How to adjust vancomycin dosing in a patient with impaired renal function?

Vancomycin Dosing in Renal Impairment (eGFR 65, Creatinine 95)

For a patient with moderate renal impairment (eGFR 65 mL/min), administer a loading dose of 25-30 mg/kg based on actual body weight, followed by maintenance dosing adjusted to achieve target trough levels of 15-20 mg/L, with dose reductions or extended intervals based on creatinine clearance. 1

Loading Dose Strategy

• Always initiate therapy with a weight-based loading dose of 25-30 mg/kg (based on actual body weight) regardless of renal function, as loading doses are not affected by renal impairment 2
• This loading dose is critical to rapidly achieve therapeutic concentrations, as a fixed 1-gram dose fails to reach early therapeutic levels in most patients 2
• The loading dose should be no less than 15 mg/kg even in patients with mild to moderate renal insufficiency 1

Maintenance Dosing Adjustment

For creatinine clearance of approximately 60-70 mL/min (corresponding to eGFR 65):

• The FDA label recommends approximately 925 mg per 24 hours for a creatinine clearance of 60 mL/min, or 770 mg per 24 hours for 50 mL/min 1
• This can be administered as either reduced individual doses (e.g., 500 mg every 12 hours) or extended intervals (e.g., 1 gram every 18-24 hours) 1
• Extended interval dosing is often preferred as it maintains concentration-dependent efficacy while reducing nephrotoxicity risk 2

Target Trough Levels and Monitoring

• Target trough concentration: 15-20 mg/L for serious infections including sepsis 2
• Measure trough levels before the 4th or 5th dose to ensure steady-state has been reached 1
• For patients over 65 years, prefer regimens that avoid aminoglycoside combinations due to increased risk of 8th cranial nerve toxicity and nephrotoxicity 2

Critical Monitoring Parameters

Measure the following at baseline and regularly:

• Serum creatinine and calculate creatinine clearance (not just eGFR) before each dose adjustment 1
• Trough vancomycin levels before the 4th dose, then weekly or with any change in renal function 1
• Monitor for acute kidney injury, which occurs in 10-28% of patients depending on dosing frequency 3

Important Caveats

Avoid common pitfalls:

• Do not use eGFR alone for dosing calculations; the FDA label specifically requires creatinine clearance using the Cockcroft-Gault equation 1
• Nephrotoxicity risk increases with: higher trough levels (>20 mg/L), longer duration of therapy (>7 days), concomitant nephrotoxins (NSAIDs, aminoglycosides), and increasing age 4
• In patients with fluctuating renal function (sepsis, heart failure, volume depletion), creatinine clearance calculations overestimate actual clearance—use more conservative dosing and closer monitoring 1
• Ototoxicity risk is elevated in renal impairment, especially with concurrent ototoxic drugs 2

Infusion Rate

• Administer each dose over at least 60 minutes, or at a rate no faster than 10 mg/min (whichever is longer) to minimize infusion-related reactions 1
• Use concentrations ≤5 mg/mL; concentrations up to 10 mg/mL may be used in fluid-restricted patients but increase infusion reaction risk 1

AUC/MIC Targeting (Preferred Approach)

• The optimal pharmacodynamic target is AUC/MIC >400-600 mg×hr/L rather than trough-only monitoring 2, 3
• In patients with moderate renal impairment, standard every-12-hour dosing often fails to achieve adequate AUC targets 3
• Consider pharmacokinetic consultation for AUC-guided dosing, particularly in critically ill patients or those with changing renal function 3