Ciclosporin

Ciclosporin is an immunosuppressant and is mainly used after organ transplantation to prevent rejection reactions. For this purpose, a high dose is started initially, reduced over several months, and then a low maintenance dose must be taken for the rest of the patient's life. Another possible application is autoimmune diseases such as psoriasis, glomerulonephritis or inflammatory bowel diseases such as ulcerative colitis. In the case of inflammation of the conjunctiva or cornea of the eye, ciclosporin can also be applied as a cream.

Pharmacodynamics

The immunosuppressant binds to cyclophilin and the resulting complex inhibits the activity of calcineurin. This regulates the release of inflammatory cytokines. Thus, ciclosporin inhibits the activity of T cells and the normally resulting immune response. The full effect unfolds only after three months of intake.

Pharmacokinetics

Maximum plasma levels are reached after approximately one hour. The immunosuppressant is metabolized via the cytochrome P450 system, primarily via CYP3A4. It is eliminated particularly via bile, with a half-life of approximately 6 hours.

Drug Interactions

Concomitant use of drugs that affect this enzyme CYP3A4 may alter the efficacy of ciclosporin. Thus, inducers of CYP3A4, such as rifampicin or dexamethasone, may reduce the efficacy of immunosuppression, while inhibitors such as fluconazole or verapamil may reduce degradation and thus increase side effects.

Side effects
Sehr häufig treten Kopfschmerzen, erhöhte Blutfette und Blutdruckwerte sowie Störungen der Nierenfunktion auf. Weitere häufige Nebenwirkungen sind Leberfunktionsstörungen, Elektrolytstörungen, Muskelkrämpfe und Magen-Darm-Beschwerden.

Many of these complaints can usually be alleviated by dose reduction.

Toxicological data
Durch die Schwächung des Immunsystems besteht bei Einnahme von Ciclosporin eine erhöhte Infektgefahr. Bei Transplantationspatienten liegt zudem das Krebsrisiko 3- bis 5-mal höher als in der Normalbevölkerung.