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Also known as: 171099-57-3, Ly333328, Oritavancin [inn], Ly-333328, Chlorobiphenyl-chloroeremomycin, Pug62frz2e

Molecular Formula

C₈₆H₉₇Cl₃N₁₀O₂₆

Molecular Weight

1793.1 g/mol

InChI Key

VHFGEBVPHAGQPI-LXKZPTCJSA-N

FDA UNII

PUG62FRZ2E

Oritavancin is a glycopeptide antibiotic used for the treatment of skin infections. It was developed by The Medicines Company (acquired by Novartis). Oritavancin was initially approved by the FDA in 2014 and formulated to combat susceptible gram-positive bacteria that cause skin and skin structure infections. It boasts the option of single-dose administration and has been proven as non-inferior to a full course of [vancomycin] therapy. On March 12, 2021 the FDA approved Kimyrsa, a complete course of therapy in a single, 1 hour 1200 mg infusion. Orbactiv, the other FDA approved oritavancin product, is administered over a 3 hour infusion and contains a lower dose of 400 mg. Marketed by Melinta Therapeutics, Kimyrsa offers effective and time-efficient treatment for skin and skin structure infections.

Oritavancin is a Lipoglycopeptide Antibacterial. The mechanism of action of oritavancin is as a Cytochrome P450 2C19 Inhibitor, and Cytochrome P450 2C9 Inhibitor, and Cytochrome P450 3A4 Inducer, and Cytochrome P450 2D6 Inducer.

1 2D Structure

Oritavancin

2 Identification

2.1 Computed Descriptors

2.1.1 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

2.1.2 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

2.1.3 InChI Key

VHFGEBVPHAGQPI-LXKZPTCJSA-N

2.1.4 Canonical SMILES

CC1C(C(CC(O1)OC2C3C(=O)NC(C4=C(C(=CC(=C4)O)O)C5=C(C=CC(=C5)C(C(=O)N3)NC(=O)C6C7=CC(=C(C(=C7)OC8=C(C=C2C=C8)Cl)OC9C(C(C(C(O9)CO)O)O)OC1CC(C(C(O1)C)O)(C)NCC1=CC=C(C=C1)C1=CC=C(C=C1)Cl)OC1=C(C=C(C=C1)C(C(C(=O)NC(C(=O)N6)CC(=O)N)NC(=O)C(CC(C)C)NC)O)Cl)O)C(=O)O)(C)N)O

2.1.5 Isomeric SMILES

C[C@H]1[C@@H]([C@@](C[C@@H](O1)O[C@H]2[C@H]3C(=O)N[C@@H](C4=C(C(=CC(=C4)O)O)C5=C(C=CC(=C5)[C@H](C(=O)N3)NC(=O)[C@H]6C7=CC(=C(C(=C7)OC8=C(C=C2C=C8)Cl)O[C@H]9[C@@H]([C@H]([C@@H]([C@H](O9)CO)O)O)O[C@H]1C[C@]([C@H]([C@@H](O1)C)O)(C)NCC1=CC=C(C=C1)C1=CC=C(C=C1)Cl)OC1=C(C=C(C=C1)[C@H]([C@H](C(=O)N[C@H](C(=O)N6)CC(=O)N)NC(=O)[C@@H](CC(C)C)NC)O)Cl)O)C(=O)O)(C)N)O

2.2 Other Identifiers

2.2.1 UNII

PUG62FRZ2E

2.3 Synonyms

2.3.1 MeSH Synonyms

1. (4''r)-22-o-(3-amino-2,3,6-trideoxy-3-c-methyl-alpha-l-arabinohexopyranosyl)-n3''-(p-(p-chlorophenyl)benzyl)vancomycin

2. Ly 333328

3. Ly-333328

4. Ly333328

5. Orbactiv

2.3.2 Depositor-Supplied Synonyms

1. 171099-57-3

2. Ly333328

3. Oritavancin [inn]

4. Ly-333328

5. Chlorobiphenyl-chloroeremomycin

6. Pug62frz2e

7. Chebi:82699

8. Kimyrsa

9. (4''r)-22-o-(3-amino-2,3,6-trideoxy-3-c-methyl-alpha-l-arabinohexopyranosyl)-n3''-(p-(p-chlorophenyl)benzyl)vancomycin

