Dosing and uses of Sivextro (tedizolid)
Adult dosage forms and strengths
tablet
- 200mg
lyophilized powder for reconstitution
- 200mg/vial
Skin & Skin Structure Infections
Indicated for acute bacterial skin and skin structure infections
200 mg PO/IV qDay for 6 days
Susceptible isolates of gram-positive microorganisms
- Staphylococcus aureus (including methicillin-resistant [MRSA] and methicillin-susceptible [MSSA] isolates)
- Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group (including Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus)
- Enterococcus faecalis
Dosage modifications
Hepatic impairment: No dosage adjustment required
Renal impairment or hemodialysis: No dosage adjustment required
Administration
May take PO with or without food
Infuse IV over 1 hr
Missed dose
- Take missed dose as soon as possible anytime up to 8 hr prior to the next scheduled dose
- If <8 hr remain before the next dose, wait until the next scheduled dose
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Sivextro (tedizolid) adverse (side) effects
2-10%
Nausea (8%)
Headache (6%)
Diarrhea (4%)
Hemoglobin <10.1 g/dL (3.1%)
Vomiting (3%)
Platelets <112 x 10³/mm³ (2.3%)
Dizziness (2%)
<2%
Blood and lymphatic system disorders: Anemia
Cardiovascular: Palpitations, tachycardia
Eye disorders: Asthenopia, vision blurred, visual impairment, vitreous floaters
General disorders and administration site conditions: Infusion-related reactions
Immune system disorders: Drug hypersensitivity
Infections and infestations: Clostridium difficile colitis, oral candidiasis, vulvovaginal mycotic infection
Investigations: Hepatic transaminases increased, decreased WBCs
Nervous system disorders: Hypoesthesia, paresthesia, seventh nerve paralysis
Psychiatric disorders: Insomnia
Skin and subcutaneous tissue disorders: Pruritus, urticaria, dermatitis
Vascular disorders: Flushing, hypertension
Warnings
Contraindications
None
Cautions
Safety and efficacy in patients with neutropenia (<1000 cells/mm³) is uncertain; in animal models of infection, tedizolid antibacterial activity was reduced in animal models with neutropenia
Clostridium difficile-associated diarrhea (CDAD) reported with nearly all systemic antibacterial agents, including tedizolid; evaluate if diarrhea occur
Prescribing antibiotics in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit and increases the risk of the development of drug-resistant bacteria
Serotonin syndrome: Avoid coadministration with serotonergic psychiatric drugs (eg, SSRIs, SNRIs, TCAs, MAOIs) unless indicated for life-threatening or urgent infections (eg, vancomycin-resistant enterococcal infections, nosocomial pneumonia, complicated skin and skin structure infections such as methicillin-resistant S aureus), due to increased risk of serotonin syndrome; tedizolid may increase serotonin CNS levels by MAO-A inhibition
Clinical trials of tedizolid to date have excluded patients receiving MAOIs, SSRIs, and SNRIs and TCAs; however, the risk of serotonin syndrome may be a class effect and appropriate caution should be taken to avoid coadministration of these agents with tedizolid
Pregnancy and lactation
Pregnancy category: C
Lactation: Unknown if distributed in human breast milk
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Sivextro (tedizolid)
Mechanism of action
Tedizolid phosphate is the prodrug of tedizolid
Oxazolidione antibiotic; action is mediated by binding to the 50S subunit of the bacterial ribosome, resulting in inhibition of protein synthesis
Absorption
Bioavailability: 91% (PO and IV); no dosage adjustment is needed between IV and PO dose
Peak plasma concentration, steady-state: 2.2 mcg/mL (PO); 3 mcg/mL (IV)
Peak plasma time: 3 hr (PO fasting); at end of 1 hr infusion (IV)
AUC, steady-state: 8.4 mcg•hr/mL (PO); 5.9 mcg•hr/mL (IV)
Distribution
Protein bound: 70-90%
Vd: 67-80 L
Metabolism
There was no degradation of tedizolid in human liver microsomes, indicating tedizolid is unlikely to be a substrate for hepatic CYP450 enzymes
Elimination
Half-life: 12 hr
Excretion: 82% feces; 18% urine
Administration
IV Compatibilities
0.9% NaCL
IV Incompatibilities
Any solution containing divalent cations (eg, Ca2+, Mg2+), including lactated Ringer injection and Hartmann solution
IV Preparation
Reconstitute 200 mg vial with 4 mL sterile water for injection
Gently swirl the contents and let the vial stand until the lyophilized powder cake has completely dissolved and any foam disperses
Inspect vial for particulate matter
Reconstituted solution should be clear and colorless to pale-yellow
Tilt the upright vial and insert a syringe with appropriately sized needle into the bottom corner of the vial and remove 4 mL of the reconstituted solution; do not invert the vial during extraction
Must be further diluted with 250 mL of 0.9% NaCl; slowly inject the 4 mL of reconstituted solution into the 250 mL bag, invert IV bag gently to mix
Do NOT shake IV bag (may cause foaming)
IV Administration
Administer as IV infusion over 1 hr
Do NOT give as IV push or bolus
Not for intra-arterial, IM, IT, intraperitoneal, or SC administration
Storage
Unreconstituted vial: Store at controlled room temperature (20-25°C [68-77°F]); excursions permitted to 15-30°C (59-86°F)
Reconstituted vial or diluted IV bag: Do not exceed 24 hr at either room temperature or refrigerated (2-8°C [36-46°F])
