™
Sivextro
(tedizolid phosphate)
Manufacturer: Cubist Pharmaceuticals
FDA Approval Date: June 20, 2014
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
Sivextro™ - tedizolid phosphate
Clinical Application
• Contraindications:
• None
• Warnings and Precautions:
• Neutropenia (<1000 cells/mm3)
• Bacterial or Fungal Super-infections
Sivextro™ - tedizolid phosphate
Clinical Application
• Pregnancy:
• Category C
• Adverse event noted in animal studies
• Lactation:
• Not known if it enters breast milk
Sivextro™ - tedizolid phosphate
Drug Facts
• Pharmacology:
• Prodrug (tedizolid phosphate  tedizolid)
• Binds to the 50S bacterial ribosomal
subunit
• Bacteriostatic against
• Enterococci
• Staphylococci
• Streptococci
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
Sivextro™ - tedizolid phosphate
Drug Interactions
• Drug Interactions – Object Drugs:
• No known drug interactions
• Drug interactions – Precipitant Drugs:
• No known drug interactions
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%)
Sivextro™ - tedizolid phosphate
Monitoring Parameters
• Efficacy Monitoring:
• Signs of clinical improvement
• Toxicity Monitoring:
• Reduction in circulation RBCs, WBCs,
and platelets
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
Sivextro™ - tedizolid phosphate
Prescription Information
• Cost:
Brand (generic)
Sivextro
(tedizolid phosphate)
Dose(s)
Cost
Oral – 200 mg
tablets #6
$2124.00
IV – 200 mg vial #10
$2820.00
Lexi-Comp via UpToDate; Accessed 10/16/2014
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):559-569
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):559-569
Sivextro™ - tedizolid phosphate
Literature Review
Tedizolid
Phosphate
(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):559-569
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.
Sivextro™ - tedizolid phosphate
References
•
http://sivextro.com/. 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):559-569