Lecture 13 Drug dosing in renal impairment

Question 1

How is ADME affected by CKD?

Answer 1

A: potential changes in GI transit time, gastric pH, vomiting and diarrhea

D: sig altered in Stage 4-5, altered protein binding (reduced) - acidic drugs like phenytoin have decreased protein binding ⇒ increases Vd, altered tissue binding, for ex digoxin has decreased tissue binding ⇒ decreased Vd

M: reduced due to uremic toxins and chronic oxidative stress on liver, reduction in CYP450, difficult to predict on individual drugs

E: reduced excretion of drugs that are renally eliminated, drug accumulation, active metabolite accumulation, increased risk of AE

Question 2

How is creatinine used to assess kidney fxn?

Answer 2

metabolic by-product of muscle, serum conc primarily determined by pt muscle mass

almost exclusively eliminated by glomerular filtration - around 15% eliminated by tubular secretion

elderly and malnourished may have relatively low muscle mass and produce less, if actual SCr used then Cockcroft-Gault formula can overestimate renal fxn, General rule: don’t use a SCr < 100 micromol/L in C-G formula

Question 3

Which weights do you use in Cockcroft-Gault formula?

Answer 3

equation becomes less accurate in weight extremes (underweight and obesity)

Underweight (BMI < 18.5) - use actual/total body weight (ABW)

Normal Weight (BMI 18.5 - 24.9) - use ideal body weight (IBW)

Overweight/Obese (BMI > 25) - use adjusted (dosing) weight (DW)

IBW may underestimate CrCl, ABW may overestimate CrCl, DW may slightly improve accuracy

Question 4

What is weight corrected or normalized creatinine clearance formula?

Answer 4

used to compare normal CrCl for a 70 kg male (around 108-120 mL/min)

CrCl (mL/min/70 kg) = [(140 - age) x 90] / SCr (micromol/L) multiply by 0.85 for females

Question 5

How should we assess GFR?

Answer 5

C-G formula is gold standard for drug adjustment, majority of drug-dosing studies use this and majority of monographs will recommend it

all methods are only estimates of renal fxn, need to consider other info as well

bottom line is to have lab reported eGFR as initial info about kidney fxn, calculate CrCl using weight based or non-weight based formula

Question 6

What are some questions to consider about medications when adjusting for renal dosing?

Answer 6

A. is immediate effect required? - when immediate response is needed drug dosing should be aimed at therapeutic response within minutes or hours irrespective of renal fxn

B. if immediate effect isn’t required, can we titrate? - can be used to determine lowest effective dose

C. Is drug effective/safe in pt with renal impairment?

D. Is drug nephrotoxic?

E. Is drug > 50% renally eliminated or does it have active or toxic metabolites? - drugs primarily eliminated by kidney require empiric dose adjusting, some drugs should be avoided

F. Can the drug be dialyzed?

Question 7

What are some drug classes that require dosage adjustment in CKD?

Answer 7

anticoagulants, anti-hyperglycemic agents, antimicrobials and related drugs, centrally acting drugs (opioids, gabapentin), cardiac drugs, GI drugs, other

Question 8

What are good resources to check for drug information about dose adjustment in decreased renal fxn?

Answer 8

Lexi, Bennett’s Drug Prescribing in Renal Failure, Dialyze IHD, Sanford/Bugs and Drugs, Micromedex, ckdpathway.ca