**Vancomycin Dosing Tools**

Vancomycin Bayesian AUC Dosing Calculator, Excel File Downloadable, open compartment open model, for
use with varying dosing frequencies, doses, and steady state or Non-Steady State
levels using the method of superposition. The tool creates a data file of data fittings that may be used to perform Medication
Usage Evaluations and pharmacokinetic parameter optimization. The Solver Add-in must be available for the file to run. In Excel do the following: Click File, Click Options, Click Add-ins, Manage Excel Add-in Click Go, Check Solver Add-in, and select OK.

Excel
Program Instructions

Vancomycin
Dosing Charts: Overview of Dosing Charts,
Vancomycin
Dosing Chart I &
Vancomycin
Dosing Chart II

Vancomycin Dosing ** Calculator** and Data Fitting For Troughs,
Web-Based

Vancomycin Bayesian AUC Dosing Calculator For Steady State Levels Using a Peak and Trough, Downloadable Excel File. Error corrected 9/4/22

Vancomycin Two Compartment Model Intermittent Infusion Pharmacokinetics

**Medication Usage Evaluation and Pharmacokinetic Analyses**

Vancomycin Pharmacokinetic Dosing: Analysis of Patient Data &
Optimization of Kinetic Parameters

Vancomycin Hemodialysis MUE Dose During Dialysis

Vancomycin
Hemodialysis
MUE Dose After Dialysis

Comparison of Vancomycin Dosing Predictions for A One-Compartment Open Model
Versus

Vancomycin Dosing Prediction One-Compartment Model Versus Two Compartment Models
1/2022

Vancomycin Dosing Predictions One-Compartment Model
Versus Optimize Goti and Carreno Two Compartment Models 4/2022

**Monte Carlo Analysis of Vancomycin Bayesian Pharmacokinetic
Modeling Using a Peak & Trough, Trough or Peak Serum Level For AUC Calculations**

If you have questions about the dosing tools contact Marshall Pierce PharmD.

Please help support the development and maintenance of this educational site. Donate at PayPal

**Vancomycin Pharmacokinetic Dosing Information****Spectrum of activity:**
Most aerobic and anaerobic gram-positive cocci and bacilli including staphylococcal and enterococcus infections,
most often used for methicillin-resistant staphylococci and for patients
allergic to cephalosporin such as cefazolin. Vancomycin is bactericidal with time-depend killing,
but bacteriostatic for most strains of enterococci.

**Toxicity:** Nephrotoxicity rates of 5% to 15%; when combined with
aminoglycosides the rate may be as high as 25-35%. Nephrotoxicity has been
associated with an AUC > 600 mg/L/Day.

**Bioavailability (F):**
Oral absorption is less than 5% if the bowel is non-inflamed, administered IV for systemic and urinary
infections.

Fraction IV: 1

**Salt: **1**Protein binding:** 30-55% normal,
20% in ESRD

**Vd: **0.65 L/kg Total Body Weight, 0.72-0.9 L/kg in ESRD

**Cl: **is similar to creatinine clearance with a
small amount of non-renal elimination

**K:** (0.00107*Clcr(ml/min/1.73 meters^{2}) +
0.0052; normalization of creatinine clearance minimizes bias due to patients
with low or high body weight. If creatinine clearance is not normalized heavy
patients will receive too high of a dose and small patients will receive too
low of a dose, see MUEs below.

**T' (Infusion period):** 2 hour (500 mg/hr)**Usual Interval: ** every
6, 8, 12, 16, 24, 36, 48, 72, 96, 120 hours

**Usual Dose: **Load: 20-25 mg/kg, Maintenance: 15 mg/kg of total
body weight. LD capping of 3-4 grams is recommended in HD patients and 2-3 grams
in non-HD patients. Loading doses are independent of renal function in
hemodialysis patients unless residual renal function is present. **Low Flux Hemodialysis: **approximately 8% removed
during a dialysis session, no supplemental dose is needed after dialysis.**
High Flux Hemodialysis Dosing: **
approximately 30-46% of the administered dose is extracted or removed if
administered during dialysis.** **Loading dose: 20-25 mg/kg of
actual body weight,
Maintenance Dose: 500-1000 mg after each HD depending on the severity of infection and
serum level obtained. Without an adequate loading dose, it will take two weeks
before levels stabilize. If dosed during HD session a dose 13-34% higher
than post HD dosing may be required. See information further down the page.**CAPD Peritoniti**s: Intermittent
dosing 15-30 mg/kg in overnight dwell re-dose when the level is above 15 mcg/ml
(every 3-5 days). Up to 90% of the dose may be absorbed when peritonitis is
present. Goal serum level is 15-20 mcg/ml. The first trough should be drawn 3
days after the first dose. Duration of therapy: coagulase negative-staphylococci
14 days, S. aureus 21 days, Enterococci 21 days (severe infections add
aminoglycoside 0.6 mg/kg/day overnight), other streptococci 14 days. ISPD Peritonitis
Recommendation 2016 Update on Prevention and Treatment

