Tigecycline Dosing in Chronic Kidney Disease
No dose adjustment of tigecycline is required for patients with CKD, including those on hemodialysis or continuous renal replacement therapy (CRRT). 1
Standard Dosing Regimen for CKD Patients
- Loading dose: 100 mg IV once 1
- Maintenance dose: 50 mg IV every 12 hours 1
- This standard regimen applies regardless of creatinine clearance level, including severe renal impairment (CrCl <30 mL/min) 1
Pharmacokinetic Rationale
- Tigecycline undergoes minimal renal elimination, with renal clearance representing only approximately 20% of total systemic clearance in patients with normal renal function 1
- In patients with severe renal impairment, tigecycline clearance is reduced by only approximately 20%, with AUC increased by approximately 30% - changes that are not clinically significant enough to warrant dose adjustment 1
- Tigecycline is not efficiently removed by hemodialysis and can be administered without regard to timing of dialysis sessions 1
Special Considerations for CRRT Patients
- Despite high dialysability (saturation coefficients of 0.79 for CVVHD and 0.90 for CVVHDF), CRRT contributes minimally to tigecycline elimination 2
- CRRT clearance (1.69 L/h for CVVHD, 2.71 L/h for CVVHDF) is minor compared to physiological clearance of 18.3 L/h 2
- No dose adjustment is necessary for patients receiving CRRT 2, 3
- Pharmacokinetic parameters in CRRT patients are similar to non-CRRT patients, with no statistically significant differences 3
High-Dose Tigecycline Considerations
- For severe infections caused by carbapenem-resistant organisms, high-dose tigecycline (200 mg loading dose, then 100 mg every 12 hours) may be considered as part of combination therapy 4
- This dosing relates to infection severity and pathogen resistance, not renal function 5
- High-dose tigecycline has demonstrated reduced mortality in carbapenem-resistant bacterial infections (OR 0.20,95% CI 0.09-0.45) without increased adverse events 4
Important Clinical Caveats
- Avoid tigecycline monotherapy for bacteremia due to poor serum concentrations (Cmax does not exceed 0.87 mg/L with standard dosing) 5
- Tigecycline achieves low urinary concentrations and should not be used for urinary tract infections 4
- Bilirubin levels may affect tigecycline clearance in critically ill patients, but this is independent of renal function 2
- Wide interindividual variability in plasma concentrations exists in critically ill patients, though routine therapeutic drug monitoring is not currently standard practice 3