Transcript sivextro
™ 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