Tedizolid Phosphate

Approved Indications:

• Acute Bacterial Skin and Skin Structure Infections (ABSSSI):
  Indicated for the treatment of adult and pediatric patients (12 years and older) with ABSSSI caused by susceptible Gram-positive bacteria, including:
• Staphylococcus aureus (including methicillin-resistant strains, MRSA)
• Streptococcus pyogenes
• Streptococcus agalactiae
• Streptococcus anginosus group
• Enterococcus faecalis

Off-label/Clinically Accepted Uses (Emerging or Investigational):

• Complicated skin infections in immunocompromised patients (used with caution)
• Infections caused by multi-drug resistant Gram-positive organisms when alternative agents are unsuitable
  (Note: Off-label uses should be guided by microbiologic data and antimicrobial stewardship.)

Adults:

• Recommended Dose: 200 mg once daily for 6 days
• Route: May be administered orally or by intravenous (IV) infusion over 1 hour
• Switching: Can switch from IV to oral without dose adjustment due to equivalent bioavailability

Pediatrics (≥12 years):

• Same as adult dosing (200 mg once daily for 6 days)

Elderly:

• No dose adjustment required based on age alone

Renal Impairment:

• No dosage adjustment needed, including for patients with end-stage renal disease or on dialysis

Hepatic Impairment:

• No adjustment necessary for mild to moderate impairment (Child-Pugh A or B); insufficient data for severe hepatic impairment (Child-Pugh C)

Administration Notes:

• Oral tablets may be taken with or without food
• Do not mix IV solution with other drugs; infuse over 1 hour using a dedicated line

Tedizolid phosphate is a prodrug converted in vivo to the active moiety tedizolid, which is an oxazolidinone-class antibiotic. It inhibits bacterial protein synthesis by binding to the 23S ribosomal RNA of the 50S subunit of the bacterial ribosome. This action prevents the formation of the functional 70S initiation complex, essential for bacterial translation. The result is bacteriostatic activity against a broad range of Gram-positive pathogens, including MRSA and VRE (vancomycin-resistant enterococci).

• Absorption: Rapidly absorbed orally; tedizolid phosphate is converted to tedizolid during first-pass metabolism
• Bioavailability: Approximately 91% (oral vs. IV)
• Time to Peak Plasma Concentration: ~3 hours (oral); ~1 hour (IV)
• Distribution: Widely distributed with volume of distribution ~67–80 L
• Protein Binding: ~70–90%
• Metabolism: Hepatic conversion of prodrug to tedizolid via phosphatases; minor further metabolism by sulfation
• Half-life: Approximately 12 hours
• Elimination: Primarily via hepatic/biliary excretion; <20% excreted in urine
• Steady-State: Reached within 3 days of once-daily dosing

Pregnancy:

• FDA Pregnancy Category: Not assigned (per new labeling regulations)
• Use in Pregnancy: Limited human data; animal studies have shown adverse effects at high doses (e.g., fetal weight reduction). Use only if clearly needed.

Lactation:

• Unknown whether tedizolid is excreted in human milk
• Due to the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or the drug

Caution: Use only when benefits justify risks in pregnancy or lactation.

• Primary Class: Antibacterial agent
• Subclass: Oxazolidinone antibiotic
• Generation: Second-generation oxazolidinone

• Known hypersensitivity to tedizolid phosphate or any formulation excipients
• Concomitant use with MAO inhibitors (theoretical risk, though tedizolid has minimal MAO inhibition)
• Severe neutropenia in patients without close monitoring (risk of treatment failure)

• Myelosuppression: Thrombocytopenia, anemia, and neutropenia may occur, especially with prolonged use (>6 days)
• Peripheral and optic neuropathy: Has been reported with other oxazolidinones; monitor with extended therapy
• Serotonin Syndrome Risk: Though low, caution advised in patients on serotonergic drugs (SSRIs, SNRIs, etc.)
• Clostridioides difficile–associated diarrhea (CDAD): May occur with antibiotic use, including tedizolid
• Immunocompromised Patients: Efficacy not well established

Common Side Effects:

• Gastrointestinal: Nausea, vomiting, diarrhea
• Neurological: Headache, dizziness
• Hematologic: Decreased platelet count (thrombocytopenia)

Less Common or Serious:

• Liver enzyme elevations
• Insomnia or anxiety
• Visual disturbances (rare)

Rare but Severe:

• Serotonin syndrome (especially with SSRIs/SNRIs)
• Severe neutropenia
• Peripheral neuropathy (usually after prolonged use)

Onset: Most side effects occur within the first few days of treatment
Dose-dependence: Hematologic effects may be dose- or duration-dependent

• Serotonergic Agents (SSRIs, SNRIs, Triptans):
• Outcome: Potential for serotonin syndrome; use cautiously
• MAO Inhibitors:
• Outcome: Avoid use; risk of hypertensive crisis or serotonin syndrome (though tedizolid is a weaker MAOI)
• CYP450 Interactions:
• Minimal interaction; tedizolid is neither a substrate, inhibitor, nor inducer of major CYP450 enzymes

Food Interactions:

• No clinically significant interactions with food

Alcohol:

• No known direct interaction, but CNS side effects may be potentiated

• Guideline Update (IDSA 2023): Tedizolid is included as a recommended agent for MRSA skin infections, especially for patients requiring shorter treatment courses
• Labeling Update: Reinforced safety in renal and hepatic impairment (no dose adjustments)
• Pediatric Use Extended: Approved for adolescents ≥12 years with ABSSSI
• Surveillance Reports: Continued efficacy confirmed against MRSA strains with minimal resistance reported globally

• Oral Tablets:
• Store at 20°C to 25°C (68°F to 77°F)
• Excursions allowed to 15°C–30°C
• Protect from moisture; store in original container
• IV Powder for Solution:
• Store below 25°C (77°F)
• Reconstituted solution: Use within 24 hours if refrigerated
• Do not freeze the IV solution
• Protect from light until use