Tigecycline Dosing in Chronic Kidney Disease
No dose adjustment of tigecycline is required in patients with chronic kidney disease, including those with severe renal impairment or on dialysis. The standard dosing regimen of 100 mg loading dose followed by 50 mg IV every 12 hours should be maintained regardless of renal function 1.
Pharmacokinetic Rationale
Tigecycline elimination is minimally affected by renal impairment because renal clearance accounts for only approximately 20% of total systemic clearance in patients with normal renal function 1. Key pharmacokinetic findings include:
- In patients with severe renal impairment (creatinine clearance <30 mL/min), tigecycline clearance is reduced by only approximately 20%, with AUC increased by approximately 30% 1
- These modest changes do not warrant dose adjustment 1
- Tigecycline is not efficiently removed by hemodialysis and can be administered without regard to timing of dialysis sessions 1
Dosing in Continuous Renal Replacement Therapy (CRRT)
For critically ill patients receiving CRRT, standard tigecycline dosing (100 mg loading dose, then 50 mg q12h) should be maintained 2, 3. Despite high dialysability of tigecycline:
- CRRT clearance contributes only moderately to total elimination (CVVHD: 1.69 L/h; CVVHDF: 2.71 L/h) compared to physiological clearance of 18.3 L/h 2
- The saturation coefficients are high (0.79 for CVVHD and 0.90 for CVVHDF), but this does not significantly impact overall drug elimination 2
- No dose adjustment is necessary in patients on CRRT 2
Important Clinical Considerations
Higher doses may be required for certain infections and pathogens, independent of renal function 4. For severe infections:
- The standard 50 mg q12h regimen may be inadequate for hospital-acquired pneumonia (HAP) and certain multidrug-resistant organisms 4
- Higher dose regimens (100 mg q12h after 200 mg loading dose) have been used successfully in severe infections, though this relates to infection severity rather than renal impairment 4
- Tigecycline achieves poor serum concentrations (Cmax does not exceed 0.87 mg/L with standard dosing) and should not be used as monotherapy for bacteremia 4
Practical Approach
Administer tigecycline using standard dosing (100 mg IV loading dose, then 50 mg IV q12h) in all CKD patients, including:
- Patients with any stage of CKD 1
- Patients with severe renal impairment (CrCl <30 mL/min) 1
- Patients on intermittent hemodialysis (no timing adjustment needed) 1
- Patients on CRRT (CVVHD or CVVHDF) 2, 3
Monitor for therapeutic efficacy rather than adjusting for renal function, as individual pharmacokinetic variability is substantial in critically ill patients 3. Consider therapeutic drug monitoring in critically ill patients due to wide interindividual variability 3.