**Therapeutic Goals: AUC 400-600 mg*hours/L per 24 hours/MIC for efficacy
and AUC < 600 mg*hour/L per 24 hours to
minimize toxicity. **Peak: 30-40 mcg/ml,** **trough levels
10-20 mcg/ml were used in the past. Trough goals for hemodialysis dialysis
patients are pre-dialysis levels as the post-dialysis level is
brief and can not easily be incorporated into the risk of toxicity and adds little
to the AUC.

**Serum Sampling Times: **

Dosage calculations and
predictions are best when samples are drawn close to steady state, after 3-5 doses.

*Dosing for Trough goals:* Trough after 3-5 doses.

*Dosing for
AUC goals:*
Draw both a peak and trough after the same dose. Peak post distribution: 2 hours
post completion of infusion, Trough before the next dose. Calculating the AUC is
the most accurate with a peak and trough, less accurate with a trough level, and
least accurate with a peak. The chance of inappropriate dosage adjustments is
lowest with a peak and trough analysis and highest with a peak analysis. Using a peak for AUC dosing is
not recommended as the information supplied is of low quality. If the desired
AUC range is 500-600 using a trough is not recommended as the chance of
inappropriate dosage adjustment is higher than using a peak and trough. See the
Monte Carlo
Analysis for details.

Hemodialysis: AUC Dosing: Peak 2 hours after completion of infusion, trough
before next HD. If levels after drawn after dialysis wait at least 6 hours post dialysis,
as levels will be falsely low, and will increase over time due to
redistribution from tissues. The redistribution phase may last up to 12 hours.
Levels increase 20-40% post redistribution after HD. A random level after the loading
dose may be helpful to ensure
an adequate load has been given
then a peak and trough level after the second hemodialysis maintenance dose.

**Pharmacokinetic Model: **A** **one-compartment open model is most often
used, but peak levels must be drawn after the distribution phase as noted above.** **Vancomycin has been modeled with 1, 2 and, 3 compartment models. If the peak is
drawn 2 hours after the end of an infusion (post-infusion) a one-compartment model is adequate for dosage
predictions and AUC calculations.

**Dosage Calculations: **

**Lean Body Weight: **

LBW_{(kg)}
Adult Males (18 years and older) in kg: 50 kg + 2.3*(Height in inches greater
than 60 inches)

LBW_{(kg)} Adult Female (18 years and older): 45.5 + 2.3*(Height in
inches greater than 60 inches)

Body Surface Area in Meters Squared = ((Weight in kg)^{0.425})*((Height
in centimeters)^{0.725})*(71.84/10000)

Dosing Weight_{(kg)} = TBW_{kg}

**Creatinine Clearance: **

Adult
Males: Creatinine Clearance _{(mL/min)}= (140-age_{(years)})*(LBW
or actual weight if lower) /(serum creatinine_{(mg/dl)}*72)

Adult
Females: Creatinine Clearance _{(mL/min)} = 0.85 *( (140-age_{(years)})*(LBW
or actual weight if lower)/(serum creatinine_{(mg/dl)}*72))

Crcl_{(ml/min/1.73 meters2)} = above *1.73/(BSA of patient)

Serum creatinine
is rounded up to 0.7 mg/dL for all adult patients at my institution without paralysis or malnutrition.
LBW is recommended to be used in the creatinine clearance equations, even in
obese patients, as dosing predictions are improved. The equation below was
derived using the lower of LBW or actual body weight in the calculation of
creatinine clearance and with the serum creatinine rounding practice as
described above.

**K**_{(1/hours)}= (0.00107*Crcl_{(ml/min/1.73
meters2)} + 0.0052, Example of Renal
function versus K and Half-Life

**Tau**_{(hours)} = ((ln(Cmaxxss_{(mcg/ml)} desired)/Cminss_{(mcg/ml)} desired))/K) + T'

**Vd**_{(L)} = 0.65*Dosing weght_{(kg)}

**Loading Dose _{(mg)}** = Cp

**Vancomycin Use in Hemodialysis Patients:**

**Drug removal or clearance by dialysis is
determined by the type of dialyzer (high flux, low flux), blood and dialysate
flow during dialysis, duration of dialysis, and frequency of dialysis. The
clearance for the same dialyzer unit using the same blood flow and dialysate
flow rates in patients of various body sizes, in the same physiologic condition,
is the same. Dialysis clearance is not weight-related. **

