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/.