10. Unii-pug62frz2e

11. Chembl1688530

12. Orita-vancin

13. Ly 333328

14. C12034

15. Oritavancin [mi]

16. Oritavancin [vandf]

17. Oritavancin [mart.]

18. Oritavancin [who-dd]

19. Oritavancin; Ly-333328

20. Schembl9947049

21. Gtpl10877

22. Dtxsid20897570

23. Bdbm513037

24. Ex-a2372

25. Db04911

26. Ncgc00485478-01

27. Ncgc00485478-02

28. Q7102878

29. (4''r)-22-o-(3-amino-2,3,6-trideoxy-3-c-methyl-.alpha.-l-arabino-hexopyranosyl)-n(sup 3)''-(p-(p-chlorophenyl)benzyl)vancomycin

30. (4''r)-22-o-(3-amino-2,3,6-trideoxy-3-c-methyl-alpha-l-arabino-hexopyranosyl)-n(3'')-((4'-chloro(1,1'-biphenyl)-4-yl)methyl)vancomycin

31. (4'r)-22-o-(3-amino-2,3,6-trideoxy-3-c-methyl-alpha-l-arabino-hexopyranosyl)-n(sup 3)' -(p-(p-chlorophenyl)benzyl)vancomycin

32. Vancomycin, 22-o-(3-amino-2,3,6-trideoxy-3-c-methyl-.alpha.-l-arabino-hexopyranosyl)-n3''-((4'-chloro(1,1'-biphenyl)-4-yl)methyl)-, (4''r)-

2.4 Create Date

2007-07-04

3 Chemical and Physical Properties

Molecular Formula	C₈₆H₉₇Cl₃N₁₀O₂₆
Molecular Weight	1793.1 g/mol
XLogP3	1.5
Hydrogen Bond Donor Count	20
Hydrogen Bond Acceptor Count	29
Rotatable Bond Count	19
Exact Mass	1790.564106 g/mol
Monoisotopic Mass	1790.564106 g/mol
Topological Polar Surface Area	561 Å²
Heavy Atom Count	125
Formal Charge	0
Complexity	3700
Isotope Atom Count	0
Defined Atom Stereocenter Count	22
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Covalently Bonded Unit Count	1

4 Drug and Medication Information

4.1 Drug 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. There are two preparations of oritavancin; the 400 mg dose that is administered over 3 hours, and the 1200 mg dose administered over 1 hour. Both are indicated for susceptible gram-positive skin and skin structure infections in adults. As antimicrobial susceptibility patterns are geographically distinct, local antibiograms should be consulted to ensure adequate coverage of relevant pathogens prior to use.

FDA Label

Tenkasi is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) in adults (see sections 4. 4 and 5. 1).

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

5 Pharmacology and Biochemistry

5.1 Pharmacology

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

5.2 MeSH Pharmacological Classification

Anti-Bacterial Agents

Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)

5.3 FDA Pharmacological Classification

5.3.1 Active Moiety

ORITAVANCIN

5.3.2 FDA UNII

PUG62FRZ2E

5.3.3 Pharmacological Classes

Cytochrome P450 2C9 Inhibitors [MoA]; Cytochrome P450 2D6 Inducers [MoA]; Cytochrome P450 3A4 Inducers [MoA]; Lipoglycopeptide Antibacterial [EPC]; Lipoglycopeptides [CS]; Cytochrome P450 2C19 Inhibitors [MoA]

5.4 ATC Code

J01XA05

J - Antiinfectives for systemic use

J01 - Antibacterials for systemic use

J01X - Other antibacterials

J01XA - Glycopeptide antibacterials

J01XA05 - Oritavancin

5.5 Absorption, Distribution and Excretion

Absorption

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

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.

Volume of Distribution

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

Clearance

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

5.6 Metabolism/Metabolites

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

5.7 Biological Half-Life

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

5.8 Mechanism of Action

The cell wall is vital for the survival and replication of bacteria, making it a primary target for antibiotic therapy. 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.