Neonatal Drug Therapy Manual

Tobramycin

Disclaimer: Official controlled document is the CHEO and Ottawa Hospital online copy. It is the responsibility of user to ensure that any paper copy version is the same as the online version before use.

Alternate Name(s): 
Tobrex
Classification: 
Antibiotic (aminoglycoside)
Original Date: 
September 2003
Revised Date: 
Sept 2022
Indications: 
  • Treatment of documented or suspected infections caused by susceptible Gram (-) bacilli including Pseudomonas aeruginosa. 
Administration: 
  • IV Intermittent infusion: over 30 minutes
Dosage: 

EXTENDED INTERVAL DOSING: preferred method. SEE BELOW for therapeutic cooling dose

Gestational Age and Post-Natal Age

Dose

Therapeutic Drug Levels1

Preterm

<30 weeks GA

 0- 14 days 5 mg/kg/dose Q48h

 

 

 

Target for Extended-Interval trough concentrations:

  • <2mg/L for pre-third dose (pre-second if applicable)1

 

If renal dysfunction is present,  longer dosing intervals and/or lower doses may be required if the aminoglycoside is to be continued.2 A trough value of ≤1mg/L may be considered as the goal in these certain cases; consult clinical pharmacist. 

>14 days

5 mg/kg/dose 

Q36h

Preterm

30-34 weeks 

GA

0-10 days

5 mg/kg/dose

Q36h

>10 days

5 mg/kg/dose

Q24h

Preterm & Term

> 35 weeks

 

0-7 days

4 mg/kg/dose

Q24h

>7 days

5 mg/kg/dose

Q24h

Therapeutic Cooling dosing for infants

>35 weeks gestation

3 mg/kg/dose given 

once. 

Draw PRE level 24 hours later, and wait for result prior to administration of second dose.

1 TDM may not be necessary if therapy is anticipated to stop at 36-48 hours. A trough level can be obtained prior to the anticipated second dose but may be postponed to pre-third dose if there is no concern for renal dysfunction. Trough levels are obtained 0-60 minutes prior to the next anticipated dose and are a safety measure.

2 This would include neonates with suspected, possible or confirmed hypoxic ischemic events, undergoing therapeutic cooling, fluid imbalance, possible or suspected renal thrombosis, congenital renal anomalies or any other conditions that may be associated with transient or prolonged renal dysfunction.

 

TRADITIONAL DOSING
Gestational Age and Post-Natal Age  Traditional Dose Therapeutic Drug Levels3
Preterm (< 36 weeks GA) 0-14 days < 28 weeks GA 3 mg/kg/dose Q24h

Traditional Dosing (Pre and Post levels obtained after 48 hours if renal function remains normal)

 

Pre (0 - 30 minutes before dose): 0.5 - 2 mg/L

                                        AND

Post (30 minutes after end of a 30 minutes infusion): 5 - 10 mg/L

 

If renal dysfunction is present, consult clinical pharmacist as longer dosing intervals and/or lower doses may be required if the aminoglycoside is to be continued2

 

29-36 weeks GA 3.5 mg/kg/dose Q24h
> 14 days < 28 weeks corrected GA 3-3.5 mg/kg/dose Q18h
> 29 weeks corrected GA 3-3.5 mg/kg/dose Q12h
Term (> 37 weeks GA) 0-7 days > 37 weeks GA 3-3.5 mg/kg/dose Q18h
> 7 days 2.5 mg/kg/dose Q8h4

Traditional Dosing

Pre and Post levels obtained on Day 3. For dosage adjustment and timing of levels in renal impairment, consult pharmacist

2 This would include neonates with suspected, possible or confirmed hypoxic ischemic events, undergoing therapeutic cooling, fluid imbalance, possible or suspected renal thrombosis, congenital renal anomalies or any other conditions that may be associated with transient or prolonged renal dysfunction.

3TDM may not be necessary if therapy is anticipated to stop at 36-48 hours. Trough (pre) AND peak (post) levels are recommended for traditional dosing. 

Typically, we would start extended interval dosing here (see Extended Interval Chart above), which is the preferred method in normal renal function 

 

Current dosing for infants >35 weeks gestation undergoing therapeutic cooling:

  • ​3 mg/kg/dose given once. 
    Draw PRE level 24 hours later, and wait for result prior to administration of second dose.

