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. |
| Molecular Weight | 450.5 Da |
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 | Limited human data; animal studies show no evidence of teratogenicity at clinically relevant exposures. Use only if clearly needed. |
| 2nd trimester | Limited human data; animal studies show no evidence of fetal harm. Use only if potential benefit justifies risk. |
| 3rd trimester | Limited human data; avoid use near term due to theoretical risk of kernicterus based on bilirubin displacement from albumin binding. |
Clinical note
Comprehensive clinical and safety monograph for SIVEXTRO (SIVEXTRO).
| Placental transfer | Tedizolid crosses the placenta in rats, with fetal plasma levels approximately 50% of maternal levels. No human data are available. |
| Breastfeeding | Sivextro (tedizolid) is excreted into rat milk at concentrations similar to maternal plasma; no human data. Because of the potential for adverse effects in nursing infants, caution is recommended. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for tedizolid. |
■ 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. |
| Food/Dietary | No significant food interactions. SIVEXTRO can be taken with or without food. A high-fat meal reduces peak concentration and total exposure by approximately 20%, but this is not clinically significant and does not require dose adjustment. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
| Clinical Pearls | SIVEXTRO (tedizolid phosphate) is an oxazolidinone antibiotic with once-daily dosing and a shorter treatment course (6 days) than linezolid (10-14 days) for acute bacterial skin and skin structure infections (ABSSSI). It has less monoamine oxidase inhibition compared to linezolid, but caution is still advised with serotonergic drugs. No dose adjustment needed for renal impairment, including end-stage renal disease on hemodialysis. Monitor for myelosuppression (thrombocytopenia) with prolonged use beyond 6 days. Administer with or without food; high-fat meal decreases Cmax and AUC by about 20%, but no dose adjustment required. |
| Patient Advice | Take SIVEXTRO once daily with or without food. · Complete the full 6-day course even if you feel better. · Avoid taking SIVEXTRO with serotonergic drugs like antidepressants (SSRIs, MAOIs), migraine medications (triptans), or St. John's wort due to risk of serotonin syndrome. · Report symptoms of diarrhea, abdominal pain, or bloody stools as these may indicate Clostridioides difficile infection. · Tell your doctor if you have a history of seizures, as SIVEXTRO may lower seizure threshold. · Inform your doctor about all medications and supplements you take. · Seek medical attention if you develop unusual bruising, bleeding, or signs of infection (fever, sore throat). |