Drug Dosing in Special Populations

Drug Dosing in Special Populations

• Presentation by Gretchen Ray, PharmD, PhC, BCACP, CDCES, Associate Professor, UNM College of Pharmacy
• Date: January 17, 2025

Objectives

• Describe how renal and hepatic disease alter drug elimination/metabolism
• Accurately calculate CrCl and eGFR for renal function
• Adjust medication doses using CrCl and eGFR, referencing Lexi-Drug
• Define lab tests and clinical symptoms for Child-Pugh score calculation
• Provide general recommendations for hepatic-related dose reduction based on Child-Pugh score
• Describe pharmacokinetic and pharmacodynamic changes in geriatric populations
• Identify adverse drug event risk factors in geriatrics and mitigation strategies

Renal Disease

• Kidney disease reduces drug elimination
• Water-soluble drugs are primarily eliminated by the kidneys via glomerular filtration.
• Kidney function measured by glomerular filtration rate (GFR)
• Average young adult eGFR: 120-140 mL/min
• Average 65-year-old eGFR: 50-60 mL/min

Renal Function Assessment Equations

• Cockcroft-Gault: calculates creatinine clearance (CrCl)
  • CrCl = (140-age)×BW / (72×SCr) (×0.85 if female)
• CKD-EPI: calculates estimated GFR (eGFR)
  • Recommended by the National Kidney Foundation
    • eGFRcr = 142 x min(Scr/k, 1) ^ 1.200 x max(Scr/k, 1) ^ -1.200 x 0.9938Age x 1.012 [if female]

Renal Function Considerations

• CrCl developed for drug dosing.
• Accurate CrCl calculation requires ideal, actual, or adjusted patient weight.
• Prior to 2010, drug renal dosing primarily relied on CrCl
• eGFR calculated since 2010 frequently replaces CrCl calculations for renal drug dosing.
• CrCl and eGFR are not interchangeable

Renal Dose Adjustment Considerations

• Overdosing consequences when CrCl or eGFR is below 60 mL/min
• Underdosing consequences (goal of therapy: cure vs symptom management)
• Dosage range of the drug

Tools for Renal Function Calculation

• Global RPh (www.globalrph.com)
• Multiple creatinine clearance calculators
• National Kidney Foundation (https://www.kidney.org/professionals/KDOQI/gfr)
• Professionals GFR Calculator
• FAQs
• MD Calc (www.mdcalc.com)

Hepatic Disease

• Most lipid-soluble drugs are metabolized by the liver
• Hepatitis: Liver inflammation, reducing hepatocyte function, and causing potential mild, transient decrease in drug metabolism.
• Cirrhosis: Permanent loss of functional hepatocytes; reduced intrinsic clearance and reduced hepatic blood flow reduce the delivery of drugs to functioning parts of the liver.

Liver Function Assessment: Child-Pugh Score

• No single lab test to assess liver function
• The Child-Pugh score uses 5 lab tests/ clinical symptoms to evaluate liver metabolic ability
• Includes serum albumin, total bilirubin, prothrombin time, ascites, and hepatic encephalopathy.

Hepatic Dose Adjustment

• If a drug is ≥ 60% hepatically metabolized, dose reduction is often required in patients with hepatic impairment.
• Typical recommendations:
• CP Score 8–9: ~25% dose decrease
• CP Score >10: ~50% dose decrease
• Consult Lexidrug or other databases for hepatic dosing adjustments.
• Clinical reasoning based on the Child-Pugh score is advised.

Drug Dosing in Geriatrics

• Aging affects drug metabolism (liver is common site of drug metabolism )
• Decrease in liver blood flow reduces first-pass effect, increases bioavailability.
• Decreased liver size and reduced metabolizing enzymes impacts drug clearance and half-life.
• Reduced lean body mass results in lower creatinine production and lower GFR (glomerular filtration rate).
• CrCl and eGFR should be calculated for older patients.

Pharmacodynamics in Geriatrics

• Time course and intensity of drug effects vary greatly with age
• Medication use in older adults: follow 2023 Beers Criteria update for inappropriate and potentially risky medications.

Adverse Drug Events (ADE) Prescribing Cascade

• Adverse drug effects can be misinterpreted as new medical conditions.
• Subsequent drug therapies may exacerbate the issue leading to a cascade of complications.

Risk Factors for ADEs in Geriatric Patients

• 6 or more concurrent chronic conditions
• 12 or more doses of drugs/day
• 9 or more medications
• Prior adverse drug reaction
• Low body weight or BMI
• Age 85
• Estimated CrCl <50 mL/min

Principles of Prescribing for Older Patients

• Start with low doses
• Slowly titrate upward, as tolerated by the patient
• Avoid starting multiple new medications simultaneously
• Consider deprescribing medications if they are no longer necessary