Medicines Q&As
Q&A 167.5
What factors need to be considered when dosing patients with
renal impairment?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Before using this Q&A, read the disclaimer at www.ukmi.nhs.uk/activities/medicinesQAs/default.asp
Date prepared: 7th May 2013
Background
Many commonly used drugs or their metabolites are excreted by the kidney, and this has particular
significance for people with renal impairment (RI). Impaired renal function alters drug
pharmacokinetics,
potentially changing drug efficacy and increasing the likelihood of unwanted effects, including renal
toxicity (1). There may also be pharmacodynamic changes (2). Drugs that are most affected by RI are
those that are normally substantially renally excreted (≥ 30%) (3) or have active or toxic metabolites
which are renally excreted (4).
Answer
General drug dosing guidance in renal impairment
Drugs, or their metabolites, that are mainly excreted by the kidney may have a prolonged half-life in
RI, and accumulation may occur, which can result in toxicity (3,5). Drug accumulation sufficient to be
of clinical concern occurs in patients with RI if ≥30% of the drug is eliminated unchanged in the urine
(3), and dose reduction needs to be considered, depending on the degree of RI and fraction of drug
excreted unchanged (6)
There are three approaches to altering drug maintenance doses in patients with RI, depending on the
desired goal of therapy (1,3,7):
i)
either the standard dose can be given but at extended intervals or
ii)
a reduced dose is given at the usual intervals or
iii)
a combination of reduced dose and extended interval
Drugs that require maintenance of a serum concentration over the dosing interval should be
administered at the usual intervals, but with reduced doses. Drugs for which specific peak serum
concentrations must be achieved will be dosed with the standard dose at extended intervals (8). In
general, the latter approach will achieve similar peak and trough concentrations and AUC to those in
patients with normal renal function (9).
A suggested approach to calculating the dose is to calculate the dosage adjustment factor. This factor
is the ratio of the half-life of the drug in the patient to the half- life of the drug in the person with normal
kidney function. Use the dosage adjustment factor in one of the following ways after considering
which is most appropriate for the individual drug:
i) Divide the dose you determined for normal renal function by the dosage adjustment factor and
continue with the same dosage interval
ii) Continue with the same dose but multiply the dosage interval you determined for normal renal
function by the dosage adjustment factor
iii) A regimen of combined dose reduction and dose interval prolongation (10)
Drugs with a narrow therapeutic index (e.g. vancomycin, lithium) require the greatest care in use (4).
Careful monitoring of plasma levels and clinical response are needed, followed by dose adjustments,
if appropriate. When a rapid therapeutic response is needed, a loading dose may even be needed if
one was not routinely recommended for patients with normal renal function (9). The plasma half-life of
drugs excreted by the kidney is prolonged in RI and it takes about five times the half-life of a drug to
reach steady state concentrations, therefore it can take many doses for the reduced dosage to
achieve a therapeutic plasma concentration (11).The size of the loading dose should normally be the
same size as for a patient with unimpaired renal function (11). There may be some exceptions, e.g.
drugs with a narrow therapeutic index whose volume of distribution (Vd) may be altered in chronic
kidney disease (CKD) (8). The loading dose may be calculated by the following formula: patient’s
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loading dose= usual loading dose x [(patient’s VD)/(normal VD)](9). The initial dose/s of a course of
antibiotic should not be reduced because otherwise it may take a long time to reach therapeutic
levels. Single doses are not thought to be dangerous as accumulation is unlikely (4).
If a drug has a narrow therapeutic index with no potential for monitoring, potential renal adverse
effects, or serious dose-related adverse effects, an alternative should be found, if possible.
Additionally,
 Use recommended dosage regimens for renal failure
 Use plasma concentration measurements to adjust dose wherever possible
 Monitor the patient carefully for evidence of clinical effectiveness and toxicity (2,5)
 Exercise caution in patients with severe hepatic dysfunction, which is usually accompanied by
some RI (hepato-renal syndrome)(6)
Pharmacokinetics
The absorption, distribution, metabolism and excretion of drugs can be affected by RI to varying
degrees (2, 4, 7). These will be discussed individually.
