Pharmacological Class:
Oxazolidinone.
Active Ingredient(s):
Tedizolid phosphate 200mg; tablets; and lyophilized pwd for IV infusion after reconstitution; preservative-free.
Company
Cubist Pharmaceuticals, Inc.
Indication(s):
Acute bacterial skin and skin structure infections (ABSSSI) caused by the following susceptible Gram (+) organisms: Staphylococcus aureus (including MRSA and MSSA), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus Group (including Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus), and Enterococcus faecalis.
Pharmacology:
Tedizolid phosphate is a prodrug that is converted by phosphatases to tedizolid, the microbiologically active moiety, following oral and intravenous administration.
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 other non-oxazolidinone class antibiotics. In vitro time-kill studies show that tedizolid is bacteriostatic against enterococci, staphylococci, and streptococci.
Clinical Trials:
A total of 1,315 adults with ABSSSI were randomized in two multicenter, multinational, double-blind, non-inferiority trials. Both trials compared Sivextro 200mg once daily for 6 days vs. linezolid 600mg every 12 hours for 10 days. In Trial 1, patients were treated with oral therapy, while in Trial 2, patients could receive oral therapy after a minimum of one day of intravenous therapy. Patients with cellulitis/erysipelas, major cutaneous abscess, or wound infection were enrolled in the trials.
In Trial 1, patients with ABSSSI were randomized to Sivextro (N=323) and to linezolid (N=326). 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 intent-to-treat (ITT) population. The treatment difference was 0.1 (95% CI: −6.2, 6.3) between responders in the Sivextro 200mg (n=256) and linezolid 1200mg (n=258) treatment groups.
In Trial 2, patients with ABSSSI were randomized to Sivextro (N=332) and to linezolid (N=334). The primary endpoint was early clinical response defined as ≥ 20% decrease from baseline lesion area at 48–72 hours after the first dose in the ITT population. The treatment difference was 2.6 (95% CI: −3.0, 8.2) between responders in the Sivextro 200mg (n=283) and linezolid 1200mg (n=276) treatment groups.
An investigator assessment of clinical response was made at the post-therapy eva luation (7–14 days after end of therapy) in the intent-to-treat and clinically eva luable populations.
Clinical success was defined as resolution or near resolution of most disease-specific signs and symptoms, absence or near resolution of systemic signs of infection if present at baseline, and no new signs, symptoms, or complications attributable to the ABSSSI requiring further treatment of the primary lesion.
For more clinical trial data, see full labeling.
Legal Classification:
Rx
Adults:
≥18 years: Oral: 200mg once daily for 6 days. IV: Infuse 200mg once daily over 1 hour for 6 days. If switching from IV to oral: no dose adjustment necessary.
Children:
<18 years: not established.
Warnings/Precautions:
Not adequately eva luated in patients with neutropenia (ANC <1000 cells/mm3); consider alternate therapies. Risk of Clostridium difficile-associated diarrhea (CDAD); discontinue if suspected or confirmed. Pregnancy (Category C). Nursing mothers.
Adverse Reaction(s)
Nausea, headache, diarrhea, vomiting, dizziness.
How Supplied:
Tabs—6 (blister pack), 30; single-use vials—10
LAST UPDATED:
8/25/2014
