Antimicrobial Prescribing Guidelines
Tobramycin (Paediatric version of Neutropenic Sepsis Guideline)

• Once Daily Tobramycin Dosing and Administration
• Once Daily Tobramycin Therapeutic Drug Monitoring (checking levels)
• Divided daily dosing Tobramycin Dosing and Administration
• Divided daily dosing Tobramycin Therapeutic Drug Monitoring (checking levels)
• Interpretation of Tobramycin doses
• Adjustment of Tobramycin Divided daily dosing
• Tobramycin dosing in renal impairment

This document provides guidance for pharmacists regarding the situations where tobramycin is recommended in the paediatric version of the neutropenic sepsis guideline.

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Once Daily Tobramycin Dosing and Administration

NB: This dosing schedule is for patients treated at Leeds General Infirmary Only
Once daily tobramycin for children < 13 years of age

Dose
First course of once daily tobramycin

• Dose 12mg/kg once daily as a 30 minute IV infusion
• Maximum starting dose = 480mg/day
• If the child’s weight exceeds the 98th centile then the dose MUST be calculated from the 98th centile weight on the relevant growth chart.

Second and subsequent courses
Either: If the dose of tobramycin was not modified from 12mg/kg in the last cycle: Prescribe 12mg/kg once daily.
Or: If the dose of tobramycin was reduced in the last cycle: Prescribe the reduced dose from the last course. This dose will be documented in the child’s notes from the previous admission for neutropenic fever.

NB: Always confirm that there has been no significant change in renal function since the last course. If any concerns then the dosage MUST be discussed with an oncology pharmacist or consultant.

Inclusion Criteria

• Patient > one year of age
• Patient must have a GFR (estimated or measured) of > 60mL/min/1.73m²
• Either use recent DTPA result or Est. GFR =

  40 x height (cm)

  creatinine (micromol/L)

Exclusion Criteria

• Patient with GFR < 60mL/min/1.73m²
• Patient on concomitant ciclosporin

Patients who are excluded from once daily tobramycin should be prescribed divided daily dose regimen of tobramycin (See below)

Administration

• IV Infusion in 20mL of sodium chloride 0.9%.
• Infusion rate: Infuse at 50 mL/hr for 30 minutes.
• This allows the 20mL drug volume plus a 5mL flush to be given over 30 minutes

Once Daily Tobramycin for children 13 years old and above. For patients treated at LTHT and shared care centres.

Dose

• Dose 7mg/kg once a day, given as a 30 minute IV infusion.
• If obese, (> 98th centile), then calculate the dose from the 98th centile weight on the relevant growth chart.

Inclusion Criteria

• Patient must have GFR (estimated or measured) of > 60mL/min/1.73m²
• Use recent DTPA result if available.
• If 18 years or below use equation creatinine clearance =

  40 x height (cm)

  creatinine (micromol/l)

• If > 18 years creatinine clearance =

  F x (140 – age) x wt (kg)

  creatinine (micromol/l)

• F= 1.23 for males and 1.04 for females.

Exclusion Criteria

• Patient with GFR < 60mL/min/1.73m²

Patients who are excluded from once daily tobramycin must be started on divided daily dose regimen of tobramycin. (See below)

Administration

• IV Infusion in 20mL of either sodium chloride 0.9% or glucose 5%.
• Infusion rate: Infuse at 50 ml/hr for 30 minutes.
• This allows the 20mL drug volume plus a 5mL flush to be given over 30 minutes

Once Daily Tobramycin for children and adolescents treated at shared care centres ONLY

A lower dose schedule of tobramycin is used at Shared care centres as the laboratories at these sites are unable to process the higher levels of tobramycin associated with the high dose regime. If any queries regarding this once daily protocol please contact paediatric oncology unit at Leeds General Infirmary.

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Once Daily Tobramycin Therapeutic Drug Monitoring (checking levels)

Patients treated at Leeds General Infirmary Only

Once daily tobramycin for children < 13 years of age

Monitoring
NB: State on request card: Four hour level for once daily tobramycin.

First dose of tobramycin only.

• One sample is taken for all patients after the first dose of tobramycin
• Take level four hours after the start of the infusion.
• Obtain tobramycin level before the second dose is given.

If level is 10 or below
Continue at the current dose. No further monitoring is required as long as there is no significant change in renal function. Repeat level if the tobramycin is continued for more than 7 days. Or if there is a significant change in renal function.

If level is greater than 10
Contact a paediatric oncology pharmacist for dosing advice.
Out of hours only: Reduce the dose by the percentage this level is above 10. Take a trough tobramycin concentration 24 hours after the previous dose was given and do not give the reduced tobramycin dose until the pre dose level is < 1.

