SIVEXTRO®

(tedizolid phosphate) 200 mg injection, for intravenous use; 200 mg tablet, for oral use

Efficacy

Efficacy in phase 3 clinical trials

SIVEXTRO was evaluated in 2 randomized controlled noninferiority phase 3 trials in patients with acute bacterial skin and skin structure infection (ABSSSI):

  • ESTABLISH 1 trial: All-oral course of SIVEXTRO vs linezolid (n=667)
  • ESTABLISH 2 trial: IV/oral switch of SIVEXTRO vs linezolid (n=666)

ESTABLISH 1 ABSSSI trial

SIVEXTRO (tedizolid phosphate) delivered efficacy with a short, 6-day course of treatment

Clinical Responses in All-Oral Course of SIVEXTRO® in Phase 3 ESTABLISH 1 Trials in Patients With Acute Bacterial Skin and Skin Structure Infection (ABSSSI).

(a) Intent-to-treat (ITT) population.

Noninferiority for the primary and secondary endpoints was concluded if the lower limit of the 95% confidence interval was greater than –10%. The treatment difference (95% confidence interval) was 0.1 (–6.1, 6.2) for the primary endpoint and –0.5 (–5.8, 4.9) for the secondary endpoint.1

ESTABLISH 2 ABSSSI trial

SIVEXTRO® (tedizolid phosphate) delivered efficacy with a short, 6-day course of treatment

Clinical Responses in IV/Oral Switch of SIVEXTRO® in Phase 3 ESTABLISH 2 Trials in Patients With Acute Bacterial Skin and Skin Structure Infection (ABSSSI).

(a) Intent-to-treat (ITT) population.

Noninferiority for the primary and secondary endpoints was concluded if the lower limit of the 95% confidence interval was greater than -10%. The treatment difference (95% confidence interval) was 2.6 (-3.0, 8.2) for the primary endpoint and 0.3 (-4.8, 5.3) for the secondary endpoint.1

ABSSSI patients

Trials included ABSSSI patients with significant lesions1,2 

Trials included ABSSSI patients with significant lesions, such as
  • Cellulitis/erysipelas
  • Major cutaneous abscess
  • Wound infection
ABSSSI Patient With Abscess on Lower Back.ABSSSI Patient With Cellulitis/Erysipelas on Leg.ABSSSI Patient With Wound Infection on Upper Arm.

Patients evaluated had infection surrounded by erythema with a minimum total lesion surface area of at least 75 cm2, which were suspected or documented to be associated with a Gram-positive pathogen.1,2

Patients also exhibited at least 1 of the following regional or systemic signs of infection1:

  • Lymphadenopathy, fever, white blood cell count ≥10,000 cells/mm3, or
  • <4000 cells/mm3, or >10% immature neutrophils

The median infection area for patients treated with SIVEXTRO (tedizolid phosphate) was 188 cm2 in ESTABLISH 1 and 231 cm2 in ESTABLISH 2.

Trial design

ESTABLISH 1 and ESTABLISH 2 Trial Design for SIVEXTRO® (tedizolid phosphate) Clinical Trials.

Both randomized, multicenter, multinational, double-blind, noninferiority ESTABLISH trials compared SIVEXTRO (tedizolid phosphate) 200 mg once daily for 6 days to linezolid 600 mg every 12 hours for 10 days. Patients with cellulitis/erysipelas, major cutaneous abscess, or wound infection were enrolled in the trials. Patients with wound infections could have received aztreonam and/or metronidazole as adjunctive therapy for Gram-negative bacterial coverage, if needed. In the ESTABLISH 2 trial, patients taking SIVEXTRO received at least 1 day of IV treatment.

For the secondary endpoint of post-therapy evaluation, clinical success was defined as resolution or near resolution of disease-specific signs and symptoms, absence or near resolution of systemic signs of infection if present at baseline (lymphadenopathy, fever, >10% immature neutrophils, abnormal white blood cell count), and no further antibiotic treatment required for the treatment of the primary ABSSSI lesion.

Definitions

ABSSSI = acute bacterial skin and skin structure infections 

IV = intravenous

Indication

Indication: SIVEXTRO is an oxazolidinone-class antibacterial 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 anginosus, Streptococcus intermedius and Streptococcus constellatus), and Enterococcus faecalis.

Usage: To reduce the development of drug-resistant bacteria and maintain the effectiveness of SIVEXTRO and other antibacterial drugs, SIVEXTRO should be used only to treat ABSSSI that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Selected Safety Information

Patients with neutropenia: The safety and efficacy of SIVEXTRO in patients with neutropenia (neutrophil counts <1000 cells/mm3) have not been adequately evaluated. In an animal model of infection, the antibacterial activity of SIVEXTRO was reduced in the absence of granulocytes. Alternative therapies should be considered when treating patients with neutropenia.

Clostridium difficile–associated diarrhea (CDAD), ranging from mild diarrhea to fatal colitis, has been reported with nearly all systemic antibacterial agents, including SIVEXTRO. Evaluate all patients who present with diarrhea following antibiotic use. Careful medical history is necessary because CDAD has been reported to occur more than two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, antibacterial use not directed against C. difficile should be discontinued, if possible.

Development of drug-resistant bacteria: Prescribing SIVEXTRO in the absence of a proven or strongly suspected bacterial infection or prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Adverse reactions: The most common adverse reactions for SIVEXTRO are nausea (8%), headache (6%), diarrhea (4%), vomiting (3%), and dizziness (2%). Infusion site reactions (phlebitis) have been reported (3.1%) in patients receiving SIVEXTRO (when administered intravenously), particularly among Asian patients.

Drug interactions with BCRP substrates: SIVEXTRO (when administered orally) can increase the plasma concentrations of orally administered Breast Cancer Resistance Protein (BCRP) substrates and the potential for adverse reactions. Monitor for adverse reactions related to the concomitant BCRP substrates if coadministration cannot be avoided.

Before prescribing SIVEXTRO, please read the accompanying Prescribing Information. The Patient Information also is available.

References

1. Prokocimer P, De Anda C, Fang E, et al. Tedizolid phosphate vs linezolid for treatment of acute bacterial skin and skin structure infections: the ESTABLISH-1 randomized trial. JAMA. 2013;309(6):559-569.

2. Moran GJ, Fang E, Corey GR, et al. Tedizolid for 6 days versus linezolid for 10 days for acute bacterial skin and skin-structure infections (ESTABLISH-2): a randomised, double-blind, phase 3, noninferiority trial. Lancet Infect Dis. 2014;14(8):696-705.

AINF-1180496-000404/18