Oritavancin
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Pronunciation | /oʊˌrɪtəˈvænsɪn/ oh-RIT-ə-VAN-sin |
Trade names | Orbactiv, Kimyrsa |
Other names | LY333328 |
AHFS/Drugs.com | Monograph |
MedlinePlus | a614042 |
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Intravenous | |
ATC code | |
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Pharmacokinetic data | |
Elimination half-life | 16 d)[4] |
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Oritavancin, sold under the brand name Orbactiv among others, is a
The U.S.
Medical uses
Oritavancin is considered a long-lasting antibiotic due to its extended half-life (up to 16 d), high protein binding capacity, and ability to penetrate tissues effectively. It binds strongly to plasma proteins (around 85%), resulting in prolonged release into surrounding tissues. Furthermore, oritavancin exhibits excellent tissue penetration and distribution throughout various sites, including skin structures, synovial fluid (found in joints), bone tissue, and macrophages. Less frequent dosing requirements still keep efficacy against gram-positive infections, which is convenient for prolonged treatment courses such as osteoarticular infections and endocarditis, making it an option for outpatient antibiotic therapy in difficult-to-treat populations where adherence may be challenging and those with limited access to healthcare facilities.[4]
In vitro activity
Oritavancin shares certain properties with other members of the glycopeptide class of antibiotics, which includes
Oritavancin has potential use as a therapy for exposure to Bacillus anthracis, the Gram-positive bacterium that causes anthrax, having demonstrated efficacy in a mouse model both before and after exposure to the bacterium.[10] Oritavancin demonstrates in vitro activity against both the planktonic and biofilmstates of staphylococci associated with prosthetic joint infection (PJI), albeit with increased minimum biofilm bactericidal concentration (MBBC) compared to Minimum inhibitory concentrations (MIC) values.[11] Moreover oritavancin has demonstrated activity against in vitro to vancomycin-susceptible enterococci (VSE) and vancomycin-resistant enterococci (VRE) in both planktonic and biofilm states.[12]
Mechanism
The 4'-chlorobiphenylmethyl group disrupts the cell membrane of Gram-positive bacteria.[13] It also acts by inhibition of transglycosylation and inhibition of transpeptidation.[14]
Synergism
Several antibiotics have been tested as partner drugs of oritavancin.[15][16] Among these "companions" drugs, fosfomycin displayed (in vitro and in vivo) synergistic activity when administered together with oritavancin against VRE strains (both vanA and vanB), including biofilm-producing isolates.[17][18]
Spectrum of Activity
Oritavancin is active against gram-positive aerobic bacteria such as enterococci, staphylococci, streptococci, and anaerobic bacteria such as
Clinical trials
In 2003, results were presented from two pivotal phase-III clinical trials testing the efficacy of daily intravenous oritavancin for the treatment of
Osteomyelitis remains a formidable foe in an era of increasing incidence of Methicillin-resistant Staphylococcus aureus (MRSA) with limited guidance for treatment optimization. The success observed in many patients suggests multi-dose oritavancin may prove advantageous for chronic osteomyelitis but further research is needed to define the optimal dose and frequency of oritavancin for the treatment of chronic osteomyelitis.[23]
History
Originally discovered and developed by Eli Lilly, oritavancin was acquired by InterMune in 2001 and then by Targanta Therapeutics in late 2005.[24] In December 2008, the U.S. Food and Drug Administration (FDA) declined to approve oritavancin without additional studies, and an EU application was withdrawn.[citation needed]
In 2009, The Medicines Company acquired the development rights, completed clinical trials and submitted a
A marketing authorisation valid throughout the European Union was granted on 19 March 2015, for the treatment of acute bacterial skin and skin structure infections in adults.[27]
References
- ^ "Orbactiv- oritavancin injection, powder, lyophilized, for solution". DailyMed. Retrieved 18 December 2020.
- ^ "Kimyrsa- oritavancin diphosphate injection, powder, lyophilized, for solution". DailyMed. Retrieved 31 March 2021.
- ^ a b "Orbactiv EPAR". 17 September 2018.
- ^ PMID 38075413.
- PMID 19450541.
- ^ "FDA approves Orbactiv to treat skin infections" (Press release). U.S. Food and Drug Administration (FDA). 6 August 2014. Archived from the original on 8 August 2014.
- PMID 17373167.
- PMID 18505390.
- PMID 26831328.
- PMID 18606841.
- S2CID 47010590.
- S2CID 5021157.
- PMID 20876372.
- PMID 22431851.
- PMID 25645208.
- PMID 30753495.
- PMID 36289992.
- S2CID 261048377.
- PMID 22183169.
- PMID 24505091.
- PMID 19738026.
- PMID 25709561.
- S2CID 54475167.
- ^ Tomoko Okudaira (2014-05-09). "The Daily Biopharmaceutical News Source". BioWorld. Retrieved 2014-06-06.
- ^ "Biotechs pick up slack in antibiotics development". 17 May 2011.
- ^ "FDA approves Orbactiv to treat skin infections" (Press release). U.S. Food and Drug Administration (FDA). 6 August 2014. Archived from the original on 8 August 2014.
- ^ "EPAR summary: Orbactiv" (PDF). European Medicines Agency. Archived from the original (PDF) on 2018-06-19. Retrieved 2017-02-12.