This document provides information on estimating kidney function and adjusting drug dosing in patients with chronic kidney disease (CKD). It describes the differences between creatinine clearance (CrCl), estimated glomerular filtration rate (eGFR), and their respective formulas (Cockcroft-Gault and MDRD/CKD-EPI). While both CrCl and eGFR can be used to estimate kidney function and guide drug dosing, CrCl may be preferred in the elderly and for drugs with a narrow therapeutic index. The document reviews drug classes that commonly require dosage adjustments in CKD and provides an example case of adjusting anticoagulation therapy in a patient with CKD.
adaptive methods are doing with feedback in population pharmacokinetics---- clinical pharmacokinetics and therapeutic drug monitoring-- fifth pharm D notes
adaptive methods are doing with feedback in population pharmacokinetics---- clinical pharmacokinetics and therapeutic drug monitoring-- fifth pharm D notes
measurement of GFR and creatinine clearence-- design of dosage for hepatic patients -- therapeutic drug monitoring and clinical pharmacokinetics fifth pharm D notes
In this presentation I have tried to explain in brief about the dosage adjustment in renal disorders, how to carry out this process and the important formulae which are used in it.
conversion from INTRAVENOUS TO ORAL DOSING----- design of dosage regimenpavithra vinayak
conversion from INTRAVENOUS TO ORAL DOSING----- TYPES OF IV TO PO THERAPY CONVERSIONS: MEDICATIONS INCLUDED IN AN IV TO PO CONVERSION PROGRAM: SELECTION OF PATIENTS FOR IV TO PO THERAPY CONVERSION: design of dosage regimen--clinical pharmacokinetics and therapeutic drug monitoring-- fifth pharm D notes
Dose Adjustment in Renal Failure ...Practical Approach for Clinical Pharmacists to help them perfectly adjust doses for medications according to best evidence to date
Therapeutic drug monitoring (TDM) of drugs used in seizure disordersAbel C. Mathew
Therapeutic drug monitoring (TDM) of drugs used in seizure disorders- Phenytoin, Valproic acid, Carbamazepine are major drugs used in epilepsy disorders. These drug need TDM to ensure their proper usage.
Genetic polymorphism in drug transport and drug targets.pavithra vinayak
Genetic polymorphism in drug transport and targets.--pharmacogenetics
DRUG TRANSPORTER
Two types of transporter :
•ATP binding Cassette (ABC) – Found in ABCB, ABCD and ABCG family. Associated with multidrug resistance (MDR) of tumor cells causing treatment failure in cancer.
•Solute Carrier (SLC) – Transport varieties of solute include both charged or uncharged
P-glycoprotein
• ATP binding cassette subfamily B member- 1 (ABCB 1)
• Multidrug resistance protein 1 (MDR1)
• Transport various molecules, including xenobiotic, across cell membrane
• Extensively distributed and expressed throughout the body
Mechanism of Pglycoprotein
Substrate bind to P-gp form the inner leaflet of the membrane
ATP binds at the inner side of the protein
ATP is hydrolyzed to produce ADP and energy
Nomograms and tabulations in design of dosage regimens pavithra vinayak
Nomograms and tabulations in the design of dosage regimens --- NOMOGRAM IN UREMIC PATIENTS: NOMOGRAM FOR RELATIONSHIP BETWEEN CREATININE CLEARANCE AND ELIMINATION RATE CONSTANT FOR FOUR DRUGS clinical pharmacokinetics and therapeutic drug monitoring ---fifth PharmD notes
measurement of GFR and creatinine clearence-- design of dosage for hepatic patients -- therapeutic drug monitoring and clinical pharmacokinetics fifth pharm D notes
In this presentation I have tried to explain in brief about the dosage adjustment in renal disorders, how to carry out this process and the important formulae which are used in it.
