ORITAVANCIN

1793.1

1793.10

PUG62FRZ2E

J01XA05|J - Antiinfectives for systemic use

4.1

1.59±0.1 g/cm3(Predicted)

810.3

10

2.93±0.70(Predicted)

2.93±0.7

Store at -20°C

The LD50 of oritavancin in rats is >500m mg/kg. 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.

In prelicensure controlled trials, serum ALT elevations during therapy with dalbvancin, oritavancin or telavancin were common, occurring in up to 25% of patients. Serum aminotransferase elevations above three times the upper limit of normal, however, were uncommon, occurring in 0.8% to 6% of patients receiving dalbavancin, oritavancin or telavancin. Furthermore, these rates of liver test abnormalities were not very different from those in comparator arms. The ALT elevations during glycopeptide antibiotic therapy were in general transient, asymptomatic and only mild-to-moderate in severity, rarely leading to dose modifications or early discontinuations. There were no reports of clinically apparent liver injury with jaundice in the registration trials of these agents. Since their approval and more wide scale use, there have been no published reports of liver injury attributed to glycopeptide antibiotics, although hypersensitivity reactions have been reported which can sometimes be associated with a mild-to-moderate degree of liver injury. Regardless, these three agents are relatively new, have not been widely used and when used, are given for a relatively short period of time and none have been linked to serious cases of liver injury.

Oritavancin is about 85% bound to plasma proteins.

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. 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.

The glycopeptide antibiotics are semisynthetic macromolecules that are structurally related to vancomycin and have antibacterial activity against several gram positive organisms including methicillin resistant Staphylococcus aureus (MRSA). Three lipoglycopeptide antibiotics are available for use in the United States: dalbavancin, oritavancin and telavancin. All three agents have been associated with transient serum enzyme elevations during therapy, but they have yet to be linked convincingly to cases of clinically apparent acute liver injury.

Antineoplastic Agents

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.

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

Pharmacokinetic analysis of oritavancin revealed a Cmax of 138 and μg/mL and an AUC0-∞ of 2800 μg•h/mL. The AUC0-t in a study of healthy volunteers after an 800 mg dose 1,1111 μg•h/mL. was also be Another pharmacokinetic study reported a Cmax of 4.7-7.6 micrograms/mL, generally achieved within 24 hours of administration.|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.|The volume of distribution of oritavancin is estimated at 87.6 L, suggesting extensive tissue distribution.|The clearance of oritavancin is approximately 0.445 L/h. One study revealed a renal clearance of 0.457 mL/min.

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

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.

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.

LY 333328

Human drugs -> Tenkasi (previously Orbactiv) -> EMA Drug Category|Antibacterials for systemic use -> Human pharmacotherapeutic group|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients