Vancomycin TDM Flashcards
Vancomycin follows a __ compartment PK profile
2-3 compartment, however for calculation we take as 1 compartment
What is the estimate distribution time of Vancomycin?
30min-1h
Therefore Cmax is measured ~1h after eoi (to ensure drug has been distributed)
What is the estimated elimination half-life of Vanco?
4-12h
(4-6h in normal renal function)
*Vancomycin is cleared renally (dose adj required in renal impairment)
Why is TDM required for Vancomycin?
- Significant PK variability
Vd ranges from 0.4-1L/kg (we use Ave 0.7L/kg) - Lack of predictable dose-response relationship
- PK-PD target to maximise efficacy and minimize toxicity
AUC/MIC 400-600 for MRSA infection - Available lab assay for Vanco concentration
The PK-PD target is a daily Vancomycin AUC/MIC b/w 400 to 600mg for MRSA infections. What are the reasons for this recommendation?
Efficacy: AUC/MIC >= 400
Development of resistance: AUC < 400
Increased nephrotoxicity: AUC > 600
What is the vancomycin MIC value used in this therapeutic range and what are the reasons for this assumption
1mg/L
- Most MIC <1mg/L
- MIC measurement is imprecise, 10-20% variation considered acceptable
- High degree of variability b/w commercial MIC testing methods relative to BMD method
- MIC results typically not available within first 72h
What if MIC > 1mg/L?
May not want to use Vancomycin as there would be higher risk of nephrotoxicity (given we must incr conc. to incr AUC, to achieve same AUC/MIC target of 400-600)
Why did the guideline recommend a change in therapeutic monitoring from using vancomycin trough of 15 - 20 mg/L (as a surrogate for AUC) to AUC/MIC?
- Previously difficult to estimate AUC, trough-based monitoring approach more practical (however, now guidelines make AUC estimation practicable)
- Ctrough 15-20mg/L shown to be:
- Not optimal surrogate for AUC values (as wide range of AUC values can yield similar Ctrough value)
*AUC is a cumulative exposure for a defined period
*Ctrough is a single point exposure measurement of end of dosing interval - Associated with incr risk of nephrotoxicity when Ctrough >= 15mg/L
How soon should vancomycin target PK-PD goal be achieved from vancomycin initiation?
Within 24-48h
For which groups of patients is vancomycin TDM recommended?
Patients with serious MRSA infections (efficacy)
Patients at high risk for nephrotoxicity (toxicity)
- concurrent nephrotoxins
- unstable renal function
- prolonged course of therapy >3-5 days
Should Vancomycin TDM be carried out for nonbaccteremic skin and skin structure and UTIs?
No, not considered serious MRSA infections
A loading dose of 25 to 30 mg/kg (based on actual body weight, capped at vancomycin 3000 mg) is recommended for critically ill patients. How does giving a loading dose help in achieving the PK-PD target?
- Rapidly achieves targeted ranges of serum vancomycin concentrations
- Decreases the risk of subtherapeutic concentrations during the first few days of therapy
In what groups of patient are loading doses recommended for and why?
Critically ill or in ICU (Need to achieve conc. faster)
Require dialysis or renal replacement therapy (Renal impairment causes incr in half-life, hence take longer time to reach steady state)
Receiving vancomycin continuous infusion therapy
Vancomycin is dosed based on _____
Actual body weight
*Do not use AdjBW (like in aminoglycoside)
Vancomycin distributed into both water and lipid layers (distributed into fats)
What is the recommended initial dose (as intermittent infusion) for patients with normal renal function, assuming vancomycin MIC 1 mg/L?
Doses of 15 to 20 mg/kg (based on actual body weight) administered every 8 to 12 hours as an intermittent infusion