conversion from INTRAVENOUS TO ORAL DOSING----- design of dosage regimenpavithra vinayak
conversion from INTRAVENOUS TO ORAL DOSING----- TYPES OF IV TO PO THERAPY CONVERSIONS: MEDICATIONS INCLUDED IN AN IV TO PO CONVERSION PROGRAM: SELECTION OF PATIENTS FOR IV TO PO THERAPY CONVERSION: design of dosage regimen--clinical pharmacokinetics and therapeutic drug monitoring-- fifth pharm D notes
Dose Adjustment in Renal Failure ...Practical Approach for Clinical Pharmacists to help them perfectly adjust doses for medications according to best evidence to date
Therapeutic drug monitoring (TDM) of drugs used in seizure disordersAbel C. Mathew
Therapeutic drug monitoring (TDM) of drugs used in seizure disorders- Phenytoin, Valproic acid, Carbamazepine are major drugs used in epilepsy disorders. These drug need TDM to ensure their proper usage.
Genetic polymorphism in drug transport and drug targets.pavithra vinayak
Genetic polymorphism in drug transport and targets.--pharmacogenetics
DRUG TRANSPORTER
Two types of transporter :
•ATP binding Cassette (ABC) – Found in ABCB, ABCD and ABCG family. Associated with multidrug resistance (MDR) of tumor cells causing treatment failure in cancer.
•Solute Carrier (SLC) – Transport varieties of solute include both charged or uncharged
P-glycoprotein
• ATP binding cassette subfamily B member- 1 (ABCB 1)
• Multidrug resistance protein 1 (MDR1)
• Transport various molecules, including xenobiotic, across cell membrane
• Extensively distributed and expressed throughout the body
Mechanism of Pglycoprotein
Substrate bind to P-gp form the inner leaflet of the membrane
ATP binds at the inner side of the protein
ATP is hydrolyzed to produce ADP and energy
Nomograms and tabulations in design of dosage regimens pavithra vinayak
Nomograms and tabulations in the design of dosage regimens --- NOMOGRAM IN UREMIC PATIENTS: NOMOGRAM FOR RELATIONSHIP BETWEEN CREATININE CLEARANCE AND ELIMINATION RATE CONSTANT FOR FOUR DRUGS clinical pharmacokinetics and therapeutic drug monitoring ---fifth PharmD notes
Modeling Algorithm of Estimation Of Renal Function by the Cockcroft and M...hiij
The purpose of this study was to determine the concordance between two equations used for estimating
glomerular filtration rate, in order to verify the possibility to be used interchangeably in the clinical
practice. The two equations are of Cockcroft & Gault (CG) (1976) formula and MDRD (modification of
Diet in Renal Disease) (1999) formula, these two models allow the assessment of glomerular filtration rate
(GFR) by calculating creatinine clearance (CLCR).To make a comparison between these two formulas
different models were examined for Subjects with normal renal function, Patients with renal impairment,
Diabetic patients, Age and sex, finally lean and obese patients by modeling two algorithms with the two
functions. Results show that the formula of Cockcroft & Gault remains the method of choice for estimating
renal function in clinical practice.
Correlation of Serum Creatinine Based Calculation of Glomerular Filtration Ra...ijtsrd
INTRODUCTION GFR is best index of kidney function in health and disease and accurate values are needed for optimal decision making in clinical settings. Estimated GFR eGFR based on serum creatinine is first line test of kidney function. CG formula is creatinine based equation and widely applied. Tc99m DTPA Diethylene Triamine Penta Acetic acid is the most commonly used radiopharmaceutical for GFR studies. The Gate method has been most common in the routine setting. AIM AND OBJECTIVES To study correlation of serum creatinine based calculation of GFR with measured ratio isotope GFR in healthy individuals and CKD patients. To assess the accuracy of GFR as calculated by CG GFR formulae using serum creatinine against measured RI GFR Tc 99m DTPA . METHODS This study observational study, which is done in department of medicine and department of nuclear medicine at Army Hospital RandR, Delhi Cantt in CKD and healthy individuals. Our study includes a total of 100 subjects with varying renal functions which includes 50 healthy individual and 50 CKD patients. RESULTS In this study it has been observed that in healthy group CG GFR has weak correlation with DTPA GFR r = 0.104 with p 0.471 . Lt Col (Dr.) Rahul Soni | Dr. Jayita Debnath "Correlation of Serum Creatinine Based Calculation of Glomerular Filtration Rate with Measured Radio Isotope Glomerular Filtration Rate in Healthy Individuals and Chronic Kidney Disease Patients" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-2 , February 2021, URL: https://www.ijtsrd.com/papers/ijtsrd38443.pdf Paper Url: https://www.ijtsrd.com/medicine/other/38443/correlation-of-serum-creatinine-based-calculation-of-glomerular-filtration-rate-with-measured-radio-isotope-glomerular-filtration-rate-in-healthy-individuals-and-chronic-kidney-disease-patients/lt-col-dr-rahul-soni
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A review of pharmacist-led transition of care systems, specifically post-discharge follow-up phone calls, and the opportunity for pharmacy students to lead a new service. A review of the “Post-Discharge Follow-up Phone Call SPEP Standard Work” project will be provided, including an overview of the methodology, results, and discussion.
