SIVEXTRO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SIVEXTRO (SIVEXTRO).
Tedizolid is an oxazolidinone antibiotic that inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit, preventing formation of the initiation complex.
| Metabolism | Primarily metabolized via hepatic carboxylesterases (CES1, CES2) and xanthine oxidase (XO); minor CYP450 involvement (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP3A4). |
| Excretion | Approximately 66% of the dose excreted in urine as unchanged drug, with an additional small amount as metabolites; ~15% in feces as metabolites. |
| Half-life | Terminal elimination half-life is approximately 20–22 hours, allowing once-daily dosing. |
| Protein binding | Approximately 90% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Steady-state volume of distribution ~1.1 L/kg, indicating extensive tissue penetration. |
| Bioavailability | Oral bioavailability is approximately 70%, unaffected by food. |
| Onset of Action | Intravenous: peak plasma concentration at end of infusion; oral: time to peak concentration ~1–2 hours; clinical effect onset within first dosing interval due to concentration-dependent killing. |
| Duration of Action | Duration of bactericidal effect spans the entire 24-hour dosing interval due to long half-life and post-antibiotic effect. |
200 mg orally or intravenously every 12 hours for 10 days.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min) including hemodialysis, no dose adjustment is necessary except for IV formulation: administer after hemodialysis. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not recommended in severe hepatic impairment (Child-Pugh C) due to lack of data. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established. Not recommended for use in patients <18 years. |
| Geriatric use | No specific dose adjustment recommended; clinical studies included patients ≥65 years with no overall differences in safety or efficacy observed. Use with caution due to potential age-related renal or hepatic dysfunction. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SIVEXTRO (SIVEXTRO).
| Breastfeeding | It is not known whether tedizolid is excreted in human breast milk. In animal studies, tedizolid was present in milk of lactating rats at concentrations similar to maternal plasma. The M/P ratio is not determined in humans. Caution is advised; discontinue nursing or discontinue drug, considering importance to the mother. |
| Teratogenic Risk | Sivextro (tedizolid phosphate) is classified as FDA Pregnancy Category C. Animal studies have shown adverse effects on fetal development at doses producing maternal toxicity. No adequate and well-controlled studies in pregnant women. First trimester: potential risk based on animal data; avoid use unless benefit outweighs risk. Second/third trimester: limited data; use only if clearly needed. Embryofetal developmental toxicity studies in rats and rabbits revealed no teratogenic effects at clinically relevant exposures, but fetal body weight reductions and delayed ossification were observed at maternally toxic doses. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to tedizolid or any component of the formulation"]
| Precautions | ["Myelosuppression (including anemia, leukopenia, pancytopenia, thrombocytopenia) with prolonged use; monitor CBC weekly.","Peripheral and optic neuropathy reported with extended courses; discontinue if neuropathy develops.","Clostridioides difficile-associated diarrhea; evaluate if diarrhea occurs.","Use in patients with neutropenia limited; safety and efficacy not established."] |
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| Fetal Monitoring | Monitor for signs of infection, including fever and white blood cell count. No specific fetal monitoring required; however, standard antenatal monitoring is recommended. If used in pregnancy, consider ultrasound to assess fetal growth and development. |
| Fertility Effects | In animal fertility studies, tedizolid had no effects on male or female fertility at doses up to 2-fold the human exposure. No human data available. |