What is the appropriate oral linezolid (Zyvox) dosing for adults and children, recommended treatment duration, need for renal or hepatic dose adjustment, and precautions with serotonergic or sympathomimetic agents?

Linezolid Dosing Guidelines

Standard Adult Dosing

The standard adult dose of linezolid is 600 mg orally or intravenously every 12 hours for most serious infections, with no dose adjustment required for renal or hepatic impairment. 1

Dosing by Indication (Adults)

• Complicated skin and soft tissue infections: 600 mg PO/IV every 12 hours for 10-14 days 2, 1
• Pneumonia (community-acquired or nosocomial): 600 mg PO/IV every 12 hours for 7-21 days, with most patients completing 10-14 days 3, 1
• Vancomycin-resistant Enterococcus faecium infections: 600 mg PO/IV every 12 hours for 14-28 days 1
• MRSA bacteremia (uncomplicated): 600 mg PO/IV every 12 hours for 7-14 days 3
• MRSA bacteremia (complicated): 600 mg PO/IV every 12 hours for 4-6 weeks 3
• MRSA osteomyelitis: 600 mg PO/IV every 12 hours for minimum 8 weeks, with consideration for additional 1-3 months of oral therapy 2, 3
• Septic arthritis: 600 mg PO/IV every 12 hours for 3-4 weeks 2, 3
• CNS infections (meningitis): 600 mg PO/IV every 12 hours for 2 weeks 2
• CNS infections (brain abscess, subdural empyema, spinal epidural abscess): 600 mg PO/IV every 12 hours for 4-6 weeks 2, 3

Pediatric Dosing

Children under 12 years require 10 mg/kg IV or PO every 8 hours (not to exceed 600 mg per dose), while children 12 years and older receive adult dosing of 600 mg every 12 hours. 1

Age-Specific Pediatric Dosing

• Neonates <7 days (especially preterm <34 weeks gestational age): Start with 10 mg/kg every 12 hours, then advance to 10 mg/kg every 8 hours by 7 days of life 1
• Neonates ≥7 days through 11 years: 10 mg/kg IV or PO every 8 hours 1
• Children 12 years and older: 600 mg IV or PO every 12 hours (adult dosing) 1
• Uncomplicated skin infections in children <5 years: 10 mg/kg PO every 8 hours 1
• Uncomplicated skin infections in children 5-11 years: 10 mg/kg PO every 12 hours 1

Special Pediatric Consideration for Drug-Resistant TB

• For multidrug-resistant tuberculosis in children, linezolid dosing is not precisely defined in the dosing table, but treatment should be as long as tolerated as part of a multi-drug regimen 2, 3

Renal and Hepatic Dose Adjustment

No dose adjustment is necessary for any degree of renal impairment, including patients on hemodialysis, or for mild to moderate hepatic impairment. 4, 5

• Linezolid maintains fixed dosing of 600 mg every 12 hours regardless of renal function 4
• However, use caution in severe renal insufficiency requiring hemodialysis, as metabolite accumulation occurs (7-8 fold higher exposure to metabolites) 5
• Oral and IV formulations are interchangeable without dose adjustment due to 100% oral bioavailability 1, 5

Critical Monitoring Requirements

Complete blood counts must be monitored weekly in all patients receiving linezolid, particularly those treated for longer than 2 weeks, due to risk of reversible myelosuppression. 3, 6

Additional Monitoring

• Visual acuity and color discrimination testing: Perform monthly in patients receiving extended linezolid treatment due to risk of optic neuropathy 3
• Thrombocytopenia risk: Increases significantly with treatment duration >2 weeks; discontinue if myelosuppression develops 3, 6
• Peripheral neuropathy prophylaxis: Consider pyridoxine supplementation in high-risk patients (diabetes, alcohol abuse, malnutrition) 3

Drug Interactions and Contraindications

Linezolid is a reversible monoamine oxidase inhibitor and must not be used concomitantly with MAO inhibitors or within 2 weeks of discontinuing such medications. 3, 5

Serotonergic and Sympathomimetic Agents

• Avoid concomitant use with serotonergic agents due to risk of serotonin syndrome 3
• Use with caution when coadministered with adrenergic agents (pseudoephedrine, phenylpropanolamine), as modest blood pressure increases may occur 5
• Avoid tyramine-rich foods during linezolid therapy 6

Absolute Contraindications

• Uncontrolled hypertension 3
• Pheochromocytoma 3
• Carcinoid tumor 3
• Thyrotoxicosis 3
• Bipolar depression, schizophrenia, or acute confusional states 3

Administration Considerations

• IV administration: Infuse over 30-120 minutes 1
• Oral-to-IV conversion: Switch freely between formulations at physician discretion based on clinical indication, maintaining same dose and frequency 1
• Food effect: Food slightly decreases absorption rate but not extent; may be taken with or without food 5
• Do not use once-daily dosing: Twice-daily administration is essential to maintain adequate drug exposure for bactericidal activity 3

Common Pitfalls to Avoid

• Never reduce dosing frequency to every 24 hours as this fails to maintain therapeutic drug levels 3
• Do not skip weekly CBC monitoring even if patient appears clinically well, as myelosuppression can develop insidiously 3, 6
• Do not mix linezolid IV with incompatible drugs including amphotericin B, diazepam, phenytoin, or trimethoprim-sulfamethoxazole during Y-site administration 1
• Consider therapeutic drug monitoring in special populations (children, renal replacement therapy patients, those with suboptimal clinical response) to optimize dosing 7