The fraction eliminated during dialysis is 1-exp(-Clearance Dialysis + Clearance Renal)* Length of Dialysis(hours) /Vd

As the volume of distribution increases due to increasing
body size the fraction eliminated during dialysis decreases as does the fraction
eliminated between dialysis sessions. The post-dialysis level increases with
increasing Vd. The required peak to maintain the desired trough decreases
as Vd increases due to elimination rate decline. This all couples in the
replacement dose calculations. High post-HD levels and lower required peaks for
large patients cause the calculated required replacement dose to maintain the desired pre-HD trough to be similar to smaller patients. The graphic below
demonstrates the effects of Vd on elimination and the effect of Vd on the
replacement dose. **Note that the replacement dose is basically the same
for the various patient weights**.

The AUC calculated is greater than 500 mg*hr/L per 24 hours with troughs of 20 mg/L. The AUC calculated is greater than 600 mg*hr/L per 24 hours for troughs of 25 mcg/ml.

Replacement dose calculation:

The replacement dose replaces that which is removed during dialysis plus the amount lost between dialysis sessions.

The peak required to achieve the pre dialysis trough desired = Pre HD Trough Desired / [exp((-Clearance Renal/Vd) *(Time Between HD Sessions(Hours) - Length of Dialysis(hours)))]

Post HD Level = Pre HD Trough Desired*exp(-(Clearance HD +Clearance Renal)*Length of Dialysis/Vd)

Post HD replacement dose (mg) = (Peak Required to Maintain PreHD trough - Post HD level)*Vd(liters)

The following educational tool may be used to observe the effects of length of dialysis, time between dialysis sessions, desired pre-HD trough, and volume of distribution on the post-HD dose required to maintain the desired pre-HD level.

The Vancomycin Elimination During and Between Dialysis Sessions In High Flux Dialysis Patients Dosed Once Dialysis Complete may be downloaded (Excel File). This tool has been updated to demonstrate the impact of length of dialysis, frequency of dialysis, HD clearance, and residual renal function on required post-HD dose.

As patient weight increases so does their volume of distribution. The loading
dose is related to the weight and Vd.** If a patient receives a loading
dose and is dialyzed the same day the replacement dose after dialysis would be
the amount lost during dialysis and is less than the normal maintenance dose.**

Clearance is unrelated to weight and the elimination rate constant decreases as
weight increases (K=Cl/Vd). As patient weight increases the total amount of drug
in the body must increase to maintain the same level. These factors and the
limited duration of dialysis cause the amount of drug lost during dialysis not
to change much for varying weights and maintenance doses are similar.

Even though renal clearance is very low compared to dialysis clearance the time
for renal clearance is much longer and a greater amount of drug is eliminated
between dialysis sessions than during dialysis.

Length of dialysis, HD clearance, residual renal function, and frequency of
dialysis impact maintenance dose requirements. More frequent dialysis schedules
(daily) require lower maintenance doses as less renal elimination occurs.

Vd, HD clearance,
and renal clearance have little impact on the AUC if the
dose is adjusted to maintain the same trough.

**The desired/obtained trough has the greatest impact on AUC. Target
troughs of 15 -20 mcg/ml give AUCs ~ 400-600 for most weights and are
recommended in the guidelines. **

Higher troughs produced AUCs above 600 mg*hour/L per 24 hours with the potential
to impact residual renal function. Quality of life is better in HD patients with
higher residual renal function. Overdosing or excessive AUCs should be avoided
to minimize the impact on residual renal function.

**Dialysis Dosing - Dose During High Flux Dialysis**

Approximately 30% of the infused dose of vancomycin is
removed if given during dialysis. Residual renal function impacts vancomycin
levels and the appropriate maintenance dose. If residual creatinine
clearance is 5 ml/min the maintenance dose would need to be increased by 200 mg
and 400 mg if creatinine clearance is 10 ml/min to obtain equivalent levels to a patient without
residual renal function. The following chart demonstrates serum levels during a
typical three-times-a-week dialysis scenario (M/W/F or T/Th/Sat) with 750 mg
during the last hour of
each dialysis without a loading dose being administered. The method of
superposition was used to calculate levels. Note weight has little impact on the
steady state levels achieved. As weight increases K decreases and T_{1/2} increases
due to increasing volume of distribution with heavier patients reaching steady
state later, but with similar levels as smaller patients. This highlights the
need to give adequate loading doses, otherwise, initial levels will be low
leading to too high of a maintenance dose being ordered.

Elimination occurs during and between dialysis. Bolus
dosing equations may be applied.