Absorption and bioavailability
Absorption (proportion of drug absorbed from the gastrointestinal tract) and bioavailability (the
proportion of the administered dose which reaches the systemic circulation of the patient) can both be
affected in renally impaired patients. Absorption may be reduced due to a number of factors such as
nausea, vomiting or diarrhoea associated with uraemia and gut oedema. An increase in the gut pH
from increased gastric ammonia production in uraemia, or from co-administered drugs, reduces the
bioavailability of drugs requiring an acidic environment for absorption. The increase in pH may
increase the bioavailability of weakly acidic drugs (2). The effect of CKD on intestinal cytochrome P
450 metabolic enzymes and transporters may lead to an increase in bioavailability of orally
administered drugs, e.g. tacrolimus, in these patients (12).
Drug doses are not routinely altered to allow for these factors alone, but a change in dose or route of
administration may be considered if the desired therapeutic effect is not being achieved (2).
Distribution
The state of hydration of a patient will affect the volume of distribution (Vd) of water soluble drugs with
a small Vd e.g. aminoglycosides with a Vd of approximately 0.25L/kg (2, 8). For example, the Vd of
gentamicin will increase in patients with oedema or ascites; consequently dose adjustment may be
needed to achieve satisfactory plasma concentrations in extremely volume overloaded patients
(>110% of ‘dry’ weight’) (8). Another factor affecting Vd in patients with CKD is reduction in protein
binding(Pb), caused by decreased serum albumin concentrations, reduction in albumin affinity for
drugs and competition for binding sites from accumulated metabolites and endogenous substances.
This is clinically important for highly protein bound drugs (>80%) (2, 5, 8). Apparently low total plasma
concentrations of these drugs will still be therapeutic as the proportion of free, therefore active, drug
will be higher. An important example of this is phenytoin (2, 5, 8). Alterations in tissue binding may
also affect the Vd of a drug (2). For example, the Vd of digoxin is decreased in patients with severe
RI, probably due to a decreased in tissue binding (3,6). However changes to distribution (Pb and Vd)
are most likely to be a significant issue in renal replacement therapies (refer to Q&A168.5)
Metabolism
Renal impairment affects the metabolism of drugs (5) e.g. reduction and hydrolysis are slower. This
may increase serum concentrations of the parent drug and consequent toxicity if the drug is
metabolised to inactive metabolites (2). Many drugs and/or their phase I metabolites are eliminated by
glucuronidation and the glucuronides are excreted by renal mechanisms. Therefore in patients with
RI, glucuronide conjugates will accumulate in the plasma. For some drugs, e.g. ketoprofen, systemic
hydrolysis of the glucuronide will occur, leading to increased levels of the parent compound (3,6).
Many studies have also shown reduced acetylation in patients with RI (12). Many active or toxic
metabolites depend on renal function for elimination; therefore they may accumulate in RI, for
example norpethidine following the administration of pethidine (2,13). Norpethidine is a central
nervous system stimulant but not an analgesic. Even in patients with mild RI, such as elderly patients,
this metabolite can reach sufficient concentrations to cause seizures. The use of lower doses of
pethidine may limit its efficacy, therefore alternative analgesics should be considered (3). There is
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also clinical evidence that alterations in drug metabolism and transport occur during acute and chronic
renal failure (13,14). In patients with severe chronic RI the accumulation of uraemic toxins and
inflammatory cytokines affects the activity of cytochrome P 450 metabolic enzymes and of Pglycoprotein, organic anion-transporting peptides and multidrug resistance-associated protein
transporters in the liver and gastro-intestinal tract (12,14). Drugs affected include imipenem,
meropenem, vancomycin(13), digoxin and erythromycin (12). For example, uraemic toxins inhibit
organic-anion-transporting polypeptide (OATP)-mediated uptake of erythromycin into hepatocytes,
which may be responsible for its reduced hepatic clearance in severe CKD (12). Studies have shown
that non-renal clearance of these drugs is lower in patients with acute RI and lowest in patients with
chronic RI, compared with patients with normal renal function (13). Even drugs such as lidocaine
which is mostly metabolized by hepatic CYP1A2 and CYP3A4 have been reported to have reduced
clearance and prolonged half-life in patients with CKD, compared with control subjects (12). However,
prediction of the effect of RI on the metabolism of a particular drug is difficult, and there is currently no
quantitative strategy to predict changes for one drug based on data from another drug of the same
class(9). Careful monitoring of patients is therefore essential.
