Pharmacokinetics in children

No information

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

Prophylaxis for rejection response in solid organ transplants

Oral 1 month up to 18 years [5] Initial dose: Start within 12 hours before the transplant with 10 - 15 mg/kg/day in 2 doses. for 1-2 weeks after the transplant.. Maintenance dose: Gradually reduce the dose to 2 - 6 mg/kg/day in 2 doses. for 3 or preferably 6 months, before the dose is gradually reduced to zero, 1 year after the transplant.. Intravenous 1 month up to 18 years [6] Initial dose 3 - 5 mg/kg/day in 2 doses. Maintenance dose: Orally. Duration of treatment: 1-2 weeks after transplant

Prophylaxis of rejection after bone marrow transplant

Intravenous 1 month up to 18 years [6] Initially: 1 day before the transplant: 3 - 5 mg/kg/day in 2 doses. Maintenance dose: Orally. Duration of treatment: up to 1-2 weeks after transplant Oral 1 month up to 18 years Initial dose: Start on the day before the transplant 12.5 - 15 mg/kg/day in 2 doses. Maintenance dose: 12.5 mg/kg/day in 2 doses. Duration of treatment: At least 3 months. (and preferably 6 months) before the dose is gradually reduced to zero, 1 year after the transplant.

Rescue therapy in ulcerative colitis to postpone colectomy
Intravenous 1 month up to 18 years [3] Initial 2 mg/kg/day, continuous infusion. Maintenance dose: adjust based on blood concentrations, target value 150-250 ng/ml. Duration of treatment: 7 days. If there is clinical remission, switch to oral dosing. Oral 1 month up to 18 years [3] After remission is achieved with intravenous administration: 5 mg/kg/day in 2 doses.

Psoriasis, severe, refractory
Oral 1 month up to 18 years Initial dose: 3 - 5 mg/kg/day in 2 doses. Maintenance dose: < 3 mg/kg/day in 2 doses. Treatment by or after consultation with a pediatric specialist (dermatologist) who has experience in the use of cyclosporine in this indication.

Severe constitutional eczema

Oral 1 year up to 18 years [4] [7] [10] [12] [15] [16] [17] [18] [21] Initial dose: 3 - 5 mg/kg/day in 2 doses. For 3-6 weeks. Maintenance dose: 2 - 5 mg/kg/day in 2 doses. Duration of treatment: If no improvement occurs within 4 weeks at the highest tolerated dose, discontinuation of ciclosporine should be considered. Continue treatment for at least 3 months when proven effective. Decrease dose gradually at discontinuation of treatment. ALTERNATIVE: After 1 year of daily use or more, consider treatment on 2 consecutive days per week, followed by a 5 day break (Garrido Colmenero, Blasco Morente, and Tercedor Sanchez 2015). In obesity, lower doses are required to achieve the same plasma concentration, close monitoring is recommended (Ross et al. 2015). Treatment by or after consultation with a pediatric specialist (dermatologist) experienced in the use of cyclosporine in this indication

Nephrotic syndrome
Oral ≥ 1 year [5] 6 mg/kg/day in 2 doses.

Renal impaiment in children > 3 months

Reconsider use in patients with renal impairment. When use outweighs the (potential) nephrotoxicity: if possible start with a low dose (2.5mg / kg / d in 2 doses) and titrate to the lower limit of the target bloodlevels. In addition to bloodlevels regularly monitor the renal function.

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

Hypertension, neurotoxicity (tremors, convulsions, transient white matter abnormalities), gingival hyperplasia, hirsutism, hypomagnesaemia. Pseudotumor cerebrihas been reported in 5 cases (Somech and Doyle 2007, Costa et al. 2010, Büscher et al. 2004, Bilginer et al. 2010, Dogulu et al. 2004).

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

Be aware of the possibility of nephrotoxicity, hypertension, and elevated cholesterol and triglyceride levels.

Monitoring:

• Monitor blood pressure, creatinine, ALT and complete blood count at the start of treatment, 6 weeks after start, 12 weeks after start and after each dose increase (Yee and Orchard 2018).
• Subsequently, at a stable dose, follow-up every 12 weeks (if earlier labvalues were normal).
• The following recommendations apply when lab values are abnormal:
  • Liver enzymes> 2x normal: reduce dose and monitor every 4-6 weeks. If> 3x normal value: temporarily stop and evaluate the lowest possible safe dosage on restart.
  • For thrombocytes <100x10⁹ / L and / or neutrophils <1.5x10⁹ / L: reduce dose and consult with pediatric rheumatologist / immunologist if necessary. Monitor weekly.
• Pay attention to vaccination advice during cyclosporine use.
• Pay attention to adequate contraception / desire to have children. Ciclosporin can be used during pregnancy if necessary, but extra monitoring of the newborn is needed.

