Usage
Tedizolid phosphate is an oxazolidinone-class antibacterial indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) in adults and pediatric patients 12 years and older. These infections are often caused by susceptible Gram-positive bacteria, including Staphylococcus aureus (including methicillin-resistant strains (MRSA) and methicillin-susceptible strains (MSSA)), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group (including Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus), and Enterococcus faecalis.
Alternate Names
Tedizolid phosphate is also known by its prodrug form, tedizolid. It is marketed under the brand name Sivextro®.
How It Works
Pharmacodynamics: Tedizolid acts by binding to the 50S subunit of the bacterial ribosome. This action inhibits protein synthesis, preventing bacterial growth and replication. It primarily affects Gram-positive bacteria.
Pharmacokinetics:
- Absorption: Tedizolid phosphate is a prodrug rapidly converted to tedizolid after administration. Oral bioavailability is approximately 91%. Food does not significantly affect the overall exposure (AUC). Peak plasma concentrations are achieved within approximately 3 hours after oral administration under fasting conditions.
- Distribution: Tedizolid is widely distributed in the body and exhibits 70% to 90% protein binding. Its steady-state volume of distribution is roughly 67-80 L.
- Metabolism: Tedizolid is primarily eliminated by metabolism, not renal or hepatic excretion of the parent drug. Less than 3% of the administered dose is excreted in feces and urine as unchanged drug.
- Elimination: The average elimination half-life is about 12 hours, with steady-state achieved within 3 days. No dosage adjustment is required for patients with renal or hepatic dysfunction.
Dosage
Standard Dosage
Adults and Adolescents (12 years and older):
- 200 mg once daily for 6 days, administered either orally or intravenously.
- Tablets may be taken with or without food.
- Intravenous administration should be infused over 60 minutes.
Children (under 12 years):
- The safety and efficacy have not yet been established for children under 12.
Special Cases:
- Elderly Patients (≥65 years): No dosage adjustment required. Clinical experience with patients ≥75 years is limited.
- Patients with Renal Impairment: No dosage adjustment required.
- Patients with Hepatic Dysfunction: No dosage adjustment required.
- Patients with Comorbid Conditions: No specific dosage adjustments are described for these conditions. However, clinical monitoring is recommended.
Clinical Use Cases
The recommended dose is consistent across various clinical settings related to ABSSSI, including those requiring intubation, surgical procedures, mechanical ventilation, and ICU care.
Dosage Adjustments
No dosage adjustments are needed based on renal or hepatic function, age, gender, race, weight, or body mass index. No adjustment is required when switching between intravenous and oral administration.
Side Effects
Common Side Effects:
Nausea, headache, diarrhea, vomiting, dizziness.
Rare but Serious Side Effects:
- Myelosuppression (decreased production of blood cells).
- Serotonin syndrome (a potentially life-threatening reaction caused by medication).
- Peripheral or optic neuropathy (nerve damage).
- Clostridium difficile-associated diarrhea.
- Hypersensitivity reactions.
Long-Term Effects:
Long-term side effects from prolonged use are not fully defined due to the short 6-day treatment course. However, potential long-term effects from the oxazolidinone class include peripheral and optic neuropathy, and myelosuppression.
Adverse Drug Reactions (ADR):
Clinically significant ADRs mentioned include hypersensitivity reactions and the potential for serotonin syndrome in individuals taking serotonergic medications.
Contraindications
Known hypersensitivity to tedizolid phosphate is a contraindication. Concurrent use with monoamine oxidase inhibitors (MAOIs) is contraindicated.
Drug Interactions
Tedizolid inhibits intestinal BCRP (Breast Cancer Resistance Protein), potentially increasing exposure to drugs transported by BCRP (e.g., rosuvastatin, imatinib). Potential interactions with serotonergic drugs exist, and caution is advised. It is a reversible MAO inhibitor in vitro, but clinical interaction studies with pseudoephedrine and tyramine have not shown significant pressor effects.
Pregnancy and Breastfeeding
- Pregnancy: Animal studies indicate a potential risk to the fetus. Use only if the potential benefit outweighs the potential risk. Safer alternatives exist.
- Breastfeeding: It is unknown if tedizolid is excreted in human milk. Exercise caution if administering to nursing mothers.
Drug Profile Summary
- Mechanism of Action: Binds to the 50S ribosomal subunit of bacteria, inhibiting protein synthesis.
- Side Effects: Nausea, headache, diarrhea, vomiting, dizziness. Rarely, myelosuppression, serotonin syndrome, peripheral/optic neuropathy.
- Contraindications: Hypersensitivity to tedizolid phosphate, concurrent use with MAOIs.
- Drug Interactions: BCRP inhibitors, serotonergic drugs.
- Pregnancy & Breastfeeding: Potential risk to the fetus, unknown if excreted in human milk.
- Dosage: 200 mg once daily for 6 days, oral or IV.
- Monitoring Parameters: Monitor for signs of myelosuppression, serotonin syndrome, neuropathy, and C. difficile infection.
Popular Combinations
No specific popular combinations are widely recognized. The concurrent use of other antibacterials should be guided by culture and susceptibility testing.
Precautions
Patients with neutropenia should be monitored closely, as the efficacy in this population is unknown. Closely monitor patients with pre-existing mitochondrial dysfunction. Evaluate for C. difficile infection in any patient who develops diarrhea during or after treatment. Conduct thorough pre-screening for allergies, drug interactions, and organ dysfunction. Exercise caution with patients taking serotonergic medications or those with a history of hypersensitivity reactions.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Tedizolid Phosphate?
A: 200 mg once daily for 6 days for adults and adolescents 12 years and older.
Q2: What is the mechanism of action of Tedizolid Phosphate?
A: It inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit.
Q3: What are the common side effects of Tedizolid Phosphate?
A: Nausea, headache, diarrhea, vomiting, and dizziness.
Q4: Can Tedizolid Phosphate be used in pregnant women?
A: Use with caution during pregnancy only if the potential benefit justifies the potential risk to the fetus. Safer alternatives exist.
Q5: How is Tedizolid Phosphate administered?
A: It can be administered orally or intravenously. The intravenous infusion should be administered over 60 minutes.
Q6: What are the contraindications for Tedizolid Phosphate?
A: Hypersensitivity to the drug and concurrent use with MAOIs.
Q7: Are there any drug interactions I should be aware of?
A: Yes, potential interactions exist with BCRP substrates and serotonergic drugs.
Q8: Does renal or hepatic impairment require dosage adjustments?
A: No.
Q9: How long is the standard treatment duration?
A: 6 days.
