Pharmacokinetics in children

The median steady state exposure in children aged 6-17 yrs was 20% lower than in adults. In children aged 2-6, it was as much as 40% lower [SmPC]

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

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

Inflammatory bowel disease (IBD), sarcoid-related uveitis, juvenile Idiopathic arthritis (JIA), hereditary autoinflammatory conditions including Blau syndrome

Intravenous 1 year up to 18 years [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [17] [18] [19] [20] [21] 5 mg/kg/dose in weeks 0, 2 and 6. And then every 8 weeks.. Allow the infusion to run in over a period of 2 hours. The administration frequency depends on the clinical response. If necessary, adjust the dosage interval per patient to maintain the clinical response. The literature describes dosages of up to 20 mg/kg/4 weeks. For children with severe inflammatory bowel disease (IBD) and IBD patients < 10 years of age, higher doses (up to 10 mg/kg/dose) may be required at initiation of therapy (Jongsma 2020; Winter 2020).

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.

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

General: infusion reactions, antibodies against infliximab. In Crohn's disease: anaemia, blood in the faeces, leukopenia, flushing, viral/bacterial infections, neutropenia, bone fractures and allergic reactions have been reported more often in children. In ulcerative colitis: upper respiratory tract infections, pharyngitis, abdominal pain, fever and headache are commonest in children.

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

The risk of malignancies or hepatosplenic T-cell lymphoma developing in children and adolescents who have been treated with TNF blockers cannot be excluded.

 

Interactions

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

Other immunosuppressants
	Azathioprine Related Medicines Menu">	L04AX01
	Methotrexate Related Medicines Menu">	L04AX03

Tumor necrosis factor alpha (TNF-alpha) inhibitors
	Adalimumab Related Medicines Menu">	L04AB04
	Etanercept Related Medicines Menu">	L04AB01

Calcineurin inhibitors
	Ciclosporin Related Medicines Menu">	L04AD01
	Tacrolimus Related Medicines Menu">	L04AD02

Mammalian target of rapamycin (mTOR) kinase inhibitors
	Everolimus Related Medicines Menu">	L04AH02

References

1. Centocor BV, SPC Remicade (EU/1/99/116/001-005) 12-12-2018, www.ema.europa.eu
2. Nederlandse Vereniging voor Kindergeneeskunde, CBO Richtlijn Diagnostiek en behandeling van Inflammatoire darmziekten bij Kinderen,, 2008, 111-116
3. Beresford MW et al. , New advances in the management of juvenile idiopathic arthritis--2: the era of biologicals., Arch Dis Child Educ Pract Ed. , 2009 , Oct;94(5), 151-6
4. Kahn P et al. , Favorable response to high-dose infliximab for refractory childhood uveitis., Ophthalmology. , 2006 , May;113(5):, 860-4.e2
5. Lahdenne P et al. , Infliximab or etanercept in the treatment of children with refractory juvenile idiopathic arthritis: an open label study., Ann Rheum Dis., 2003 , Mar;62(3), 245-7
6. Levälampi T et al. , Effects of infliximab on cytokines, myeloperoxidase, and soluble adhesion molecules in patients with juvenile idiopathic arthritis., Scand J Rheumatol. , 2007 , May-Jun;36(3), 189-93
7. Milman N et al. , Favourable effect of TNF-alpha inhibitor (infliximab) on Blau syndrome in monozygotic twins with a de novo CARD15 mutation. , APMIS. , 2006 , Dec;114(12), 912-9
8. Petiti Martin G et al. , Misdiagnosed childhood sarcoidosis as non-Langerhans' cell histiocytosis treated with tumor necrosis factors-? antagonists., An Pediatr (Barc). , 2012 , Oct;77(4), 267-71
9. Ruperto N et al. , A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis., Arthritis Rheum. , 2007 , Sep;56(9), 3096-106
10. Ruperto N et al. , Long-term efficacy and safety of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis: findings from an open-label treatment extension. , Ann Rheum Dis., 2010, Apr;69(4), 718-22
11. Simonini G et al. , Prevention of flare recurrences in childhood-refractory chronic uveitis: an open-label comparative study of adalimumab versus infliximab., Arthritis Care Res (Hoboken). , 2011 , Apr;63(4), 612-8
12. Tynjälä P et al. , Drug survival of the first and second course of anti-tumour necrosis factor agents in juvenile idiopathic arthritis., Ann Rheum Dis., 2009 , Apr;68(4), 552-7
13. Pfizer, SmPC Inflectra 100 mg Pulver zur Herstellung einer Infusionslösung (EU/1/13/854/001, EU/1/13/854/002,EU/1/13/854/003, EU/1/13/854/004, EU/1/13/854/005), 02/2018
14. MSD, SmPC Remicade 100mg Pulver zur Herstellung einer Infusionslösung (EU/1/99/116/001;EU/1/99/116/002;EU/1/99/116/003;EU/1/99/116/004;EU/1/99/116/005), 03/2018
15. DAZ.online, Individuell für Kinder, Accessed May 14, 2018
16. Breitkreutz J and Boos J, Paediatric and geriatric drug delivery. - PubMed - NCBI, Accessed May 14, 2018
17. Jongsma, M. M. E., et al. , First-line treatment with infliximab versus conventional treatment in children with newly diagnosed moderate-to-severe Crohn's disease: an open-label multicentre randomised controlled trial., Gut, 2020, Online ahead of print
18. van Rheenen, P. F., et al. , The Medical Management of Paediatric Crohn's Disease: an ECCO-ESPGHAN Guideline Update, J Crohns Colitis, 2020, Online ahead of print.
19. Walters, T. D., et al. , Increased effectiveness of early therapy with anti-tumor necrosis factor-α vs an immunomodulator in children with Crohn's disease, Gastroenterology, 2014, 146(2), 383-91
20. Lee, Y. M., et al. , Infliximab "Top-Down" Strategy is Superior to "Step-Up" in Maintaining Long-Term Remission in the Treatment of Pediatric Crohn Disease, J Pediatr Gastroenterol Nutr, 2015, 60(6), 737-43
21. Kang, B., et al. , Mucosal Healing in Paediatric Patients with Moderate-to-Severe Luminal Crohn's Disease Under Combined Immunosuppression: Escalation versus Early Treatment., J Crohns Coliti, 2016, s10 (11), 1279-1286
22. Jongsma, M. M. E., et al. , Infliximab in young paediatric IBD patients: it is all about the dosing, Eur J Pediatr, 2020, 179 (12), 1935-44
23. Winter, D. A., et al. , Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Infliximab in Pediatric Inflammatory Bowel Disease: A Systematic Review and Revised Dosing Considerations., J Pediatr Gastroenterol Nutr, 2020, 70(6), 763-776

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