Ciclosporin

Generic name
Ciclosporin
Brand name
ATC Code
L04AD01
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Ciclosporin

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

Interactions
PK
Renal impairment
References

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

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Severe constitutional eczema
  • Oral
    • 1 year up to 18 years
      • 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

    • 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
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.

    • 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.
Nephrotic syndrome
  • Oral
    • ≥ 1 year
      • 6 mg/kg/day in 2 doses.
Prophylaxis for rejection response in solid organ transplants
  • Intravenous
    • 1 month up to 18 years
      • Initial dose 3 - 5 mg/kg/day in 2 doses. Adjust dose based on TDM.

      • Switch to oral maintenance therapy as soon as possible
Prophylaxis of rejection after bone marrow transplant
  • Intravenous
    • 1 month up to 18 years
      • Initially: 1 day before the transplant: 3 - 5 mg/kg/day in 2 doses. Adjust dose based on TDM.
  • Oral
    • 1 month up to 18 years
      • 12.5 - 15 mg/kg/day in 2 doses. Adjust dose based on TDM.
Rescue therapy in ulcerative colitis to postpone colectomy
  • Intravenous
    • 1 month up to 18 years
      • Initial 2 mg/kg/day, continuous infusion. Maintenance dose: adjust dose based on TDM.
      • Duration of treatment:

        If there is clinical remission, switch to oral dosing.

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

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.

Selective immunosuppressants
L04AA24
L04AA32
L04AA13
L04AA02
L04AA06
L04AA31
L04AA04
L04AA44
Other immunosuppressants
L04AX01
L04AX03
Tumor necrosis factor alpha (TNF-alpha) inhibitors
L04AB04
L04AB01
L04AB06
L04AB02
Interleukin inhibitors
L04AC03
L04AC02
L04AC08
L04AC13
L04AC19
L04AC10
L04AC22
L04AC07
L04AC05
Calcineurin inhibitors
L04AD02
Sphingosine-1-phosphate (S1P) receptor modulators
L04AE01
Janus-associated kinase (JAK) inhibitors
L04AF02
L04AF02
L04AF08
L04AF01
Monoclonal antibodies
L04AG04
Mammalian target of rapamycin (mTOR) kinase inhibitors
L04AH02
L04AH01
Complement inhibitors
L04AJ01
L04AJ02
Dihydroorotate dehydrogenase (DHODH) inhibitors
L04AK02

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
  28. Novartis Pharma B.V., SmPC Sandimmune (RVG 09846) 14-03-2025, www.geneesmiddeleninformatiebank.nl

Changes

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