Linezolid Dosing in CKD Stage IIb
No dosage adjustment of linezolid is required for patients with CKD stage IIb as linezolid pharmacokinetics are not altered by renal dysfunction. 1, 2
Pharmacokinetics of Linezolid in Renal Impairment
- Linezolid's parent drug pharmacokinetics are not altered in patients with any degree of renal insufficiency, including those with severe renal dysfunction 1
- Total apparent oral clearance of linezolid does not change with renal function, ranging from 92.5 to 109.6 ml/min for subjects not requiring dialysis 2
- While the two primary metabolites of linezolid may accumulate in patients with renal insufficiency, the clinical significance of this accumulation has not been determined 1
Standard Dosing Recommendations
- The standard adult dose of 600 mg every 12 hours can be maintained in patients with CKD stage IIb 1, 2
- No adjustment of linezolid dosage is needed in subjects with renal dysfunction of any severity 1
- For patients on hemodialysis, linezolid should be given after hemodialysis sessions as approximately 30% of a dose can be eliminated during a 3-hour dialysis session 1
Monitoring Considerations
- Despite no need for dose adjustment, patients with renal impairment have been shown to have a higher risk of thrombocytopenia (OR 3.17,95% CI 1.10-9.12) and higher trough concentrations 3
- Consider monitoring complete blood counts regularly, particularly if treatment extends beyond 2 weeks, as the median time to development of myelosuppression is approximately 12 days 4
- The threshold trough concentration (Cmin) for predicting myelosuppression with 50% probability is 7.8 mg/L 4
Special Considerations
- For critically ill patients with significant renal dysfunction (CrCL <30 ml/min), some research suggests dose reduction to 450 mg every 24 hours might be considered to minimize the risk of myelosuppression while maintaining efficacy 4
- For patients undergoing continuous venovenous hemofiltration (CVVH), the standard dose of 600 mg every 12 hours remains appropriate as linezolid is highly removable by CVVH 5
Common Pitfalls to Avoid
- Do not reduce the dose of linezolid solely based on renal function as this could lead to subtherapeutic levels and treatment failure 1, 2
- Do not overlook the potential for drug accumulation and toxicity in prolonged therapy courses despite normal dosing 3
- Be aware that pediatric patients have higher clearance of linezolid compared to adults (0.107 L/h/kg vs. 0.098 L/h/kg), which may require different dosing considerations in pediatric CKD 6