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November 2019

Using eGFR risks wrong dosing for kidney-sensitive drugs



The MHRA has warned prescribers not to use estimated glomerular filtration rate (eGFR) to estimate renal function before prescribing drugs with a narrow therapeutic index, such as direct-acting oral anticoagulants (DOACs).

eGFR can overestimate renal function compared with creatinine clearance (CrCl) in some patient groups or clinical situations. This means that some patients receive higher than recommended doses of their medication in relation to their renal function.

In line with existing guidance from the BNF, the MHRA recommends using calculated CrCl based on the Cockcroft-Gault formula rather than eGFR when starting, or adjusting the dose in:

  • People taking nephrotoxic drugs, such as vancomycin and amphotericin B
  • Elderly patients, aged 75 years and older, and
  • Patients with a BMI <18kg/m2 or >40kg/m2.

CrCl should also be considered for dosage adjustments of medicines that are substantially renally excreted and have a narrow therapeutic index, and always used for DOACs (apixaban, dabigratran etexilate, edoxaban and rivaroxaban) to avoid increased risk of bleeding events. Other drugs that are largely renally excreted and have a narrow therapeutic index include digoxin and sotalol.

The warning was prompted by reports of suspected adverse drug reactions, including significant bleeding events, related to the use of eGFR. In addition a recent study based on data from 80 general practices in the UK found that prescribing of drugs outside the recommendations for use in patients with reduced kidney function was widespread for the eight drugs analysed.

However, for most drugs and for most adult patients of average build and height, eGFR should be used to determine dosage adjustments. In situations where eGFR and/or CrCl change rapidly, such as in patients with acute kidney injury, renal function and drug dosing should be reassessed.

A CrCl (Cockgroft-Gaultt) calculator is available at https://www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation