TITLE: Aminoglycoside Dosing (Extended Interval / Conventional) Adult

PURPOSE:

To provide guidelines for the management of aminoglycosides dosed conventionally and via
extended interval in Adult patients admitted to SHMC. Aminoglycosides continue to play an
important role in the management of life threatening bacterial infections. However, since
aminoglycosides are not innocuous agents, inappropriate dosing and monitoring can lead to long-
term complications in patients whom receive aminoglycosides.

Appropriate aminoglycoside dosing decreases but does not always prevent the potential risk for
irreversible oto- and nephrotoxicity in patients receiving therapy.

REQUIREMENTS:

Pharmacist / Pharmacy Interns will assess all patients, regardless of pharmacy being consulted,
initiated on an aminoglycoside while admitted to SHMC for appropriateness.

PROCEDURE:
1) Assessment:
a) Upon receipt of an order for an aminoglycoside, (either per pharmacy or physician)
dosing the Pharmacist / Pharmacy Student / Pharmacy Intern, will assess the dosing
regimen based on but not limited to the following:
i) Patient Specific Factors
(1) Age
(2) Weight
(3) Site and Severity of Infection
(4) Fluid Status
(a) Fluid overloaded due to:
(i) 3rd spacing fluid
(ii) Ascities
(iii)Fluid resuscitation
(5) Concurrent drug therapy
(6) Concurrent disease states
(7) Culture and Susceptibility Data

2) Dosing: Treatment of Gram Negative Infection

a) Calculation of Dosing Body Weight (DBW)
i) Step 1: Calculate ideal body weight (IBW)
(1) Males = 50 + (2.3 x inches greater than 5 feet)
(2) Females = 45 + (2.3 x inches greater than 5 feet)
(3) If patient less than 5 feet subtract [2.3(every inch less than 5 feet)]
ii) Step 2: If actual body weight (ABW) is greater than 120% of IBW then calculate
dosing body weight (DW)
(1) IBW x 1.2
 (2) DW= IBW + [0.4 (Actual Body Weight - IBW)
iii) If ABW is less than IBW x 1.2, use ABW
b) Extended Interval Dosing will be used for all patients without exclusions criteria
i) Exclusion Criteria
(1) Hypersensitivity to aminoglycosides
(2) Pregnancy
(3) Renal impairment < 40 ml/min or on dialysis
(4) Gram positive infections
(5) Burn patients
(6) Gross ascites
(7) Fluid overloaded
(8) Evidence of hearing loss or vestibular damage
(9) CNS Infections
(10) Cystic Fibrosis See Dosing Recommendations below
(11) Amikacin (No published dosing recommendations)
ii) Extended Interval Dosing Algorithm:
(1) Dosing per Gilbert nomogram for gentamicin/tobramycin will be initiated at 5
mg/kg DBW
(a) Dosing Nomogram
Dosage
Est CrCl* Interval Dose T Estimated serum level*** mcg/mL at:
(mL/min) (hrs) (mg/kg)** (hrs) 1hr 12hrs 18hrs 24hrs

90-100 24 5 2.5 20 1.0 <1

80-89 24 5 3.1 20 2.0 <1
70-79 24 5 3.4 20 2.5 <1
60-69 24 4 3.9 16 2.0 <1
50-59 24 4 4.5 16 3.0 1.5
40-49 24 3.5 5.3 14 3.5 1.5

c) Conventional Dosing Recommendations:

i) Calculate Dosing Body Weight per part (a) of the procedure.
ii) For Empiric Dosing MathMenu should be utilized.
(1) If MathMenu is not available use the following tables for empiric dosing

Gentamicin/ Amikacin
Tobramycin
Loading Dose (mg/Kg) 2 10
Initial maintenance Dose
1.7 7.5
(mg/Kg/dose)

Initial Dosing frequency: <65 yo: q8hr

Normal renal function > 65 yo: q12hr
 (Clcr > 80 mL/min)

Clcr Interval
65-80 q12hr
Initial Dosing Frequency: 50-64 q24h
Reduced renal function 35-50 q36h
(Clcr < 80 mL/min) 20-34 q48
q72h (post
<20 dialysis)

d) Patient Specific Dosing:

i) When obtained levels are outside the desired goal ranges then GlobalRPH may be
utilized to help determine a patient specific dosing regimen.

e) Targeted Concentrations: Conventional Dosing

i) Based on
Peak (mg/L) Trough (mg/L)
Gentamicin / Tobramycin
Serious Gram Negative
Infection 8-10 <1
Moderate Gram Negative
Infection 6-8 <1
Uncomplicated UTI 4-5 <1
Synergy in Gram Positive
Infections Gentamicin Only 3-5 <1

Amikacin 20-30 1-4

ii) Dosing will be adjusted to maintain a trough of less than 1 mcg / mL.

3) Special Populations:
a) Hemodialysis (HD) Patients
i) Dosing
(1) Conventional dosing should be utilized to achieved concentrations noted above
(2) All doses should be given post HD
(3) Dialysis uses a High Flux Hemodialysis membrane for patients at SHMC
ii) Monitoring
(1) Post Hemodialysis levels should be obtained at least 4 hours after the end of
dialysis to allow for redistribution from the 3rd space
(2) If levels are drawn pre-dialysis expect a reduction in serum concentration by
about 50%
b) Cystic Fibrosis Patients
 i) Dosing:
(1) 10 mg/kg/day based on dosing body weight
ii) Reason for this is because of the increased metabolic rate in this patient population
iii) Monitoring is the same as other patients receiving extended interval aminoglycosides
c) Gram Positive Synergy
i) Only gentamicin is indicated for synergy dosing in gram positive infections
ii) Dosing
(1) 1 mg/kg q8 hrs unless renal function warrants less frequent dosing
iii) Monitoring
(1) Not routinely warranted target concentrations if drawn are listed above
4) Administration
i) Doses should be administered over at least 60 min when using extended interval
regimen.

5) Monitoring:
a) Extended Interval
i) Obtain a random level 14-16 hours after the end of infusion
(1) If level less than 1 mcg/mL continue dosing regimen
(2) If the random level is greater than 1 mcg/mL, then draw a second level and
evaluate pharmacokinectically to determine appropriate regimen
b) Conventional Dosing Regimens
i) Serum Concentrations
(1) Should be drawn when steady state is reached; around 4th dose
(2) Peaks should be drawn
(a) Approximately 15 min after the end of a 60 min infusion time
(3) Trough Concentration
(a) Draw 30 minutes prior to the infusion of the next dose
(4) Levels will be drawn at a minimum of once per week, more frequent monitoring
will be at the discretion of the clinical pharmacist.
ii) Laboratory
(1) BUN and serum creatinine
(a) At a minimum of every 3 days
(2) Urine output
(3) Urinalysis should be noted if obtained by the MD
(a) Request if patient showing signs of nephrotoxicity
(i) Proteinuria
(ii) Casts hyaline and granular
c) Patients will also be monitored for other signs and symptoms of ototoxicity via chart
review and/or patient interview.
i) These will include, but not limited to
(1) Hearing loss
(2) Dizziness or vertigo
(3) Tinnitus
d) The pharmacist will re-evaluate therapy after 7 days. If no duration has been noted the
pharmacist will contact the physician for duration of therapy.
 i) If the physician wishes to continue therapy, they should be made aware of the
increased potential for adverse reactions.

DEFINITIONS:
Aminoglycisides amikacin, gentamicin, and tobramycin.

REFERENCES:

HELP:

Approval Summary
Policy Writer
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