Excretion
The extent to which a reduction in glomerular filtration is important for the elimination of a drug
depends on the proportion of the administered drug or any active or toxic metabolites which are
eliminated by the kidney (2). For some drugs, e.g. methotrexate, reduction of renal excretion in
patients with advanced CKD is thought to occur also through a competitive inhibition of renal
transporter proteins by uraemic toxins (12). The excretion of several other drugs mainly eliminated in
the urine by active tubular secretion, is also reduced in RI e.g. sitagliptin and varenicline. Sitagliptin is
a substrate for human organic anion transporter-3 (hOAT-3), which may be involved in the renal
elimination of sitagliptin. However the clinical relevance of hOAT-3 in sitagliptin transport has not been
established (15).
A small number of drugs (for example, carbamazepine, theophylline) are mainly excreted hepatically
without toxic metabolites. The effect of RI on their metabolism has not yet been fully studied, but
appears to be unaffected by RI in humans (13,14). Monitoring of efficacy, blood levels or adverse
events is advisable however, in view of the emerging data on the effect of CKD on drug metabolism
(4,12). The effects of a number of drugs are measured by direct physiological response. These drugs
can be used, with caution (i.e. lower starting doses), in renally impaired patients. Indeed many of the
drugs used to manage renal failure (e.g. calcitriol, phosphate binders) are titrated according to
response (4).
Pharmacodynamics
Uraemia in RI can alter the clinical response to certain drugs (2,16) for example;
 Increased sensitivity to drugs acting on the central nervous system
 Increased risk of hyperkalaemia with drugs such as potassium-sparing diuretics
 Increased risk of gastrointestinal bleeding or oedema with non-steroidal anti-inflammatory
drugs (NSAID).
 Reduced efficacy or increased toxicity of drugs such as warfarin or statins, independent of
changes in the pharmacokinetics of these drugs. Kidney disease is thought to alter the
physiological or pathological processes involved in the condition being treated (17).
Measuring renal function
Accurate measurement of renal function is essential in patients with RI so that drug dosages can be
adjusted accordingly. Because the production and excretion of creatinine decline with age, normal
serum creatinine values may not represent normal renal function in older patients (18).The estimation
of glomerular filtration rate (eGFR) provided by the Modification of Diet in Renal Disease trial (MDRD)
is now the most widely used method of estimating renal function (19). It is calculated using serum
creatinine concentration, age, sex and ethnic origin (20) which is different from the traditional
Cockcroft and Gault (C&G) estimation of creatinine clearance (CrCl). Drug dosing calculations for
patients with RI have traditionally been based on estimations of CrCl using C&G (16,20) and the vast
majority of published drug dosing information is based on C&G estimation of CrCl (7).
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Advice on adjustment of drug doses in RI in the BNF is now expressed in terms of eGFR, rather than
CrCl, for most drugs (11). Although the two measures of renal function are not interchangeable, in
practice, for most drugs and for most patients (over 18 years) of average build and height, eGFR
(MDRD ‘formula’) can be used to determine dosage adjustments in place of CrCl (11).The national
Kidney Disease Education Program in the USA has also endorsed the use of eGFR for drug dosing in
renal disease (21,22). When calculating renal function, MDRD eGFR normalised estimates largely
correlate with C&G estimates for CKD stages 3-5 (23), except for patients at extremes of body weight
(11,16,23). The MDRD formula is not validated for use in children under 18 years (11). The BNF
advises that for potentially toxic drugs with a narrow therapeutic index, CrCl (calculated from the C&G
formula) should be used to adjust drug dosages in addition to plasma-drug concentration and clinical
response (11).
Neither the C&G equation nor the MDRD equation give reliable estimates in patients with normal or
mildly impaired renal function. Estimates of eGFR becomes less accurate as true GFR increases (24)
or in individuals with extremes of body size or muscle mass, or those with unusual dietary habits (22).
The limitations in creatinine-based estimating equations are particularly relevant for populations with
reduced muscle mass, including frail, elderly, critically ill or cancer patients (22). There is evidence
that in elderly patients with CKD the use of the MDRD equation to calculate eGFR instead of an
estimated CrCl, leads to the calculation of higher doses of drugs such as enoxaparin, gentamicin and
digoxin in up to 50% of these patients(25).
The eGFR calculated by the MDRD equation is normalised to a standard body surface area (BSA) of
1.73m2.Therefore there is a potential for under- or over- dosing patients at extremes of body weight.
In order to calculate the correct dose the normalised eGFR should be converted to the patient’s
absolute GFR using the following formula: GFR ABSOLUTE = (eGFR x BSA ACTUAL/1.73) (11).
