32
VOLUME 7 NUMBER 1 • MARCH 2010
However, other antibiotics require dose adjustment and should be checked
in the BNF. Nitrofurantoin should generally be avoided in patients with cre-
atinine clearance below 60 ml/min.
Antihyperglycaemic treatments and insulin
Metformin is excreted by the kidneys and has the potential to cause lactic
acidosis, particularly during acute illness.
22
The lower the GFR, the older
the patient, and the higher the dose of metformin, the more likely there
is to be a problem. The SPC advises that the drug is not used when cre-
atinine clearance is below 60 ml/min but many clinicians use metformin
until eGFR is
<
30 ml/min/1.73 m
2
, which is in line with the NICE Diabe-
tes guideline from 2008. Special caution should be applied when start-
ing metformin in patients who are already on antihypertensive or diuretic
therapy or NSAIDs.
23
However, a recent systematic review concluded that the risk of fatal and
non-fatal lactic acidosis with metformin in type 2 diabetes was no higher
than with other antihyperglycaemic treatments when prescribed under
study conditions.
24
Therefore, the benefits of metformin in these patients
need to be weighed against the potential risk, which may be significantly
lower than previously thought. It is, however, advisable to temporarily stop
metformin during a period of intercurrent illness or dehydration in patients
with pre-existing kidney disease.
Sulphonylureas are associated with a higher risk of hypoglycaemia as
renal function deteriorates and therefore doses need to be titrated in this
situation. Gliclazide is not dependent on the kidneys for clearance of the
active drug or metabolite and is a more sensible choice than glibencla-
mide, which depends on renal clearance. Rosiglitazone, pioglitazone and
repaglinide do not require dose reduction in stage 1–3 CKD.
CKD significantly alters insulin metabolism. In people with diabetes
without renal disease the kidneys metabolise about 30% of the insulin
dose. However, insulin metabolism decreases with diminishing renal func-
tion and in stages 3 or 4 CKD an insulin dose reduction of 25% may be
indicated, and in patients in stage 5 the dose may need to be reduced
to 50%.
25
This will depend on the patient’s response and needs ongoing
careful monitoring.
Lipid-lowering drugs
Lipid-lowering drugs such as atorvastatin, fluvastatin and ezetimibe do
not require dose adjustment. However, the simvastatin dose may need
to be reduced in CKD stage 4 or 5. Fibrates should be avoided when the
GFR is reduced.
1
Conclusion
CKD has been the focus of much attention in the UK over the last two
years due to the Quality and Outcomes Framework (QOF) revisions, which
require GPs to keep a renal register of patients with CKD with an eGFR
below 60 ml/min. These patients set us a challenge when prescribing de-
cisions are being made regarding drugs that depend on renal elimination
or when renal disease is significant enough to disturb the pharmacokinetic
processes involved in drug disposition.
Many of our patients with CKD are elderly or are at high risk of develop-
ing advanced disease and suffering adverse effects. In addition, many of
these patients have significant co-morbidities requiring multiple therapies.
Therefore, dosages of drugs eliminated by the kidneys need to be ad-
justed according to creatinine clearance or glomerular filtration rates. The
absolute GFR may need to be used in patients at extremes of weight and
when potentially toxic drugs with a small safety margin are being used.
Medications with toxic metabolites should be avoided wherever possible
and potential drug interactions assessed. When in doubt, the Renal Drug
Handbook is a useful reference.
26
Alternatively, try the UK Medicines Information via their website – www.
swmit.nhs.uk/Renal.htm.
Acknowledgement
The author wishes to thank Elizabeth Lamerton, Senior Clinical Pharmacist
– Renal Medicine, Salford Royal NHS Foundation Trust, for her contribution
to this article.
Useful resources:
UK Medicines Information – Tel: 0117 9282867
BNF –
Summaries of product characteristics –
Medicines information services and specialist renal pharmacists
Joint Formulary Committee.
1.
British National Formulary. Edition 52. London: Royal
Pharmaceutical Society of Great Britain and British Medical Association, September
2006.
.
Cassidy MJ, Kerr DN. Renal disorders. In: Davies DM.
2.
Textbook of Adverse Drug
Reactions. Oxford. Oxford University Press, 1991.
Munar MY, Singh H. Drug dosing adjustments in patients with chronic kidney dis-
3.
ease. Am Fam Physician 2007;
75
(10): 1487–1496.
Drug and Therapeutics Bulletin
4.
2006, Vol 44, No 12.
MacGregor MS. The implementation of eGFR reporting.
5.
Br J Renal Med 2006;
11
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5–8.
Monstellar RD. Simplified calculation of body-surface area.
6.
New Engl J Med 1987;
315
: 1098.
Lord GM,Tagore R,CookT,Gower P,Pusey CD.Nephropathy caused by Chinese herbs
7.
in the UK. Lancet 1999;
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