GN-AZATHIOPRINE

What it is

GN-AZATHIOPRINE tablets contain 50 mg azathioprine. The tablets are pale yellow, round, film coated, biconvex tablets engraved with "AZA", breakline & "50" on one face. Azathioprine is used as an immunosuppressant / antimetabolite either alone or, more commonly, in combination with other agents (usually corticosteroids) and procedures which influence the immune response.

Approved indications —

Organ transplant recipients, in combination with corticosteroids and / or other immunosuppressive agents and procedures. — Severe rheumatoid arthritis, either alone or in combination with corticosteroids and/or other procedures. — Systemic lupus erythematosus, either alone or in combination with corticosteroids and/or other procedures. — Dermatomyositis/polymyositis, either alone or in combination with corticosteroids and/or other procedures. — Autoimmune chronic active hepatitis, either alone or in combination with corticosteroids and/or other procedures. — Pemphigus vulgaris, either alone or in combination with corticosteroids and/or other procedures. — Polyarteritis nodosa, either alone or in combination with corticosteroids and/or other procedures. — Autoimmune haemolytic anaemia, either alone or in combination with corticosteroids and/or other procedures. — Chronic refractory idiopathic thrombocytopenic purpura, either alone or in combination with corticosteroids and/or other procedures.

Dosing overview

For transplantation in adults and children, an initial dosage of up to 5 mg/kg bodyweight/day may be given orally on the first day of therapy, with maintenance dosage ranging from 1 to 4 mg/kg/day orally, adjusted according to clinical requirements and haematological tolerance. Azathioprine therapy should be maintained indefinitely, even if only low doses are necessary, because of the risk of graft rejection. For other conditions in adults and children, the starting dose is generally 1 mg/kg/day, gradually increasing in increments of 0.5 mg/kg per day over several weeks, if necessary up to a maximum of 2.5 mg/kg/day. The maintenance dosage required may range from less than 1 mg/kg per day to 3 mg/kg per day depending on the clinical condition being treated and individual patient response, including haematological tolerance.

Key safety warnings

Azathioprine should be prescribed only if the patient can be adequately monitored for toxic effects throughout the entire duration of treatment. During the first eight weeks of therapy, complete blood counts including platelets must be performed weekly or more frequently if high dosage is used or if a co-existent severe renal and/or hepatic disorder is present, with frequency reduced later but repeated at intervals of not longer than one month or more frequently if dosage alterations or other changes to therapy are made. Individuals with an inherited deficiency of the enzyme thiopurine methyltransferase (TPMT) may be unusually sensitive to the myelosuppressive effect of azathioprine and prone to developing rapid bone marrow depression, and there have been fatal cases of myelosuppression in patients with low or absent TPMT activity treated with thiopurines. Patients should be tested for TPMT activity before starting azathioprine. Patients with inherited mutated NUDT15 gene are at increased risk for severe thiopurine toxicity, such as early leukopenia and alopecia, from conventional doses, with patients of Asian ethnicity particularly at risk due to increased frequency of the mutation in this population. Patients receiving immunosuppressive therapy, including azathioprine, are at an increased risk of developing lymphoproliferative disorders and other malignancies, notably skin cancers (melanoma and non-melanoma), sarcomas (Kaposi's and non-Kaposi's) and uterine cervical cancer in situ, with the increased risk appearing to be related to the degree and duration of immunosuppression. Azathioprine is hepatotoxic and liver function tests should be routinely monitored during treatment.

Contraindications

The use of GN-AZATHIOPRINE is contraindicated in patients with a previous history of hypersensitivity to azathioprine, any other component of the preparation, or any of the excipients in this product. Patients with rheumatoid arthritis previously treated with alkylating agents (cyclophosphamide, chlorambucil, melphalan or others) may have a prohibitive risk of neoplasia if treated with azathioprine. Therapy with GN-AZATHIOPRINE should not be initiated in patients who may be pregnant, who are likely to become pregnant in the near future, or who are known to be pregnant.

Regulatory history

GN-AZATHIOPRINE azathioprine 50 mg tablet blister pack was first listed on the Australian Register of Therapeutic Goods on 5 June 2012. A 25 mg tablet formulation was also first listed on the same date.