Ciclosporin a

Immunosuppressive, highly lipophilic, membrane-permeable, cyclic polypeptide(calcineurin inhibitors). Binds in the cytoplasm to the immunophilin cyclophilin (CyP; responsible for intracellular metabolism of newly synthesized proteins).

The binding of the CyA/CyP complex to the Ca/Calmodulin dependent phosphatase calcineurin is responsible for the therapeutic effect.

Calcineurin is responsible for the dephosphorylation of the nuclear factor of activated T cells (NFAT).

NFAT is translocated into the cell nucleus where it induces the transcription of numerous genes.

The phosphatase activity of the enzyme calcineurin is inhibited by binding to the CyA/CyP complex, thus inhibiting the translocation of NFAT. The result: inhibition of the transcription of numerous cytokine genes such as IL-1, IL-2, IL-4, IL-8 (see below interleukins), TNF-alpha, INF-gamma.

• Systemic: Initial 2.5-7.5 mg/kg bw/day p.o., after one month gradual reduction to a maintenance dose of 1-2.5 mg/kg bw/day. By determining the blood plasma level, an optimal effective level of 100-200 ng/ml can be set (blood sample in the morning, before taking the preparation!).

Notice! Before the therapy: BB and check of the kidney function!

• Topical: Ciclosporin can also be used locally in a 1-2.5% application form. See below; see dentistry Ciclosporin A eye drops.

Cutaneous ADRs: hyperhidrosis, allergic reactions, urticaria, pruritus, periorbital edema, benign(sebaceous gland hyperplasia) and malignant skin tumors (especially in combination with phototherapy), acne, hirsutism, hypertrichosis, gingival hyperplasia.

Extracutaneous UAWs: BB changes, hyperglycemia, gynecomastia, amenorrhea, spermatogenesis inhibition, sinusitis, gastrointestinal disturbances, liver damage, hypertension, edema, headache, seizures, paresthesias, renal damage, hearing loss, visual disturbances, myalgias, arthralgias, rhabdomyolysis.

Interaction of ciclosporin with CYP enzymes (CYP3A4) may result in increased or decreased clearance of drugs (see also Enzyme Induction). S. Tab.

Hypertension, renal insufficiency, children and adolescents < 18 years (for indication psoriasis vulgaris), severe liver damage (for indication psoriasis vulgaris), lactation, hypersensitivity to the active substance or excipient Cremophor EL, psoriasis pustulosa, psoriatic erythroderma.

Notice. PUVA therapy must not be performed after ciclosporin therapy due to an increased risk of spinocellular carcinomas!

Ciclosporin A adhesive paste 2,5%.

Ciclosporin A solution 1-2% (according to Altmeyer - R047)

Sandimmun, Sandimmun Optoral; SANDIMMUN Neoral 50 mg soft capsules; immunosporin; ^Ikervis®.

• Conclusion for the indication psoriasis: Ciclosporin is an effective antipsoriatic agent (rapid reduction of PASI and skin findings as well as increase of the patient's quality of life); side effects (malignomrisko, nephrotoxicity, hypertension) are to be minimized by an advantage of short-term therapy over long-term therapy.
• Ciclosporin A (e.g. immunosporin) is approved for systemic therapy of atopic eczema. Encouraging studies have been published regarding the effectiveness of Ciclosporin for the systemic treatment of severe forms of atopic eczema. 73 volunteers were treated with Ciclosporin (2.5-5 mg/kg bw/day) on average over 1.13 years. Within the first weeks of therapy, a rapid clinical improvement was observed, with 77% of the subjects receiving successful treatment. The main adverse drug reactions were creatinine increase and arterial hypertension. A rebound phenomenon (recurrence of clinical symptoms, more severe than before therapy) occurred in 8% of the subjects after the end of treatment.

Notice! Practical advice to reduce potential nephrotoxicity: Limit the dose of Ciclosporin to max. 5 mg/kg bw/day. Check creatinine 2 times before starting therapy. Serum creatinine follow-up every 2 weeks for the first 3 months, then monthly. Regular control of the blood pressure. The duration of therapy should be kept as short as possible.

1. Bornhovd EC et al (2000) Immunosuppressive macrolides and their use in dermatology. Dermatologist 51: 646-654
2. Boschnakow A et al (2003) Ciclosporin A-induced sebaceous gland hyperplasia. Br J Dermatol 149: 198-200
3. Heydendael VM et al (2003) Methotrexate versus cyclosporine in moderate to severe chronic plaque psoriasis. N Engl J Med 349: 658-665
4. Hijnen DJ et al (2007) Efficacy and safety of long-term treatment with cyclosporin A for atopic dermatitis. J Eur Acad Dermatol Venereol 21: 85-89
5. Ho VC (2004) The use of ciclosporin in psoriasis: a clinical review Br J Dermatol 150 (Suppl. 67): 1-10
6. Ortiz-Urda S et al (2003) New immunosuppressive agents for treating psoriasis. dermatologist 54: 230-236
7. Sano S et al (2003) Treatment of primary erythromelalgia with cyclosporine. N Engl J Med 349: 816-817
8. Zouboulis C et al (2003) Ciclosporin A - induced sebaceous glands hyperplasia. Br J Dermatol 149: 198-200

Significant interactions of Ciclosporin A