Dosages
Side effects in children
Warnings & precautions in children
Contra-indications in children

Interactions
PK
Renal impairment
References

Tobramycin inhalation

Generic name
Tobramycin inhalation
Brand name
ATC Code
J01GB01

Pharmacokinetics in children

The study by Geller et al. shows that in children older than 6 years, the serum concentration is about 0.95 mcg/ml one hour after the inhalation of a single dose of 300 mg. After 20 weeks of therapy, the median serum concentration of tobramycin was 1.05 mcg/ml one hour after administration. The bioavailability was about 11.7%.

In children aged < 6 years, the serum concentration was about 0.6 mcg/ml 1 hour after the inhalation of 300 mg of tobramycin [Rosenfeld et al.].

Elimination: via the urine (systemically resorbed tobramycin) and probably via coughed-up sputum (non-resorbed tobramycin).

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dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

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Available formulations

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Dosages

Infections in cystic fibrosis
  • Inhalation
    • Inhalation powder
      • 6 years up to 18 years
        • (only for chronic infections) 224 mg/day in 2 doses.
        • Duration of treatment:

          A cycle should be followed comprising 28 days of tobramycin inhalation treatment and 28 days without tobramycin inhalation treatment.

        • Directions for administration:

          The time between 2 doses should be 12 hours and may not be less than 6 hours.

        • If there are multiple respiratory treatments, apply them in the following order: bronchodilator, mucolytic, sputum expectoration, other inhalation drugs and lastly tobramycin nebulization solution or inhalation powder.

      • 6 years up to 18 years
        [11]
        • (only for chronic infections) 224 mg/day in 2 doses.
        • Duration of treatment:

          A cycle should be followed comprising 28 days of tobramycin inhalation treatment and 28 days without tobramycin inhalation treatment.

        • Directions for administration:

          The time between 2 doses should be 12 hours and may not be less than 6 hours.

        • If there are multiple respiratory treatments, apply them in the following order: bronchodilator, mucolytic, sputum expectoration, other inhalation drugs and lastly tobramycin nebulization solution or inhalation powder.
Pulmonary Pseudomonas infections in non-CF patients
  • Inhalation
    • 1 month up to 18 years

      • No dose recommendations due to very limited evidence. There are indications that nebulization of tobramycin (80-300 mg twice daily) in non-CF patients leads to a higher systemic intake and renal function disorders. Early level determination is indicated.

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Renal impaiment in children > 3 months

GFR ≥10 ml/min/1.73m2: Dose adjustment not required.

GFR <10 ml/min/1.73m2: A general recommendation on dose adjustment cannot be provided.

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The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

Voice changes, hoarseness, tinnitus, bronchial spasm, increased coughing, increased sputum, sputum discolouration, dyspnoea, pharyngitis. Nephrotoxicity and ototoxicity (loss of high tones), particularly in young children [Guy 2010].

Inhalation of capsules is associated with coughing more often compared to inhalation of solution especially in children younger than 13 years. Coughing wasn't associated with bronchospasm [SmPC].

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The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

Caution is needed in patients who are known or suspected to have kidney, hearing, balance or neuromuscular transmission disorders or severe active haemoptysis. In inhalation it is recommended to check the renal function before starting the treatment and after each 6 full cycles. If tinnitus occurs and/or in patients with a known risk because of earlier, lengthy systemic aminoglycoside treatment, consider an auditory examination.
Signs of bronchial spasm can indicate an allergic reaction, when an allergic reaction is suspected the treatment with tobramycin must be stopped. Sometimes administering a bronchodilator prior to tobramycin inhalation can elevate bronchial spasm complaints.

Tobramycin inhalation fluid is registered for administration with the PariLCPlus nebulizer with matching compressor that can generate a flow of 4-6 litres/min and/or a counter-pressure of 110-217 kPa. When deviating from the registered nebulizer on the doctor’s instructions, the dose recommended for that nebulizer must be used and the effectiveness and safety should be monitored carefully. When using vibrating mesh nebulizers for nebulizing tobramycin, it is known that the mesh may clog, which can result in a reduction of the inhalation dose. The mesh must therefore be cleaned carefully and replaced in good time.

