General Information

Sivextro (tedizolid phosphate) is an antibacterial agent of the oxazolidinone class.

Sivextro is specifically indicated for the treatment of adults with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following Gram-positive microorganisms: Staphylococcus aureus (including methicillin-resistant [MRSA] and methicillin-susceptible [MSSA] isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus Group (including Streptococcus inosus, Streptococcus intermedius, and Streptococcus constellatus), and Enterococcus faecalis.

Mechanism of Action

Sivextro (tedizolid phosphate) is an antibacterial agent of the oxazolidinone class. The antibacterial activity of tedizolid is mediated by binding to the 50S subunit of the bacterial ribosome resulting in inhibition of protein synthesis. Tedizolid inhibits bacterial protein synthesis through a mechanism of action different from that of other non-oxazolidinone class antibacterial drugs; therefore, cross-resistance between tedizolid and other classes of antibacterial drugs is unlikely. The results of in vitro time-kill studies show that tedizolid is bacteriostatic against enterococci, staphylococci and streptococci.

Side Effects

Adverse effects associated with the use of Sivextro may include, but are not limited to, the following:

• nausea
• headache
• diarrhea
• vomiting
• dizziness

Dosing/Administration

Sivextro is supplied as a tablet or solution, for oral and/or intravenous administration. The recommended dosage of Sivextro is 200 mg administered once daily for six days either orally (with or without food) or as an intravenous (IV) infusion.

Clinical Trial Results

The FDA approval of Sivextro was based on two multicenter, multinational, randomized, double-blind, non-inferiority trials. Both trials compared Sivextro 200 mg once daily for six days versus linezolid 600 mg every 12 hours for 10 days. In trial 1, subjects were treated with oral therapy, while in trial 2, subjects could receive oral therapy after a minimum of one day of intravenous therapy. Subjects with cellulitis/erysipelas, major cutaneous abscess or wound infection were enrolled in the trials. Subjects with wound infections could have received aztreonam and/or metronidazole as adjunctive therapy for gram-negative bacterial coverage, if needed. The intent-to-treat (ITT) patient population included all randomized patients. 

Trial 1
This trial randomized 323 subjects to Sivextro and 326 subjects to linezolid. The overall median surface area of infection was 190 cm2. The types of ABSSSI included were cellulitis/erysipelas (40 percent), wound infection (30 percent) and major cutaneous abscess (30 percent). In addition to local signs and symptoms of infection, subjects were required to have at least one regional or systemic sign of infection at baseline. The primary endpoint was early clinical response defined as no increase from baseline lesion area at 48-72 hours after the first dose and oral temperature of ≤37.6°C, confirmed by a second temperature measurement within 24 hours in the ITT population. The percentage of responders to the primary endpoint was 79.3 percent and 79.1 percent in the Sivextro and linezolid arms, respectively. 

Trial 2
This trial randomized 332 subjects to Sivextro and 334 subjects to linezolid. The overall median surface area of infection was 231 cm2. The types of ABSSSI included were cellulitis/erysipelas (50 percent), wound infection (30 percent) and major cutaneous abscess (20 percent). In addition to local signs and symptoms of infection, subjects were also required to have at least one regional or systemic sign of infection at baseline. The primary endpoint was early clinical response defined as at least a 20 percent decrease from baseline lesion area at 48-72 hours after the first dose in the ITT population. The percentage of responders to the primary endpoint was 85.2 percent and 82.6 percent in the Sivextro and linezolid arms, respectively.