1. Sivextro™ (tedizolid phosphate)
Manufacturer: Cubist Pharmaceuticals
FDA Approval Date: June 20, 2014

2. Sivextro™ - tedizolid phosphate Clinical Application
Indications:
Acute bacterial skin and skin structure infections
Susceptible Gram-positive organisms
Place in therapy:
First line against gram positives?
Think good antimicrobial stewardship

3. Sivextro™ - tedizolid phosphate Clinical Application
Contraindications:
None
Warnings and Precautions:
Neutropenia (<1000 cells/mm3)
Bacterial or Fungal Super-infections

4. Sivextro™ - tedizolid phosphate Clinical Application
Pregnancy:
Category C
Adverse event noted in animal studies
Lactation:
Not known if it enters breast milk

5. Sivextro™ - tedizolid phosphate Drug Facts
Pharmacology:
Prodrug (tedizolid phosphate  tedizolid)
Binds to the 50S bacterial ribosomal subunit
Bacteriostatic against
Enterococci
Staphylococci
Streptococci
This prevents the formation of a functional 70S initiation complex that is essential for the bacterial translation process and subsequently inhibits protein synthesis.

6. Sivextro™ - tedizolid phosphate Drug Facts
Pharmacokinetics A
Well absorbed
F= 91%
Cmax: ~ 3 hour D
Vd = 67 to 80 L, 70 to 90% protein bound
Tissue penetration similar to plasma free drug concentration M
No significant metabolite E
Feces 82%, Urine 18%
Most occurs within 96 hours

7. Sivextro™ - tedizolid phosphate Drug Interactions
Drug Interactions – Object Drugs:
No known drug interactions
Drug interactions – Precipitant Drugs:

8. Sivextro™ - tedizolid phosphate Adverse Effects
Sivextro (200 mg) vs non-placebo (linezolid 600 mg)
Nausea
8% (12%)
Headache
6% (6%)
Diarrhea
4% (5%)
Vomiting
3% (6%)
Dizziness
2% (2%)

9. Sivextro™ - tedizolid phosphate Monitoring Parameters
Efficacy Monitoring:
Signs of clinical improvement
Toxicity Monitoring:
Reduction in circulation RBCs, WBCs, and platelets

10. Sivextro™ - tedizolid phosphate Prescription Information
Dosing:
200 mg Oral or Intravenous
Infusion time 1 hour
Daily for six days
IV to oral – no dose adjustment

11. Sivextro™ - tedizolid phosphate Prescription Information
Cost:
Brand (generic)
Dose(s)
Cost
Sivextro (tedizolid phosphate)
Oral – 200 mg tablets #6 $
IV – 200 mg vial #10 $
Lexi-Comp via UpToDate; Accessed 10/16/2014

12. Sivextro™ - tedizolid phosphate Literature Review
Study Design (ESTABLISH-1)
Phase 3, randomized, double blind, double dummy, non-inferiority trial
81 study centers from North America, Latin American and Europe
Interventions
Tedizolid 200 mg daily for 6 days
Linezolid 600 mg twice daily for 10 days
Prokocimer et al., JAMA. 2013;309(6):

13. Sivextro™ - tedizolid phosphate Literature Review
Endpoints
Primary
Early clinical response (48-72hr)
Temp ≤ 37.6°C
Cessation of primary lesion spread
Classified as responders, non-responders, and indeterminate
Prokocimer et al., JAMA. 2013;309(6):

14. Sivextro™ - tedizolid phosphate Literature Review
(n = 332)
Linezolid
(n = 335)
Absolute difference (95% CI)
48- to 72-h assessment (ITT) No. (%) [95% CI]
264 (79.5)
[74.8 to 83.7]
266 (79.4) [74.7 to 83.6]
0.1 (-6.1 to 6.2)
Sustained at EOT assessment (ITT)
No. (%) [95% CI]
230 (69.3)
[64.0 to 74.2]
241 (71.9)
[66.8 to 76.7]
-2.6 (-9.6 to 4.2)
Prokocimer et al., JAMA. 2013;309(6):

15. Sivextro™ - tedizolid phosphate Summary
Sivextro is a new oxazolidinone for acute bacterial skin and skin structure infections for gram positive organisms.
IV or oral 200 mg once daily dosing.
It has a simple metabolism and does not interfere with other medications
Sivextro should be used as a second line medication for ABSSSI. More uses could become available.

16. Sivextro™ - tedizolid phosphate References
10/14.
Sivextro package insert. Cubist. October 2014.
Prokocimer et al., Tedizolid Phosphate vs Linezolid for Treatment of Acute Bacterial Skin and Skin Structure Infections. JAMA. 2013;309(6):