Linezolid Dosing in Acute Kidney Failure
No dose adjustment of linezolid is required in patients with acute kidney failure, as the parent drug clearance remains unchanged regardless of renal function. 1, 2
Pharmacokinetic Rationale
Linezolid clearance is primarily non-renal, with approximately 65% of the drug eliminated through hepatic metabolism to inactive metabolites and only 35% excreted unchanged in urine. 2 The total apparent oral clearance of linezolid does not change with renal function, ranging from 92.5 to 109.6 ml/min in patients with varying degrees of renal impairment. 1
Standard dosing of 600 mg every 12 hours should be maintained in acute kidney failure. 1, 2
Critical Monitoring Requirements
While dose adjustment is unnecessary, patients with severe renal impairment (creatinine clearance <40 ml/min) accumulate linezolid metabolites at 7-8 fold higher concentrations than those with normal renal function. 1, 2 This metabolite accumulation, combined with reduced drug clearance in some critically ill patients, creates significant risk for hematologic toxicity. 3, 4
Hematologic Monitoring Protocol
- Weekly complete blood counts for the first 2 months, then monthly if stable 5
- Platelet count monitoring is essential, as thrombocytopenia correlates directly with elevated linezolid AUC₀₋₂₄ in renal dysfunction (r = 0.593, p < 0.01) 3
- Hemoglobin monitoring is equally critical, showing even stronger correlation with drug exposure (r = 0.783, p < 0.01) 3
Neurological Monitoring
- Monthly screening for peripheral neuropathy symptoms 5
- Monthly visual acuity and color discrimination testing to detect optic neuritis 5
- Neurological toxicity typically manifests after 12-20 weeks of treatment and may be irreversible 5
Dose Reduction Strategy for Toxicity
If hematologic or neurological toxicity develops despite standard dosing:
Reduce to 300 mg once daily rather than discontinuing therapy, as this lower dose maintains efficacy while substantially reducing adverse events. 5 The 600 mg daily dose causes adverse events in 46.7% of patients versus 74.5% at 1200 mg daily, demonstrating clear dose-dependent toxicity. 6, 5
Hemodialysis Considerations
For patients on hemodialysis, approximately one-third to one-half of the linezolid dose is removed during dialysis sessions. 1, 7
Administer one of the twice-daily doses immediately after dialysis to maintain therapeutic levels. 7 During the first three dialysis sessions, consider administering the dose 4 hours before dialysis begins to ensure levels remain above the MIC for the causative organism. 7
Contraindications and Drug Interactions
Linezolid is absolutely contraindicated with concurrent serotonergic agents or monoamine oxidase inhibitors due to risk of serotonin syndrome. 5 This includes ondansetron, which should be replaced with metoclopramide if antiemetic therapy is needed. 5
Avoid tyramine-rich foods during treatment due to linezolid's MAO inhibitor properties. 5
Common Pitfall to Avoid
The most critical error is assuming that "no dose adjustment required" means no special monitoring is needed. 4 While the standard 600 mg twice daily dose is appropriate, renal dysfunction significantly increases the risk of severe thrombocytopenia and anemia through metabolite accumulation and altered drug clearance in critically ill patients. 3, 4 Blood linezolid concentrations in renal dysfunction patients are significantly higher than predicted by population pharmacokinetics (p < 0.01), and severe thrombocytopenia develops as blood concentrations increase. 3
Therapeutic drug monitoring should be utilized when available to optimize dosing and reduce adverse events, particularly targeting trough levels <2.0 mg/L. 6, 5