Assessing Renal Function
Renal function in adults is
now commonly reported via NOTIS on the basis of estimated glomerular filtration
rate (eGFR) normalised to a body surface area of 1.73m2 and derived
from the Modification of Diet in Renal Disease (MDRD) formula. Published
information on the effects of renal impairment on drug elimination has
historically been stated in terms of creatinine clearance (not normalised for
body surface area). The Cockgroft-Gault formula has been used to estimate this
and in recent years the advice has been to continue to use Cockcroft-Gault
estimates for drug dosing in renal impairment. The Cockcroft Gault equation is
shown below and there is a calculator on the antibiotic website.
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CrCl (ml/min) = F
x (140-age)
x weight (kg)
serum
creatinine (micromol/L)
The latest edition of the British National
Formulary gives dosage adjustments for many drugs expressed in terms of eGFR
rather than creatinine clearance. Although the two equations are not
interchangeable, there is relatively good correlation between the two for
calculating renal function in patients of average build and height, and either
could be used for the majority of drugs. However, eGFR should not be used for
calculating drug doses in patients at extremes
of body weight (BMI of less than
18.5 kg/m2 or greater than 30 kg/m2), nor for potentially toxic drugs of a narrow
therapeutic index. In these cases, the correlation between the two measures
can be significant and potential drug over/under doses could arise.
BMI = Weight
(kg)
Height
(m2)
·
eGFR should not be used for
calculating drug doses in patients at extremes of body weight (BMI of less than 18.5 kg/m2
or greater than 30 kg/m2) therefore for those who are
obese (>20% above IBW) ideal body weight should be calculated and then used
to create a creatinine clearance using Cockcroft-Gault.
·
IBW
for males = 50 + (2.3 x (height in inches - 60))
·
IBW
for female = 45 + (2.3 x (height in inches - 60))
·
Equally
for those patients who have a BMI<18.5kg/m2 creatinine clearance using
Cockcroft-Gault should be calculated.
·
eGFR should not be used for
calculating drug doses for potentially toxic drugs of a narrow therapeutic
index. For the purposes of this
guideline creatinine clearance using Cockcroft-Gault should always be used for
vancomycin, gentamicin, foscarnet, ganciclovir, valganciclovir.
·
Neither equation is a perfect
marker of renal function. When using the equation, creatinine levels should be
stable and the clinical picture should always be taken into account.
·
Patients that are oligoanuric (dialysis
dependency/acute kidney injury) should be assumed to have a GFR <10 ml/min and
neither equation is valid.
Renal
dosing monographs
·
The doses recommended are
derived from the references stated and represent those commonly used in Nottingham (these may vary from the SPC)
·
If 50% quoted, give half
the dose but retain the normal frequency
·
For dosing advice in
haemodialysis (HD) and continuous ambulatory
peritoneal dialysis (CAPD) patients: refer to Renal Pharmacist (bleep
80-7078)
·
For dosing
advice in continuous veno-venous haemofiltration
(CVVH): refer to Critical Care Pharmacist
·
Drugs marked * = Contact
microbiologist for advice on assays where appropriate.
·
The sodium content of
some IV antibiotic preparations may be significant
(refer to ward pharmacist or Medicines Information)
·
Give post HD
(haemodialysis): If patient is on daily or alternate day therapy this advice refers only
to administration on dialysis days: ie
on non-dialysis days the drug is given at the normal time.
Contact microbiology or pharmacy for advice on dosing in renal
impairment for any antimicrobial agents that are not included in the table below.
Antimicrobial
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Creatinine clearance (ml/min)
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Comments
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50-20
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20-10
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<10
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*Aciclovir
IV
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Normal dose
every 24h
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50% of normal dose every 24h
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Give post HD
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Aciclovir
po
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Simplex: 200mg qds
Zoster: 800mg tds
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Simplex: 200mg bd
Zoster: 800mg bd
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Give post HD
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*Amikacin
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5-6 mg/kg 12h
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3-4 mg/kg 24h
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2mg/kg 24-48h
HD: 5mg/kg post HD and monitor levels
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Give post HD
Monitor blood levels & adjust dose as
req’d
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Amoxicillin
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250mg-1g 8h
Endocarditis (refer to microbiology):max
6g per day
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Give post HD
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Lipid
associated Amphotericin IV
(Abelcet© and Ambisome©)
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For further advice on dosing and administration see antibiotic
website, local guidelines and Trust IV guide
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Amphotericin is highly NEPHROTOXIC.