This is particularly important for drugs with a narrow therapeutic index. Failure to correct to absolute,
non-normalised GFR in patients with a BSA smaller than 1.73m 2 will overestimate GFR and potentially
result in drug overdosing. Conversely, in patients with a BSA greater than 1.73m 2 this will
underestimate GFR and will potentially result in drug under-dosing (7,16).
The BNF advises that in patients at both extremes of weight (BMI of less than 18.5 kg/m2 or greater
than 30 kg/m2) the absolute GFR or CrCl (calculated from the C&G formula) should be used to adjust
drug dosages (11).When using the C&G equation to calculate CrCl it is important to note that it uses
body weight as a marker of muscle mass (creatinine being a breakdown product of muscle).
Therefore in obese or extremely underweight patients there is also potential for over- or underestimation of CrCl. Guidance is available on when to use actual or ideal body weight in these
circumstances (16,23). Furthermore, estimating CrCl from a serum creatinine level assumes that renal
function is stable, and that the serum creatinine level is fairly constant. With rapidly changing renal
function the serum creatinine levels will no longer reflect the true creatinine clearance rate (23).
Where an accurate GFR is deemed necessary e.g. in chemotherapy dosing, an isotope GFR
determination should be performed (7,23).
It is also worth noting that historically, there has been substantial variability in serum creatinine values
reported by different clinical laboratory creatinine measurement methods. Consequently, the results of
pharmacokinetic studies on which this dosing information was based, were dependent upon the
particular method for measuring serum creatinine used in a given study (9,22). However it is not
possible or practical to repeat all the studies using a standardised creatinine measurement method.
The estimated GFR based on current standardised creatinine assays is likely to lead to different
dosage recommendations from those intended by the original study, even if the same estimating
equation is used, because of the change in analytical methodology (9,21).
Acute Kidney Injury
Patients with acute kidney injury (AKI) will often develop multiorgan dysfunction syndrome or
multisystem organ failure. When dosing patients with AKI, these and other factors - rapidly fluctuating
levels of renal function, changes in volume status and the effects of renal replacement therapy (RRT)
- need to be considered in addition to those discussed above(9). Dosage adjustment should be
guided by clinical judgement and monitoring, in addition to published guidance which may be based
on older studies in CKD patients or patients on RRT. Refer to Q&A168.5 .The VD of some drugs,
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Medicines Q&As
especially highly water soluble antibiotics, are increased in the presence of AKI so a larger (25-50%)
loading dose may be needed (9)
Summary
The absorption, distribution, metabolism and excretion of drugs can be affected by renal impairment
(RI) to varying degrees (2,4,7). Generally, changes in drug absorption and bioavailability are unlikely
to be a clinically significant problem for most drugs, but the effect of CKD on intestinal cytochrome P
450 metabolic enzymes and transporters may lead to an increase in bioavailability of some orally
administered drugs in patients with RI (12). Changes to drug distribution (protein binding and Vd) are
more likely to be an issue in renal replacement therapies (refer to Q&A168.5) `
Drugs that are most affected by RI are those that are normally substantially renally excreted or have
active or toxic metabolites which are renally excreted (4). Renal excretion of a drug is dependent on
GFR and when renal function is impaired, clearance of the drug is decreased and the plasma half-life
prolonged. The excretion of some drugs that are mainly eliminated in the urine by active tubular
secretion, is also reduced in RI (12). Therefore patients with RI who are given drugs that are mainly
renally cleared will require the dose or dose frequency to be adjusted. This is usually either by the
standard dose being given at extended intervals or a reduced dose given at the usual intervals (1, 7).
Single doses are not thought to need adjustment as accumulation is unlikely (4).