Cpmaxss = S*F*D/(Vd*(1-e^{(-((Krenal*Tau)+(Kdialysis*Tdialysis))})),
assuming dialysis every Tau

Cpminsspredialysis = Cpmaxss*e^{(-Krenal*(Tau-Tdialysis))}
, assume trough drawn just before dialysis and dialysis is at end of dosage
interval.

As dialysis is usually 3 days a week the method of superposition would be give a more accurate
representation of levels.

Cpmax after Dose1-3 = S*F*D/(Vd*(1-e^{(-((Krenal*7*24)+(Kdialysis*Tdialysis*3))})),
each dose administered once weekly, with 3 dialysis sessions.

The highest level of the week is after the
dose on the last dialysis day of M/W/F or T/Th/S series.
The highest trough is before the third dialysis in the series. The lowest tough is
before the first dialysis in the series.

Highest Peak
in the series. Dose1 is Monday or Tuesday depending on series.

Cmax1
=D1/(Vd*(1-e^{(-((Krenal*7*24)+(Kdialysis*Tdialysis*3)))}))e^{(-(Krenal*24*4+Kdialysis*Tdialysis*2))
}

Cmax2 =D2/(Vd*(1-e^{(-((Krenal*7*24)+(Kdialysis*Tdialysis*3)))}))e^{(-(Krenal*24*2+Kdialysis*Tdialysis*1))}

Cmax3 =D3/(Vd*(1-e^{(-((Krenal*7*24)+(Kdialysis*Tdialysis*3)))}))

*Highest Cmaxss* in series =
Cmax1+Cmax2+Cmax3*Lowest Trough* in series is just before first
dialysis is the series = *Highest Cmaxss in series**e^{(-(Krenal*(3*24)-Tdialysis))}

The lowest trough and peak is just before and after the
dose in the first dialysis in
M/W/F or T/Th/S
series.

Lowest Peak in the series. Dose1
is Wednesday or Thursday in the series.

Cmax1 =D1/(Vd*(1-e^{(-((Krenal*7*24)+(Kdialysis*Tdialysis*3)))}))e^{(-(Krenal*24*5+Kdialysis*Tdialysis*2))}

Cmax2 =D2/(Vd*(1-e^{(-((Krenal*7*24)+(Kdialysis*Tdialysis*3)))}))e^{(-(Krenal*24*3+Kdialysis*Tdialysis*1))}

Cmax3 =D3/(Vd*(1-e^{(-((Krenal*7*24)+(Kdialysis*Tdialysis*3)))}))

*Lowest
Cmaxss in series* = Cmax1+Cmax2+Cmax3

The highest trough is just
before the third dialysis in
M/W/F or T/Th/S
series.

Highest trough in the series.
Dose1 is Friday or Saturday in the series.

Cmax1 =D1/(Vd*(1-e^{(-((Krenal*7*24)+(Kdialysis*Tdialysis*3)))}))e^{(-(Krenal*24*5+Kdialysis*Tdialysis*2))}

Cmax2 =D2/(Vd*(1-e^{(-((Krenal*7*24)+(Kdialysis*Tdialysis*3)))}))e^{(-(Krenal*24*2+Kdialysis*Tdialysis*1))}

Cmax3 =D3/(Vd*(1-e^{(-((Krenal*7*24)+(Kdialysis*Tdialysis*3)))}))

*Cmaxss after middle dose in series* = Cmax1+Cmax2+Cmax3 *Highest trough
in series* = Cmax after middle dose *e^{(-(Krenal*(2*24)-Tdialysis))}

**Serum sampling for dialysis**

**
Vancomycin Medication Usage Evaluation - Dose
During Dialysis (Printable
Copy)**

**
Vancomycin Medication Usage Evaluation - Vancomycin Dose After High Flux Dialysis
(Printable Copy)**

**Comparison of Vancomycin Dosing Predictions For A One-Compartment Open
Model Versus**** ****Optimized Goti
and Carreno Two-Compartment Open Models 3/2023**

**
Vancomycin Dosing Predictions One-Compartment Open Model Versus Two-Compartment
Open Models
(Printable Copy)**

**
Comparison of Vancomycin Dosing Predictions for
a One-Compartment Open Model
Versus Optimize Goti and Carreno Two-Compartment Open Models During A Concurrent
MUE
(Printable Copy)**

Optimized Carreno Model for All Patients

Optimized Goti Model for Patients BMI less than 30

This site is developed and maintained for educational use. No warranties are expressed or implied.

If you have questions or suggestions concerning the dosing tools please contact
Marshall Pierce PharmD.

Please help support the development and maintenance of this educational site.
Donate at PayPal

© 2020 Marshall Pierce