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f you offer a service on the web, odds are that someone will abuse it. Be it an API, a SaaS, a PaaS, or even a static website, someone somewhere will try to figure out a way to use it to their own needs. In this talk we'll compare measures that are effective against static attackers and how to battle a dynamic attacker who adapts to your counter-measures.
About the Speaker
===============
Diogo Sousa, Engineering Manager @ Canonical
An opinionated individual with an interest in cryptography and its intersection with secure software development.
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This presentation was uploaded with the author’s consent.
Sharpen existing tools or get a new toolbox? Contemporary cluster initiatives...Orkestra
UIIN Conference, Madrid, 27-29 May 2024
James Wilson, Orkestra and Deusto Business School
Emily Wise, Lund University
Madeline Smith, The Glasgow School of Art
2. Objectives
Describe the difference between creatinine clearance
(CrCl ) and estimated glomerular filtration rate (eGFR)
Explain when and how to use which formula
Identify when to recommend a change in dose or
medication
3. Case
CG is a 75yr old male Caucasian with T2DM and stable
CKD. He is 175cm and 85kg. His serum creatinine =
198umol/L, eGFR (MDRD) on the lab is 31.2ml/min/1.732
and CrCl (CG)is 29.5ml/min. His BP is 135/86 and
ACR=60mg/mmol. He has some pitting edema and has a
history of A. Fib. He is also complaining of some muscle
soreness in his legs. He is taking the following:
Metformin 1g AM and 500mg PM
Rosuvastatin 20mg AM
Coversyl Plus HD 8/2.5mg daily
Warfarin to INR 2-3
Have has had trouble stabilizing on warfarin and the Dr.
would like to switch to rivaroxiban and would like your
help to dose. Anything else?
4. Endogenous Filtration Markers
Creatinine & Cystatin C6,7
Creatinine Cystatin C
Small Amino Acid derived from muscle mass Relatively small molecule derived from all
nucleated cells
Both filtered by the glomerulus and secreted (10-
15%) by the proximal tubule
Filtered but not secreted by the kidney
Dependant on age, sex, race and muscle mass Only determinants are age and sex, therefore more
uniform across populations
Can be affected by alterations in muscle mass and
drugs that inhibit tubular secretion (cimetidine,
trimethoprim)
Not affected by muscle mass. May be influenced by
thyroid function and corticosteroid use
Inexpensive and easy to use Expensive, therefore will be reserved for
confirmatory testing of renal function
Used in estimation of CrCl and eGFR Incorporated into equations (CKD-EPI) estimating
eGFR
Am J Kidney Dis. 2014; 63(5): 820-834
Curr Opin Nephol Hypertens 2014; 23: 258-266
5. Creatinine Clearance - 1976
Is a measure of how much creatinine is filtered and
secreted by the kidney over time expressed as ml/min
Surrogate used to estimated GFR, but tends to
overestimate true GFR
Traditionally used for decades in conjunction with the
Cockcroft-Gault (CG) equation to estimate kidney
function for drug dosing purposes
Uses serum creatinine in the calculation
Pharmacotherapy 2011; 31(11): 1130-1144
Nephron 1976; 16: 31-41
6. eGFR -1999
Glomerular filtration rate is a measure of the ultrafiltrate of
blood as it passes through the glomerulus.
