Products
Ciclosporin is commercially available as capsules, a drinkable solution, and an infusion concentrate (Sandimmune, Sandimmune Neoral, generics). It has been approved in many countries since 1995. Neoral is the microemulsion formulation that has more stable bioavailability than traditional Sandimmune. In 2016, ciclosporin eye drops were approved (see there).
Structure and properties
Ciclosporin (C62H111N11O12, Mr = 1203 g/mol) exists as a white powder that is practically insoluble in water. It is extracted from the mushroom ( chamois) or produced by other methods. The fungus was originally found by a Sandoz employee in a soil sample from Norway. Ciclosporin is a lipophilic cyclic polypeptide consisting of 11 amino acids (undecapeptide).
Effects
Ciclosporin (ATC L04AD01) has immunosuppressive properties, prolonging the life of grafts. It is a calcineurin inhibitor and is mainly active against lymphocytes (T cells). It passes through the cell membrane and binds to cyclophilin. This complex inhibits the calcium-dependent phosphatase calcineurin, which is involved in gene activation and transcription of mediators such as interleukins (e.g., IL-2).
Indications
- Prophylaxis of graft rejection.
- Endogenous uveitis
- Severe psoriasis
- Severe atopic dermatitis
- Chronic polyarthritis / rheumatoid arthritis
- Nephrotic syndrome
- Severe keratitis see under ciclosporin eye drops.
- Other indications (off-label)
Dosage
According to the professional information. Oral medicines are usually administered twice daily, i.e. in the morning and in the evening, independently of meals. Concomitant ingestion of a high-fat meal or grapefruit juice may increase bioavailability.
Contraindications
- Hypersensitivity
If ciclosporin is not used after transplantation, additional contraindications apply:
- Renal insufficiency
- Inadequately controlled hypertension
- Insufficiently controlled infections
- Malignant diseases
For complete precautions, see the drug label.
Interactions
Ciclosporin has a high interaction potential. It is a substrate of CYP3A and of P-glycoprotein. In addition, other drug-drug interactions are possible.
Adverse effects
The most common potential adverse effects include renal dysfunction, tremor, hirsutism, hypertension, and gingival hyperplasia. Because of immunosuppression, there is an increased risk of infections and neoplasms.
