Tedizolid

PHARMACOKINETICS

Absorption:

Tedizolid phosphate is rapidly absorbed after oral administration and converted to active tedizolid; oral bioavailability ~91%..

Distribution:

Widely distributed in body tissues with a volume of distribution ~67–80 L; ~70–90% plasma protein binding.

Metabolism:

Tedizolid primarily undergoes phase II metabolism via sulfate conjugation, independent of CYP450 enzymes, resulting in minimal cytochrome P450 interactions

Elimination:

Primarily eliminated via the liver and feces (80%) and urine (20%) as inactive sulfate conjugate, half-life 12 hours, supporting once-daily dosing

PHARMACODYNAMICS

Tedizolid exhibits bacteriostatic activity by inhibiting protein synthesis in Gram-positive bacteria, including MRSA and VRE. Its antibacterial effect is primarily time-dependent, but efficacy also correlates with the AUC/MIC ratio (area under the concentration-time curve to minimum inhibitory concentration). This pharmacodynamic profile supports once-daily dosing and effective bacterial suppression over a 24-hour period.

DOSAGE AND ADMINISTRATION

Tedizolid is prescribed at a fixed dose of 200 mg once daily for a duration of 6 days for the treatment of acute bacterial skin and skin structure infections (ABSSSI). It is available in both oral tablets and intravenous (IV) infusion, with no need for dose modification when switching between the two routes. The oral tablet can be taken with or without food, offering flexibility in administration. Additionally, no dosage adjustment is required in patients with mild to moderate renal or hepatic impairment, including those undergoing hemodialysis

DRUG INTERACTIONS

• Monoamine Oxidase Inhibitors (MAOIs): Tedizolid is a reversible MAO inhibitor; concurrent use with other MAOIs or serotonergic agents may increase the risk of serotonin syndrome.
• Serotonergic Drugs (e.g., SSRIs, SNRIs, Tricyclics): Caution is advised due to potential serotonin toxicity.
• Tyramine-rich Foods: Though risk is low, high intake of tyramine-containing foods may cause hypertensive reactions.
• Anticoagulants (e.g., warfarin): No significant interactions, but monitor INR when initiating or discontinuing tedizolid.
• CYP450 Enzyme Interaction: Tedizolid does not inhibit or induce major CYP450 enzymes, so it has a low potential for metabolic drug interactions.

CONTRAINDICATIONS

• Hypersensitivity to tedizolid or formulation ingredients.
• Cross-reactivity with oxazolidinones like linezolid.
• Severe hepatic impairment – use not recommended.
• Concomitant serotonergic agents – risk of serotonin syndrome.
• Pregnancy – use only if clearly needed.
• Breastfeeding – caution advised; data unavailable.
• Myelosuppression history – avoid if prior bone marrow suppression from oxazolidinones.

SIDE EFFECTS

Common Side Effects:

• Nausea
• Headache
• Diarrhea
• Vomiting
• Dizziness
• Constipation
• Insomnia

Serious Side Effects (Rare):

• Peripheral neuropathy
• Optic neuropathy (especially with long-term use)
• Clostridioides difficile-associated diarrhea
• Hypersensitivity reactions (rash, urticaria)

TOXICITY

Tedizolid has low acute toxicity and is generally well tolerated. Its main toxicities include hematologic effects like thrombocytopenia (especially with prolonged use), mild liver enzyme elevations, and rare neurological effects (e.g., peripheral neuropathy). It shows lower mitochondrial and hematologic toxicity than linezolid. Animal studies indicate potential fetal toxicity at high doses.