Aminoglycoside& Vancomycin

Dosing..a conversation..

………

Part 1 - dosing considerations -

“All drugs are controlled poisons”.

“Drugs don’t have dosages… ……patients have dosages….”.

Goldilocks Principle

Goldilocks principle states that something must fall

within certain margins, as opposed to reaching

extremes. When the effects of the principle are observed, it

is known as the Goldilocks effect.

Dosing objective: Hit the therapeutic window

> Too much = toxicity.> Right dose: eradicate the bacteria without injuring the patient.> Too little = ineffective.

“Pharmacy to dose”

Essentially 3 things: - a dose - a frequency (interval) - monitoring labs

Dosing our pts is problematicLack of experience/practice on part

of prescribers, nursing staff and pharmacists in dosing aminoglycosides & vancomycin.

Patients difficult to assess, remote to both prescriber & pharmacy staff.

Delay in lab results. We’re not 24/7.Inherently difficult population to

dose (elderly, bedridden, other potentially nephrotoxic medications).

The dose?Dosage based predominantly on:

Size of patientSite of infection

Severity of infectionResistance of organism

Hydration status of patient…and 163 other variables…

The dose?

How much?

Think conceptually

Big people get big doses….

Little people get little doses….

Big dogs get big doses…

Little dogs get little doses…

The interval?

Dosing interval based on:Clearance – the speed at

which the body eliminates the drug (predominantly

renal, with a small amount of clearance from the liver)

Younger patients who are otherwise healthy?

Think shorter dosing intervals (more frequent dosing,i.e., Q4H,Q6H, Q8H).

Elderly patients and patients with renal insufficiency?

Think longer dosing intervals (less frequent dosing, i.e., q12h, q24h, q48h, q72h)…

Quick review of dosing concepts…..

Dose?

Big patients = big doses

Little patients = little doses

Interval?Younger and otherwise healthy patients = more frequent dosing.

Older, elderly patients and patients with renal insufficiency =less frequent dosing.

Serum Creatinine – it’s just a number.Before you put the numbers in the calculator

think about the pt.

If your patient: - has a stable renal function SCr/UOP AND - is within the age range (18-65 years) AND - is reasonably well nourished/hydrated AND - doesn’t have renal disease (i.e., not diabetic, no diuretics, good urine output, etc.) The calculated answer may be reasonably close to actual clearance.

CrCl: which equation??

Simplified 4-variable MDRD study formula?

CKD-EPI equation?

Cockcroft-Gault based on: CG - Total Body Weight? CG - Ideal Body Weight? CG - Adjusted Body Weight? – use this one….

Fudge factor(s)?

→ If the reported SCr is < 1 mg/dL and the patient is: Is older than 65 years of age and/or Is sedentary/bedridden, paralysis and/or Has poor nutritional status and/or Has poor urine output

Fudge factor(s)→ Consider using “1 mg/dL” in your calculations and/or

→“Lowballing” the dose, i.e., - if the recommended peak level for the condition is 8-10 mcg/ml, consider using 6-8 mcg/ml in your calculations. - if the recommended trough level for the condition is <1 mcg/ml, consider using 0.3-0.5 mcg/ml in your calculations.

Why fudge the numbers?For patients:

- who are elderly (>65 years). - who have diminished muscle mass (bedridden, paralysis, malnourished, who are on diuretics, who are volume overloaded, etc.), the calculated CrCl tend to overestimate the actual clearance.

Fudging will give a more conservative dose

Using a larger than true SCr number will result in a lower calculated CrCl (slower clearance).

Fudging will give you a lower dose and/or a longer dosing interval.