Used to stage and monitor those with chronic kidney
disease (CKD) – and has been utilized for drug dosing???
Uses the Modification of Diet in Renal Disease (MDRD) and
Chronic Kidney Disease Epidemiology Collaboration
(CKD-EPI) equations to provide a more accurate assessment of
GFR compared to CG. Expressed as ml/min/1.73m2. Also uses
serum creatinine in the calculation
eGFR results reported by the laboratory are derived by MDRD
MDRD is less accurate at levels above 60 ml/min/1.73m2 ,
therefore will eventually be replaced with the CKD-EPI
7. KDIGO classification of CKD
eGFR less the 60 ml/min/1.73m2 for 3 months or more is diagnostic for CKD
Albuminuria is an independent risk factor for the progression of CKD
Green: low risk (if no other markers of kidney disease, no CKD); Yellow: moderately increased risk;
Orange: high risk; Red, very high risk.
Kidney International 2013; suppl 3(1)
8. Cockroft-Gault equation -1976
[((140-age)x weight*) x 1.23] ÷ Scr(umol/L) x 0.85 if female reported in
ml/min. Reflective of actual renal function
Modified CG equation normalized to 70kg10 (used by RQHR and found
in eCPS) does not use weight in its formula and correlates well with
weight based versions of CG11 . Reflects relative renal function.
((140-age) x 90) ÷ Scr (umol/L) x 0.85 if female reported in
ml/min/70kg
eCPS reports as ml/second – multiply by 60 to get ml/min
Because CG is creatinine based, adjustments may be required for obese
patients (BMI greater than 30 or 30% above ideal body weight)
[((140-age) x ABW*) x1.23 ] ÷ Scr (umol/L) x 0.85 if female
ABW = adjusted body weight
Calculators: http://www.globalrph.com/multiple_crcl.htm
* weight in kg
Am J Health-Syst Pharm 1996: 53: 1028-32 Obes Surg 2013; 23: 1427-1430
Pharmacotherapy 2011; 31(7): 658-664 Am J Health-Syst Pharmacy 2009; 66: 642-648
9. MDRD
GFR = 186.3 x (SCR)-1.154 x (age in years)-0.203 x 1.212 (if
patient is African American) x 0.742 (if female)
Normalized to ml/min/1.732
Calculator: many: http://www.globalrph.com/multiple_crcl.htm
Does not require weight in calculation
Provides a more accurate estimate of eGFR, but MDRD
underestimates eGFR at levels > 60 ml/min/1.732
Pharmacotherapy 2011; 31(11): 1130-1144
10. CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration
Provides a more accurate estimate of eGFR at levels
greater than 60 ml/min/1.732 compared to MDRD
Can be used with Cystatin C to estimated eGFR
Likely to replace MDRD on laboratory reports
JAMA 2012; 307(18): 1941-51
Am J Kidney Dis. 2013; 62(3)” 595-603
11. Which equation for drug dosing?
CrCl (CG) or eGFR (MDRD/CKD-EPI)
CrCl
Considerable experience with CG (50 years)
Pharmacokinetic studies (the relationship between CrCl
and total drug clearance) and recommendations for
dose adjustment in renal impairment based on CG
equation
Reported in units (ml/min) not adjusted for body
surface area which is appropriate for drug dosage
adjustment
May underestimate GFR in elderly as kidney function
does not decrease linearly with age as described in the
CG equation19
Current Opinion in Hephrology and Hypertension 2011; 20: 482-91 Clin Pharm Therapeutics 2009; 86(5):468-470
Am J Health-Syst Pharm 1996; 53: 1028-32
12. Which equation for drug dosing?
CrCl (CG) or eGFR (MDRD/CKD-EPI)
eGFR
Easy availability as reported on all or most lab reports
Stevens et al15 studied 5504 participants comparing
MDRD and CG
Their conclusion was MDRD had greater concordance with
measured GFR for drug dosage recommendations relative to
the CG equation
Stevens et al6 in a recent review found a 78% vs 73%
concordance of drug dosing recommendations with
MDRD and CG respectively.
