What is the appropriate dosing for Vancomycin (Vancomycin hydrochloride) in patients with Impaired renal function?

From the Guidelines

Vancomycin dosing in patients with impaired renal function should be adjusted by extending the dosing interval rather than reducing the dose to maintain adequate peak concentrations, with a target trough concentration of 15-20 μg/mL for serious infections 1.

Key Considerations

• The dosing interval should be extended based on the patient's estimated creatinine clearance to avoid nephrotoxicity.
• For patients with renal impairment, it is crucial to monitor trough levels closely and adjust the dosing interval accordingly.
• The use of actual body weight for initial dosing is recommended, even for obese patients, but with close monitoring of trough levels.
• A loading dose of 25-30 mg/kg may be considered for critically ill patients to achieve target trough concentrations quickly.

Monitoring and Adjustment

• Trough levels should be obtained just before the fourth dose (at steady state) when dosing every 12 hours, or before the fifth or sixth dose when dosing every 8 hours.
• Doses should be adjusted based on trough levels and the patient's clinical response.
• Regular monitoring of renal function is essential, as vancomycin can cause nephrotoxicity, especially when combined with other nephrotoxic agents or at high trough levels.

Additional Recommendations

• Area under the curve (AUC) monitoring is becoming preferred over trough levels in many institutions, with a target AUC/MIC ratio of 400-600 for most infections 1.
• Continuous infusion may be used in certain settings with target steady-state concentrations of 20-25 μg/mL, but it is not recommended as a standard practice 1.

From the FDA Drug Label

DOSAGE TABLE FOR VANCOMYCIN IN PATIENTS WITH IMPAIRED RENAL FUNCTION (Adapted from Moellering et al. 1) Creatinine ClearancemL/minVancomycin Dosemg/24 h 1001,545 901,390 801,235 701,080 60925 50770 40620 30465 20310 10155 The initial dose should be no less than 15 mg/kg, even in patients with mild to moderate renal insufficiency. The table is not valid for functionally anephric patients For such patients, an initial dose of 15 mg/kg of body weight should be given to achieve prompt therapeutic serum concentrations. The dose required to maintain stable concentrations is 1. 9 mg/kg/24 hr. In patients with marked renal impairment, it may be more convenient to give maintenance doses of 250 to 1,000 mg once every several days rather than administering the drug on a daily basis. In anuria, a dose of 1,000 mg every 7 to 10 days has been recommended

The appropriate dosing for Vancomycin in patients with impaired renal function can be calculated using the provided dosage table, which takes into account the patient's creatinine clearance.

• Initial dose: should be no less than 15 mg/kg, even in patients with mild to moderate renal insufficiency.
• Maintenance dose: can be calculated based on creatinine clearance, with doses ranging from 1,545 mg/24h for a creatinine clearance of 100 mL/min to 155 mg/24h for a creatinine clearance of 10 mL/min.
• Alternative dosing: in patients with marked renal impairment, maintenance doses of 250 to 1,000 mg once every several days may be more convenient.
• Anuria: a dose of 1,000 mg every 7 to 10 days is recommended 2

From the Research

Vancomycin Dosing in Patients with Impaired Renal Function

• The appropriate dosing for Vancomycin in patients with impaired renal function is a topic of ongoing debate, with various studies providing insights into the optimal approach 3, 4, 5, 6, 7.
• A study published in 2009 found that increased rates of nephrotoxicity have been reported with vancomycin doses of 4 g/day or higher, highlighting the need for careful dosing in patients with impaired renal function 3.
• In contrast, a 2019 study found that loading doses of vancomycin do not increase nephrotoxicity compared to lower doses in patients with severe renal dysfunction, suggesting that higher doses may be safe in certain patient populations 4.
• Another study published in 2018 proposed two user-friendly and scientifically based dosing strategies to improve the efficiency of vancomycin dosing while avoiding the risk of nephrotoxicity and minimizing the cost of therapeutic drug monitoring 5.
• A 2014 study found that using trough concentrations alone to manage vancomycin dosing may not be adequate, as it can lead to underestimation of the area under the plasma concentration-time curve (AUC) and potentially result in suboptimal dosing 6.
• A 2019 study in critically ill trauma patients found that even with aggressive loading doses, the rate of initial therapeutic vancomycin troughs was lower than expected, highlighting the challenges of achieving optimal vancomycin dosing in patients with impaired renal function 7.

Key Considerations

• The area under the concentration-time curve (AUC): minimum inhibitory concentration (MIC) ratio is a key pharmacodynamic parameter to predict vancomycin effectiveness, with a target ratio of 400 or greater recommended to eradicate S. aureus 3.
• Trough serum concentration monitoring is the most accurate and practical method to monitor vancomycin serum levels, but may not be sufficient to achieve optimal dosing in all patients 3, 6.
• Alternative dosing strategies, such as continuous infusion or AUC-based dosing, may be necessary to optimize vancomycin dosing in patients with impaired renal function 5, 6.