Sivextro (tedizolid phosphate)

Tedizolid phosphate is an oxazolidinone antibacterial agent.

Tedizolid phosphate is an oxazolidinone anti-infective agent. Tedizolid phosphate is a prodrug that is inactive until hydrolyzed in vivo to tedizolid. The phosphate prodrug is highly water soluble, which facilitates oral absorption and enhances bioavailability of tedizolid.

The mechanism of activity of tedizolid is mediated by binding to the 50S subunit of bacterial ribosomes resulting in inhibition of bacterial translation and inhibition of protein synthesis. Although the binding site for tedizolid is similar to the binding site for other oxazolidinones (e.g., linezolid), tedizolid may engage additional ribosomal sites compared with linezolid.

In vitro, tedizolid is bacteriostatic against certain gram-positive bacteria, including staphylococci, streptococci, and enterococci. The drug is active in vitro and in clinical infections against Staphylococcus aureus (including methicillin-resistant S. aureus (MRSA; also known as oxacillin-resistant S. aureus)), S. pyogenes (group A beta-hemolytic streptococci, GAS), Streptococcus agalactiae (group B streptococci, GBS), S. anginosus group (includes S. anginosus, S. intermedius, and S. constellatus), and Enterococcus faecalis. There is some evidence from in vitro studies that tedizolid may be more potent than linezolid against susceptible bacteria, and tedizolid has been active against some strains of S. aureus resistant to linezolid.

Tedizolid also has in vitro activity against E. faecium, S. epidermidis (including methicillin-resistant strains (oxacillin-resistant strains)), S. haemolyticus, and S. lugdunensis; however, safety and efficacy of the drug in treating clinical infections caused by these bacteria have not been established in adequate and well-controlled clinical studies to date. Although further study is needed, there is some in vitro evidence that tedizolid has activity against Mycobacterium tuberculosis.

Reduced susceptibility or resistance to tedizolid has been produced in vitro by serial passage of S. aureus or E. faecium in the presence of increasing concentrations of the drug. In vitro, spontaneous mutations conferring reduced susceptibility to tedizolid have occurred at a frequency rate of approximately 10-10.

Cross-resistance between tedizolid and linezolid has been reported. Bacteria resistant to oxazolidinones (e.g., linezolid) because of mutations in chromosomal genes encoding the 23S rRNA or ribosomal proteins (L3 and L4) usually are cross-resistant to tedizolid. However, in vitro date indicate that the presence of the chloramphenicol-florfenicol resistance (cfr) gene in S. aureus that results in resistance to linezolid may not result in resistance to tedizolid in the absence of chromosomal mutations.

Cross-resistance between tedizolid and non-oxazolidinone anti-infectives is unlikely.

Tedizolid phosphate is rapidly converted in vivo by phosphatases to the active moiety, tedizolid. The drug is well absorbed following oral administration (absolute bioavailability approximately 91%); systemic exposure is similar whether the drug is given orally in the fasted state or with a high-fat, high-calorie meal. Peak plasma concentrations of tedizolid are achieved approximately 3 hours after oral administration of tedizolid phosphate in the fasted state or at the end of a 1-hour IV infusion.

Steady-state concentrations are achieved within approximately 3 days with oral or IV administration; accumulation is approximately 30% after 7 or more days of once-daily dosing. Tedizolid has a half-life of approximately 12 hours. The drug is distributed into the interstitial space fluid of adipose and skeletal muscle tissue at concentrations similar to plasma concentrations; the drug also has been shown to distribute into epithelial lining fluid of pulmonary tissue in concentrations higher than those found in plasma.

Tedizolid is 70-90% bound to plasma proteins. Tedizolid phosphate and tedizolid do not appear to be substrates of cytochrome P-450 (CYP) enzymes. A major metabolite (tedizolid sulfate) and several minor metabolites have been identified in feces and urine.

Following a single oral dose of tedizolid phosphate, tedizolid is excreted in feces (82%) and urine (18%), principally as the noncirculating sulfate conjugate; less than 3% of the tedizolid phosphate dose is eliminated in feces and urine as unchanged tedizolid. Approximately 10% of a dose is removed by hemodialysis.

USES: This medication is used to treat or prevent serious bacterial infections of the skin. It works by stopping the growth of bacteria. This antibiotic treats only bacterial infections.

It will not work for viral infections (such as common cold, flu). Using any antibiotic when it is not needed can cause it to not work for future infections.

Generic name: tedizolid phosphate
Pronunciation: (te-DIZ-oh-lid)

The following indications are listed for Sivextro:

• Bacterial Skin And Skin Structure Infection
• Complicated Skin And Skin Structure Enterococcus Faecalis Infection
• Skin And Skin Structure Streptococcus Agalactiae Infection
• Skin And Skin Structure Streptococcus Pyogenes Infection
• Staphylococcus Aureus Skin And Skin Structure Infection

Also known as: Bacterial Skin Infection, Complicated Skin And Skin Soft Tissue Enterococcus Faecalis Infection, Skin & Skin Soft Tissue Streptococcus Pyogenes Infection, Skin And Skin Soft Tissue Infection Due To S. Agalactiae, Skin And Skin Soft Tissue S. Agalactiae Infection, Skin And Skin Soft Tissue Staphylococcus Aureus Infection.

No ICD codes are available for this drug.