 

Side Effects: 
  • Hematologic: anemia, granulocytopenia, thrombocytopenia
  • Otic: vestibular/auditory toxicity
  • Renal: nephrotoxicity, increase risk with concurrent use of nephrotoxic drugs (eg. furosemide, indomethacin) 
Parameters to Monitor: 
  • Renal: serum creatinine, urea, urine output
  • Therapeutic drug levels: see tables

** When checking level, administer next dose as scheduled. Do not wait for levels to be reported unless otherwise advised

Reconstitution and Stability: 

IV intermittent infusion:

CHEO:

  • Tobramycin 40 mg/mL (doses < 10 mg)
    • Take 1 mL (40 mg) and add to 39 mL D5W
    • Final concentration: 1 mg/mL
  • Tobramycin 40 mg/mL (doses > 10 mg)
    • Take 1 mL (40 mg) and add to 3 mL D5W or 0.9% NaCl
    • Final concentration: 10 mg/mL

TOH:

  • Tobramycin 40 mg/mL
    • Take 1 mL (40 mg) and add to 39 mL D5W

    • Final concentration: 1 mg/mL

Compatibility: 

- Solutions Compatible: D5W, D10W, 0.9% NaCl, dextrose-saline combinations

- Y-site Compatible: acyclovir, dexmedetomidine, fentanyl, fluconazole, heparin (low concentrations of 0.5 to 1 unit/mL that are used to maintain IV line patency), hydromorphone, midazolam, milrinone, morphine, TPN (amino acids- dextrose)

- Incompatible: heparin (concentration greater than 1 unit/mL), indomethacin, piperacillin/tazobactam, SMOF

  • Direct contact of a penicillin antibiotic (eg, ampicillin, piperacillin) with an aminoglycoside (gentamicin, tobramycin) may cause inactivation.  Rinse thoroughly between both administration if given via the same line. 

 

Notes: 
  • Extended interval dosing is being introduced to help optimize efficacy and minimize aminoglycoside toxicity in this patient population
  • A trough level can be obtained prior to the anticipated second dose but may be postponed to pre-third dose if there is no concern for renal dysfunction and if it is anticipated that the duration will be > 48 hours. 
  • Peak concentrations 6-12 mg/L are generally obtained to see if targets for efficacy are being attained or for pharmacokinetic modeling purposes.
References: 

-Taketomo CK, Hodding JH, Kraus DM. Pediatric and Neonatal Dosage Handbook 22nd Editions. Hudson: Lexi-Comp Inc.; 2015

- Low YS, Tan SL, Wan A. Extended-Interval Gentamicin Dosing in Achieving Therapeutic Concentrations in Malaysian Neonates. J Pediatr Pharmacol Ther. 2015. Mar-Apr, 20 (2): 119-127.

- Bergenwall M, Walker SAN, Elligsen M, Iaboni DC, Findlater C, Seto W, Ng E. Optimizing gentamicin conventional and extended interval dosing in neonates using Monte Carlo simulation - a retrospective study. BMC Pediatr. 2019 Sep 6;19(1):318. 

- König K, Lim A, Miller A, Saker S, Guy KJ, Barfield CP. Gentamicin trough levels using a simplified extended-interval dosing regimen in preterm and term newborns. Eur J Pediatr. 2015 May;174(5):669-73. doi: 10.1007/s00431-014-2450-z. 

- van Maarseveen EM, Sprij A, Touw DJ. Extended-Interval Dosing of Gentamicin Aiming for a Drug-Free Period in Neonates: A Prospective Cohort Study. Ther Drug Monit. 2016 Jun;38(3):402-6. 

-Red Book (Committee on Infectious Diseases, American Academy of Pediatrics); David W. Kimberlin, MD, FAAP, Elizabeth D. Barnett, MD, FAAP, Ruth Lynfield, MD, FAAP, Mark H. Sawyer, MD, FAAP. American Academy of Pediatrics. Publication date: January 2021.

-American Society on Health-System Pharmacists (ASHP). Handbook on Injectable Drugs. 19thEdition. Bethesda: American Society of Health-System Pharmacists; 2017

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