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

Interactions
PK
Renal impairment
References

Colistin

Generic name
Colistin
Brand name
ATC Code
J01XB01

Pharmacokinetics in children

The following kinetic parameters have been observed (after one-time administration):

  IV
(1 dose)		 IV (1 dose) Inhalation (1 dose)
  Neonates
[Nakwan]		 ≥14 years with CF
[Reed]		 ≥12 years with CF
[Ratjen]
Dose 150,000 IU/kg 150,000-210,000 IU/kg 2 million IU
Cmax 3.0 ± 0.7 µg/ml 21.4 ±5 mg/l 0.178 ± 0.018 mg/l
Tmax 1.3 ± 0.9 hours - 1.47 ± 0.16 hours
t½ 9.0 ± 6.5 hours 3.4 ± 1.4 hours 4.09 ± 0.31 hours
Vd 7.7 ± 9.3 l/kg 0.09 ± 0.02 l/kg -
Cl 0.6 ± 0.3 l/h/kg 0.35 ± 0.09 ml/min/kg 787 ± 65.9 ml/min

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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

Severe infections; chronic lung infection with Pseudomonas aeruginosa in cystic fibrosis
  • Intravenous
    • Neonates Gestational age < 37 weeks
      • (Colistimetat sodium) 50.000 - 75.000 IU/kg/day in 3 doses.

      • This dose may be too low, based on the MIC. Higher doses in consultation with a paediatric specialist (infectiologist) who has experience of using colistin for this indication.

    • 1 month up to 18 years and < 40 kg
      [11] [12] [15] [16] [18] [19]
      • (Colistimetat sodium) 75.000 - 150.000 IU/kg/day in 3 doses.

      • There have been reports of doses of > 150,000 IU/kg/day being used in children with cystic fibrosis.

    • 1 month up to 18 years and ≥ 40 kg
      [12]
      • (Colistimetat sodium) 9.000.000 IU/day in 3 doses. Max: 12.000.000 IU/day. In severely ill patients, a loading dose of 9,000,000 IU should be given..
(Chronic) lung infection with Pseudomonas aeruginosa in cystic fibrosis
  • Inhalation
    • Solution for nebulization
      • 1 month up to 2 years
        [7] [11] [12] [14]
        • (Colistimetat sodium) 1.000.000 - 2.000.000 IU/day in 2 doses.
        • Duration of treatment:

          3 months

        • Eradication of an initial infection should be combined with oral ciprofloxacin.

      • 2 years up to 18 years
        [3] [8] [12] [13] [15]
        • (Colistimetat sodium) 2.000.000 - 6.000.000 IU/day in 2 - 3 doses. Max: 2.000.000 IU/dose.
        • Duration of treatment:

          3 months

        • Eradication of an initial infection should be combined with oral ciprofloxacin

    • Inhalation powder
      • ≥ 6 years
        [20]
        • (Colistimetat sodium) 3.325.000 IU/day in 2 doses.
        • Directions for administration:

          Administer using a Turbospin inhaler.

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Renal impaiment in children > 3 months

Dose adjustments are not required for colistin for inhalation.

The following recommendations apply for intravenous colistin:
If a loading dose is given, the loading dose should not be adjusted; the maintenance dose is as follows:
GFR 50-80 ml/min/1.73m²: Dose adjustment is not required
GFR 30-50 ml/min/1.73m²: 60-80% of the normal dose each time and the interval between two doses: 8 hours
GFR 10-30 ml/min/1.73m²: 50-60% of the normal dose each time and the interval between two doses: 8 hours
GFR < 10 ml/min/1.73m²: 40% of the normal dose each time and the interval between two doses: 8 hours

Clinical consequences

Colistin pentasodium mesylate has little effect itself; it is hydrolysed in vivo to colistin. It is primarily excreted in unchanged form in the urine. In patients with reduced renal function, the secretion of colistin pentasodium mesylate decreases. As a result, a larger amount can be converted into colistin. Symptoms of overdose are apnoea, muscular weakness, vertigo, transient paraesthesia of the face, unclear speech, vasomotor instability, vision disorders, confusion, psychosis and renal insufficiency.

Patients on dialysis

Haemodialysis and peritoneal dialysis: 20-45% of the normal dose each time and the interval between two doses: 8 hours

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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

On inhalation [Alothman, Cunningham]: coughing, bronchial spasm, poor sense of taste, painful mouth or throat and hypersensitivity reactions.
On intravenous administration: dose-dependent nephrotoxicity and neurotoxicity. A case of thrombocytopenia has also been described [Kupeli].

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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

Nebulization of colistimethate sodium can trigger coughing or bronchial spasms. For that reason, it is recommended that the first dose should be given under medical supervision and that a bronchodilator should be administered as standard beforehand. Bronchial hyperactivity that continues despite the use of a bronchodilator can indicate an allergic reaction, in which case the use of colistin should be discontinued.
In intravenous administration, the renal function should be checked regularly. On administration by inhalation, the renal function should be checked if reduced renal function is involved. Be aware of the possibility of neurological side effects too.

