eGFR and Creatinine clearance

Think with me ㅡ The physician is about to prescribe rivaroxaban (Xarelto) to someone with atrial fibrillation (AF). Their eGFR is 45. The recommended dose in AF is 20 mg once daily, but the dose should be reduced to 15 mg once daily if creatinine clearance is 15–49 mL/min.

• Should physician prescribe 15 or 20 mg?
• You decide you had better calculate the patient’s creatinine clearance. But which of the several formulas should you use?

CREATININE CLEARANCE VS eGFR

The MHRA is keen to remind us that harm has come to patients because clinicians have (wrongly) equated eGFR with creatinine clearance. This is particularly true for DOACs. When calculating creatinine clearance, we should use the Cockcroft-Gault formula. There are many online tools to calculate this, including MDCalc; Cockcroft-Gault creatinine clearance calculator can be found here: https://www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation.

So, when is creatinine clearance important? ㅡ For most drugs, and for most adults of average height and build, the MHRA says eGFR is an acceptable estimate of renal function. However, eGFR is likely to overestimate renal function in those ≥ 75 years and those at extremes of muscle mass (BMI < 18 or > 40).

Calculation of creatinine clearance is also important when, (1) Using a DOAC (it is known that relying on eGFR results in an over estimation of renal function and increased bleeding events). (2) Prescribing drugs that are renally excreted and have a narrow therapeutic index (e.g. digoxin, sotalol). (3) Using nephrotoxic drugs (e.g., amphotericin B, vancomycin, which are not widely prescribed in primary care). Creatinine clearance should be calculated using the Cockcroft-Gault formula, and for this you need to know the patient’s age, gender, weight and creatinine.

WHAT DOES THIS MEAN IN PRACTICE FOR PHARMACISTS

Do not rely on eGFR as an estimate of renal function in certain circumstances AND use the Cockcroft-Gault formula to estimate creatinine clearance...

• In those ≥ 75 years.
• In those with a BMI < 18 or > 40 (so you need an up-to-date weight!).
• Whenever doctors prescribe a DOAC.
• If prescribing a renally-excreted drug with a narrow therapeutic index (e.g., digoxin, sotalol).
• In the unlikely event we prescribe a significantly renally toxic drug such as vancomycin.

REFERENCES

• Prescribing medicines in renal impairment: using the appropriate estimate of renal function to avoid the risk of adverse drug reactions. [online] Available at: https://www.gov.uk/drug-safety-update/prescribing-medicines-in-renal-impairment-using-the-appropriate-estimate-of-renal-function-to-avoid-the-risk-of-adverse-drug-reactions

  Wood, S., Petty, D., Glidewell, L. and Raynor, D.T. (2018). Application of prescribing recommendations in older people with reduced kidney function: a cross-sectional study in general practice. British Journal of General Practice, [online] 68(670), pp.e378–e387. Available at: https://bjgp.org/content/68/670/e378.short