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Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

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Other aminoglycosides
J01GB06
J01GB03
J01GB01

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References

  1. CBO, Richtlijn Diagnostiek en behandeling Cystic Fibrosis, www.cbo.nl, 2007
  2. Bowman CM, The long-term use of inhaled tobramycin in patients with cystic fibrosis, J Cyst Fibros, 2002, Dec;1(Suppl 2), 194-8.
  3. Cheer SM, et al., Inhaled tobramycin (TOBI): a review of its use in the management of Pseudomonas aeruginosa infections in patients with cystic fibrosis, Drugs, 2003, 63, 2501-20
  4. Geller DE, et al, Pharmacokinetics and bioavailability of aerosolized tobramycin in cystic fibrosis, Chest, 2002, 122, 219-26
  5. Gibson RL, et al, Duration of treatment effect after tobramycin solution for inhalation in young children with cystic fibrosis, Pediatr Pulmonol., 2007, 42, 610-23
  6. Gibson RL, et al, Significant microbiological effect of inhaled tobramycin in young children with cystic fibrosis, Am J Respir Crit Care Med., 2003, 167, 841-9
  7. Hodson ME, et al, A randomised clinical trial of nebulised tobramycin or colistin in cystic fibrosis., Eur Respir J., 2002, 20, 658-64
  8. Murphy TD, et al, Treatment with tobramycin solution for inhalation reduces hospitalizations in young CF subjects with mild lung disease, Pediatr Pulmonol, 2004, 38, 314-20
  9. Ramsey BW, et al, Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group., N Engl J Med, 1999, 340, 23-30
  10. Rosenfeld M, et al, Serum and lower respiratory tract drug concentrations after tobramycin inhalation in young children with cystic fibrosis, J Pediatr, 2001, 139, 572-7
  11. Novartis Europharm Limited, SPC TOBI Podhaler (EU 1/10/652/001-003) 20-07-2011, www.ema.europa.eu
  12. Hennig S, et al., Safety of inhaled (Tobi®) and intravenous tobramycin in young children with cystic fibrosis, J Cyst Fibros, 2014, Jul;13(4), 428-34
  13. Abdulhamid I. et al, Elevated serum tobramycin concentrations after treatment with tobramycin inhalation in a preterm infant, Pharmacotherapy, 2008, Jul;28(7), 939-44
  14. De Velde, F et al, High tobramycin serum concentrations after tobramycin inhalation in a child with renal failure., J Antimicrob Chemother, 2014, Nov;69(11):, 3163-4
  15. PARI Pharma GmBH, SmPC Vantobra (EU/1/14/932) 19-03-2015, www.geneesmiddeleninformatiebank.nl
  16. Guy EL et al., Serum tobramycin levels following delivery of tobramycin (Tobi) via eFlow advanced nebuliser in children with cystic fibrosis., J Cyst Fibros., 2010, Jul;9(4), 292-5
  17. Novartis Pharma BV., SmPC Tobi (RVG 25484) 8-3-2013., www.geneesmiddeleninformatiebank.nl
  18. Pacifici GM, Clinical pharmacokinetics of aminoglycosides in the neonate: a review, Eur J Clin Pharmacol, 2009, Apr;65(4), 419-27
  19. Stichting Werkgroep Antibiotica Beleid, Antibioticaboekje: Tobramycine, Geraadpleegd 28 jan 2013, http://customid.duhs.duke.edu/NL/Main/Antibiotic.asp?AntibioticID=205
  20. Eurocept BV, SPC Obracin (RVG 08886), www.cbg-meb.nl, geraadpleegd 28 jan 2013
  21. Novartis, SmPC Tobi Podhaler 28 mg Htkps. m. Plv. z. Inhal. (EU/1/10/652/001/003), https://www.univadis.at/, 02/2016
  22. Cheer SM, et al., Inhaled tobramycin (TOBI): a review of its use in the management of Pseudomonas aeruginosa infections in patients with cystic fibrosis, Drugs, 2003, 63, 2501-20
  23. Hodson ME, et al, A randomised clinical trial of nebulised tobramycin or colistin in cystic fibrosis., Eur Respir J., 2002, 20, 658-64

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Changes

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