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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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Glycopeptide antibacterials
J01XA01
Nitrofuran derivatives
J01XE01
Other antibacterials
J01XX08
J01XX01

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References

  1. Alothman GA, et al, Bronchial constriction and inhaled colistin in cystic fibrosis, Chest, 2005, 127, 522-9
  2. Centraal Begeleidings Orgaan (CBO), Richtlijn Diagnostiek en behandeling van Cystic Fibrosis, 2007, Geraadpleegd 17 februari 2010, http://www.cbo.nl/Downloads/466/rl_cf_2007.pdf
  3. Cunningham S, et al, Bronchoconstriction following nebulised colistin in cystic fibrosis, Arch Dis Child, 2001, 84, 432-3
  4. Falagas ME, et al, Systemic colistin use in children without cystic fibrosis: a systematic review of the literature, Int J Antimicrob Agents, 2009, 33, 503.e1-503.e13
  5. Frederiksen B, et al, Antibiotic treatment of initial colonization with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis, Pediatr Pulmonol., 1997, 23, 330-5
  6. Hansen CR, et al, Early aggressive eradication therapy for intermittent Pseudomonas aeruginosa airway colonization in cystic fibrosis patients: 15 years experience., J Cyst Fibros, 2008, 7, 523-30
  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. Ratjen F, et al, Pharmacokinetics of inhaled colistin in patients with cystic fibrosis, J Antimicrob Chemother, 2006, 57, 306-11
  9. Reed MD, et al, The pharmacokinetics of colistin in patients with cystic fibrosis, J Clin Pharmacol, 2001, Jun;41(6), 645-54
  10. Taccetti G, et al, Early eradication therapy against Pseudomonas aeruginosa in cystic fibrosis patients, Eur Respir J, 2005, 26, 458-61
  11. Tamma PD, et al, Use of colistin in children, Pediatr Infect Dis J, 2009, 28, 534-5
  12. Profile Pharma Limited, SmPC Tadim (RVG 106362 en 109891) 29-04-2015, www.geneesmiddeleninformatiebank.nl
  13. Nakwan N et al. , Pharmacokinetics of Colistin Following a Single Dose of Intravenous Colistimethate Sodium in Critically Ill Neonates., Pediatr Infect Dis J., 2016, Jun 7
  14. Proesmans M et al. , Comparison of two treatment regimens for eradication of Pseudomonas aeruginosa infection in children with cystic fibrosis., J Cyst Fibros. , 2013, Jan;12(1), 29-34
  15. Karbuz A et al. , The use of colistin in critically ill children in a pediatric intensive care unit., Pediatr Infect Dis J, 2014, Jan;33(1), e19-24
  16. Kumar PP et al. , Safety and efficacy of intravenous colistin in children., Indian Pediatr., 2015 , Feb;52(2), 129-30
  17. Kupeli S et al. , Colistin-related thrombocytopenia. , Platelets., 2015, 26(8), 812-3
  18. Iosifidis E et al. 2010 Jul;169(7):867-74, Colistin administration to pediatric and neonatal patients., Eur J Pediatr. , 2010, Jul;169(7), 867-74
  19. Al-Iawama M et al. , Intravenous Colistin in the treatment of multidrug-resistant Acinetobacter in neonates. , Ann Clin Microbiol Antimicrob. , 2016 , Feb 12;15, 8
  20. TEVA BV, SmPC Colobreathe (RVG EU/1/11/747/001-003) 26-09-2016, www.geneesmiddeleninformatiebank.nl
  21. TEVA, SmPC Colobreathe 1662500 I.E. Hartkapsel mit Pulver zur Inhalation (EU/1/11/747/001 - 003), 02/2017
  22. CNP, SmPC Diarönt mono 95mg Tabletten (6154074.00.00), 06/2015
  23. Zambo, SmPC Promixin 1 Mio. I.E. Pulver zur Herstellung einer Lösung für einen Vernebler (59210.00.00), 01/2016
  24. TEVA, SmPC Colistin CF 1 Mio. I.E. Pulver und Lösungsmittel zur Herstellung einer Lösung für einen Vernebler (6728664.00.00), 04/2017
  25. Pari, SmPC ColiFin 2 Mio. I.E. Pulver zur Herstellung einer Lösung für einen Vernebler (73870.00.00), 03/2018
  26. Pari, SmPC ColiFin 1 Mio. I.E. Pulver zur Herstellung einer Lösung für einen Vernebler (73869.00.00), 03/2018
  27. Zambo, SmPC Promixin 1 Mio. I.E. Pulver zur Herstellung einer Infusionslösung (85425.00.00), 01/2016
  28. TEVA, SmPC Colist-Infusion 2 Mio. I.E. Pulver zur Herstellung einer Infusionslösung (86684.00.00), 10/2016
  29. TEVA, SmPC Colist-Infusion 1 Mio. I.E. Pulver zur Herstellung einer Infusionslösung (86683.00.00), 10/2016
  30. Infectopharm, SmPC Colistimethat-Natrium 1 Mio. I.E. Pulver zur Herstellung einer Injektions- oder Infusionslösung (84394.00.00), 04/2017
  31. Infectopharm, SmPC ColistiFlex 2 Mio. I.E. Pulver zur Herstellung einer Injektions-, Infusions- oder Inhalationslösung (98050.00.00), 08/2017
  32. Infectopharm, SmPc ColistiFlex 1 Mio. I.E. Pulver zur Herstellung einer Injektions-, Infusions- oder Inhalationslösung (89172.00.00), 01/2018

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Changes

Changes