SANDIMMUN

What it is

Sandimmun contains ciclosporin and is available as capsules of 25 mg, 50 mg or 100 mg, or as a concentrate for intravenous infusion containing 250 mg/5 mL or 50 mg/1 mL.

Approved indications

— Prevention of graft rejection following kidney, liver and heart allogeneic transplantation. — Induction and/or maintenance of remission in nephrotic syndrome. — Treatment of severe, active rheumatoid arthritis in patients for whom classical slow-acting antirheumatic agents (including methotrexate) are inappropriate or ineffective. — Treatment of severe psoriasis in patients in whom conventional therapy is ineffective or inappropriate and the disease has caused significant interference with quality of life. — Treatment of severe atopic dermatitis when other treatment is ineffective or inappropriate.

Dosing overview

For organ transplantation, a single oral dose of 10–15 mg/kg is given 4–12 hours prior to transplantation and maintained for one to two weeks post-operatively before being gradually reduced until a maintenance dose of about 2–6 mg/kg per day is reached. For nephrotic syndrome induction, the recommended dose is 5 mg/kg per day for adults and 6 mg/kg per day for children if renal function is normal. For rheumatoid arthritis, the recommended dose for the first 6 weeks is 3 mg/kg per day orally in two divided doses, with up to 12 weeks required to achieve full effectiveness; if no clinical response occurs in 4–8 weeks, the dose may be increased at 1–2 month intervals by 0.5–1.0 mg/kg per day up to a maximum of 5.0 mg/kg per day. For psoriasis induction, the recommended initial dose is 2.5 mg/kg per day orally in two divided doses; if there is no improvement after one month, the dose may be increased gradually but should not exceed 5 mg/kg. For atopic dermatitis, the recommended dose range is 2.5–5 mg/kg per day in two divided oral doses; if a starting dose of 2.5 mg/kg per day does not achieve satisfactory response within two weeks, the daily dose may be rapidly increased to a maximum of 5 mg/kg.

Key safety warnings

Ciclosporin increases the risk of developing lymphomas and other malignancies, particularly those of the skin, with the increased risk appearing to be related to the degree and duration of immunosuppression rather than to the use of specific agents. Patients taking ciclosporin should be strongly advised to avoid excessive unprotected exposure to ultraviolet light or the sun. Ciclosporin predisposes patients to the development of a variety of bacterial, fungal, parasitic and viral infections, often with opportunistic pathogens. Activation of latent Polyomavirus infections may lead to Polyomavirus-associated nephropathy, especially BK virus nephropathy, or to JC virus-associated progressive multifocal leukoencephalopathy. Hypertension induced by ciclosporin has been reported in up to 50% of post-transplant patients and 8.5% of patients being treated for non-transplant indications. Regular monitoring of blood pressure is required during ciclosporin therapy; if hypertension develops, appropriate antihypertensive treatment must be instituted. Hyperkalaemia, which may become life-threatening, can occur with ciclosporin treatment, especially in patients with renal dysfunction. An increase in serum creatinine and urea may occur during the first few weeks of ciclosporin therapy; these functional changes are dose-dependent and reversible, usually responding to dose reduction. During long-term treatment, some patients may develop structural changes in the kidney such as arteriolar hyalinosis, tubular atrophy and interstitial fibrosis.

Contraindications

Known hypersensitivity to ciclosporin and/or polyoxyethylated castor oil (Cremophor EL) or any of the other excipients of Sandimmun. For non-transplant indications: uncontrolled hypertension and uncontrolled infection. Primary or secondary immunodeficiency excluding autoimmune diseases and selective IgA deficiency. For nephrotic syndrome: ciclosporin is contraindicated in patients with impaired baseline renal function (serum creatinine greater than 200 micromol/L in adults and greater than 140 micromol/L in children). In other non-transplant indications, ciclosporin is contraindicated in patients with impaired renal function of any degree of severity.

PBS listing

Sandimmun concentrate for intravenous infusion 50 mg in 1 mL is listed on the PBS with 2 items under streamlined restrictions at an ex-manufacturer price of A$54.10.

Regulatory history

Sandimmun ciclosporin 50 mg/1 mL injection ampoule was first registered on the ARTG on 21 August 1991, and the 250 mg/5 mL injection ampoule was first registered on 6 December 1993.