In obese children, lower doses are required to achieve the same plasma concentration. Close monitoring is recommended (Ross et al. 2015).

Therapeutic blood concentration: 0.1-0.3 mg / l (HPLC determination) depending on indication and stage of treatment.

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
	Infliximab Related Medicines Menu">	L04AB02

Calcineurin inhibitors
	Tacrolimus Related Medicines Menu">	L04AD02

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

References

1. Rademaker C.M.A. et al, Geneesmiddelen-Formularium voor Kinderen, 2007
2. Heijden, van der AJ et al, Werkboek Kindernefrologie, VU Uitgeverij, 2002, 1e druk
3. Nederlandse Vereniging voor Kindergeneeskunde., CBO Richtlijn Diagnostiek en behandeling van Inflammatoire darmziekten bij Kinderen, 2007, 114-115
4. CBO, Richtlijn Constitutioneel Eczeem, www.cbo.nl, Maart 2015
5. Teva Nederland BV, SmPC Ciqorin (RVG 111629) 28-03-2018, www.cbg-meb.nl
6. Novartis Pharma B.V. , SmPC Sandimmune (RVG 09846) 27 feb 2020, www.geneesmiddeleninformatiebank.nl
7. Bemanian, M. H., et al, High doses intravenous immunoglobulin versus oral cyclosporine in the treatment of severe atopic dermatitis., Iran J Allergy Asthma Immunol, 2005, 4(3), 139-43
8. Bilginer, Y., et al, Pseudopapilledema in a pediatric kidney transplant recipient, Pediatr Transplant , 2010, 14(7), E83-5
9. Costa, K. M., et al, Pseudotumor cerebri associated with cyclosporin use following renal transplantation, J Bras Nefrol , 2010, 31(1), 136-9
10. Berth-Jones, J., A. et al, Cyclosporine in severe childhood atopic dermatitis: a multicenter study., J Am Acad Dermatol, 1996, 34(6), 1016-21
11. Somech, R., et al, Pseudotumor cerebri after allogeneic bone marrow transplant associated with cyclosporine a use for graft-versus-host disease prophylaxis, J Pediatr Hematol Oncol , 2007, 29(1), 66-8
12. Guarneri, B., et al, Cyclosporin A treatment of severe atopic dermatitis in a child., Pediatr Dermatol, 1994, 11(2), 186
13. Dogulu, C. F., et al , Idiopathic intracranial hypertension in cystinosis., J Pediatr, 2004, 145(5), 673-8
14. Yee, J., et al, Monitoring recommendations for oral azathioprine, methotrexate and cyclosporin in a paediatric dermatology clinic and literature review, Australas J Dermatol , 2018, 59(1), 31-40
15. Nederlandse Vereniging voor Dermatologie en Venerelogie, Richtlijn constitutioneel eczeem., https://nvdv.nl/professionals/richtlijnen-en-onderzoek/richtlijnen/richtlijn-constitutioneel-eczeem, 2019
16. Bunikowski, R., et al, Low-dose cyclosporin A microemulsion in children with severe atopic dermatitis: clinical and immunological effects., Pediatr Allergy Immunol , 2001, 12(4), 216-23
17. Gonzalez-Otero, F., et al, Ciclosporina A en Microemulsión Oral, en niños con Dermatitis Atópica Severa., Derm Vene, 1997, z35, 111-114
18. Harper, J. I.,et al, Cyclosporin for severe childhood atopic dermatitis: short course versus continuous therapy., Br J Dermatol , 2000, 142(1), 52-8
19. Büscher, R., et al, Pseudotumor cerebri following cyclosporine A treatment in a boy with tubulointerstitial nephritis associated with uveitis., Pediatr Nephrol, 2004, 19(5), 558-60
20. Garrido Colmenero, C., et al, Oral Cyclosporine Weekend Therapy: A New Maintenance Therapeutic Option in Patients with Severe Atopic Dermatitis, Pediatr Dermatol, 2015, 32(4), 551-2
21. Ross, E. L., et al , Development of recommendations for dosing of commonly prescribed medications in critically ill obese children., Am J Health Syst Pharm, 2015, 72(7), 542-56
22. Novartis, SmPC Sandimmun® 100 mg/ml Lösung zum Einnehmen (26418.00.00), 09/2015
23. Novartis, SmPC Sandimmun 25/100 mg Weichkapseln (26418.00.01), 09/2015
24. Novartis, SmPC Sandimmun® 50 mg/ml Konzentrat zur Herstellung einer Infusionslösung (3123.00.00), 07/2015
25. Hexal, SmPC Ciclosporin 25/50/100 mg Weichkapseln (53545.00.00), 04/2014
26. Teva, SmPC Ciclosporin Pro 100 mg/ml Lösung zum Einnehmen (62306.00.00), 04/2018
27. Wirkstoffdossier, Monografie Ciclosporin, Accessed 02/08/2018

Changes