Am J Kidney Dis 2009; 54(1): 33-42
Am J Kidney Dis 2014; 63(5) 820-834
Clin Pharm Therapeutics 2009; 86(5): 465-467
13. The Answer
Both can be used to recommend drug dosing
National Kidney Disease Education Program (2010)16
U. S. FDA – Guidance for Industry (2010)4
Kidney Disease: Improving Global Outcomes (KDIGO)
(2011)17
Canadian Society of Nephrology (2015)8
Remember, no equation can accurately estimate
kidney function for all patients. Therefore estimates
MUST be made in conjunction with the patients
clinical status (ie: creatinine must be at steady
state, etc.)
U.S. FDA. Center for Drug Evaluation and Research. Guidance for Industry: March 2010
Am J Kidney Dis. 2015; 65(2): 177-205
NKDEP. Chronic Kidney Disease nd Drug Dosing: Information for Providers. Jan. 2010
Kidney International 2011; 80: 1122-1137
14. Concerns with MDRD
Tends to overestimate dosing compared to CG particularly in the
elderly greater than 75 years of age19,5.
This may have implications when making recommendations for
drugs:
with a narrow therapeutic window
With significant adverse event profile
Substitution with an alternate agent
Direct toxic effects on the kidney
MDRD has not been validated for drug dosing in a number of
circumstances including the elderly and obesity18
May require recalculation from ml/min/1.732 to ml/min
(MDRDIND) for drug dosing recommendations in those who
are below ideal body weight or above by >30% or BSA
>304,8,16,17
http://mdrd.com/
Pharmacotherapy 2013; 33(9): 912-921 Pharmacotherpay 2011; 31(11): 1130-1144
PLOS ONE 2015; March: 1-31 J Am Pharmacists Association 2013; 53(1): 54-57
Int J Clin Pract 2015; 69(3): 313-320
15. Estimates of Kidney function by
age group
The magnitude of difference
between CrCl and eGFR as
calculated by MDRD and
CKD-EPI increases with each
decade of life.
In the elderly the MDRD
overestimates renal function
which could lead to higher
doses of drugs compared to
CG.5, 19,20
Hudson, JQ et al. Int J Clin Pract(2015): 69(3) 313-320
Pharmacotherapy 2013; 33(9): 912-921
Ann Pharmacotherapy 2012; 46: 1174-87
16. Bottom Line
CG vs MDRD/CKD-EPI
Both equations can be used to estimate renal function for
drug dosing in particular for drugs with broad therapeutic
range where a 2-3 fold increase in drug exposure will not have
significant impact on safety and efficacy.
At this time, it MAY be best to use CG in the elderly (>70
years) and with drugs with narrow therapeutic index such
as new oral anticoagulants
MDRD should be “normalized” at extremes of body mass.
Not for everyone:
Amputees, low muscle mass (paraplegic), AKI, malnourished,
vegetarian diet.
Must be combined with sound clinical judgment in drug dose
decision making
Pharmacotherapy 2011; 31(11): 1130-1144 J Am Pharmacists Association 2013; 53: 54-57
Pharmacotherapy 2013; 33(9): 912-921
Curr Opin Nephrol Hypertens 2011; 20: 482-491
17. Drug therapy in CKD
General Goals of Therapy 20,21
Most renally excreted drugs (>30% renally excreted) will require
some dosage adjustment at <60ml/min / ml/min/1.732
Loading doses may be required for drugs with long half life and
the need for rapid achievement of steady state (AMG,
levofloxacin, digoxin)
Maintenance dose:
Maintain usual peak/trough level same dose with longer interval
(certain antibiotics : AMG; quinolones)
Maintain average steady state lower dose with same dosing
interval (antihypertensives, penicillins)
Many references :
“Drug Prescribing in Renal Failure: Dosing Guidelines for Adults”
(Bennett's), eCPS/e-Therapeutics, Lexi-Comp, Micromedex,
calculators : http://www.globalrph.com/renaldosing2.htm
Ann Pharmacotherapy 2012; 46: 1174-87
Ann Acad Med Singapore 2009; 38: 1095-1103
18. When should a change in drug or dosing
recommendation be made in CKD?
