Linezolid Dosing for Adults
Standard Dose Recommendation
The recommended dose of linezolid for adults is 600 mg administered either intravenously or orally every 12 hours (twice daily), regardless of the indication. 1, 2, 3
Dosing Across Different Infections
The 600 mg twice daily regimen applies uniformly across various serious infections, including:
- Central nervous system infections (brain abscess, subdural empyema, spinal epidural abscess, meningitis): 600 mg IV/PO every 12 hours 1
- Complicated skin and soft tissue infections: 600 mg IV/PO every 12 hours for 7-14 days 2
- Pneumonia: 600 mg IV/PO every 12 hours for 7-14 days 2
- Osteomyelitis: 600 mg IV/PO every 12 hours for minimum 8 weeks 2
- Multidrug-resistant enterococcal endocarditis: 600 mg IV/PO every 12 hours for >6 weeks 1
Renal Impairment Considerations
No dose adjustment is required for linezolid in patients with any degree of renal impairment, including end-stage renal disease. 3 The pharmacokinetics of the parent drug remain unchanged regardless of renal function 3. However, the two primary metabolites accumulate in renal impairment, with accumulation severity increasing proportionally to renal dysfunction 3.
Hemodialysis Patients
- Continue standard dosing of 600 mg every 12 hours 3
- Approximately 30% of a dose is eliminated during a 3-hour hemodialysis session 3
- Administer linezolid after hemodialysis to avoid removing the drug before it achieves therapeutic effect 3
- Use with caution due to 7-8 fold higher metabolite exposure compared to patients with normal renal function 3, 4
Extended Dialysis in Critically Ill Patients
For septic patients with acute renal failure undergoing extended daily dialysis, clearance increases by 3.5 L/h during dialysis 5. Therapeutic drug monitoring should be considered in this complex population to optimize dosing 5.
Hepatic Impairment
No dose adjustment is required for patients with mild-to-moderate hepatic impairment (Child-Pugh class A or B). 3 The pharmacokinetics remain unchanged in these patients 3, 4.
Caution: Linezolid has not been studied in severe hepatic impairment 3. Patients with liver transplantation or resection may have 60% reduced clearance 5.
Bioavailability and Route of Administration
Linezolid is 100% bioavailable when administered orally, making IV and oral dosing interchangeable. 4 This allows seamless transition between routes without dose adjustment 4. Food slightly decreases absorption rate but not extent 4.
Special Population Considerations
Gender Differences
No dose adjustment by gender is necessary, despite females having 38% lower oral clearance and slightly higher plasma concentrations due to body weight differences 3. The exposure increase remains within well-tolerated levels 3.
Critically Ill Patients
Debilitated and septic patients demonstrate approximately 60% higher intrinsic clearance and twice the maximum rate of metabolism compared to healthy volunteers, resulting in lower AUC values 6. Despite this variability (AUC range 57-871 mcg/ml·24h), standard dosing provides high clinical cure rates 6.
Important Clinical Caveats
Duration-Related Toxicity
- Monitor complete blood counts weekly for treatment exceeding 14 days 7
- Reversible thrombocytopenia, anemia, and neutropenia are associated with prolonged therapy (≥2 weeks) 7
- Discontinue if myelosuppression develops 7
- Neuropathy risk increases with longer treatment duration 8
Drug Interactions
- Linezolid is a reversible monoamine oxidase inhibitor: avoid tyramine-rich foods and use caution with adrenergic or serotonergic agents 7
- No dose adjustment needed when coadministered with aztreonam, gentamicin, or warfarin 3, 4
- Rifampin may alter linezolid pharmacokinetics 3
Therapeutic Drug Monitoring
Consider TDM in populations with altered pharmacokinetics: children, patients with renal insufficiency on renal replacement therapy, critically ill septic patients, and those on interacting medications 8, 5. TDM can optimize dosing to maximize efficacy while minimizing toxicity 8.