Before prescribing a drug to a patient with RI consider the following (2);
 Use drugs only when there is a definite indication
 Choose a drug that has no or minimal nephrotoxicity
 Use recommended dosage regimens for renal failure
 Use plasma concentration measurements to adjust dose wherever possible
 Monitor the patient carefully for evidence of clinical effectiveness and toxicity of drugs
The estimation of the GFR is the cornerstone of any alteration of a dose of a drug. (16, 23,26). The
vast majority of published drug dosing information is based on Cockcroft & Gault (C&G) estimation of
creatinine clearance (CrCl) (7). However the estimation of glomerular filtration rate (eGFR) provided
by the Modification of Diet in Renal Disease trial (MDRD) is now the most widely used method of
estimating renal function (19). Although the two measures of renal function are not interchangeable, in
practice, for most drugs and for most patients (over 18 years) of average build and height, eGFR
(MDRD ‘formula’) can be used to determine dosage adjustments in place of CrCl (11). The
information on dosage adjustment in the BNF is now expressed in terms of eGFR, rather than CrCl for
most drugs. However, dose regimens based on CrCl calculated by C&G should be used for potentially
toxic drugs with a narrow therapeutic index, together with monitoring of plasma-drug concentrations
and clinical response. The absolute GFR or CrCl calculated by the C&G formula should be used to
adjust drug dosages in patients at extremes of body weight (BMI <18.5kg/m 2 or >30kg/m2)(11). If
using C&G for these patients it may be necessary to base the calculation on ideal body weight
(16,23). Where an accurate GFR is considered necessary e.g. in chemotherapy dosing, an isotope
GFR determination should be performed (7,23).
It is worth noting that published data on drug dosage adjustment in RI are sparse and include mainly
case reports and pharmacokinetic studies in small numbers of subjects. They are also subject to
variability in serum creatinine assays performed by different clinical laboratory creatinine
measurement methods (22). In addition the level of RI is often defined differently among the
pharmacokinetic studies and each category (‘mild’, ‘moderate’, ‘severe’) often encompasses a broad
range of kidney function. The drug dosage adjustment recommendations that use broad ranges of
kidney function may not be optimal for all patients whose kidney function lies within the specified
range, especially for drugs that have a narrow therapeutic index(9). For new drugs most studies are
designed and performed by the manufacturer. This was highlighted by a study comparing secondary
sources of prescribing information for patients with RI. The study found a considerable degree of
variability amongst the definitions and recommendations in four different standard sources (27, 28).
For this reason clinical judgement should be used alongside any estimates derived from equations
(21).
Limitations
This Q&A discusses general principles of drug dosage adjustment in adults. For information on dose
adjustment of specific drugs or information on drug dosage adjustment in children, please consult the
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latest BNF, BNF for children, SPC and Renal Drug Handbook and other specialist texts or sources of
information.
References
(1) Consumers Association. The patient, the drug and the kidney. Drug and Therapeutics Bulletin
2006; 44 (12): 89-95.
(2) Millsop A. Drug Dosing in patients with renal impairment and during renal replacement therapy.
In: Ashley C, Morlidge C, editors. Introduction to renal therapeutics. London: Pharmaceutical Press;
2008. p. 127-137.
(3) Brater DC. Drug dosing in patients with impaired renal function. Clin Pharmacol Ther 2009; 86:
483-9
(4) Sexton J. Drug use and dosing in the renally impaired adult. Pharmaceutical Journal 2003; 271:
744-746.
(5) Aronoff GR et al. Drug Prescribing in Renal Failure. Dosing Guidelines for Adults and Children.
5th ed. Philadelphia: American College of Physicians; 2007. p.1-10
(6) Verbeeck RK and Musuamba F. Pharmacokinetics and dosage adjustment in patients with renal
dysfunction. Eur J Clin Pharmacol 2009; 65:757-73
(7) Ashley C, Currie A. editors. Renal Drug Handbook. 3rd Edition 2009. Oxford Radcliffe Medical
Press Ltd p.xiv – xvii
(8) Churchwell MD, Mueller BA. Selected pharmacokinetic issues in patients with chronic kidney
disease. Blood Purif 2007;25: 133-38
(9) Matzke GR et al. Drug dosing consideration in patients with acute and chronic kidney disease – a
clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney International
2011; 80: 1122-37
(10) Bennett W, Sica D. Effect of impaired kidney function on drug pharmacokinetics and
pharmacodynamics. Drug Prescribing in Kidney Disease: Initiative for Improved Dosing (2010)
KDIGO Controversies Conference: Drug Prescribing in Kidney Disease: Initiative for Improved
Dosing, Baltimore, USA, May, 2010. Accessed via
http://www.kdigo.org/meetings_events/drug_Prescribing_in_KD-Initiative_for_Improved_Dosing.php
on 3.5.13
(11) Joint Formulary Committee. British National Formulary. April 2013. London: British Medical
Association and Royal Pharmaceutical Society of Great Britain; 2013, Prescribing in renal impairment.
www.bnf.org Accessed 12th April 2013
(12) Naud J et al. Current understanding of drug disposition in kidney disease. J Clin Pharmacol
2012;52: 10S-22S
(13) Vilay AM et al. Clinical review: Drug metabolism and nonrenal clearance in acute kidney injury.