With a narrow therapeutic window
New oral anticoagulants, digoxin
With significant or increased adverse event profile
Diabetic medications, statins
Substitution with an alternate agent
Certain antibiotics, thiazide diuretics
Direct toxic effects on the kidney
ACE inhibitors
Toxic or active metabolites
Meperidine, morphine
19. Drug Classes Requiring Dosage Adjustment in CKD
Drug Class Adjust Dose Avoid in Stages 4 and 5 CKD
B
Beta Blockers
Acebutolol, atenolol, bisoprolol, nadolol, sotalol Sotalol
A ACE inhibitors/ARBs Most ACE inhibitors
(adjust according to response)
Watch for hyperkalmia and possible decrease
in renal function
N NSAIDS, Opioids Codeine, Morphine, oxycodone, tramadol, long
term NSAIDS
All NSAIDS, meperidine
D
Diuretics
Potassium sparing diuretics, loop diuretics Thiazide diuretics, caution with potassium
sparing diuretics-monitor closely for
hyperkalemia
D
Diabetic medications
Gliclazide, acarbose, insulin, gliptins
Metformin: 50% of present or max dose at
eGFR 30-60ml/min/1.732
Glyburide exanitide
Metformin: may be used with caution in select
individuals
C Cholesterol medications Statins.
Fibrates –may increase serum creatinine
Avoid fibrate/statin combinations due to risk
of muscle side effects
A Antimicrobials
(Dose reductions are often
delayed for 24-48 hours to
allow for aggressive
dosing/drug to reach steady
state)
Antibiotics: Most antibiotics EXCEPT
Cloxacillin, clindamycin, metronidazole,
erythromycin, azithromycin
Antifungals: fluconazole, itraconazole
Antivirals, acyclovir, famciclovir, valacyclovir,
valgancyclovir
Nitrofurantoin
Watch for hyperkalemia and increase in serum
creatinine with trimethoprim
M Miscellaneous Allopurinol, colchicines, digoxin, H2RAs, New anticoagulants: rivaroxiban, dabigatran
Apixaban: decrease dose; avoid <15ml/min)
Magnesium/Phosphate containing bowel
preps or laxatives
P Psychotropics Lithium; gabapentin, pregabalin, topiramate,
vigabatrin, bupropion, fluoxetine, paroxetine,
venlafaxine
Adapted from: Saskatchewan Drug Information Services, College of Pharmacy and Nutrition, U of S. www.druginfo.usask.ca
20. New Oral Anticoagulants
Apixiban: Usual dose: 5mg bid
2.5mg bid if ≥2 of: age ≥ 80, wt ≤60kg, CrCl <25ml/min
Avoid: CrCl<15mL/min
Rivaroxiban: Usual dose: 20mg daily with food
CrCl 30‐50mL/min: 15mg daily with food
CrCl <30mL/min: not recommended
Dabigatran: usual dose: 150mg bid
110mg if >75yr & CrCl 30‐50mL/min
Avoid if CrCl <30ml/min
21. Diabetic Medications
Requiring dose adjustment: – monitor for signs of
hypoglycemia22
Sufonylureas
Avoid glyburide <60ml/min
Gliclazide: consider lower dose <30ml/min. Switch to
alternative <15ml/min such as meglitinide.
Insulin
30-50% renal elimination. Dose adjustments usually required
as renal function declines
DPP-4 inhibitors (gliptins)
Linagliptin only agent that does not require dose adjustment
in renal dysfunction.
Can J Diabetes 2014; 38: 334-343
22. Metformin
KDIGO and CSN
Renally cleared and clearance decreases by ~75% with CrCl
<60ml/min
Concern of lactic acidosis (LA)
Limited evidence for increased incidence of LA in those with renal
function 30-60ml/min (3-10 per 100,000 person-years)23
Greater reduction in 2-year mortality compared to other glucose
lowering therapies.
