What is Tedizolid (Sivextro)?

From the Guidelines

Tedizolid (Sivextro) is an oxazolidinone antibiotic used to treat acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). The recommended dosage is 200 mg once daily for 6 days, administered either orally or intravenously, as evidenced by the Efficacy and Safety of 6-day Oral Tedizolid in Acute Bacterial Skin and Skin Structure Infections vs 10-day Oral Linezolid Therapy trials 1. This treatment regimen has been shown to have similar rates of early clinical response compared to 10-day oral linezolid therapy, with 80% vs. 81% in the ESTABLISH-1 trial and 92% vs. in another study 1.

Some key benefits of tedizolid include:

• Once-daily dosing, which improves patient adherence and convenience
• Shorter treatment duration of 6 days, compared to 10-14 days for linezolid
• Potential for fewer drug interactions and side effects compared to linezolid
• Mechanism of action involves binding to the 50S subunit of bacterial ribosomes, inhibiting protein synthesis

Common side effects of tedizolid include:

• Nausea
• Headache
• Diarrhea Patients should be monitored for peripheral and optic neuropathy with prolonged use, though these occur less frequently than with linezolid 1. Additionally, tedizolid should be used cautiously in patients taking serotonergic agents due to potential serotonin syndrome risk, though this interaction appears less significant than with linezolid. Food does not affect oral bioavailability, so tedizolid can be taken with or without meals, improving patient convenience and adherence.

From the FDA Drug Label

SIVEXTRO (tedizolid phosphate), a phosphate prodrug, is converted to tedizolid in the presence of phosphatases. The pharmacologically active moiety, tedizolid, is an antibacterial agent of the oxazolidinone class

Tedizolid (Sivextro) is an antibacterial agent of the oxazolidinone class. It is a phosphate prodrug that is converted to its active form, tedizolid, in the presence of phosphatases 2. Key points about Tedizolid include:

• It is administered orally or by intravenous infusion
• It has a molecular weight of 450.32 and an empirical formula of C17H16FN6O6P Tedizolid is the pharmacologically active moiety.

From the Research

Overview of Tedizolid

• Tedizolid phosphate is a once-daily oxazolidinone approved by the United States Food and Drug Administration for the treatment of acute bacterial skin and skin structure infections (ABSSSI) 3.
• It is more potent in vitro than linezolid against methicillin-resistant Staphylococcus aureus (MRSA) and other gram-positive pathogens causing ABSSSI 3, 4.

Mechanism of Action and Pharmacokinetics

• The mechanism of action of tedizolid is similar to other oxazolidinones and occurs through inhibition of bacterial protein synthesis by binding to 23S ribosomal RNA (rRNA) of the 50S subunit of the ribosome 4.
• Tedizolid is approximately 90% protein bound, leading to lower free-drug concentrations than linezolid 3.
• It has a half-life of approximately 12 hours, allowing for once-daily dosing, and demonstrates linear pharmacokinetics with high oral bioavailability of approximately 90% 4, 5.

Clinical Efficacy and Safety

• Two Phase III clinical trials have demonstrated the non-inferiority of tedizolid 200 mg once daily for 6 days to linezolid 600 mg twice daily for 10 days in patients with ABSSSI 3, 4.
• Tedizolid has several key advantages over linezolid, including once-daily dosing, decreased treatment duration, minimal interaction with serotonergic agents, and possibly associated with less adverse events 3, 6, 5.
• Tedizolid may have fewer significant interactions with serotonin reuptake inhibitors or monoamine oxidase inhibitors than linezolid, and thrombocytopenia may occur less often with tedizolid than linezolid 6, 5.

Comparison to Other Treatments

• Tedizolid is an attractive agent for use in both the hospital and community settings due to its enhanced in vitro activity against a broad-spectrum of Gram-positive aerobic bacteria, convenient once-daily dosing, and short 6-day course of therapy 4.
• Economic analyses are needed to describe the cost-effectiveness of tedizolid compared to other options used for ABSSSI, particularly treatment options active against MRSA 3.