Pharmacokinetics in children

Younger children (4 years) have a higher clearance than children of 12 and adults. Simulations show that younger children have lower serum levels than older children and adults [SmPC].

Average steady state trough concentrations in children ranged from 1.6 to 2.1 mcg/ml after 12, 24 and 48 hours. This is comparable to adults [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

Juvenile idiopathic arthritis (JIA), plaque psoriasis, psoriatic arthritis, enthesitis-related arthritis, hereditary autoinflammatory conditions including hyperimmunoglobulin D syndrome (HIDS), TNF receptor-associated periodic syndrome (TRAPS)
Subcutaneous 2 years up to 18 years [1] [8] [9] [10] [11] [12] [13] [14] 0.8 mg/kg/week in 1 - 2 doses per week. Max: 50 mg/week. Max single dose: 50 mg/dose. Set the dose depending on the effect. Younger children may need higher doses because of the higher clearance.

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

In general, side effects in children were similar in frequency and type to those seen in adults.
Headaches, nausea, vomiting and abdominal pain occur more often in children than in adults.

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

It is recommended that paediatric patients should be given all immunizations if possible
as per the applicable immunization guidelines before starting etanercept. There have been reports of IBD and uveitis in JIA patients during etanercept treatment.

The risk of malignancies developing in children and adolescents who have been treated with TNF antagonists cannot be excluded.

Interactions

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

• ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
• IMMUNOSUPPRESSANTS

IMMUNOSUPPRESSANTS

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

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

Tumor necrosis factor alpha (TNF-alpha) inhibitors
	Adalimumab Related Medicines Menu">	L04AB04
	Infliximab Related Medicines Menu">	L04AB02

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. Wyeth Europa Ltd., SmPC Enbrel EU/1/99/126/001 3-2-2010, www.emea.europa.eu
2. Yim DS, et al, Population pharmacokinetic analysis and simulation of the time-concentration profile of etanercept in pediatric patients with juvenile rheumatoid arthritis., J Clin Pharmacol, 2005, Mar;45(3), 246-56
3. Prince FH, et al, Initiating etanercept in a once weekly dose in children with juvenile idiopathic arthritis., Rheumatol Int, 2008, Feb;28(4), 397-8
4. Prince FH, et al, Effectiveness of a once weekly double dose of etanercept in patients with juvenile idiopathic arthritis: a clinical study., Ann Rheum Dis, 2007, May;66(5), 704-5
5. Horneff G, et al, Safety and efficacy of once weekly etanercept 0.8 mg/kg in a multicentre 12 week trial in active polyarticular course juvenile idiopathic arthritis., Rheumatology (Oxford)., 2009, Aug;48(8), 916-9
6. Kuemmerle-Deschner JB, et al, Safety and efficacy of once-weekly application of Etanercept in children with juvenile idiopathic arthritis., Rheumatol Int, 2007, Dec;28(2), 153-6
7. Immunex Corporation, Thousand Oaks, CA,, Product Information: ENBREL(R) subcutaneous injection, etanercept subcutaneous injection., 2008a.
8. Aróstegui JI et al. , Etanercept plus colchicine treatment in a child with tumour necrosis factor receptor-associated periodic syndrome abolishes auto-inflammatory episodes without normalising the subclinical acute phase response. , Eur J Pediatr. , 2005 , Jan;164(1):, 13-6
9. Bulua AC et al. , Efficacy of etanercept in the tumor necrosis factor receptor-associated periodic syndrome: a prospective, open-label, dose-escalation study., Arthritis Rheum. , 2012 , Mar;64(3):, 908-13
10. Cantarini L et al. , Tumour necrosis factor receptor-associated periodic syndrome caused by a rare mutation in the TNFRSF1A gene, and with excellent response to etanercept treatment., Clin Exp Rheumatol., 2009 , Sep-Oct;27(5):, 890-1
11. Dhanrajani A et al. , Modified regimen of etanercept for tumor necrosis factor receptor associated periodic syndrome (TRAPS) like illness., Indian Pediatr., 2014 , Jan;51(1):, 55-7
12. Harambat J et al. , First report of rapidly progressive glomerulonephritis in tumor necrosis factor receptor-associated periodic syndrome., Arthritis Rheum. , 2008 , Oct;58(10), 3275-6
13. Kostjukovits S et al. , Treatment of hyperimmunoglobulinemia D syndrome with biologics in children: review of the literature and Finnish experience., Eur J Pediatr. , 2015 , Feb 27
14. Morbach H et al. , Tumor necrosis factor receptor 1-associated periodic syndrome without fever: cytokine profile before and during etanercept treatment., Rheumatol Int. , 2009 , Dec;30(2):, 207-12

Changes

Therapeutic Drug Monitoring

Overdose