From the Guidelines
When faced with different dose adjustment recommendations based on eGFR versus CrCl, prioritize using CrCl for medication dosing in most clinical scenarios, particularly for medications like non-vitamin K antagonist oral anticoagulants (NOACs) as recommended by the 2018 European Heart Rhythm Association practical guide 1.
Importance of CrCl in Medication Dosing
CrCl calculated by the Cockcroft-Gault equation has historically been used in drug development and pharmacokinetic studies, making it the preferred method for medication dosing adjustments, especially for NOACs such as dabigatran, edoxaban, rivaroxaban, and apixaban 1. This is because CrCl estimates renal drug elimination more directly, which is crucial for medications with narrow therapeutic indices.
Clinical Considerations
For patients with extremes of age, weight, or muscle mass, CrCl is particularly important as eGFR may not accurately reflect drug clearance. In practice, use CrCl for medications like NOACs, while eGFR may be sufficient for medications with wider therapeutic windows. The 2018 European Heart Rhythm Association practical guide emphasizes the importance of assessing renal function using CrCl for patients with atrial fibrillation who need oral anticoagulation 1.
Monitoring Renal Function
Renal function needs to be monitored diligently, at least yearly, to detect changes in renal function and adapt the dose accordingly. If renal function is impaired (i.e., CrCl < 60 mL/min), a more frequent evaluation is recommended, and in patients with additional risk factors, it may be evaluated even more frequently 1.
Specific Medication Considerations
For medications like edoxaban, a possibly decreased efficacy was observed in patients with a CrCl of >95 mL/min, leading to recommendations to use other oral anticoagulants in these patients or to carefully evaluate the individual thromboembolic and bleeding risk 1. Rivaroxaban, apixaban, and edoxaban are approved in Europe for use in patients with severe CKD (Stage 4, i.e., a CrCl of 15–29 mL/min), with a reduced dose regimen 1.
Conclusion is not needed, and the answer continues directly to the final thoughts
In clinical practice, when in doubt about critical medications like NOACs, consulting with a clinical pharmacist can help resolve discrepancies between different dosing recommendations based on eGFR versus CrCl. The key is to prioritize CrCl for medication dosing adjustments, especially for medications with narrow therapeutic indices, to ensure optimal patient outcomes in terms of morbidity, mortality, and quality of life.
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. When only serum creatinine is known, the following formula (based on sex, weight and age of the patient) may be used to calculate creatinine clearance. Men:[Weight (kg) × (140 – age in years)] 72 × serum creatinine concentration (mg/dL) Women:0. 85 × above value
The vancomycin dose should be adjusted based on creatinine clearance (CrCl). If different sources recommend different dose adjustments, the CrCl should be used to determine the dose. The provided dosage table can be used to calculate the dose based on CrCl. If CrCl cannot be measured, it can be estimated using the provided formula. eGFR is not mentioned in the label as a method for dose adjustment. 2
From the Research
EGFR vs CRCL in Vancomycin Dosing
When different sources recommend different dose adjustments for vancomycin, it is essential to consider the most accurate method for estimating glomerular filtration rate (GFR). The following points highlight the comparison between EGFR (estimated GFR) and CRCL (creatinine clearance) in vancomycin dosing:
- EGFR, particularly when estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, has been shown to be a better predictor of vancomycin clearances than CRCL 3, 4, 5.
- The CKD-EPI equation, which incorporates both creatinine and cystatin C levels, provides a more accurate estimation of GFR, leading to improved vancomycin trough concentration achievement 4, 5.
- CRCL, on the other hand, may not accurately reflect the renal function of critically ill patients, leading to subtherapeutic or toxic vancomycin levels 3, 6.
- Studies have demonstrated that using EGFR, especially with the CKD-EPI equation, can improve the attainment of target vancomycin trough concentrations compared to CRCL-based dosing 4, 5.
Factors Affecting Vancomycin Trough Concentrations
Several factors can influence vancomycin trough concentrations, including:
- Renal function: Patients with augmented renal clearance (ARC) are more likely to have subtherapeutic vancomycin levels 6.
- Age: Elderly patients may be more prone to lower vancomycin trough concentrations 7.
- Inflammation: Higher C-reactive protein (CRP) levels have been associated with lower vancomycin trough concentrations 7.
- Dosing regimen: Insufficient total vancomycin doses may contribute to lower trough concentrations 7.
Clinical Implications
The choice between EGFR and CRCL for vancomycin dosing adjustments has significant clinical implications:
- Using EGFR, particularly with the CKD-EPI equation, can lead to more accurate vancomycin dosing and improved patient outcomes 4, 5.
- CRCL-based dosing may result in subtherapeutic or toxic vancomycin levels, highlighting the need for caution when using this method 3, 6.
- Clinicians should consider the individual patient's characteristics, such as renal function, age, and inflammation status, when adjusting vancomycin doses 7.