Pharmacokinetics in children

The following kinetic parameters have been observed in 10 FSGS patients (6-36 years old), including 7 children [Joy]:

	Single dose	Steady state
Tmax	55 hours	34.2 hours
Cmax	9.2 µg/ml	12.8 µg/ml
t½	159 hours	273 hours
Cl/F	20.2 ml/hour	53.2 ml/hour
V/F	3.5 l	6.6 l

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

Crohn’s disease

Subcutaneous ≥ 6 years and < 40 kg [1] Initial dose: Week 0: 40 mg/dose Week 2: 20 mg/dose If a faster response to the therapy is needed: Week 0: 80 mg/dose Week 2: 40 mg/dose Maintenance dose: From  week 4 onwards: 20 mg/dose once every 2 weeks If there is insufficient response to the maintenance dose, the frequency can be increased to once a week ≥ 40 kg [1] Initial dose: Week 0: 80 mg/dose Week 2: 40 mg/dose If a faster response to the therapy is needed: Week 0: 160 mg/dose Week 2: 80 mg/dose Maintenance dose: From week 4 onwards: 40 mg/dose once every 2 weeks. If there is insufficient response to the maintenance dose, the frequency can be increased to once a week.

Polyarticular juvenile idiopathic arthritis, enthesitis-related arthritis, psoriasis, uveitis

Subcutaneous < 30 kg [1] [2] [7] [10] [13] 20 mg/dose 1 x per 2 weken. The manufacturer has stated that a loading dose of 40 mg can be given in juvenile uveitis one week before starting the maintenance treatment. ≥ 30 kg [1] [2] [7] [10] [13] [14] 40 mg/dose 1 x per 2 weken. The manufacturer has stated that a loading dose of 80 mg can be given in juvenile uveitis one week before starting the maintenance treatment.

Other autoinflammatory conditions that do not respond to conventional therapy, including sarcoid, Blau syndrome and chronic recurrent multifocal osteomyelitis (CRMO)/synovitis, acne, pustulosis, hyperostosis and ostitis (SAPHO), persistent oligoarticular juvenile idiopathic arthritis

Subcutaneous < 30 kg [3] [4] [5] [9] [12] 20 mg/dose 1 x per 2 weken. There is little evidence regarding the use of adalimumab in children with this condition. Treatment by or after consulting a paediatric specialist (rheumatology) who has experience using adalimumab for this indication. ≥ 30 kg [3] [4] [5] [9] 40 mg/dose 1 x per 2 weken. There is little evidence regarding the use of adalimumab in children with this condition. Treatment by or after consulting a paediatric specialist (rheumatology) who has experience using adalimumab for this indication.

Hidradenitis suppurativa
Subcutaneous 12 years up to 18 years and ≥ 30 kg [1] Initial dose: Week 0: 80 mg/dose Maintenance dose: From week 1 onwards: 40 mg/dose once every 2 weeks If there is insufficient response to the maintenance dose, the frequency can be increased to once a week. Alternatively the dose may be increased to 80 mg every 2 weeks.

Ulcerative colitis
Subcutaneous ≥ 6 years and < 40 kg [20] Initial dose: Week 0: 80 mg/dose, once only. Maintenance dose: From  week 2 onwards: 40 mg/dose once every 2 weeks. ≥ 40 kg [20] Initial dose: Week 0: 160 mg/dose, once only. Maintenance dose: From  week 2 onwards: 80 mg/dose once every 2 weeks.

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

Warts, weight gain, fatigue, Crohn's disease, osteoporosis, atypical cervix cells [Tarkiainen]. Cases have been described in which children develop psoriatic plaques while using adalimumab [Perman].

