substrate	Non-substrate	0.8153
CYP450 3A4 substrate	Substrate	0.6616
CYP450 1A2 substrate	Non-inhibitor	0.881
CYP450 2C9 inhibitor	Non-inhibitor	0.8283
CYP450 2D6 inhibitor	Non-inhibitor	0.8541
CYP450 2C19 inhibitor	Non-inhibitor	0.8122
CYP450 3A4 inhibitor	Non-inhibitor	0.6912
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.7622
Ames test	Non AMES toxic	0.6154
Carcinogenicity	Non-carcinogens	0.8151
Biodegradation	Not ready biodegradable	1.0
Rat acute toxicity	2.6222 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9983
hERG inhibition (predictor II)	Non-inhibitor	0.5464

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Not Available

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Drug created on October 21, 2007 16:23 / Updated on June 12, 2020 11:41