Daily monitoring of renal function is essential
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Azithromycin
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Benzylpenicillin
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600mg-2.4g
every 6 hours
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600mg-1.2g every 6 hours
Endocarditis (refer to microbiology): max
4.8g per day
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Give post HD
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Caspofungin
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Cefalexin
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250-500mg tds
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Give post HD
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Cefradine
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250mg-500mg 6h
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Give post HD
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Ceftazidime
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CrCl
30-50 ml/min
1-2g 12h
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CrCl
20-30 ml/min
1-2g 24h
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CrCl 5-20 ml/min
500mg-1g 24h
CrCl<5 ml/min
500mg-1g 48h
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Give post HD
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Ceftriaxone
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Max 2g/day
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Cefuroxime
IV
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750mg – 1.5g 12h
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750mg 12h
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Give post HD
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Chloramphenicol
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Ciprofloxacin
IV+po
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IV 200mg-400mg bd
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IV 200mg-400mg bd
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Clarithromycin
IV
+ po
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250-500mg bd
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Give post HD
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Clindamycin
IV
+po
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Co-Amoxiclav
IV
(Augmentin)
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CrCl 30-50
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CrCl 10-30
1.2g 12h
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1.2g stat then 600-1.2g 12h
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Give post HD
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Co-Amoxiclav
po
(Augmentin)
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Give post HD
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Colistin
IV
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50% of normal dose
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30% of normal dose
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*Co-trimoxazole
IV + po
(Treatment doses only)
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CrCl 30–50
ml/min
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CrCl 15-30 ml/min PCP:
Other infections: 50%
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CrCl
<15ml/min
All infections: 50%
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Give post HD
Monitor sulfamethoxazole levels
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Daptomycin
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CrCl
30-50ml/min
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CrCl<30ml/min
4mg/kg every 48 hours
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Not dialysed
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Antimicrobial
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Creatinine clearance (ml/min)
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Comments
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50-20
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20-10
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<10
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Doxycycline
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All other tetracyclines contraindicated in renal impairment
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Ertapenem
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CrCl 30-50 ml/min
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CrCl 10-30 ml/min
50-100% of dose
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50% of dose or 1g three times a week
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Give post HD
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Erythromycin
po
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250-500mg qds
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*Ethambutol
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7.5-15mg/kg/day
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5-7.5mg/kg/day
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Give post HD
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Monitor levels if Crcl < 30ml/min (contact Micro)
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Flucloxacillin
IV+po
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Normal Max 4g/day
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Fluconazole
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50%
Oral dose min 50mg
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Give post HD
No adjustments for single doses required
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*Flucytosine
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50mg/kg 12h
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50mg/kg 24h
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50mg/kg stat then dose according to levels.
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Give post HD. Monitor pre-dialysis levels
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Foscarnet
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Dose reduction required seek further advice from pharmacy/renal drug
handbook
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Fusidic
acid
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Ganciclovir
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Dose reduction required seek further
advice from pharmacy/renal drug handbook
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1) Gentamicin
ONCE DAILY
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CrCl 10–40ml/min
3mg/kg (max 300mg)
Check
levels 18-24 hours
after
first dose.
Re-dose
only when level < 1mg/L.
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CrCl<10ml/min
2
mg/kg (max 200mg) re-dose according
to
levels
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BOTH METHODS:
Give post HD
Monitor blood levels & U&Es. see
antibiotic website. In the obese use a dose determining weight- see
antibiotic website.
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2) Gentamicin
Multiple
daily dosing regimen
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80mg 12h
(60mg if <60kg)
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80mg 24h
(60mg if <60kg)
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80mg 48h
(60mg if <60kg)
HD:1-2
mg/kg post HD redose according to levels
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Isoniazid
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200mg-300mg 24h
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Give post HD
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Itraconazole
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Levofloxacin
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500mg stat
then 250mg bd**
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500mg stat
then 125mg bd**
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500mg stat
then 125mg od
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** Applies if full dose is 500mg bd.
If full dose 500mg od give the reduced dose daily
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Linezolid
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Give post HD
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Meropenem
Higher doses needed in CNS
infection d/w micro
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500mg-2g bd
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500mg-1g bd
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500mg-1g od
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Give post HD
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Metronidazole
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Give post HD
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Nitrofurantoin
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Use at normal dose with caution
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Contraindicated
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Contraindicated
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Monitor for toxicity e.g blood dyscrasias,
neuropathy
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Oseltamivir
(treatment dose)
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CrCl >30ml/min
75mg bd
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CrCl 10-30ml/min
75mg od
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30mg stat
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HD: 75mg stat then 75mg after each dialysis session
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Penicillin
V
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Give post HD
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Piperacillin/
Tazobactam
(Tazocin)
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4.5g 8-12h
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4.5g 12h
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Give post HD
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Posaconazole
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Pyrazinamide
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Rifampicin
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50-100%
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Antimicrobial
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Creatinine Clearance (ml/min)
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Comments
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50-20
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20-10
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<10
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Teicoplanin*
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Normal Loading dose 400mg every 12 hours for 3 doses
Monitor levels
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Tetracycline
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Use
Doxycycline see above
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Tigecycline
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Trimethoprim
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Use alternative agent if possible
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Ineffective for UTI, other indications:
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Give post HD
Consider short term folic acid
supplementation.
NB May cause temporary rise in creatinine
due to reduced creatinine secretion rather than a fall in CrCl
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Valaciclovir
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CrCl 30-50ml/min
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Dose reduction required for Crcl<30ml/min seek further advice from
pharmacy/renal drug handbook
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Valganciclovir
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Dose reduction required seek further
advice from pharmacy/renal drug handbook
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Vancomycin
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1g od Check
pre dose level
before 3rd dose.
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1g 48 h
Check pre dose level before 2nd dose
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1g stat (or 15mg/kg max 2g). Check level after 4-5 days. ONLY re-dose when level <12mg/L. If deep
seated when <15mg/L
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Monitor blood levels & adjust dose as
required
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Voriconazole
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Give post HD
Caution in the use of IV in renal
impairment due to accumulation of vehicle-discuss with pharmacy
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Evidence base of
guideline
Information
derived from standard reference sources:
1. BMA and RPSGB. British National
Formulary. Number 59. March 2010
2. Summary of Product
Characteristics from electronic Medicines Compendium for individual drugs.
Available from http://emc.medicines.org.uk Datapharm
Communications Ltd.
3. Ashley C and Currie A. The Renal
Drug Handbook. 3rd edition 2009. Radcliffe Publishing Ltd. Oxford
