fe is the abbreviation for fraction of drug excreted unchanged in the urine.For predominantly renally cleared drugs (fe > 0.5), dose adjustment should be considered in relation to impairment of renal function (creatinine clearance/eGFR).
General Advice
  • For general advice, see Individualising Drug Therapy.
  • Assess renal function using estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl).
  • Consider reducing maintenance doses of medicines that are predominantly renally cleared (those with fe > 0.5) in relation to impairment of renal function.
    • Loading doses are not affected.
  • Consider therapeutic drug monitoring (TDM)where available to assess dose adjustment.
  • When renal function is < 30 mL/min, preferentially use metabolised medicines over renally cleared medicines.
  • For acute kidney injury, there are other factors to consider, such as severity and nature of the injury, and time course.
Pharmacokinetic Considerations

For medicines that are renally cleared i.e. fe > 0.5.

  1. Choose the maintenance dose, i.e. dose and frequency that you would use in this patient if renal function was normal (CrCl 100 mL/min).
  2. Calculate the patient’s creatinine clearance (CrCl) using the Cockcroft and Gault calculator.

Alternatively the estimated glomerular filtration rate (eGFR) supplied by the laboratories can be used for patients whose BSA is close to 1.73m2.
3. Calculate dose rate:

  • In patients with renal dysfunction, it is essential to adjust the dose for some medicines. Dose adjustment to reduce side effects should be considered for other medicines.
  • For drugs with fe ≥ 0.9, use this equation(assume normal CrCl of 100 mL/min):
  • For drugs with fe < 0.9, use this equation:
  • If further information is required, contact the ward pharmacist or Medicines Information (03 364 0900).
Pharmacodynamic Considerations
  • Water and electrolyte handling may be significantly altered (e.g. increasing the likelihood of oedema, hyponatraemia, and hyperkalaemia).
  • Nephrotoxic drugs (e.g. non-steroidal anti-inflammatory drugs) may aggravate already impaired kidneys.
Medicines for which dose adjustment should be considered in chronic kidney disease
Note: Maintenance doses should be adjusted to achieve similar concentrations to that which would occur with standard doses in the setting of normal renal function. Adjustment of maintenance doses includes changes to dose, frequency or both (e.g. smaller dose, reduced frequency). The following is not an exhaustive list. These have been selected from a list of commonly prescribed medicines on the basis of having a high fe (fraction excreted unchanged in urine), or a moderate fe and low therapeutic index. Nephrotoxicity is not a factor for inclusion in this list.
Drug (active metabolite) fe, fraction excreted unchanged in urine Location of more detailed guidance Drug (active metabolite) fe, fraction excreted unchanged in urine Location of more detailed guidance
aciclovir 0.8 gabapentin 0.9
allopurinol (oxypurinol) 0 (0.8) Hospital HealthPathways ganciclovir 0.9
amoxicillin 0.9 gemfibrozil 0.6
atenolol 0.9 gentamicin 0.9 Pink Book
baclofen 0.8 imipenem 0.7
benzylpenicillin
0.8 lamivudine 0.8
bezafibrate 0.4
levetiracetam 0.7
bisoprolol 0.5
lisinopril 0.9
candesartan 0.6
lithium 1
captopril
0.5 meropenem 0.7
cefaclor 0.7
metformin 0.9
cefalexin 0.9
methotrexate 0.9-0.5 (saturable)
cefazolin
0.9 morphine (m-6-glucuronide) 0 (0.9) Hospital HealthPathways
cefepime 0.8
nadolol 0.8
cefotaxime
0.7 nicotinic acid 0.4
ceftazidime 0.9
pethidine (norpethidine) 0 (0.9)
ceftriaxone
0.5 phenoxymethylpenicillin 0.9
cefuroxime 0.9 piperacillin 0.8
cetirizine 0.7 pravastatin 0.5
cilazapril (cilazaprilat) 0 (0.9) quinapril (quinaprilat) 0 (0.9)
ciprofloxacin
0.5
rivaroxaban 0.4 Hospital HealthPathways
clonidine 0.6 sotalol 0.9
colchicine
0.3
teicoplanin 0.8
dabigatran 0.8 Hospital HealthPathways tobramycin 0.9 Pink Book
digoxin
0.8
Hospital HealthPathways tramadol (O-desmethyltramadol (M1)) 0.2 (0.9)
doxycycline 0.4 tranexamic acid 0.9
enalapril (enalaprilat)
0.2 (0.8)
valganciclovir 0.8
enoxaparin 0.7 Hospital HealthPathways vancomycin 0.9 Pink Book
ethambutol
0.8
varenicline 0.9
flecainide 0.3
flucloxacillin 0.7
fluconazole 0.8