Critical Care 2008; 2008;12:235
(14) Nolin T. Altered nonrenal drug clearance in ESRD. Curr Opin Nephrol Hypertens 2008; 17:555-9
(15) MSD Summary of Product Characteristics JANUVIA 25mg, 50mg, 100mg film-coated tablets
.DORT December 2012. Accessed via
http://www.medicines.org.uk/emc/medicine/19609/SPC/JANUVIA+25mg%2c+50mg%2c+100mg+filmcoated+tablets/ on 2.5.13
(16) Brown C. Prescribing principles for patients with chronic kidney disease. Pharmacy in Practice
January/February 2008.p.23-27 http://www.pharmacyinpractice.com/past-issues/2008-volume-18issue-1/7-PIP-Therapeutic-options-Jan-Feb-08.pdf
(17) Nolin TD et al. Optimizing drug development and use in patients with kidney disease. J Clin
Pharmacol 2011;51: 628- 30
(18) Munar MY, Singh H. Drug dosing adjustments in patients with chronic kidney disease. Am Fam
Physician 2007;75:1487-96
(19) UK e CKD Guide. Revised January 2009. Renal Association. Available at
http://www.renal.org/whatwedo/InformationResources/CKDeGUIDE.aspx accessed 6th June 2011
(20) Sullivan L. In Focus Review New National Guidelines for Estimating Glomerular Filtration Rate
http://www.nelm.nhs.uk/en/NeLM-Area/News/487372/487589/487603/?query=GFR&rank=1
Accessed 18th December 2008
(21) Stevens LA et al. Comparison of drug dosing recommendations based on measured GFR and
kidney function estimating equations. Am J Kidney Dis 2009; 54: 33-42
Available through NICE Evidence Search at www.evidence.nhs.uk
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(22) National Institute of Diabetes and Kidney and Digestive Diseases. CKD and drug dosing:
information for providers. http://www.nkdep.nih.gov/resources/CKD-drug-dosing.shtml#suggestedapproach accessed on 26.4.13
(23) Devaney A, Tomson C. Chronic kidney disease – new approaches to classification. Hospital
Pharmacist 2006; 13: 406-10
(24) BMA and NHS Employers. Chronic kidney disease frequently asked questions January 2010.
Accessed via http://www.britishrenal.org/getattachment/CKD-Forum/Clinical-Managment/CKD-FAQs(DH-Jan-2010).pdf.aspx on 26.4.13
(25) Denetclaw TH et al. Dofetilide dose calculation errors in elderly associated with use of the
modification of diet in renal disease equation. Ann Pharmacother 2011; 45: e44
(26) Diagnosis and management of chronic kidney disease. Guideline 103. June 2008. Scottish
Intercollegiate Guidelines Network http://www.sign.ac.uk/pdf/sign103.pdf
(27) Vidal L et al. Systematic comparison of four sources of drug information regarding dose
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(28) Mehta DK et al. Dose adjustment in renal impairment. Brit Med J 2005; 331: 291-4
Quality Assurance
Prepared by
Julia Kuczynska, South West Medicines Information and Training, Bristol, (based on earlier work by
Richard Cattell and Caroline Metters)
Date Prepared
8th May 2013
Checked by
Trevor Beswick, Director, South West Medicines Information and Training
Date of check
21st May 2013
Search strategy
 Embase: [exp *KIDNEY FAILURE or exp *ACUTE KIDNEY FAILURE or exp *CHRONIC
KIDNEY FAILURE ] and [exp *DRUG ADMINISTRATION or exp *PHARMACOKINETICS]
[Limit to: Publication Year 2011-2013]
 Medline : exp *RENAL INSUFFICIENCY + [exp *DRUG ADMINISTRATION SCHEDULE or
exp *PHARMACOKINETICS] [Limit to: Publication Year 2011-2013]
 In-house drug dosing in renal failure database and resources
 Internet Search (Google; REVIEW and PHARMACOKINETICS and KIDNEY FAILURE)
 NHS Evidence(KIDNEY FAILURE and [PHARMACOKINETICS or DRUG
ADMINISTRATION])
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