Monitor serum creatinine daily – if rising serum creatinine then recheck GFR. If GFR < 60mL/min/1.73m² once daily tobramycin must be discontinued and divided daily dosing tobramycin commenced (once tobramycin level is < 1mg/L). Refer to tobramycin dosing guidelines in renal impairment below.

Further levels may be required if significant reduction in renal function. Discuss with pharmacist/consultant.

Example tobramycin dose reduction
Patient weight = 20kg, starting dose of tobramycin = 12mg/kg = 240mg
Estimated creatinine clearance = 95 mL/min/1.73m²
Four hour tobramycin level = 12.5 mg/L

Once Daily Tobramycin for children 13 years old and above. For patients treated at LTHT and shared care centres.

Monitoring
NB: All request cards and bottles MUST be labelled with the relevant pre-prepared labels.

First dose of tobramycin only.

• NB: The exact start and finish time must be recorded on the tobramycin level request card and on the tobramycin level monitoring form.
• Level must be taken 6 hours after the start of the infusion.
• Follow the Hartford Nomogram for adjustment of dose based on the level taken after 6 hours. Contact pharmacist for advice.
• Monitor serum creatinine daily – if rising serum creatinine then recheck GFR. If GFR < 60mL/min/1.73m² once daily tobramycin must be discontinued and divided daily dosing tobramycin commenced (once tobramycin level is < 1mg/L). Refer to tobramycin dosing guidelines in renal impairment below

Using The Hartford Nomogram to review and adjust tobramycin dosing
“Adolescent Patients Only” (Age 13 years and above) at LTHT and patients treated at shared care centres.

The results of the serum monitoring, for Adolescent patients only at LTHT and all patients treated with once daily tobramycin at shared care centres will be evaluated using the Hartford Nomogram (shown below).

• If the level falls in the area designated Q24h then the same dose should be continued on a 24 hour basis.
• If the level falls into the area designated Q36h or Q48h, the interval must be increased to 36 or 48 hours respectively. Continue the same dose.
• If the point is on the line, choose the longer interval.
• If the level is off the nomogram, stop tobramycin and restart once level is <1. Refer to the tobramycin dosing guidelines in renal impairment.
• Contact pharmacist for advice if required.

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Divided daily dosing Tobramycin Dosing and Administration

Dose

• >1mth-40kg: 3mg/kg 8 hourly
• >40kg: 120mg 8 hourly
  (these are starting doses only dose should be adjusted according to levels)

Maximum starting dose 120mg 8 hourly.

Administration

• Slow IV injection 3 to 5 minutes

Check renal function before prescribing. Reduce dose in renal impairment

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Divided daily dosing Tobramycin Therapeutic Drug Monitoring (checking levels)

For multiple daily dose regimens, blood samples should be taken approximately 1 hour after intramuscular or intravenous administration (‘peak’ concentration) and also just before the next dose (‘trough’ concentration).

Monitor at 4th dose. Then TWICE weekly.
Take pre dose level immediately before dose and post dose level one hour after dose.

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Interpretation of Tobramycin doses

The following factors may account for the drug levels obtained and should be considered before altering dosages.

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Adjustment of Tobramycin Divided daily dosing

NB: Aim for a peak level of 7 to 10 mg/L and a trough level of less than 1 mg/L.

Specific advice will be provided for patients with levels outside the target range, by a clinical pharmacist and/or microbiologist.

If the pre-dose (‘trough’) concentration is high, the interval between doses must be increased. If the post-dose (‘peak’) concentration is high, the dose must be decreased.

As a general rule,

If the peak level needs adjusting, the dose of the drug is adjusted.

If the trough level needs adjusting, the dosage interval (i.e. time between doses) needs adjusting.

To be fully understood, the pharmacokinetics of aminoglycosides are complicated and many factors need to be taken into account. However, they can be simplified by assuming that aminoglycosides have “linear kinetics”, i.e. by increasing/decreasing the dose by 25%, the peak and trough will increase/decrease by 25%. For example, if trough is 1 and peak is 6, then increasing the dose by 25% would be expected to give a trough of 1.25 and a peak of 7.5.

Dose increases should be capped at 50% (i.e. new dose =1.5 x old dose).

If the trough is greater than 1mg/L, accumulation is occurring and the dosage interval needs extending, e.g. from every 8 hours to every 12 hours.

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Tobramycin dosing in renal impairment

Tobramycin dose must be reduced in children with renal impairment. The guidelines below can be followed for the initial dose. Adjust the dose depending on drug levels and changes in renal function. Contact Pharmacy for further advice.

Initial Dosing Of Tobramycin In Renal Impairment

Formula to calculate creatinine clearance: For children aged 1 to 18 years