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

Malignancies, some fatal, have been reported among children, adolescents and young adults (up to 22 years of age) treated with TNF-antagonists. Approximately half the cases were lymphomas. The other cases represented a variety of different malignancies and included rare malignancies usually associated with immunosuppression. A risk for the development of malignancies in children and adolescents treated with TNF-antagonists cannot be excluded. ^[24]

It is recommended that paediatric patients, if possible, be brought up to date with all immunisations in agreement with current immunisation guidelines prior to initiating Adalimumab therapy. Administration of live vaccines (e.g., BCG vaccine) to infants exposed to adalimumab in utero is not recommended for 5 months following the mother’s last adalimumab injection during pregnancy. ^[24]

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
	Etanercept Related Medicines Menu">	L04AB01
	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. AbbVIe Ltd, SPC Humira EU/1/03/256/002-005 (23-05-2018), www.emea.europa.eu
2. Chiu HY et al., The effectiveness and safety of adalimumab in the treatment of non-reimbursed patients with mild-to-moderate psoriasis., J Eur Acad Dermatol Venereol, 2012, Aug;26(8), 991-8
3. Eleftheriou D et al. , Biologic therapy in refractory chronic non-bacterial osteomyelitis of childhood., Rheumatology (Oxford) , 2010, Aug;49(8):, 1505-12
4. Ferguson PJ et al. , Current understanding of the pathogenesis and management of chronic recurrent multifocal osteomyelitis., Curr Rheumatol Rep, 2012, Apr;14(2):, 130-41
5. Frkovic M et al. , Effects of anti-TNF therapy on ophtalmological complications in children with rheumatic diseases., Ped Rheum. , 2014, 12 suppl. 1
6. Joy MS et al. , Phase 1 trial of adalimumab in Focal Segmental Glomerulosclerosis (FSGS): II. Report of the FONT (Novel Therapies for Resistant FSGS) study group, Am J Kidney Dis, 2010, Jan;55(1), 50-60
7. Marmon S et al. , Psoriasis and Down syndrome: A report of three cases and a potential pathophysiologic link., Dermatol Online J., 2012, Jun 15;18(6):, 13
8. Perman MJ et al. , Five cases of anti-tumor necrosis factor alpha-induced psoriasis presenting with severe scalp involvement in children, Pediatr Dermatol. , 2012, Jul-Aug;29(4):, 454-9
9. Petiti Martin G et al. , Misdiagnosed childhood sarcoidosis as non-Langerhans' cell histiocytosis treated with tumor necrosis factors-α antagonists., J Am Acad Derm., 2012, 66(4) , suppl. 1:AB165
10. Simonini G et al. , Current evidence of anti-tumor necrosis factor α treatment efficacy in childhood chronic uveitis: A systematic review and meta-analysis approach of individual drugs., Arthritis Care Res (Hoboken)., 2014, Jul;66(7):, 1073-84
11. Tarkiainen M et al. , Occurrence of adverse events in patients with JIA receiving biologic agents: long-term follow-up in a real-life setting., Rheumatology (Oxford). , 2015, Jul;54(7):, 1170-6
12. Arvesen KB et al., Diagnosis and Treatment of Blau Syndrome/Early-onset Sarcoidosis, an Autoinflammatory Granulomatous Disease, in an Infant, Acta Derm Venereol. , 2017, Jan 4;96(7), 126-127
13. Ramanan AV et al., Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis, N Engl J Med. , 2017, Apr 27;376(17), 1637-1646
14. Papp K et al., Efficacy and safety of adalimumab every other week versus methotrexate once weekly in children and adolescents with severe chronic plaque psoriasis: a randomised, double-blind, phase 3 trial, Lancet, 2017, Jul 1;390(10089), 40-49
15. Anink J et al., ., , Tumour necrosis factor-blocking agents in persistent oligoarticular juvenile idiopathic arthritis: results from the Dutch Arthritis and Biologicals in Children Register, Rheumatology (Oxford), 2013 , Apr;52(4), 712-7
16. Beukelman T et al., American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features., , Arthritis Care Res (Hoboken), 2011 , Apr;63(4), 465-82
17. Moued MM et al., Oligoarticular juvenile idiopathic arthritis among Saudi children, Ann Saudi Med, 2013, Nov-Dec;33(6), 529-32
18. Schmeling H et al., Efficacy and safety of adalimumab as the first and second biologic agent in juvenile idiopathic arthritis: the German Biologics JIA Registry, Arthritis Rheumatol., 2014, Sep;66(9), 2580-9
19. AbbVie, SmPC Humira 12/2018, https://www.ema.europa.eu/en/medicines/human/EPAR/humira#product-information-section
20. Amgen Europe B.V., SmPC Amgevita EU/1/16/1164/001-009 (23-08-2021), /www.ema.europa.eu/

Changes

Therapeutic Drug Monitoring

Overdose