May be used with dose reduction in those with
CrCl 30-60ml/min (50% reduction from present or max dose)
Reasonable to consider in <30ml/min for those with
Obesity, stable renal function, close observation and able to follow
“sick day” rules
Kidney International 2011; 80: 1122-37
Am J Kidney Dis 2015; 65(2): 177-205
JAMA 2014; 312(23): 2668-2675
24. Antihypertensive agents
Many require dose adjustment but do so in conjunction with
pharmacodynamic effects
Diuretics
Thiazide ineffective as a diuretic at <30ml/min. Switch to loop
diuretic
K+ sparing diuretics: dose adjustment and avoidance in stage
4 & 5 CKD.
β blockers
Lipid soluble β-blockers such as atenolol or sotalol can
accumulate in CKD stages 3-5D
Bradycardia can be severe
ACE inhibitors
Watch for declining kidney function/hyperkalemia in those
with declining function (stage 3b-5)
25. Antimicrobials
Dose reductions often delayed 24-48 hours to allow for
aggressive management
Maintenance doses of most penicillins, cephalosporins,
antifungals and antivirals require dose reduction
Nitrofurantoin
Ineffective with eGFR <45ml/min
Toxic metabolite can accumulate peripheral neuropathy
Cotrimoxazole
Decrease dose by 50% for those with CrCl 15-30ml/min. Avoid in
<15ml/min
trimethoprim component can worsen hyperkalemia (usually not
until stage 4-5). Increase in creatinine – competition for tubular
secretion
Sulfa component requires adequate hydration to avoid crystaluria.
26. “Sick Day Rules”
Hold the following medications if nausea or vomiting
Drug Class Mechanism of action Adverse outcome
Sulfonylureas Reduced renal elimination Increased risk of hypoglycemia
ACE inhibitors Interfere with kidney’s response to
intravascular volume contraction.
Decrease intraglomerular pressure
Increased risk of decline in renal function
Diuretics Exacerbate intravascular volume
contraction
Increased risk of decline in renal function
Metformin Reduced renal elimination; dehydration Increased risk of lactic acidosis
Angiotensin receptor
blocker
Interfere with kidney’s response to
intravascular volume contraction
Decrease intraglomerular pressure
Increased risk of decline in renal function
NSAID Afferent arteriolar constriction
decreased renal blood flow (renal
prostaglandins)
Increased risk of decline in renal function
Can J Diabetes 38(2014) 334-43
27. Case
CG is a 75yr old male Caucasian with T2DM and stable
CKD. He is 175cm and 85kg. His serum creatinine =
198umol/L, eGFR (MDRD) on the lab is 31.2ml/min/1.732
and CrCl (CG)is 29.5ml/min. His BP is 135/86 and
ACR=60mg/mmol. He has some pitting edema and has a
history of A. Fib. He is also complaining of some muscle
soreness in his legs. He is taking the following:
Metformin 1g AM and 500mg PM
Rosuvastatin 20mg AM
Coversyl Plus HD 8/2.5mg daily
Warfarin to INR 2-3
Have had trouble stabilizing on warfarin and the Dr. would
like to switch to rivaroxiban and would like your help to
dose. Anything else?
28. Case
Rivaroxiban? dose?
Use CG estimation of CrCl
CrCl <30ml/min
Consider switching to apixiban 5mg bid as CrCl <30ml/min
Metformin
Use CG estimation of CrCl
?decrease dose or discontinue?
Consider switching to meglitinide or even insulin
Could also consider continuing with metformin 500mg AM and 250mg PM if there is
enough follow-up and he is able to follow sick day rules.
Rosuvastatin
Could use eGFR or CrCl
Decrease dose to no more than 10mg daily or switch to less potent agent such as
pravastatin
Cosversyl Plus HD
Could use eGFR or CrCl.
Change to perindopril 8mg + furosemide 40mg daily (renal panel 7 days)
29. Summary
May use both CG or MDRD/CKD-EPI for estimating
renal function for the purposes of drug dosing
CG may be preferable in elderly particularly for drugs
with narrow therapeutic window
Many drugs require dose adjustment in CKD
Dose adjustment, if required, must always be done in
consideration of the clinical condition of the patient and
the desired pharmacodynamic effects, adverse
effect/toxicity profile, and desired outcome of the
particular drug