1. New Drug Review Amy Yeh APPE Internal Medicine II
Drug Sivextro (tedizolid phosphate)
Class Oxazolidinone antibiotic
MOA Inhibits bacterial translation and protein synthesis
Indication Treatment of ABSSSI caused by gram (+) bacteria in adults
Activity
Bacteriostatic activity
Has demonstrated efficacy against linezolid-resistant Staphylococcus
4-16 times more potent than linezolid
Active against Gram (+): Staphylococcus aureus including MRSA
Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus
Enterococcus faecalis
Pharmacokinetics
Half-life: 12 hrs; Protein-binding: 70-90%, Oral bioavailability: 91%
Phosphatases convert tedizolid phosphate to active tedizolid
Peak levels: 3 hrs after oral administration; 1 hr after IV infusion
Eliminated hepatically as inactive sulfate conjugate; not a CYP or PGP substrate
Dosing/Admin
Give 200 mg IV/PO once daily for 6 days.
IV infusion: Administer 200 mg in 250 mL NS over 1 hr. Do not give as IVP or IV bolus.
Give with or without food; take a missed dose up to 8 hrs prior to next scheduled dose.
No dosage adjustments in renal/hepatic impairment.
ADRs
Most common: N/V/D, headache, dizziness
< 2%: HTN, tachycardia, peripheral neuropathy, infusion rxns, ALT elevations, anemia,
neutropenia, oral candidiasis, palpitations, flushing, visual impairment
Contraindications
Lack of data in neutropenic individuals  Consider using a different abx
Hypersensitivity to oxazolidinones
DDIs
MAO inhibitor  risk of serotonin syndrome  avoid use with serotonin modulators
(tramadol, bupropion, stimulants, lithium, opioids)
Alcohol may increase incidence of MAOI toxicity  avoid use
Compatibility Stable in NS
Pregnancy Category C; use caution in lactation
Monitoring
Baseline CBC with differential, liver function tests, s/sx of super-infection.
Efficacy: temperature, WBC, clinical response, cultures.
Evidence
ESTABLISH-1: Sivextro 200 mg PO daily for 6 days was non-inferior to linezolid 600 mg PO
bid for 10 days for the tx of complicated ABSSSI in adults.
Early clinical response at 48-72 hrs: afebrile, NG in lesion size, no use of other abx, no
mortality
 79.5% Sivextro vs. 79.4% linezolid; absolute tx difference of 0.1% (95% CI: -6.1% to
6.2%)
Clinical success: 94.6% Sivextro vs. 95.4% linezolid; absolute tx difference of -0.8% (95% CI:
-4.6% to 3.0%)
ADRs: less GI distress, more headache, more ALT elevation (no liver dysfunction/toxicity),
less thrombocytopenia (normalized without medical tx)
ESTABLISH-2: Sivextro 200 mg IV daily for 6 days was non-inferior to linezolid 600 mg IV bid
for 10 days for the tx of complicated ABSSSI. Optional switch to PO tx.
Subjects: age ≥ 12, gram (+) infection, minimum lesion area of 75 cm2, ≥1 sign of infection
Early clinical response at 48-72 hrs: ≥ 20% reduction in lesion size, no use of other abx, no
mortality within 72 hrs of tx
 85% Sivextro vs. 83% linezolid; absolute tx difference of 2.6% (95% CI: -3.0% to
8.2%)
ADRs: same incidence of GI distress and HA, less thrombocytopenia and neutropenia
*Delta margin of -10%
Cost Sivextro: 200 mg tablets (6) for $2124; 200 mg vials (10) for $2820
Zyvox: 600 mg tablets (20) for $3644.29; 2 mg/mL vial (100 mL) for $93.70
Linezolid: 2 mg/mL vial (300 mL) for $147.97
Place in Therapy
Reserve for the tx of complicated gram (+) ABSSSI in pts ≥ 12 yrs of age
1) alternative to linezolid
2) linezolid-resistance

2. References
 Sivextro package insert. Revised March 2015. Accessed April 4, 2015 at www.sivextro.com/pdf/sivextro-prescribing-
info.pdf.
 Prokocimer P, De Anda C, Fang E, Mehra P, Das A. 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.
 Moran GJ, Fang E, Corey GR, Das AF, De Anda C, Prokocimer P. Tedizolid for 6 days versus linezolid for 10 days for acute
bacterial skin and skin-structure infections (ESTABLISH-2): a randomized, double-blind, phase 3, non-inferiority trial.
Lancet Infect Dis. 2014;14(8):696-705.
 Wong E, Rab S. Tedizolid phosphate (Sivextro): a second generation oxazolidinone to treat acute bacterial skin and skin
structure infections. Drug Forecast. 2014;39(8):555-579.
 Rodvold KA, McConeghy KW. Methicillin-resistant Staphylococcus aureus therapy: past, present, and future. CID.
2014;58(Suppl 1):S20-27.
 Lexi-Comp website. Tedizolid. Accessed April 4, 2015 at http://online.lexi.com.proxy.pba.edu/.