Vancomycin Therapeutic Drug Monitoring Jarred Kelly B Sc

Vancomycin Therapeutic Drug Monitoring Jarred Kelly – B. Sc. (Pharm), ACPR Year 2 Pharmacy Resident, Critical Care November 23, 2018 1

Learning Objectives By the end of this 20 -minute session and after further selfstudy and practice you should be able to: 1. Describe the pharmacokinetic properties of vancomycin (absorption, distribution, metabolism, elimination) 2. Explain when it is appropriate to measure vancomycin peak and trough levels 3. Explain when it is appropriate to target a low trough level (10 -15 mg/L) vs. a high trough level (15 -20 mg/L) 4. Calculate an empiric vancomycin dosing regimen based on patient age and renal function 2

Learning Objectives 4. Calculate an appropriate vancomycin dosage adjustment using the ratio and proportion method 5. Calculate patient specific pharmacokinetic parameters including half-life (t 1/2), volume of distribution (Vd), and elimination rate constant (k) for a patient prescribed vancomycin 6. Calculate an appropriate vancomycin dosage adjustment using patient specific pharmacokinetic parameters (t 1/2, Vd, and k) 3

Vancomycin Pharmacokinetics Absorption • Oral: poor Distribution • Vd ~ 0. 7 L/kg (adult) • Protein binding ~50% Metabolism • No apparent metabolism Elimination • Renal (t 1/2 ~ 6 hours in adult with normal renal function) 4

Vancomycin Levels When? • Trough levels NOT necessary for: – Adults: <60 years old with normal weight, stable renal function, and short course of therapy (<7 days) – Peds: normal renal function and therapy <72 hours • Peak levels – Adults: NOT normally recommended – Peds: unstable renal function 5

Vancomycin Levels Timing? • Trough: 30 minutes prior to 4 th dose • Peak: 1 hour after end of 1 hour infusion 6

Vancomycin Levels Targets? • Low-target trough (10 -15 mg/L) – Uncomplicated infections • High-target trough (15 -20 mg/L) – Serious or life-threatening infections (endocarditis, sepsis, osteomyelitis, CNS infections, S. aureus pneumonia) • Peak (20 -40 mg/L) 7

Empiric Dosing *Refer to the VCH-PHC Dosing Guidelines* • Loading dose based on target trough level • Maintenance dose based on weight • Dosing interval based on renal function and age 8

Dosing Adjustment Ratio and Proportion method Your patient with MRSA bacteremia has a vancomycin trough level (prior to 4 th dose, doses administered on-time, level drawn on-time) of 13 mg/L. His renal function has been stable (SCr 90 mcmol/L). His dose is 1250 mg IV q 12 h. He weighs 85 kg. What is your suggested dose adjustment? 9

Dosing Adjustment Using patient specific PK parameters Because of your patient’s previous unusually low trough despite reasonable empiric dosing and stable renal function, you decide to obtain new trough and peak levels. Reminder: Current dose is 1750 mg IV q 12 h Levels appropriately measured around 09: 00 (4 th) dose: Trough = 24 mg/L Peak = 46 mg/L What is your suggested dose adjustment? 10

Vancomycin Monitoring • Repeat another trough level 30 -minutes prior to 4 th dose • Repeat SCr, BUN with trough level (and as clinically indicated) • Signs and symptoms of infection • Adverse reactions to vancomycin 11

Practice 1. 68 year old male growing gram positive cocci in pairs in blood. History of MRSA infection. 70 kg, SCr 95 What is your target trough level? What is your empiric dosing recommendation? 2. 50 year old, 50 kg female started on vancomycin 1 g IV q 12 h. Renal function is stable (SCr 80). Trough level (drawn appropriately, doses administered on-time) comes back at 22 mg/L. How would you adjust the dose to target a trough level of 15 -20 mg/L? 12

Questions? 13