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The MHRA has issued guidance on the prescribing of medicines in renal impairment: using the appropriate estimate of renal function to avoid the risk of adverse drug reactions (MHRA Drug Safety Update, October 2019).
For most patients and most medicines, estimated Glomerular Filtration Rate (eGFR) is an appropriate measure of renal function for determining dosage adjustments in renal impairment; however, in some circumstances, the Cockcroft-Gault formula should be used to calculate creatinine clearance (CrCl).
Estimated glomerular filtration rate (eGFR) and creatinine clearance (CrCl) are two estimates of renal function available to prescribers. Clinical laboratories routinely report renal function in adults based on eGFR normalised to a body surface area of 1.73 m2.
For most drugs and most situations, eGFR is an acceptable estimate of renal function. However, eGFR can overestimate renal function compared with CrCL in some patient groups or clinical situations. This overestimation can result in patients receiving higher than recommended doses of their medicine in relation to their renal function.
Existing guidance from the BNF advises prescribers to use calculated CrCl rather than eGFR when initiating or adjusting dose in people taking nephrotoxic drugs, elderly patients, and patients at extremes of muscle mass.
CrCl should also be considered for dosage adjustment of medicines that are substantially renally excreted and have a narrow therapeutic index. In particular, CrCl should always be used to guide dose adjustment for direct-acting oral anticoagulants (DOACs; apixaban, dabigatran etexilate, edoxaban▼, and rivaroxaban▼). Use of eGFR for dosing of DOACs is known to increase risk of bleeding events as a consequence of overestimating renal function.
Other medicines that are largely renally excreted and have a narrow therapeutic index include digoxin and sotalol.
It is normal to calculate CrCl based on the Cockcroft-Gault formula rather than measuring it via 24-hour urine collection. Applications such as MDCalc provide the ability to use adjusted body weight, ideal body weight, or actual bodyweight as appropriate when calculating the Cockcroft-Gault CrCl value.
The MHRA Safety Update includes examples of harm related to incorrect renal impairment calculations. Suspected adverse drug reactions can be reported via the MHRA
Yellow Card Scheme.