Cyclosporine is used for the following conditions:

Transplantation

• Solid organ transplantation
• Bone marrow transplantation

Non-transplantation indications

• Endogenous uveitis
• Nephrotic syndrome
• Rheumatoid arthritis
• Psoriasis
• Atopic dermatitis

Cyclosporine is a cyclic polypeptide composed of 11 amino acids. It is a strong immunosuppressive drug that helps prolong the survival of transplanted organs such as skin, heart, kidney, pancreas, bone marrow, small intestine, and lungs. It works selectively and reversibly on lymphocytes. Unlike cytotoxic drugs, it does not suppress blood cell formation (haemopoiesis) and does not affect the function of phagocytic cells. Patients taking cyclosporine are generally less susceptible to infections compared to those receiving other immunosuppressive treatments.

Solid organ transplantation: Initially 10 to 15 mg/kg given in 2 divided doses starting 12 hours before surgery and to continue for 1 to 2 weeks post-operatively. Maintenance dose should be gradually reached to 2 to 6 mg/kg given in 2 divided doses.

Bone marrow transplantation: Initially 12.5 to 15 mg/kg given in 2 divided doses, starting on the day before transplantation. Maintenance treatment of 12.5 mg/kg in 2 divided doses should be continued for at least 3 months (and preferably for 6 months) before the dose is gradually decreased to zero by 1 year after transplantation.

Endogenous uveitis: Initially 5 mg/kg per day orally given in 2 divided doses are recommended. For maintenance treatment, the dose should be slowly reduced to the lowest effective level.

Nephrotic syndrome: Initially 5 mg/kg for adults and 6 mg/kg for children given in 2 divided doses. In case of renal impairment, the initial dose should not exceed 2.5 mg/kg per day. For maintenance treatment, the dose should be slowly reduced to the lowest effective level.

Rheumatoid arthritis: For the first 6 weeks, the recommended dose is 3 mg/kg per day in 2 divided doses. To achieve full effectiveness, up to 12 weeks of therapy may be required. For maintenance treatment, the dose has to be titrated individually according to tolerability.

Psoriasis & Atopic dermatitis: Initially 2.5 mg/kg per day orally given in 2 divided doses and 5 mg/kg per day for patients whose condition requires rapid improvement. For maintenance treatment, doses have to be titrated individually to the lowest effective level.

Drugs that decrease Cyclosporine levels: Barbiturates, carbamazepine, oxcarbazepine, phenytoin, nafcillin, sulfadimidine i.v., rifampicin, octreotide, probucol, orlistat, hypericum perforatum, ticlopidine, sulfinpyrazone, terbinafine, bosentan.

Drugs that increase Cyclosporine levels: Macrolide antibiotics (e.g., erythromycin, azithromycin and clarithromycin), ketoconazole, fluconazole, itraconazole, voriconazole, diltiazem, nicardipine, verapamil, lercanidipine, metoclopramide, oral contraceptives, danazol, methylprednisolone (high dose), allopurinol, amiodarone, cholic acid and derivatives, protease inhibitors, imatinib, colchicine.

Other relevant drug interactions: Cyclosporine may reduce the clearance of digoxin, colchicine, prednisolone and HMG-CoA reductase inhibitors (statins).

Hypersensitivity to ciclosporin or to any of the excipients of Sandimmun Neoral. The following additional contraindications apply to the non-transplant indications:

• Kidney failure, except in patients with nephrotic syndrome, in whom disease-related moderate increases in baseline serum creatinine values (max. 200 µmol/L in adults and max. 140 µmol/L in children) improve and cautious therapy (max. 2.5 mg/kg/day) is thus permitted.
• Uncontrolled hypertension
• Uncontrolled infection
• History of known or diagnosed malignancy of any kind except premalignant or malignant skin changes.

Renal: Renal dysfunction.
Cardiovascular: Hypertension.
Nervous system: Tremor, headache, paraesthesia.
Gastrointestinal tract and liver: Anorexia, nausea, vomiting, abdominal pain, diarrhoea, gingival hyperplasia and hepatic dysfunction.
Metabolic: Hyperlipidaemia, hyperuricaemia, hyperkalaemia, hypomagnesaemia.
Musculoskeletal: Muscle cramps, myalgia and rarely muscle weakness, myopathy.
Haemopoietic: Usually uncommon but anaemia, thrombocytopenia can occur.
Skin and appendages: Hypertrichosis and allergic rashes.

There are no adequate and well-controlled studies in pregnant women and, therefore, Sporium should not be used during pregnancy unless the potential benefit to the mother justifies the potential risk to the foetus. Cyclosporine passes into breast milk. Mothers receiving treatment with Sporium should not breast-feed.

Cyclosporine increases the risk of developing lymphomas and other malignancies, particularly those affecting the skin. Therefore, patients should be advised to avoid excessive exposure to ultraviolet light. Cyclosporine may predispose patients to bacterial, fungal, parasitic, and viral infections; appropriate therapeutic strategies should be followed during long-term immunosuppressive treatment. A reversible increase in serum creatinine and urea may occur during the initial weeks of Sporium therapy and usually responds to dose reduction. In elderly patients, renal function should be monitored carefully. Regular monitoring of blood pressure is necessary during Sporium therapy; if hypertension develops, suitable antihypertensive treatment should be initiated. Cyclosporine increases the risk of hyperkalaemia, especially in patients with renal impairment. Caution is required when Cyclosporine is used together with potassium-sparing drugs. Cyclosporine may increase magnesium clearance; if necessary, magnesium supplementation should be considered. Caution should be exercised in patients with hyperuricaemia. During Cyclosporine therapy, vaccination may be less effective, and the use of live-attenuated vaccines should be avoided. Non-transplant patients with impaired renal function, uncontrolled hypertension, uncontrolled infections, or any type of malignancy should not receive Cyclosporine.

Renal dysfunction may occur, which is usually reversible after discontinuation of the drug. Elimination can be achieved only by nonspecific measures, including gastric lavage, as Cyclosporine is not significantly removed by dialysis and is poorly cleared by charcoal hemoperfusion.

Immunosuppressant, Vaccines, Anti-sera & Immunoglobulin

Sporium oral solution should be used within 2 months after opening the bottle and stored at 15 to 30°C, preferably not below 20°C for prolonged periods, as it contains oily components that may solidify at lower temperatures. A jelly-like formation may occur below 20°C, which is reversible at temperatures up to 30°C. Slight sediment may be observed, which does not affect the efficacy and safety of the product.