Zoline

Approved Indications:

• Community-Acquired Pneumonia (CAP): Due to susceptible Streptococcus pneumoniae (including multidrug-resistant strains) and Staphylococcus aureus.
• Nosocomial Pneumonia: Including ventilator-associated pneumonia caused by MRSA.
• Complicated Skin and Skin Structure Infections (cSSSI): Caused by MRSA, Streptococcus pyogenes, and Streptococcus agalactiae.
• Uncomplicated Skin and Skin Structure Infections (uSSSI): Caused by methicillin-susceptible Staphylococcus aureus or Streptococcus pyogenes.
• Vancomycin-Resistant Enterococcus faecium (VRE) Infections: Including bloodstream infections.

Clinically Accepted Off-Label Uses:

• Multidrug-Resistant or Extensively Drug-Resistant Tuberculosis (MDR/XDR-TB)
• Prosthetic Joint Infections and Chronic Osteomyelitis (caused by MRSA or VRE)
• Infective Endocarditis (due to resistant Gram-positive organisms)
• Central Nervous System Infections caused by resistant Gram-positive bacteria (when other agents are unsuitable)

Adults:

• 600 mg orally or intravenously every 12 hours
  Duration: 10–14 days or as clinically indicated

Pediatrics:

• Birth to <12 years: 10 mg/kg IV or oral every 8 hours
• ≥12 years: 600 mg IV or oral every 12 hours

Elderly:

• No dose adjustment required based on age alone

Renal Impairment:

• No dosage adjustment required; however, metabolites may accumulate in severe impairment or dialysis. Caution with prolonged use.

Hepatic Impairment:

• No dose adjustment required in mild to moderate impairment; use with caution in severe hepatic dysfunction due to limited data.

Administration Route:

• Oral and IV formulations are bioequivalent
• IV infusion should be administered over 30–120 minutes
• Oral tablets and suspension may be taken with or without food

Linezolid is a synthetic oxazolidinone antibiotic that inhibits bacterial protein synthesis. It binds to the 23S rRNA of the 50S ribosomal subunit, preventing the formation of the 70S initiation complex essential for translation. This unique mechanism makes it effective against Gram-positive bacteria, including drug-resistant strains such as MRSA and VRE. Linezolid is primarily bacteriostatic but can be bactericidal against certain streptococcal species.

• Absorption: ~100% oral bioavailability; peak plasma concentrations reached within 1–2 hours
• Distribution: Widely distributed (Vd ~40–50 L); penetrates lung tissue, cerebrospinal fluid, and bone
• Metabolism: Non-enzymatic oxidation to two inactive metabolites (not involving CYP450 enzymes)
• Excretion: ~30% unchanged in urine; ~50% as metabolites
• Half-life: ~5–7 hours in adults

• Pregnancy: FDA Category C
  Animal studies showed fetal harm; no adequate studies in pregnant women. Use only if potential benefit justifies risk.
• Lactation:
  Linezolid is excreted in human breast milk. Due to the risk of serious adverse effects (e.g., myelosuppression), breastfeeding is not recommended during therapy or should be discontinued if continued.

• Primary Class: Oxazolidinone Antibiotic
• Subclass: Synthetic protein synthesis inhibitor; minimal cross-resistance with other antibiotic classes

• Known hypersensitivity to linezolid or any of its components
• Concurrent use with MAO inhibitors or within 2 weeks of MAOI use
• Uncontrolled hypertension, pheochromocytoma, thyrotoxicosis
• Use with serotonergic agents unless benefit outweighs risk

• Myelosuppression (including thrombocytopenia, anemia): Monitor complete blood count (CBC) weekly during prolonged therapy
• Lactic Acidosis: Monitor for unexplained acidosis, nausea, vomiting, or respiratory distress
• Peripheral and Optic Neuropathy: Risk increases with duration >28 days; visual function monitoring is advised
• Serotonin Syndrome: Especially with concurrent serotonergic agents (SSRIs, TCAs, SNRIs); avoid or monitor
• Hypertensive Crisis: Avoid tyramine-rich foods and monitor blood pressure when used with adrenergic agents

Common:

• Hematologic: Thrombocytopenia, anemia, leukopenia
• Gastrointestinal: Diarrhea, nausea, vomiting, constipation, taste alterations
• Neurological: Headache, dizziness, insomnia

Serious/Rare:

• Hematologic: Pancytopenia (reversible), eosinophilia
• Neurological: Peripheral neuropathy, optic neuritis
• Metabolic: Lactic acidosis
• Other: Serotonin syndrome, seizures, hypersensitivity reactions

• Serotonergic Drugs (e.g., SSRIs, SNRIs, MAOIs, TCAs): Risk of serotonin syndrome; avoid or closely monitor
• Adrenergic Agents (e.g., pseudoephedrine, dopamine): Enhanced pressor response; monitor BP
• Tyramine-rich Foods (e.g., aged cheese, fermented products): Risk of hypertensive crisis; dietary restriction advised
• CYP450 Interaction: None significant—linezolid neither inhibits nor induces CYP enzymes

• WHO/CDC Guidelines: Linezolid is included in core regimens for MDR/XDR-TB due to proven efficacy
• Safety Labeling: Updated warnings on optic neuropathy and serotonin syndrome with prolonged use or serotonergic combinations
• EMA & FDA Monitoring: Continued safety surveillance for hematologic and neurologic adverse events during long-term therapy

• Tablets and Oral Suspension (dry): Store at 20°C to 25°C (68°F to 77°F); excursions between 15°C and 30°C permitted
• Reconstituted Oral Suspension: Stable for 21 days at room temperature; do not refrigerate
• IV Solution: Store at 20°C to 25°C; protect from light and freezing; discard if discolored or contains particulates