NEORAL

What it is

Neoral is a ciclosporin medicine available in capsules of 10 mg, 25 mg, 50 mg and 100 mg strength. Neoral is also available as an oral solution containing 100 mg/mL of ciclosporin. Neoral should always be given in two divided doses.

Approved indications —

As an immunosuppressive agent for the prevention of graft rejection following kidney, liver and heart allogeneic transplantation. — For induction and/or maintenance of remission in the nephrotic syndrome. Ciclosporin is not a first-line agent. Its use should be restricted to occasions when steroids and cytostatic drugs have failed, or are not tolerated, or are considered inappropriate, and when renal function is unimpaired. — For the treatment of severe, active rheumatoid arthritis in patients for whom classical slow-acting antirheumatic agents (including methotrexate) are inappropriate or ineffective. — In patients with severe psoriasis in whom conventional therapy is ineffective or inappropriate and the disease has caused a significant interference with quality of life. — For the treatment of severe atopic dermatitis when other treatment is ineffective or inappropriate.

Dosing overview

Dosing varies by indication. For organ transplantation, treatment should be initiated within 12 hours before surgery at a dose of 10 to 15 mg/kg given in two divided doses, maintained as a daily dose 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; in patients with impaired renal function, the initial dose should not exceed 2.5 mg/kg per day. For rheumatoid arthritis, the recommended dose for the first 6 weeks is 3 mg/kg per day, with possible increases by 0.5 to 1.0 mg/kg per day up to a maximum of 5.0 mg/kg per day if there is no clinical response in 4 to 8 weeks. For psoriasis induction, the recommended initial dose is 2.5 mg/kg per day orally, which may be increased gradually if there is no improvement after one month, but should not exceed 5 mg/kg. For atopic dermatitis, the recommended dose range is 2.5 to 5 mg/kg per day, with rapid increase to 5 mg/kg possible if the starting dose does not achieve satisfactory response within two weeks.

Key safety warnings

Like other immunosuppressants, Neoral increases the risk of developing lymphomas and other malignancies, particularly those of the skin. The increased risk appears to be related to the degree and duration of immunosuppression. A treatment regimen containing multiple immunosuppressants should be used with caution as this could lead to lymphoproliferative disorders and solid organ tumours, some with reported fatalities. Because of the significantly increased risk over time of developing skin cancers, patients taking Neoral should be strongly advised to avoid excessive unprotected exposure to ultraviolet light or the sun. Like other immunosuppressants, Neoral predisposes patients to the development of a variety of bacterial, fungal, parasitic and viral infections, often with opportunistic pathogens. Activation of latent Polyomavirus infections that may lead to Polyomavirus associated nephropathy, especially to BK virus nephropathy or to JC virus associated progressive multifocal leukoencephalopathy have been observed in patients receiving Neoral. Hypertension induced by Neoral 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 Neoral therapy; if hypertension develops, appropriate antihypertensive treatment must be instituted. Hyperkalaemia, which may become life-threatening, can occur with Neoral treatment, especially in patients with renal dysfunction. Patients receiving Neoral should avoid high dietary potassium intake and not be given potassium-containing medication or potassium-sparing diuretics. Caution is also required when Neoral is co-administered with angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists. Monitoring of serum potassium is recommended, especially in patients with marked renal dysfunction. A frequent and potentially serious complication, an increase in serum creatinine and urea may occur during the first few weeks of Neoral therapy. These functional changes are dose dependent and reversible, usually responding to dose reduction.

Contraindications

All indications: Known hypersensitivity to ciclosporin and/or any excipients of Neoral. For non-transplant indications: Uncontrolled hypertension, uncontrolled infection. Primary or secondary immunodeficiency excluding autoimmune diseases and selective IgA deficiency. The use of Neoral in nephrotic syndrome is contraindicated in patients with impaired baseline renal function (serum creatinine >200 micromol/L in adults and >140 micromol/L in children). In other non-transplant indications, Neoral is contraindicated in patients with impaired renal function of any degree of severity.

PBS listing

Neoral is listed on the PBS in capsule strengths of 10 mg, 25 mg, 50 mg and 100 mg, with ex-manufacturer prices of A$37.20, A$22.04, A$45.87 and A$93.45 respectively. An oral liquid formulation at 100 mg per mL in 50 mL bottles is also listed with an ex-manufacturer price of A$315.79. Each strength has multiple PBS items with varying restrictions including restricted, streamlined and unrestricted categories.

Regulatory history

Neoral was first registered on the ARTG on 28 August 1995, with initial listings for the 25 mg, 50 mg and 100 mg capsules and the 100 mg/mL oral liquid. A 10 mg capsule formulation was added to the register on 22 September 1997.