Renal clearance – ‘fu’ is now ‘fe’ – what does this mean?

- January 1, 2014

For each of the medications listed in the Preferred Medication List (the Pink Book 2014) there is a comment on the metabolism and the fu for the medication. This fu is the abbreviation for the fraction of the medication excreted unchanged in the urine, but this is now changing to Fe

Background

  • The extent that a medication is cleared renally varies from those that are exclusively renally cleared (for example lithium, fu = 1) to those that are exclusively metabolised by the liver (for example phenytoin, fu = 0).
  • Internationally fu has a different meaning. In pharmacology it stands for the fraction unbound of a medication in the blood, i.e. it refers to the degree of plasma protein binding. The fraction of the medication excreted unchanged in urine is abbreviated to “fe” internationally. In keeping with this, we are now changing our use of “fu” to “fe

Know your fe

  • Before prescribing any renally eliminated medication the patient’s renal function and the fe of a medication must be considered.
  • The dose of a medication required for a therapeutic effect can be compared with the dose that produces toxicity. This ratio is the therapeutic index for a medication.
  • A medication with a high fe and a low therapeutic index can be associated with toxic concentrations with even mild renal impairment in the absence of appropriate dose-reduction.
Low therapeutic index medications with fe > 0.5
(dose MUST be adjusted for renal function)
ACE inhibitors
Allopurinol
Aminoglycosides (e.g. gentamicin, tobramycin, amikacin)
Digoxin
Contrast agents
Certain cytotoxics (e.g. methotrexate, cisplatin)
Lithium
Metformin
Vancomycin

Other medications have a higher therapeutic index and dose-adjustment in renal impairment may reduce the incidence of side effects.

High therapeutic index medications with fe > 0.5
(dose adjust to reduce side effects)
Aciclovir
Some beta-blockers (e.g. atenolol, sotalol)
Cephalosporins (e.g. cefuroxime, cephazolin)
Fluconazole
H2-antagonists (e.ranitidine, cimetidine)

NB: these lists are not comprehensive. Please be familiar with medications you prescribe, look them up, discuss them with the ward pharmacist, and/or consult Drug Information (ph 80900) if unsure.

 

 

 

 

 

 

 

 

 

 

 

Calculating dose-rates in patients with renal impairment

(Refer to the renal dosing section in the Pink Book 2014 – p164)
This should be done when prescribing medications with fe > 0.5, in renal impairment. The estimated glomerular filtration rate (eGFR) provided from the lab report is calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, which calculates the GFR assuming a standard body weight and height (i.e. a body surface area of 1.73m2).
Alternatively, the creatinine clearance can be calculated using the modified Cockcroft and Gault equation which is a better reflection of GFR at the extremes of age and weight (use for elderly patients and over/under weight patients).

1. Check the fe for the medication (see page 165 in the Pink Book)
2. Calculate creatinine clearance (CrCl):

*Ideal body weight (kg) = 50kg (male) or 45 kg (female) + 0.9 kg for each cm over 150cm in height

3. For medications with an fe > 0.9 calculate the dose–rate (DR) to give the renal adjusted dose:

4. If the fe < 0.9, use the following equation:

Fraction Unbound – fu

  • This relates to the protein binding of medication. Unlike fe, this generally does not need to be taken into consideration when prescribing most medications.
  • When drug concentrations are measured in the plasma, this generally means the total concentration of the drug – i.e. both ‘free’ drug and that which is protein bound. It is only the free drug that acts on receptors, regardless of how much drug is protein bound. In states of hypoalbuminaemia, a total drug plasma concentration may appear to be within the therapeutic range, but this may mask a high free drug concentration.
  • When looking at concentrations of drugs that have a high level of protein binding and a narrow-therapeutic index (such as phenytoin), it is important to also check a plasma albumin concentration, and if this is low, check a free drug concentration.
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